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Loten, Loten

Author has written 21 stories for Immortals, Tamora Pierce, and Harry Potter.

'Loten' is an Old English word, meaning moonlight bright enough to see by.

September 16th 2016: I'm alive, I promise. Just busy. Very, very busy. Buying a house, working full time busy. Almost ready to actually move now. Blog news: Final chapter of Philosopher's Stone should be up this weekend.

PTL hit 3k (quite a while ago now, I'm sorry) and there will be two one-shots for it. eventually.

I currently have a few half-finished things I don't intend to work on for a little while. I'm going to be working on something a bit different instead, something I will hopefully actually want to finish. It's a shorter project so it hopefully won't take as long. Sorry guys, I know a lot of you want to see more from me. I do too, believe me! (I'm also going to try not to forget to update this profile, oops. )

You should check out my blog, link below.

I run a blog now! With my partner Mitchell ( Explopyro ). Here it is: pointstick. wordpress. com . You should stop by and browse - we have book reviews, including the start of a complete Harry Potter shredding, some rambling, some serious topics, all sorts. You can follow it for updates via email too, I believe (I'm still figuring out how everything works, hush.)

If anything should ever happen to my account or my stories, check it out and I shall post to let everyone know what's going on and where I will be moving to. You don't need to be a member of the site to see it. Until then, this is the only place I will be posting my fics. If one appears somewhere else, tell me, because it wasn't me.

Random trivia: In parts of Scandinavia, the days are all named for saints; April 30th is St Severus' Day and September 4th is St Hermione's day. More random trivia: Severus of Avranches (one of the St. Severi) is the patron saint of migraine sufferers. Appropriate, no?

Disclaimer: I accept no responsibility for anything that occurs whilst reading my fics, including but not limited to sleep deprivation, funny looks incurred by involuntary loud noises, tasks not being completed whether academic, social or any other, and general insanity.

I have a deviantArt under the name Loten with a few bits and pieces on it. I still play a few virtual pet sites, though not much. I have a Pottermore beta test account, too (obviously I'm in Slytherin!) but I don't play enough for it to be worth giving out my username there. Fun fact - my Pottermore wand is rowan and dragon heartstring, the wand I gave Severus in PTL long before Pottermore ever existed and will continue to give him in any fic where his canon wand is broken. (I've actually abandoned Pottermore now. I covered the content of all seven books on the blog, see above, but when they redid the whole thing and it turned into Buzzfeed I walked away.)

I'm 29, I'm female, I'm a Gemini, I live in south Wales and I graduated from a Welsh university in 2008 with a degree in zoology. I work in retail, and I'm wasting a very expensive and pointless education by happily writing fanfiction. I have four tattoos, so far, and I wear glasses. I try not to take life too seriously and I'm nowhere near as complicated as I like to think I am.

I will always reply to every single signed review unless you have private messaging disabled. You took the time to review, the least I can do is answer.

I will always gladly answer questions about my fics or discuss anything about the fandoms I write for. I've been known to offer writing advice when asked, too, although how much help I've actually been is anyone's guess. Don't be afraid to message me, I don't bite.

For every 1,000 reviews for a story, I offer a prize to that reviewer, a one-shot of their choice - within limits.

I will never abandon a story half way through. I will never upload the first chapter of a story unless I have a rough draft of the entire story already completed. I will never upload the first chapter of a story unless I am happy with the rough draft and confident that I can complete it to a standard I am satisfied with.

The only things that would ever stop me completing a story are computer issues or serious real life issues. When uploading a story, I will do my best to update it every few days; once a week at the longest. I know how horrible it is to be left hanging for months waiting for an update. If I ever do stop updating, there will be a message at the top of my profile explaining why. If there isn't, and I don't reappear within a fortnight, I'm probably dead.

There isn't much I won't read. I truly hate mpreg and noncon/dubcon and I don't like incest much; I also don't see the humour in most crackfics. I won't read characters from my OTPs paired with anyone except each other, but apart from that weird pairings of any sexuality are fine as long as it makes sense in the narrative.

Finally, I'm sorry to disappoint, but Severus and Hermione will never have children in any of my HP fics. I've seen it done well, but mostly it's done really badly and OOC, and it doesn't work with my personal versions of the characters. My Severus seriously and truly dislikes children and my Hermione isn't remotely interested in being a mother, and my Severus is too emotionally damaged for it to be a good idea anyway. Hermione understands him and can deal with him, but a child wouldn't be able to. If I can't make it believable in my own head, I know I can't write it. Other authors can and have, and good luck to them, but it's not going to happen in my writing.

Awards: yes, I'm a show-off. So sue me, I'm pleased and proud that people like my work enough to nominate and vote for it!

TAMORA PIERCE, IMMORTALS Teacher: Fourth place in Knighthood of Ficship Summer 2009. Power: Second place in Knighthood of Ficship Summer 2009. Divine Intervention: Fourth place in Knighthood of Ficship Winter 2009. Lost & Found: Third place in Knighthood of Ficship Winter 2009. Little By Little: Second place in Knighthood of Ficship Summer 2010. Affirmation: Fifth place in Knighthood of Ficship Summer 2010.

Bonus Feature! Mark Oshiro of the "Mark Reads. /Mark Watches. " review sites was commissioned to read chapters 6-8 of Divine Intervention and his videos of that reading can be found here: markreads (dot) net /reviews/2013/05/mark-reads-divine-intervention-chapters-6-8/

HARRY POTTER Post Tenebras, Lux: Winner of the 2013 Hp Fanfic Fan Poll award for Best SSHG Legacy. Chasing The Sun: Second place in the 2013 Hp Fanfic Fan Poll award for Best SSHG Legacy.

Fan Art : (let me know if any of these links no longer work) - FFN hates links so this format is the best I can do right now. Eventually I'll get them all hosted on a page on my blog.

Post Tenebras, Lux After Darkness, by RaShelli . RaShelli. deviantart (dot) com /#/d39o9q2 Fan Art, by Frusie : Jeanswear. deviantart (dot) com /#/d3btyba His Patronus, by Frusie : Jeanswear. deviantart (dot) com /#/d3b76ak Post Tenebras, Lux by Tempted Sacrifice : CaughtBy. deviantart (dot) com /#/d3ccede Untitled, by Kumo: tinyurl (dot) com /bv56m2j Banner, by EreshkigalGirl : tinyurl (dot) com /3kqequ5 Untitled, by Kimber : tinyurl (dot) com /3zuruas Thank You, by A Colourless Rainbow : tinyurl (dot) com /cm2v86f Post Tenebras, Lux by RaShelli : rashelli. deviantart (dot) com /#/d3eiq0m Post Tenebras, Lux (Colour) by Ridgley Warfield: therapist-in-a-box. deviantart (dot) com /#/d3eurh9 Post Tenebras, Lux (Black and White) by Ridgley Warfield: therapist-in-a-box. deviantart (dot) com /gallery/#/d3eurwj After Darkness Light by kayeita: ravelry (dot) com /projects/softnshiny/after-darkness-light The Order of the Phoenix, by BulletTimeScully: bullettimescully. deviantart (dot) com /art/Post-Tenebras-Lux-The-Order-of-the-Phoenix-300453086 HP Fanfic Fan Poll Nomination Banner: hpfanficfanpoll. files. wordpress (dot) com /2013/10/ivebeennominated-2013fallwinter. jpg HP Fanfic Fan Poll Winner Banner: hpfanficfanpoll. files. wordpress (dot) com /2014/01/snermione-legacy-1-posttenebraslux-loten. jpg Czech translation banner by Solace: hpkizi (dot) sk/images/topics/post_tenebras1.jpg

Chasing The Sun Agony, by RaShelli: rashelli. deviantart (dot) com /art/Agony-260991601 Your Ocean, by Ukirra: arriku. deviantart (dot) com /#/d4dkfhx Elemental Magic, by frusie: jeanswear. deviantart (dot) com /gallery/#/d4flsxg Hobbies, by Ukirra: arriku. deviantart (dot) com /gallery/#/d4h83ud Late Night Brewing, by RaShelli: rashelli. deviantart (dot) com /#/d4ih3tj Hallelujah, by BulletTimeScully: bullettimescully. deviantart (dot) com /art/Hallelujah-Chasing-the-Sun-277337333 Chapter 28, by RaShelli: rashelli. deviantart (dot) com /art/Chasing-the-Sun-Chapter-28-276887565 Waiting for the Mediwitch, by Peanut . gloriouspeanut. deviantart (dot) com /art/Waiting-for-the-mediwitch-277280898 Black Mood, by Ukirra: arriku. deviantart (dot) com /art/Chasing-the-Sun-Black-moods-278947703 At The Gates, by Noweia: noweia. deviantart (dot) com /art/At-The-Gates-279410263 I'm Free, by RaShelli: rashelli. deviantart (dot) com /art/I-m-free-281125614 Plotting Revenge, by RaShelli: rashelli. deviantart (dot) com /art/Plotting-the-Revenge-on-Umbridge-282085860 A Sign of Change, by doll-fin-chick: doll-fin-chick. deviantart (dot) com /art/Loten-A-Sign-of-Change-282075209 Fox Patronus, by doll-fin-chick: doll-fin-chick. deviantart (dot) com /art/Fox-Patronus-282075421 A Surprise Patronus, by Lilandriel: lilandrial. deviantart (dot) com /art/A-surprise-Patronus-282884296 Snape Duelling, by lucife56: lucife56.deviantart (dot) com /art/Snape-dueling-283288051 Snape Duelling (Coloured), by lucife56: lucife56.deviantart (dot) com /gallery/#/d52w885 Safe and Sound, by shamandaliewolf: shamandaliewolf. deviantart (dot) com /art/Safe-and-Sound-284883628 Patronus, by djfox31: ravenwing31.deviantart (dot) com /#/d4qk9o6 Chasing the Sun, by kitty-gurl1: namara-ashina. deviantart (dot) com /art/Chasing-the-Sun-288870688 He Was Never Truly Yours, by PickedYou: pickedyou. deviantart (dot) com /art/He-was-never-truly-yours-284108001 Snape, by Noa: flyingninjapig. deviantart (dot) com /gallery/#/d4mpnzs Fox Patronus, by FionaTyne: fionatyne. deviantart (dot) com /gallery/?catpath=scraps#/d592335 Portrait of Hermione, by frusie: jeanswear. deviantart (dot) com /art/Portrait-of-Hermione-317932334 The Otter and the Fox, by TaraSindar: aquasindar. deviantart (dot) com /art/The-Otter-and-the-Fox-Chasing-The-Sun-318311312 Morning Hair, by nene27: nene27.deviantart (dot) com /#/d59qq45 May God Have Mercy . by AngelicFayth : angelic-fayth. deviantart (dot) com /art/Chasing-the-Sun-May-God-have-mercy-on-my-soul-319463662 Banner, by Solace: tinyurl (dot) com /b35cv7m German translation cover by upac: ffcdn2012.fictionpressllc. netdna-cdn (dot) com /image/713173/180/ HP Fanfic Fan Poll Nomination Banner: hpfanficfanpoll. files. wordpress (dot) com /2013/10/ivebeennominated-2013fallwinter. jpg HP Fanfic Fan Poll Second Place Banner: hpfanficfanpoll. files. wordpress (dot) com /2014/01/snermione-legacy-2-chasingthesun-loten. jpg I See No Difference, by Sophie Nobody: phia-nobody. deviantart (dot) com /art/I-see-no-Difference-426861607 Expecto Patronum, by diAngelo57 : nukasclaw. deviantart (dot) com /art/Expecto-Patronum-507109182

Silence Heated Silence, by RaShelli : rashelli. deviantart (dot) com /art/Heated-Silence-324282685 Featured Author banner from the SSHG quiz on livejournal: ic. pics. livejournal (dot) com /morethansirius/10616016/169999/169999_original. png

Crossroads Czech translation cover by Lupina75: hp. kizi (dot) sk /images/topics/rapidez. jpg A Winter's Tale Featured Author banner from the SSHG quiz on livejournal: ic. pics. livejournal (dot) com /morethansirius/10616016/344977/344977_original. png

Translations by some wonderfully talented people. I'm always happy to grant permission if you want to translate anything I've written (though if you take on one of the long ones, make sure you have time to finish it, please). If it's not on this list, I haven't authorised it. If you happen to notice that any of the long translations haven't been updated in a while, let me know - if I can't get hold of the person translating, I'm happy to let someone else take over.

Telda Lady Bittersweet has translated several fics into German: I Beg to Differ : https://www. fanfiction. net/s/11748794/1/Was-zu-beweisen-war-oder-I-beg-to-differ Perception: https://www. fanfiction. net/s/11954518/1/Lotens-Perception-Wahrnehmung and fanfiktion dot de /s/573de65d0004e22316f9f48d /1/ Lotens-Perception-Wahrnehmung Here I Am Not: fanfiktion dot de/s/575d62900004e2231286eb0c/1/Lotens-quot-Here-I-am-not-quot - Post Tenebras Lux: fanfiktion dot de /s/56b32c840004e2232aa46d3b /1/ Post-Tenebras-Lux-von-Loten-neu-uebersetzt-und-bearbeitet Chasing the Sun : fanfiktion dot de /s/570a28830004e22312becee4/1/Lotens-quot-Chasing-the-sun-quot-neu-uebersetzt

flower0719 has translated Post Tenebras Lux into Chinese on a private forum for Chinese speakers, PM her if you want to log in and look at it.

frostbffr has translated Crossroads into Chinese: tieba dot baidu dot com/p/4730831178 And Feeding Time : tieba dot baidu dot com/p/4776828935

Lupina75 has translated Chasing The Sun into Czech/Slovak at hp. kizi (dot) sk/modules (dot) php? name=News&new_topic=193 She has also translated Second Year: hp. kizi (dot) sk/modules (dot) php? name=News&file=article&sid=3320 And Feeding Time: hp. kizi (dot) sk/modules (dot) php? name=News&file=article&sid=3450 And Crossroads: hp. kizi (dot) sk/modules (dot) php? name=News&file=article&sid=3449 And I Beg To Differ: hp. kizi (dot) sk/modules (dot) php? name=News&file=article&sid=3593 And Silence: hpkizi (dot) sk/modules (dot) php? name=News&file=article&sid=3731 And Here I Am Not: hpkizi (dot) sk/modules (dot) php? name=News&file=article&sid=3831 And Picture Perfect : hpkizi (dot) sk/modules (dot) php? name=News&file=article&sid=3817 And Summer: hpkizi (dot) sk/modules (dot) php? name=News&file=article&sid=4075 And The Search: hpkizi (dot) sk/modules (dot) php? name=News&file=article&sid=4115 And Post Tenebras Lux : hpkizi (dot) sk/modules (dot) php? name=News&file=article&sid=3867 And Acceptance: hpkizi (dot) sk/modules (dot) php? name=News&file=article&sid=4277 And A Winter's Tale . Part I: hpkizi (dot) sk/modules (dot) php? name=News&file=article&sid=4367 Part II: hpkizi (dot) sk/modules (dot) php? name=News&file=article&sid=4371 And Perception: hpkizi (dot) sk/modules (dot) php? name=News&file=article&sid=4388

chrishoo has translated A Winter's Tale into Chinese (you need to be a member of the site to see it): thelosteden (dot) net/forum (dot) php? mod=viewthread&tid=705&page=1&extra=#pid12595

Anchemcom is translating Chasing the Sun into Russian: ficbook (dot) net /readfic/4372197

Adrista will be translating Chasing the Sun into Chinese.

And now for something completely different. on my blog, linked at the top of this profile, my partner and I are doing a sporking of the Harry Potter series. This spork is being translated into Chinese by lanmenglu . Link One: tieba. baidu (dot) com /p/3367563664 Link Two (registration required): thelosteden (dot) net/forum (dot) php? mod=viewthread&tid=583&extra=page%3D1

I haven't heard from any of these in a while, feel free to claim them if you like:

Disincanto294 will be translating Post Tenebras Lux into Italian.

polinaluur will be translating Post Tenebras Lux into Russian.

Darcy91 will be translating one of my long fics into Dutch.

Polypocket will be translating I Beg to Differ and Silence into French.

Future fics, a. k.a. Attack of the Killer Plotbunnies.

These ideas may not necessarily all become fics, so don't get your hopes up. HP fics have priority, I'm not sure if/when I'll ever get around to stories from other fandoms.

Harry Potter: All SS/HG unless explicitly stated otherwise. The Mark of Cain: AU post-DH EWE. After the war, Snape survives and is punished by the Ministry for his crimes, but the details are kept secret until Harry stumbles on the truth and asks Hermione for help. Quite dark in places. First draft was half finished, but it needs a lot of work and keeps changing on me. I think I know what I'm doing with it now. Seven: Dark AU post-DH EWE. Canon compliant until the final battle. The Boy Who Lived. didn't. Nor did most of the Order. Hogwarts has fallen. The few surviving members of the Order are still trying to fight, but it looks hopeless until they are contacted and realise that someone else is still fighting alongside them . Probably going to be quite dark. Edicius: AU, post-DH EWE. Life has not been kind to Severus Snape. Once the war is over, he sets about changing that, and he doesn't intend letting anyone stop him. And then Harry does something everyone will regret. Shorter and less heavy than some of my other stories. On hold at the moment. The Winding Stair: AU post-DH EWE. The world is changing, and for two people there doesn't seem to be a place for them any more. Pushed aside by the new way of life within the Order, they decide to find another way to win the war. This one needs a lot of thought but I do like the idea. Gargoyle: (working title). AU post-DH, EWE. It's easy to be forgotten down in the deep cells under Azkaban, but sometimes life has a way of making sure that things aren't that simple. This promises to be quite a strange one; I'm not sure where it's going just yet. I may even dismantle it and use the ideas I have for it in other stories instead of trying to make it hang together as a full story. (Untitled): Slightly-AU DH. Dumbledore was smart enough to tell the Order about Snape's vow before his death. What is Snape going through, and how does it affect the Trio's task? Because cluelessly flailing around in the woods was really, really stupid and it never made any sense for none of the Order to know that Dumbledore asked Snape to kill him. Things would have been easier if they'd known and could help, and we all want to know how the new Headmaster coped. Drops of Jupiter: AU post-DH EWE. Harry and his Auror colleagues need Snape's help, but he wants nothing to do with any of them. Hermione has a private history with him that might be enough to persuade him. I like the initial idea but it needs more of a plot to go with it.

Tamora Pierce Lacunae : A collection of one-shots and missing scenes from between the books of the Immortals series. This is never going to be truly finished; I'll keep adding to it whenever inspiration strikes. Black and Gold: Some stories about Arram's time at university and how he arrived in Tortall and became Numair . This is a very long way down the priority list at the moment - I may well beat Tammy to it, though, especially since Exile has once again been delayed. I have a few tentative notes, but that's it so far.

Trudi Canavan Bitter Glass: The High Lord, rewritten from Akkarin's point of view . This needs a great deal of work. I had written about half of it, but looking back I don't like the writing and in some places I'm not happy with my grasp of his character. I have started rewriting it but it's not a priority. Title is only tentative. The Sound of Silence: I want to try my own take on the ' what-if-Akkarin-didn't-die ' theme that is so popular in this fandom; I've got some ideas for this, but I don't want to start it until the first story is finished. It's going to need a bit of work; I'm not sure what I want to do with it yet. Title is only tentative.

Wheel of Time Nothing concrete, but I'm tentatively batting around a few ideas for short Lan-based pieces. Because Lan is unbelievably cool and really doesn't get the attention he deserves. This is probably just going to be a little side project, something I'll work on to get over writer's block or to stop me getting too bogged down in any of my very long intense fics from other series. Not sure where I'll be going with it. Also I have now concluded that in Randland's future, Malkier will rule the world.

God help me, part of me really wants to try a novelisation of the first three Thief games, too. (The fourth one doesn't exist, shut up.) Why do I do this to myself?

Sort: Category. Published. Updated. Title. Words. Chapters. Reviews. Status .



Buy Online Loten, Loten

Mirt - What Does Mirt Stand For The Free Dictionary, Mirt

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Valpakine, Valpakine

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Valpakine (Divalproex Sodium)

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DISCLAIMER: MediGuard is not intended to be a substitute for professional medical advice. MediGuard cannot and does not take into consideration every possible interaction or account for individual responses to medicine. Different individuals may respond to medication in different ways. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective, or appropriate for any given patient. Always seek the advice of a qualified health provider with any questions you may have before making any changes to your treatment. The use of the MediGuard site and its content is at your own risk. The MediGuard site and the information contained in it is intended for users in the United States and information in other countries may be different.

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Cefuroxime - Side Effects, Dosage, Interactions, Famicef

Cefuroxime

Cefuroxime is a prescription drug available under the brand names Ceftin and Zinacef.

It's an antibiotic used to treat certain infections caused by bacteria, such as sinus infections, throat infections, Lyme disease. and gonorrhea.

Cefuroxime was originally approved by the Food and Drug Administration (FDA) under the brand name Ceftin, manufactured by GlaxoSmithKline, in 1987.

Cefuroxime Warnings

You should not take cefuroxime if you:

Are allergic to cefuroxime or any of the other ingredients contained in the drug

Are taking Theracrys (BCG live intravesical)

Talk to your doctor before taking cefuroxime if you:

Are allergic to penicillin

Are allergic to other antibiotics such as ceflacor, cefdinir, Keflex (cephalexin), or antibiotics in the cephalosporin class

Have kidney or liver problems

Have seizures

Have poor eating habits or suffer from malnutrition

Have recently had an either infection or inflammation of your intestines while or after taking antibiotics

Cefuroxime may reduce the effects of your birth control (pills, patches, or injections).

You may need to use a back-up form of birth control while taking cefuroxime.

Pregnancy and Cefuroxime

Cefuroxime falls under the FDA's Pregnancy Category B, which means that it's generally safe for your unborn baby.

Regardless, you should tell your doctor if you are pregnant or plan to become pregnant before taking this medication.

Cefuroxime is found in breast milk. Tell your doctor if you are breastfeeding or plan to breastfeed before you take this medication.

Cefuroxime (Ceftin) Side Effects

Common side effects of cefuroxime include:

Nausea, vomiting, and diarrhea

Kidney problems

Diaper rash

Yeast infection

An allergic reaction

Serious side effects of cefuroxime include but are not limited to:

Life-threatening allergic reaction called anaphylaxis in which you may have trouble breathing, your throat closes up, and your skin breaks out into hives

Swelling of the face, including eyes, lips, mouth, tongue, and throat

Severe and possibly life-threatening skin-reactions like Steven-Johnsons syndrome or toxic epidermal necrolysis (TENs)

Blood disorders like low platelet count or low levels of all blood cells

Low levels of white blood cells

Seizures

A severe form of diarrhea noted by loose, watery stool and a foul smell that is much worse than normal

Cefuroxime (Ceftin) Interactions

It's always important to share with your doctor and pharmacist all of the medications you are taking.

This includes prescription and over-the-counter (OTC) medications, supplements like vitamins and other dietary supplements (nutritional shakes, protein powders, etc.), herbals, and any illegal or recreational drugs.

You should not take cefuroxime if you are taking Theracrys (BCG live intravesical).

Some other medications that have serious interactions with Cefuroxime include:

Acid-reflux medications like Tagamet (cimetidine), Dexilant (deslansoprazole), and Aciphex (rabeprazole)

Other acid-reflux medications like Pepcid (famotidine), Zantac (ranitidine), and Axid (nizatidine)

Vivotif (live typhoid vaccine)

Aluminum hydroxide, calcium carbonate, magnesium hydroxide, sodium bicarbonate

Cellcept (mycophenolate mofetil) and Myfortic (mycophenolic acid)

Cefuroxime and Alcohol

You should avoid or limit alcohol consumption while taking cefuroxime.

Cefuroxime and Grapefruit Juice

You should avoid eating grapefruit and drinking grapefruit juice while taking cefuroxime.

Grapefruit juice slows down how quickly the body is able to break down cefuroxime, which could cause levels in the blood to rise dangerously high.

Cefuroxime (Ceftin) Dosage

Cefuroxime comes in 250 mg and 500 mg tablets.

Doses typically range from 250 mg twice a day to 500 mg twice a day to be taken for 5 to 10 days for most infections.

Lyme disease symptoms may be treated for up to 20 days.

For gonorrhea, your doctor may prescribe a one-time dose of 1000 mg.

It is very important to take cefuroxime exactly as your doctor prescribes and to finish taking all of the medication -- even if you start to feel better or your symptoms disappear.

Otherwise, the infection might return and become much more difficult to treat.

Cefuroxime Overdose

If you suspect an overdose of cefuroxime you should contact a poison control center or emergency room immediately.

You can get in touch with a poison control center at (800) 222-1222.

Missed Dose of Cefuroxime

If you miss a dose of Cefuroxime, try to take it as soon as you remember.

If it's almost time for the next dose, skip the missed dose and take your next dose at the regular time.

Do not take two doses of the medication at the same time.



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Allopurinol Side Effects In Detail, Llanol

Allopurinol Side Effects

Other dosage forms:

In addition to its needed effects, some unwanted effects may be caused by allopurinol. In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking allopurinol:

More common:

Ankle, knee, or great toe joint pain

joint stiffness or swelling

rash

rash with flat lesions or small raised lesions on the skin

Rare

Abdominal or stomach pain

agitation

ammonia-like breath odor

anxiety

bleeding gums

blistering, peeling, or loosening of the skin

blood in the urine or stools

bloody nose

bloody or black, tarry stools

blue or pale skin

bruising

changes in skin color

chest pain or discomfort

chest pain, possibly moving to the left arm, neck, or shoulder

chills

clay-colored stools

cloudy urine

coma

confusion

constipation

cough or hoarseness

coughing up blood

cracks in the skin

dark urine

decreased urine output

depression

diarrhea

difficulty with breathing

dizziness

drowsiness

dry mouth

feeling faint, dizzy, or lightheaded

feeling of warmth or heat

fever

fever with or without chills

flushing or redness of the skin, especially on the face and neck

general feeling of discomfort or illness

general feeling of tiredness or weakness

headache

hostility

incoherent speech

increased urination

irritability

itching

joint or muscle pain

large, flat, blue or purplish patches in the skin

lethargy

light-colored stools

loss of appetite

loss of heat from the body

lower back or side pain

metallic taste

muscle twitching

muscle weakness

nausea or vomiting

pain, tenderness, or swelling of the foot or leg

painful or difficult urination

pinpoint red or purple spots on the skin

rapid weight gain

rash

red, irritated eyes

red, swollen skin

redness, soreness, or itching skin

right upper abdominal or stomach pain and fullness

scaly skin

seizures

severe stomach pain

shortness of breath

slow or irregular heartbeat

sore throat

sores, ulcers, or white spots on the lips or in the mouth

sores, welting, or blisters

stupor

sweating

swelling of the face, ankles, hands, or lower legs

swollen or painful glands

swollen, painful, or tender lymph glands in the neck, armpit, or groin

thirst

tightness in the chest

unpleasant breath odor

unusual bleeding or bruising

unusual weight gain or loss

vomiting of blood or material that looks like coffee grounds

wheezing

yellow eyes or skin

Minor Side Effects

Some of the side effects that can occur with allopurinol may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Rare

Bad, unusual, or unpleasant (after) taste

blindness

blue-yellow color blindness

blurred vision

body aches or pain

burning feeling in the chest or stomach

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

burning, dry, or itching eyes

burning, numbness, tingling, or painful sensations

change in taste

change in vision

congestion

continuing ringing or buzzing or other unexplained noise in the ears

decreased interest in sexual intercourse

decreased vision

difficulty with moving

discharge or excessive tearing

feeling of constant movement of self or surroundings

hair loss or thinning of the hair

hearing loss

hives or welts

impaired vision

inability to have or keep an erection

indigestion

lack or loss of strength

loss in sexual ability, desire, drive, or performance

loss of appetite

loss of memory

multiple swollen and inflamed skin lesions

muscle aching or cramping

muscle pain or stiffness

muscular pain, tenderness, wasting, or weakness

noisy breathing

problems with memory

redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid

runny nose

sensation of spinning

sensitivity to light

sleepiness or unusual drowsiness

sleeplessness

sneezing

stomach upset

stuffy nose

sweating

swelling of the breasts or breast soreness in both females and males

swelling of the salivary glands

swelling or inflammation of the mouth

swollen joints

tearing

tender, swollen glands in the neck

tenderness in the stomach area

throbbing pain

tightness in the chest

trouble getting pregnant

trouble with sleeping

trouble with swallowing

unable to sleep

unsteadiness or awkwardness

voice changes

weakness in the arms, hands, legs, or feet

weight loss

For Healthcare Professionals

Applies to allopurinol: intravenous powder for injection, oral tablet

General

The most commonly reported adverse reactions include skin rash, diarrhea, nausea, alkaline phosphatase, and transaminase elevation. [Ref ]

Dermatologic

Skin rash is one of the most common adverse reactions and may occur at any time during treatment. Some skin reactions can be severe and sometimes fatal. In patients with the most severe reactions, systemic symptoms such as fever, chills, arthralgia, cholestatic jaundice, eosinophilia and mild leukocytosis, or leukopenia accompany the rash. Among 55 patients with gout who received this drug for an average of 1 year (3 to 34 months), 3% developed pruritic maculopapular skin eruptions, sometimes scaly or exfoliative. The incidence of skin rash appears to be greater in patients with renal insufficiency.

Angioedema has been reported with and without signs and symptoms of a more generalized hypersensitivity reaction. Skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia, and/or eosinophilia resembling Stevens-Johnson and/or Lyell syndromes have occurred rarely. Associated vasculitis and tissue responses may manifest as hepatitis, interstitial nephritis, and very rarely epilepsy. [Ref ]

Common (1% to 10%): Rash, maculopapular rash Uncommon (0.1% to 1%): Ecchymosis Rare (less than 0.1%): Steven-Johnson syndrome, Lyell syndrome Very rare (less than 0.01%): Alopecia, discolored hair, angioedema, fixed drug eruption Frequency not reported: DRESS (Drug reaction with eosinophilia and systemic symptoms), sweating [Ref ]

Hypersensitivity

Rare (less than 0.1%): Generalized hypersensitivity Very rare (less than 0.01%): Anaphylaxis, angioedema Frequency not reported: Hypersensitivity reaction [Ref ]

Generalized hypersensitivity including skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia, and/or eosinophilia resembling Stevens-Johnson and/or Lyell syndromes have occurred rarely. Associated vasculitis and tissue responses may manifest as hepatitis, interstitial nephritis, and very rarely epilepsy. When generalized hypersensitivity reactions have occurred, renal and or/hepatic disorders have often been present, particularly when the outcome has been fatal.

Angioedema has been reported with and without signs and symptoms of a more generalized hypersensitivity reaction. [Ref ]

Hepatic

Common (1% to 10%): Increases in alkaline phosphatase and serum transaminases Rare (less than 0.1%): Hepatic dysfunction including hepatitis (hepatic necrosis and granulomatous hepatitis), hepatomegaly, cholestatic jaundice, Frequency not reported: Clinical hepatotoxicity, liver failure [Ref ]

Liver failure was reported in less than 1% of patients. [Ref ]

Gastrointestinal

Common (1% to 10%): Diarrhea, nausea, vomiting Rare (less than 0.1%): Intermittent abdominal pain, gastritis, dyspepsia Very rare (less than 0.01%): Steatorrhea, recurrent hematemesis, stomatitis, changed bowel habit Frequency not reported: Hemorrhagic pancreatitis, gastrointestinal bleeding, salivary gland swelling, tongue edema, anorexia, flatulence [Ref ]

Hemorrhagic pancreatitis, gastrointestinal bleeding, salivary gland swelling, tongue edema, flatulence, and anorexia were reported in less than 1% of patients. [Ref ]

Hematologic

Eosinophilic fibrohistiocytic lesion of bone marrow, pancytopenia, anemia, hemolytic anemia, reticulocytosis, lymphadenopathy, disseminated intravascular coagulation, and lymphocytosis were reported in less than 1% of patients. [Ref ]

Very rare (less than 0.01%): Leukocytosis, leukopenia, eosinophilia, thrombocytopenia, granulocytopenia, agranulocytosis, aplastic anemia Frequency not reported: Bone marrow depression, eosinophilic fibrohistiocytic lesion of bone marrow, pancytopenia, anemia, hemolytic anemia, reticulocytosis, lymphadenopathy, lymphocytosis, disseminated intravascular coagulation [Ref ]

Renal

Common (1% to 10%): Renal failure/insufficiency Very rare (less than 0.01%): Xanthine crystalluria, azotemia [Ref ]

Xanthine crystalluria has been reported in 3 patients; 2 patients with Lesch-Nyhan syndrome and 1 patient with lymphosarcoma who produced an extremely large amount of uric acid during chemotherapy.

Increased serum creatinine and kidney function abnormality has been reported in less than 1% of patients. [Ref ]

Nervous system

Uncommon (0.1% to 1%): Headache Very rare (less than 0.01%): Ataxia, somnolence, coma, paralysis, paresthesia, neuropathy, taste perversion, neuritis Frequency not reported: Drowsiness, confusion, foot drop, seizure, status epilepticus, myoclonus, twitching, cerebral infarction, stroke, tremor [Ref ]

Confusion, foot drop, seizure, status epilepticus, myoclonus, twitching, cerebral infarction, stroke, and tremor were reported in less than 1% of patients. [Ref ]

Ocular

Very rare (less than 0.01%): Visual disorder, cataract, macular changes Frequency not reported: Optic neuritis [Ref ]

Immunologic

Very rare (less than 0.01%): Furunculosis, angioimmunoblastic lymphadenopathy [Ref ]

Metabolic

Uncommon (0.1% to 1%): Increase in acute gout attacks Very rare (less than 0.01%): Diabetes mellitus, hyperlipidemia Frequency not reported: Hypercalcemia, hypocalcemia, hyperphosphatemia, hypokalemia, hyperuricemia, electrolyte abnormality, hyperglycemia, hypernatremia, metabolic acidosis, glycosuria, hyperkalemia, lactic acidosis, water intoxication, hypomagnesemia [Ref ]

Early clinical experience with this drug found acute gouty attacks on therapy initiation to be one of the more commonly observed adverse reactions; however, current use analyses suggests this incidence is now less than 1%. The reason for this change has not been determined, but it may be due to patients initiating therapy more gradually.

Hypercalcemia, hypocalcemia, hyperphosphatemia, hypokalemia, hyperuricemia, electrolyte abnormality, hyperglycemia, hypernatremia, metabolic acidosis, glycosuria, hyperkalemia, lactic acidosis, water intoxication, and hypomagnesemia have been reported in less than 1% of patients. [Ref ]

Musculoskeletal

Rare (less than 0.1%): Myopathy, arthralgias [Ref ]

Cardiovascular

Uncommon (0.1% to 1%): Necrotizing angiitis, vasculitis, edema Very rare (less than 0.01%): Angina, bradycardia, hypertension Frequency not reported: Pericarditis, peripheral vascular disease thrombophlebitis, vasodilation, heart failure, cardiorespiratory arrest, decreased venous pressure, flushing, cardiovascular disorder, ECG abnormality, hemorrhage, ventricular fibrillation [Ref ]

Pericarditis, peripheral vascular disease thrombophlebitis, vasodilation, heart failure, cardiorespiratory arrest, decreased venous pressure, flushing, cardiovascular disorder, ECG abnormality, hemorrhage, and ventricular fibrillation were reported in less than 1% of patients. [Ref ]

Endocrine

Uncommon (0.1% to 1%): Gynecomastia [Ref ]

Genitourinary

Uncommon (0.1% to 1%): Infertility, impotence, nocturnal emission Very rare (less than 0.01%): Uremia, hematuria, male infertility, impotence, erectile dysfunction Frequency not reported: Urinary tract infection [Ref ]

Local

Injection site reactions have been reported with the parenteral product in less than 1% of patients. [Ref ]

Frequency not reported: Injection site reactions [Ref ]

Other

Uncommon (0.1% to 1%): Fever, general malaise, asthenia Very rare (less than 0.01%): Vertigo Frequency not reported: Tinnitus [Ref ]

Psychiatric

Very rare (less than 0.01%): Depression Frequency not reported: Amnesia, insomnia, agitation [Ref ]

Amnesia, agitation, and insomnia were reported in less than 1% of patients. [Ref ]

Respiratory

Rare (less than 0.1%): Epistaxis Frequency not reported: Bronchospasm, asthma, pharyngitis, rhinitis, respiratory failure/insufficiency, ARDS, increased respiration rate, apnea [Ref ]

Bronchospasm, asthma, pharyngitis, respiratory failure/insufficiency, ARDS, increased respiration rate, apnea, and rhinitis were reported in less than 1% of patients. [Ref ]

References

1. "Product Information. Zyloprim capsules (allopurinol)." Glaxo Wellcome, Research Triangle Park, NC.

2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

3. Cerner Multum, Inc. "Australian Product Information." O 0

Not all side effects for allopurinol may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here .



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Nufamox Dosis Obat, Nufamox

nufamox

nufamox dipasarkan dengan kemasan berikut :

dos 10 x 10 kaplet 500 mg

kandungan

setiap kemasan nufamox mengandung zat aktif berikut :

Amoxicillin trihidrat setara Amoxicillin anhidrat 500 mg/ kapsul

Sekilas tentang zat aktif (nama generik)

amoksisilin (Amoxicillin) adalah antibiotik golongan beta laktam yang termasuk keluarga penisillinum. Antibiotik ini mempunyai spektrum sedang, aktif terhadap bakteri gram negatif maupun gram positif. amoksisilin (Amoxicillin) adalah bakteriolitik yang bekerja dengan cara menghambat sintesis dinding sel bakteri sehingga lintas hubungan antara rantai polimer peptidoglikan linier yang membentuk komponen utama dari dinding sel bakteri menjadi terganggu.

Indikasi

Kegunaan nufamox (Amoxicillin) adalah untuk mengobati infeksi yang disebabkan oleh kuman yang peka terhadap amoxicillin seperti otitis media akut, faringitis yang disebabkan streptococcus . pneumonia, infeksi kulit, infeksi saluran kemih, infeksi Salmonella . Lyme disease . dan infeksi klamidia.

Obat ini juga digunakan untuk mencegah endokarditis yang disebabkan bakteri pada orang-orang berisiko tinggi saat perawatan gigi, untuk mencegah infeksi oleh Streptococcus pneumoniae dan infeksi bakteri lainnya.

nufamox (Amoxicillin) sangat umum digunakan untuk infeksi saluran pernafasan bagian atas dan bawah, infeksi saluran kemih, saluran cerna, kulit dan jaringan lunak.

Kontra indikasi

nufamox (Amoxicillin) harus dihindari pada pasien hipersensitifitas pada amoxicillin dan antibiotik betalaktam lainnya seperti penisillinum dan cephalosporin.

Efek Samping

kebanyakan efek samping nufamox (Amoxicillin) yang muncul adalah mual, muntah, ruam, dan antibiotik kolitis.

kadang-kadang diare juga dapat terjadi.

Efek samping yang jarang seperti perubahan mental, sakit kepala ringan, insomnia, kebingungan, kecemasan, kepekaan terhadap cahaya dan suara, dan berpikir tidak jelas.

Perawatan medis harus segera diberikan jika tanda-tanda pertama dari efek samping muncul karena jika seseorang mengalami reaksi hipersensitivitas terhadap amoxicillin, dapat mengalami shock anafilaktik yang bisa berakibat fatal.

Perhatian

Hati-hati memberikan nufamox (Amoxicillin) pada penderita dengan fungsi hati dan ginjal yang rusak terutama pada pemakaian obat dalam jangka waktu panjang.

Hentikan pemakaian nufamox (Amoxicillin) jika terjadi super infeksi yang biasanya terjadi pada saluran pencernaan (umumnya disebabkan oleh Enterobacter . Pseudomonas, S. aureus Candida )

Antibiotik golongan penicillin termasuk amoxicillin telah diketahui ikut keluar bersama air susu ibu (ASI). Oleh karena itu, jika nufamox (Amoxicillin) digunakan untuk ibu menyusui, perlu dikonsultasikan dengan dokter. Untuk menghindari efek sensitivitas nufamox (Amoxicillin) terhadap bayi, penggunaan antibiotik ini harus dilakukan dengan jarak yang cukup dengan saat menyusui.

Toleransi terhadap kehamilan

Penelitian pada reproduksi hewan tidak menunjukkan resiko pemakaian amoksisilin (Amoxicillin) pada janin dan tidak ada studi yang memadai dan terkendali dengan baik pada wanita hamil / Penelitian pada hewan telah menunjukkan efek buruk. namun studi yang memadai dan terkendali dengan baik pada ibu hamil tidak menunjukkan resiko untuk janin pada trimester berapapun.

interaksi obat

Obat-obat dengan kandungan zat aktif amoxicillin termasuk nufamox berinteraksi dengan obat-obat lain sebagai berikut :

Penggunaan bersamaan antara amoxicillin dan probenesid dapat meningkatkan kadar amoxicillin dalam darah.

Perpanjangan protrombin time secara tidak normal telah diketahui pada penggunaan amoxicillin bersamaan dengan antikoagulan oral misalnya warfarin dan dabigatran. Jika obat-obat antikoagulan diresepkan bersamaan dengan amoxicillin, pemantauan yang ketat harus dilakukan. Jika diperlukan penyesuaian dosis antikoagulan harus dilakukan.

Allopurinol meningkatkan potensi terjadinya ruam jika diberikan bersamaan dengan amoxicillin.

Antibiotik amoxicillin bisa mempengaruhi flora usus, yang menyebabkan penurunan kemampuan usus untuk reabsorpsi estrogen sehingga menurunkan efektivitas obat kontrasepsi oral yang mengandung estrogen.

Antibiotik-antibiotik golongan kloramfenikol, makrolid, sulfonamid dan tetrasiklin disinyalir menurunkan efektivitas antibiotik penicillin termasuk amoxicillin.

Dosis nufamox

nufamox (Amoxicillin) diberikan dengan dosis :

dewasa dan anak 20 kg atau lebih. 250-500 mg setiap 8 jam secara oral.

Untuk pasien dengan fungsi ginjal yang buruk, monitor kadar obat dalam plasma dan urine harus dilakukan.

dosis selengkapnya lihat amoxicillin .

Terkait

Jika informasi ini berguna bagikan ke teman-teman anda



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Anipryl 5 Mg (Canada) For Animal Use, Anipryl

Anipryl 5 mg (Canada)

Molecular Formula: C 13 H 17 N HCl

Molecular Weight: 223.75

Description

Anipryl (selegiline hydrochloride) 2 mg, 5 mg, 10 mg, 15 mg, and 30 mg tablets are almost white tablets containing 2, 5, 10, 15 or 30 mg of selegiline HCl.

ACTION: Anipryl has been shown to be effective treatment for pituitary dependent hyperadrenocorticism (PDH) in dogs as demonstrated by amelioration of clinical signs and improved regulation of the hypothalamic pituitary adrenal (HPA) axis. In each of three clinical trials there was a progressive improvement in endocrine function, as documented by results of low dose dexamethasone suppression (LDDS) tests. 1,2 Significant clinical improvement was also demonstrated. 1,2 Typical clinical signs of PDH include polydipsia, polyuria, increased frequency of urination and loss of housetraining, panting, reduced activity, changes in sleep patterns, altered appetite, obesity, alopecia, abdominal distention, reduced skin elasticity, thin skin, and poor hair growth. 1-3 In clinical trials, dogs with PDH treated with Anipryl exhibited decreased body weight and improved body conformation determined by measurement, as well as amelioration of dermatologic signs (skin thickness and elasticity, alopecia, pyoderma) and regrowth of hair. 1,2 Quality of life/general health was significantly improved based on increased behavioral and cognitive responses such as higher activity level, increased interaction with and responsiveness to the owner, decreased polydipsia and panting, improved housetraining habits and sleep patterns. 1,2

The LDDS test is used to confirm dysregulation of the HPA axis, and to monitor endocrinologic response to therapy. Adrenocorticotropic hormone (ACTH) secretion from the pars intermedia of the canine pituitary gland, and corticotropin releasing hormone (CRH) mediated ACTH release from the pars distalis are tonically inhibited by central nervous system dopamine levels. 5-7 Loss of this tonic inhibition results in increased secretion of ACTH, which results in adrenal hyperplasia and increased production of cortisol. 7 Hypothalamic dopamine concentrations are decreased in dogs with PDH. 8 Selegiline helps restore depleted central dopamine levels and facilitates dopaminergic transmission by several mechanisms, especially potent selective, irreversible inhibition of MAOB. 1,9 Selegiline also increases the synthesis and release of dopamine into the synapse, and inhibits dopamine reuptake.9 Selegiline or its metabolites may enhance release of other neurotransmitters such as norepinephrine and serotonin. 9

In the clinical trials noted above, dogs treated with Anipryl exhibited improvement in neuroendocrine function, as demonstrated by improvement (normalization in some patients) of LDDS test results. 1,2 The precise mechanism for this continued improvement is unknown, but may involve neuroprotection or nerve rescue, in addition to the mechanisms noted above. Experiments in laboratory animals demonstrated that selegiline enhanced the survival of neurons after nerve trauma or exposure to neurotoxins. 10,11

Canine PDH is a neuroendocrine disease which shares numerous features in common with several neurodegenerative disorders. 2,12 For example, behavioral signs and cognitive impairment in subjects with HPA axis dysregulation may resemble some of the behavioral and cognitive impairments in people with Parkinson’s or Alzheimer’s disease. 12,13 Clinical trials in people with these disorders have demonstrated that selegiline improves cognitive and other CNS functions. 14,15 Studies in laboratory and pet dogs have also revealed age associated cognitive dysfunction which is responsive to selegiline therapy. 12,16,17

Some neurodegenerative diseases, especially Parkinson’s disease, may represent abnormally rapid brain aging. 18 Parkinsonian patients treated with selegiline lived longer than those not receiving the drug. 19 Furthermore, laboratory animals treated with selegiline exhibited significantly longer life compared to placebo treated animals. 20

Cognitive dysfunction is a clinical syndrome recognized by veterinarians and often described by pet owners as “senility,” “simple aging,” or “old dog syndrome.” The syndrome is typified by the presence of multiple cognitive impairments and behavioral problems which impair the dog’s function as a pet and cause the owner concern. Some of the typical signs include loss of housetraining; decreased interest in food; inactivity or inattention to environment, including people or other animals; confusion or disorientation; apparent inability to recognize familiar places, people or other animals; apparent inability to recognize/respond to commands or when called by name; apparent decrease in hearing; development of “compulsive” or repetitive behaviors or habits (some examples: pacing, “fly biting,” tail chasing, floor licking); wandering, or circling to BOTH sides (unilateral circling suggests a focal lesion); tremor or shaking; changes in sleep/wake patterns; or inappropriate vocalization.

Anipryl has been shown to be an effective treatment for cognitive dysfunction in dogs as demonstrated by amelioration of cognitive and behavioral signs and problems. 1,12 After 1 month of Anipryl therapy, 75% of treated dogs exhibited cognitive improvement, and there were 78% and 77% improved at months 2 and 3, respectively. Efficacy was also evaluated for each individual parameter noted above. During the 3 months of Anipryl therapy, the population improved for all parameters at every time point, many of which attained statistical significance. Specifically, after 1 month of Anipryl therapy, the improvement reached significance or high significance for 13 (87%) of the 15 parameters; after months 2 and 3 of therapy the number of significantly improved parameters was 13 (87%) and 10 (67%), respectively.

TOXICITY: Selegiline hydrochloride was administered orally to beagle dogs once daily for one year at doses of 0, 1, 4 or 16 mg/kg. The no effect level was found to be 1 mg/kg. The following clinical signs were noted in some dogs at higher doses: salivation, panting, repetitive movements, decreased weight gain, and changes in activity level.

Anipryl 5 mg Indications

Cushing’s disease. Anipryl tablets are indicated for the treatment of uncomplicated pituitary dependent hyperadrenocorticism or Cushing’s disease in dogs. They are not indicated for other forms of Cushing’s syndrome.

Cognitive dysfunction. Anipryl tablets are indicated for the treatment of cognitive dysfunction syndrome in dogs.

Precautions

Endocrine function testing to confirm pituitary dependent hyperadrenocorticism should be performed by a licensed veterinarian prior to initiation of therapy. If complications of PDH are evident at the time of diagnosis or emerge during Anipryl therapy the patient should be evaluated and, if warranted, alternative therapy considered. Concurrent use of Anipryl in conjunction with other therapy of canine PDH has not been reported. Anipryl should not be administered at doses exceeding those recommended.

REPRODUCTION: The effect of Anipryl on reproduction in the bitch has not been determined.

Contraindications

Anipryl is contraindicated in patients with known hypersensitivity to this drug. Controlled studies to determine the interaction of selegiline when administered with other drugs have not been conducted in dogs. To date, patients enrolled in clinical trials have not been reported to exhibit adverse drug interactions with heartworm prophylaxis, a variety of antimicrobials, anthelminthics and analgesics. Concurrent use of selegiline with other MAO inhibitors, such as Amitraz, is not recommended. In humans, selegiline is contraindicated for use with meperidine and this contraindication is often extended to other opioids. Further experience in humans has revealed adverse interactions between nonspecific MAO inhibitors and tricyclic antidepressants such as fluoxetine. Although to date no such interaction has been reported for selegiline in any nonhuman species, it seems prudent to avoid such combinations in dogs.

Side Effects

During clinical trials 156 dogs treated with Anipryl for as long as 2 years were monitored for the occurrence of adverse events. No serious adverse events thought to be related to Anipryl therapy were reported and no adverse drug interactions were reported.

Dosage and Administration

Cushing’s disease. After confirmation of the diagnosis of PDH, Anipryl is recommended orally once daily at an initial dose of 1 mg/kg of body weight. During the first two months of therapy, the patient should be reevaluated periodically for clinical response by history and physical examination. If no improvement in clinical signs or physical examination findings is evident by 2 months the dose can be increased to a maximum of 2 mg/kg once daily, and the dog reevaluated in similar fashion one month later. If there is still no improvement or if at any time clinical signs progress, the patient should be evaluated for the presence of concurrent disorders, including performance of appropriate laboratory tests or other studies as warranted. In dogs whose clinical signs of PDH progress despite Anipryl therapy in the absence of concurrent disease, alternative therapy should be considered.

Cognitive dysfunction. In dogs diagnosed with signs of cognitive dysfunction, Anipryl is recommended orally once daily at an initial dose of 0.5 mg/kg of body weight. Since many dogs with cognitive dysfunction are elderly, it is likely that concurrent medical problems unrelated to cognitive dysfunction will exist at the time of diagnosis of cognitive dysfunction, or emerge during therapy. Therefore, prior to, or concurrent with, initiation of Anipryl therapy, the patient should be evaluated for the presence of concurrent medical disorders, including performance of appropriate laboratory tests or other studies as warranted. Any medical problems present at the time of diagnosis should be treated and managed by the usual appropriate methods, while continuing Anipryl therapy. During the first two months of therapy, the patient should be reevaluated periodically for behavioral and clinical response by history and physical examination. If no improvement in behavioral response is evident by 2 months the dose can be increased to a maximum of 1 mg/kg once daily, and the dog reevaluated in similar fashion one month later. If there is no behavioral improvement or the behavioral signs progress, the patient should be evaluated for the presence of concurrent medical disorders, as directed above. Any medical problems identified should be treated and managed by usual, appropriate methods. In dogs whose behavioral signs progress despite Anipryl therapy when concurrent medical disorders have been controlled or eliminated, alternative therapy should be considered.

AVAILABILITY: Five tablet sizes are available in blister packages of 30’s: 2 mg, 5 mg, 10 mg, 15 mg and 30 mg. Not all pack sizes may be marketed.

Storage

Store at or below 25°C.

References

1. Bureau of Veterinary Drugs, Health and Welfare Canada: Data on file.

2. Bruyette DS, Ruehl WW, Smidberg TL: Canine pituitary dependent hyperadrenocorticism: A spontaneous animal model for neurodegenerative disorders and their treatment with L-deprenyl. Progress in Brain Research (Yu PM, et al editors) 1995, Vol. 106; pp 207-215.

3. Feldman EC: Adrenal Gland Disease. Textbook of Veterinary Internal Medicine . 2nd Ed. (Ettinger SJ, ed). W. B. Saunders, Philadelphia, PA 1989, p 1721.

4. Rijnberk A, Mol JA, Kwant MM, et al: Effects of bromocriptine on corticotrophin, melanotrophin, and corticosteroid secretion in dogs with pituitary-dependent hyperadrenocorticism. J Endocrinol 118:271-277, 1988.

5. Kemppainen RJ, Zerbe CA, Sartin JL: Regulation and secretion of propiomelanocortin peptides from isolated perifused dog pituitary pars intermedia cells. Endocrinol 124:2208-2217, 1989.

6. Kemppainen RJ, Clark TP, Sartin JL, et al: Regulation of the adrenocorticotropin secretion from cultured canine anterior pituitary cells. Am J Vet Res 53:2355-2358, 1992.

7. Zerbe CA, Clark TP, Sartin JL, et al: Domperidone treatment enhances corticotropin-releasing hormone stimulated ACTH release from the dog pituitary. Neuroendocrinol 57:282-288, 1993.

8. Peterson ME, Palkovits M, Chiueh CC, et al: Biogenic amine and corticotropin-releasing factor concentrations in hypothalamic paraventricular nucleus and biogenic amine levels in the median eminence of normal dogs, chronic dexamethasone treated dogs, and dogs with naturally-occurring pituitary-dependent hyperadrenocorticism (canine Cushing’s disease). J Neuroendocrinol 1:169-171, 1989.

9. Heinonen EH, et al: A review of the pharmacology of selegiline. Acta Neurol Scand 84 (Suppl.) 136:44-59, 1991.

10. Tatton WG, Greenwood CE: Rescue of dying neurons: A new action for Deprenyl in MPTP parkinsonism. J Neurosci Res 30:666-672,1991.

11. Salo PT, Tatton WG: Deprenyl reduces the death of motoneurons caused by axotomy. J Neurosci Res 31:394-400, 1992.

12. Ruehl WW, et al: Canine cognitive dysfunction as a model for human age related cognitive decline, dementia and Alzheimer’s disease: Clinical presentation, cognitive testing, pathology and response to L-deprenyl therapy. Prog Brain Res (Yu PM, et al . eds) 1995, Vol 106, pp 217-225.

13. Lupien S, LeCours A, Lussier I, et al: Basal cortisol levels and cognitive deficits in human aging. J Neurosci 14:2893-2903, 1994.

14. Wessel K: MAOB inhibitors in neurological disorders with special reference to selegiline. Inhibitors of Monoamine Oxidase B (Szelenyi I, ed). Birkhauser Verlag, Basel, 1993; pp 253-275.

15. Tariot PN, Schneider LS, Patel SV, Goldstein B: Alzheimer’s disease and L-deprenyl: Rationales and findings. Inhibitors of Monoamine Oxidase B (Szelenyi I, ed). Birkhauser Verlag, Basel, 1993; pp 301-317.

16. Milgram NW, Ivy GO, Head E, et al: The effect of L-deprenyl on behavior, cognitive function, and biogenic amines in the dog. Neurochem Res 18:1211-1219, 1993.

17. Head E, Hartley J, Mehta R, et al: The effects of L-deprenyl on spatial short term memory in the dog (Abst). Soc Neurosci (Accepted for Publication).

18. Wolters ECh, Calne DB: Is Parkinson’s Disease related to aging? Parkinsonism and Aging (Calne DB, et al . eds). Raven Press, New York, 1987; pp 125-132.

19. Birkmayer W, Knoll J, Riederer P, et al: Increased life expectancy resulting from addition of L-deprenyl to madopar treatment in Parkinson’s Disease: A Long Term Study. J Neurol Transm 64:113-127, 1985.

20. Kitani K, Kanai S, et al: Chronic treatment of (-) deprenyl prolongs the life span of male fischer 344 rats. Further Evidence. Life Sci 52:281-288, 1993.

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Akbeta Ophthalmic Drug Information On Uses, Side Effects, Interactions, And User Reviews On Rxlist,

AKBeta ophthalmic

AKBeta ophthalmic Uses

This medication is used alone or with other medications to treat high pressure inside the eye due to glaucoma (open-angle type) or other eye diseases (e. g. ocular hypertension). Lowering high pressure inside the eye helps to prevent blindness. Levobunolol belongs to a class of drugs known as beta blockers and works by decreasing the amount of fluid production within the eye.

How to use AKBeta ophthalmic

To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface.

If you are wearing contact lenses, remove them before using eye drops. Wait at least 15 minutes before replacing your contact lenses.

Tilt your head back, look upward, and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and place one drop into the pouch, usually once or twice daily or as directed by your doctor. Look downward and gently close your eyes for 1 to 2 minutes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure. This will prevent the medication from draining out. Try not to blink and do not rub your eye. Repeat these steps for your other eye if so directed or if your dose is for more than 1 drop.

Do not rinse the dropper. Replace the dropper cap after each use.

If you are using another kind of eye medication (e. g. drops or ointments), wait at least 5 to 10 minutes before using the other medications. Use eye drops before eye ointments to allow the eye drops to enter the eye.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time(s) each day. It is important to continue using this medication even if you feel well. Most people with glaucoma or high pressure in the eyes do not feel sick.

AKBeta ophthalmic Side Effects

Temporary burning/stinging of the eye, itchy/red eyes, headache, or dizziness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if any of these unlikely but serious side effects occur: eye pain/swelling/discharge, reduced feeling in eye, slow/irregular heartbeat, muscle weakness, hair loss, mental/mood changes, vision changes, tiredness, swelling of the ankles/feet, sudden/unexplained weight gain.

Seek immediate medical attention if any of these rare but very serious side effects occur: trouble breathing, chest pain, weakness on one side of the body, slurred speech, confusion.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www. fda. gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

AKBeta ophthalmic Precautions

Before using levobunolol, tell your doctor or pharmacist if you are allergic to it; or to other beta-blockers (e. g. timolol, metipranolol); or if you have any other allergies. This product may contain inactive ingredients (such as preservatives like benzalkonium chloride, sulfites), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe breathing problems (e. g. asthma or a history of asthma, chronic obstructive pulmonary disease-COPD), certain types of heart rhythm problems (e. g. sinus bradycardia, second - or third-degree atrioventricular block), certain serious heart conditions (e. g. cardiogenic shock, severe heart failure).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: lung disease (e. g. bronchitis, emphysema), diabetes, heart failure (treated, stable type), blood circulation problems (e. g. cerebrovascular insufficiency), overactive thyroid (hyperthyroidism), muscle weakness disorders (e. g. myasthenia gravis).

Before having surgery, tell your doctor or dentist that you are using this medication.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

If you have diabetes, this product may mask the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of a low blood sugar level, such as dizziness/sweating, are unaffected by this drug.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known if this medication passes into breast milk. Consult your doctor before breast-feeding.

AKBeta ophthalmic Interactions

Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: digoxin, drugs for high blood pressure (e. g. clonidine, reserpine, oral beta blockers such as propranolol, calcium channel blockers such as diltiazem), epinephrine, fingolimod, phenothiazines (e. g. prochlorperazine).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

AKBeta ophthalmic Overdose

This medicine may be harmful if swallowed. If swallowing or overdose is suspected, contact a poison control center or emergency room right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. If this product is accidentally swallowed, you may experience symptoms such as trouble breathing, slow/irregular heartbeat.

Do not share this medication with others.

Laboratory and/or medical tests (e. g. eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised October 2015. Copyright(c) 2015 First Databank, Inc.



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Zithromax is used for treating mild to moderate infections caused by certain bacteria. It may also be used alone or with other medicines to treat or prevent certain infections in persons with advanced HIV infection. Zithromax is a macrolide antibiotic. It slows the growth of, or sometimes kills, sensitive bacteria by reducing the production of important proteins needed by the bacteria to survive.

Use Zithromax as directed by your doctor.

Take Zithromax by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.

Do not take an antacid that has aluminum or magnesium in it within 1 hour before or 2 hours after you take Zithromax.

Zithromax works best if it is taken at the same time each day.

To clear up your infection completely, use Zithromax for the full course of treatment. Keep using it even if you feel better in a few days.

If you miss a dose of Zithromax, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Zithromax.

Store Zithromax below 86 degrees F (30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Zithromax out of the reach of children and away from pets.

Active Ingredient: Azithromycin.

Do NOT use Zithromax if:

you are allergic to any ingredient in Zithromax, to other macrolide antibiotics (eg, erythromycin), or to ketolide antibiotics (eg, telithromycin)

you are taking dofetilide, nilotinib, pimozide, propafenone, or tetrabenazine.

Contact your doctor or health care provider right away if any of these apply to you.

Some medical conditions may interact with Zithromax. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have liver or kidney problems, myasthenia gravis, or abnormal heart rhythms.

Some medicines may interact with Zithromax. Tell your health care provider if you are taking any other medicines, especially any of the following:

Antiarrhythmics (eg, disopyramide, dofetilide ), arsenic, astemizole, cisapride, domperidone, maprotiline, methadone, paliperidone, pimozide, propafenone, quinolone antibiotics (eg, levofloxacin), terfenadine, or tetrabenazine because the risk of heart problems, including irregular heartbeat, may be increased

Nelfinavir because it may increase the risk of Zithromax's side effects

Rifampin because it may decrease Zithromax's effectiveness

Anticoagulants (eg, warfarin), carbamazepine, cyclosporine, digoxin, ergot derivatives (eg, ergotamine), nilotinib, phenytoin, rifampin, theophylline, triazolam, or tyrosine kinase receptor inhibitors (eg, dasatinib) because the risk of their side effects may be increased by Zithromax.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Zithromax may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

Important safety information:

Zithromax may cause drowsiness, dizziness, blurred vision, or lightheadedness. These effects may be worse if you take it with alcohol or certain medicines. Use Zithromax with caution. Do not drive or perform other possible unsafe tasks until you know how you react to it.

Zithromax may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to Zithromax. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.

Mild diarrhea is common with antibiotic use. However, a more serious form of diarrhea (pseudomembranous colitis) may rarely occur. This may develop while you use the antibiotic or within several months after you stop using it. Contact your doctor right away if stomach pain or cramps, severe diarrhea, or bloody stools occur. Do not treat diarrhea without first checking with your doctor.

Tell your doctor or dentist that you take Zithromax before you receive any medical or dental care, emergency care, or surgery.

Long-term or repeated use of Zithromax may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this.

Be sure to use Zithromax for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future.

Zithromax only works against bacteria; it does not treat viral infections (eg, the common cold).

Zithromax should not be used in children; safety and effectiveness in children have not been confirmed.

Pregnancy and breast-feeding: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Zithromax while you are pregnant. It is not known if Zithromax is found in breast milk. If you are or will be breast-feeding while you use Zithromax, check with your doctor. Discuss any possible risks to your baby.

All medicines may cause side effects, but many people have no, or minor, side effects.

Check with your doctor if any of these most common side effects persist or become bothersome:

Diarrhea; headache; loose stools; nausea; stomach pain; upset stomach; vomiting.

Seek medical attention right away if any of these severe side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); bloody stools; changes in hearing or hearing loss; chest pain; eye or vision problems; irregular heartbeat; muscle weakness; pounding in the chest; red, swollen, blistered, or peeling skin; ringing in the ears; seizure; severe diarrhea; stomach cramps/pain; trouble speaking or swallowing; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

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Apigrane (Imitrex) Description

Apigrane is a perfect remedy in struggle against the symptoms of migraine headaches.

Apigrane acts by narrowing blood vessels in the head and stopping pain signals from being sent to the brain. It is selective serotonin receptor agonists.

Apigrane is also known as Sumatriptan, Imigran.

Generic name of Apigrane is Sumatriptan.

Brand names of Apigrane are Apigrane, Apigrane nasal.

Apigrane (Imitrex) Dosage

Apigrane is available in:

25mg Low Dosage

50mg Standard Dosage

100mg Increased Dosage

Shake the liquid form of Apigrane before using.

Keep this remedy away from children and don't give it to other people for using.

Do not crush or chew it.

Use Apigrane once a day.

If you want to achieve most effective results do not stop taking Apigrane suddenly.

Apigrane (Imitrex) Missing of dose

Do not take double dose. If you miss a dose you should take it as soon as you remember about your missing. If it is the time for the next dose you should continue your regular dosing schedule.

Apigrane (Imitrex) Overdose

If you overdose Apigrane and you don't feel good you should visit your doctor or health care provider immediately. Symptoms of Apigrane overdosage: breathing problems, blue-colored lips or fingernails, weakness, lack of coordination, shaking, convulsions, vision problems, skin redness, watery eyes or mouth.

Apigrane (Imitrex) Storage

Store at room temperature between 2 and 30 degrees C (36 and 86 degrees F) away from moisture and heat. Throw away any unused medicine after the expiration date. Keep out of the reach of children.

Apigrane (Imitrex) Side effects

Apigrane has its side effects. The most common are:

diarrhea

muscle pain

warmth or redness under your skin

sneezing

runny nose

cough

burning

numbness

lightheadedness

sleepiness

drooling

sweating

nausea

pressure or heavy feeling in any part of your body

vomiting

stuffy nose

Less common but more serious side effects during taking Apigrane:

allergy reactions (urticaria, breathing difficulties, rash, and eruption)

pain spreading to the arm or shoulder

nausea

exudation

general ill feeling

sudden migraine

confusion

problems with vision, speech, balance

fast heart rate

agitation

muscle stiffness

lack of coordination

nausea

vomiting

diarrhea

sudden and severe stomach pain and bloody diarrhea

convulsions

numbness

tingling, pale or blue-colored appearance in your fingers or toes

chest pain or heavy feeling

sudden numbness or weakness, especially on one side of the body

seeing things or hearing voices that do not exist

Side effects manifestations are not only depend on medicine you are taking but also depend on your health state and on the other factors.

Apigrane (Imitrex) Contra-indications

Do not take Apigrane if you are allergic to Apigrane components or to aspirin.

Do not take Apigrane if you are pregnant, planning to become pregnant. Avoid breast-feeding.

Be careful with this medicine if you smoke, if you are postmenopausal, or if you are a man over 40.

Be careful using Apigrane if you take selective serotonin reuptake inhibitors (Ssris) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in symbyax), fluvoxamine, paroxetine (Paxil), and sertraline (Zoloft); and selective serotonin/norepinephrine reuptake inhibitors (Snris) such as duloxetine (Cymbalta) and venlafaxine (Effexor).

It can be dangerous to use Apigrane if you suffer from or have a history of high blood pressure, angina (recurring chest pain), heart attack, high cholesterol, obesity, stroke, transient ischemic attack (mini-stroke), ischemic bowel disease, coronary artery disease, seizures, or blood vessel, kidney, or liver disease, heart disease, diabetes.

It can be dangerous to stop Apigrane taking suddenly.

Apigrane (Imitrex) Frequently asked questions

Q: What does Apigrane mean?

A: Apigrane is a perfect remedy in struggle against the symptoms of migraine headaches.

Q: What are generic and brand names of Apigrane?

A: Generic name of Apigrane is Sumatriptan. Brand names of Apigrane are Apigrane, Apigrane nasal.

Q: What is recommended to be avoided?

A: Do not take Apigrane if you are allergic to Apigrane components or to aspirin. Do not take Apigrane if you are pregnant, planning to become pregnant. Avoid breast-feeding. Avoid alcohol.

Q: In what way does Apigrane operate?

A: Apigrane acts by narrowing blood vessels in the head and stopping pain signals from being sent to the brain. It is selective serotonin receptor agonists.

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Eltroxin

Warnings

This medication should not be used for weight loss. Normal doses of this medication will not work for weight loss, and large doses of this medication may cause serious, possibly fatal side effects, especially when taken with diet pills .

Uses

Levothyroxine is used to treat an underactive thyroid (hypothyroidism ). It replaces or provides more thyroid hormone, which is normally produced by the thyroid gland. Low thyroid hormone levels can occur naturally or when the thyroid gland is injured by radiation /medications or removed by surgery. Having enough thyroid hormone is important for maintaining normal mental and physical activity. In children, having enough thyroid hormone is important for normal mental and physical development.

This medication is also used to treat other types of thyroid disorders (such as certain types of goiters, thyroid cancer ).

This medication should not be used to treat infertility unless it is caused by low thyroid hormone levels.

How to use Eltroxin

Take this medication by mouth as directed by your doctor, usually once daily on an empty stomach. 30 minutes to 1 hour before breakfast. Take this medication with a full glass of water unless your doctor directs you otherwise.

If you are taking the capsule form of this medication, swallow it whole. Do not split, crush, or chew. People who cannot swallow the capsule whole (such as infants or small children) should use the tablet form of the medication.

For infants or children who cannot swallow whole tablets, crush the tablet and mix in 1 to 2 teaspoons (5 to 10 milliliters) of water, and give using a spoon or dropper right away. Do not prepare a supply in advance or mix the tablet in soy infant formula. Consult your pharmacist for more information.

Dosage is based on your age, weight. medical condition, laboratory test results, and response to treatment.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time each day.

Do not stop taking this medication without first consulting with your doctor. Thyroid replacement treatment is usually taken for life.

There are different brands of levothyroxine available. Do not change brands without first consulting your doctor or pharmacist.

Certain medications (such as cholestyramine. colestipol. colesevelam. antacids, sucralfate, simethicone. iron, sodium polystyrene sulfonate, calcium supplements. orlistat. sevelamer. among others) can decrease the amount of thyroid hormone that is absorbed by your body. If you are taking any of these drugs, separate them from this medication by at least 4 hours.

Symptoms of low thyroid hormone levels include tiredness, muscle aches, constipation. dry skin. weight gain, slow heartbeat, or sensitivity to cold. Tell your doctor if your condition worsens or persists after several weeks of taking this medication.

Side Effects

Hair loss may occur during the first few months of treatment. This effect is usually temporary as your body adjusts to this medication. If this effect persists or worsens, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if any of these unlikely but serious effects of high thyroid hormone levels occur: increased sweating. sensitivity to heat, mental/mood changes (such as nervousness, mood swings), tiredness, diarrhea. shaking (tremor), headache. shortness of breath.

Get medical help right away if any of these rare but serious effects of high thyroid hormone levels occur: chest pain. fast/pounding/irregular heartbeat. swelling hands/ankles /feet, seizures .

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction. including: rash. itching /swelling (especially of the face/tongue /throat), severe dizziness. trouble breathing .

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www. fda. gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking levothyroxine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: increased thyroid hormones (thyrotoxicosis), decreased adrenal gland function, heart disease (such as coronary artery disease, irregular heartbeat), high blood pressure, diabetes.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Current information shows that this drug may be used during pregnancy. Tell your doctor if you are pregnant because your dose may need to be adjusted.

Levothyroxine passes into breast milk but is unlikely to harm a nursing infant. Consult your doctor before breast-feeding.

Interactions

See also How to Use Section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: "blood thinners" (such as warfarin), digoxin, sucroferric oxyhydroxide, theophylline.

Overdose

If overdose is suspected, contact a poison control center or emergency room right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: fast/pounding/irregular heartbeat, loss of consciousness, confusion, seizures.

Notes

Do not share this medication with others.

Laboratory and/or medical tests (such as thyroid function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Missed Dose

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up unless your doctor tells you to do so. Call your doctor if you miss 2 or more doses in a row. Ask your doctor ahead of time what to do about a missed dose and follow your doctor's specific directions.

Storage

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised October 2015. Copyright(c) 2015 First Databank, Inc.

Images

No data available at this time.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, expect as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

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Brock: "Voluntary Active Euthanasia"

I. Brock's Main Goal

To formulate and evaluate the main arguments for and against voluntary active euthanasia (10).

II. Some Distinctions (10-11)

A paradigm case of physician-assisted suicide: A competent patient voluntarily ends her life with a lethal dose of a medication persistently requested of and eventually provided by a physician for that purpose.

A paradigm case of voluntary active euthanasia: A competent patient makes a voluntary and persistent request to a physician for help in dying. The physician administers a lethal dose of medication because the patient cannot do so herself.

A paradigm case of involuntary active euthanasia: A physician administers a lethal dose of medication to a competent patient even though she has refused euthanasia.

A paradigm case of non-voluntary active euthanasia: A physician administers a lethal dose of medication to a patient who is not competent and who is unable to indicate whether she wants euthanasia.

Some commentators use "passive euthanasia" to refer to withholding or withdrawing life-sustaining treatment.

III. Main Argument for Voluntary Active Euthanasia (11)

We believe that it is legitimate for patients to make decisions about whether to initiate or continue life-sustaining treatment.

The basis of our judgment that this is legitimate is an appeal to the goodness of self-determination (autonomy) and well-being.

But voluntary active euthansia would also promote these values.

So we have significant reason to be in favor of voluntary active euthanasia.

IV. Objection and Replies

Even when voluntary active euthanasia would promote a patient's autonomy and well-being, it is wrong. For it involves the deliberate killing of an innocent person and such killing is wrong.

Reply: Withdrawal of treatment is also deliberate killing of an innocent person. (Greedy son thought experiment.) So either we are mistaken in concluding that it is morally permissible or deliberately killing an innocent person can be right.

Reply: Even if withdrawal of treatment is not deliberate killing of an innocent person, voluntary active euthanasia might be morally permissible. For deliberately killing a person when he has waived his right not to be killed can be morally permissible.

V. Advantages and Disadvantages of Legally Permitting Voluntary Active Euthanasia

Advantages:

We would respect the self-determination of those who are competent and want to die, but cannot under current law.

We would give people the comfort of knowing that if they find themselves in a situation in which they would prefer voluntary active euthansia, it would be available to them.

We would relieve pain and suffering, both physical and psychological.

Disadvantages:

We would undermine the fundamental professional and moral committments of physicians. (Disputed by Brock.)

We would make certain people worse off by giving them the choice of whether to opt for euthanasia. (Not seen as particularly serious by Brock.)

We would fall down a slippery slope to non-voluntary or involuntary active euthanasia. (Considered as potentially serious, but not conclusive, by Brock.)



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Adele

About Adele

When the U. K. press began dubbing Adele "the next Amy Winehouse" in late 2007, the hype didn't touch upon the singer/songwriter influence found in the Londoner's music. Influenced by Roberta Flack and Suzanne Vega as much as Jill Scott, Adele soon became a phenomenon in her own right; her second album, 21, eventually sold an estimated 30 million copies worldwide, making her one of the few sales successes in an age of digital streaming.

Adele first made an impression in 2006 when her demo landed her a deal with XL Recordings. She toured as an opening act for Jack Penate, and graduated to headlining status by the end of 2007, thanks to BBC Radio 1 playing her single "Daydreamer"; another song, "Hometown Glory," was also released as a single on Jamie T.'s label, Pacemaker. An appearance alongside Paul McCartney and Bjork on the BBC 2 television show Later with Jools Holland came next, and a recording contract with XL Recordings was finalized soon after. Early 2008 brought similar luck as Adele found herself atop the BBC's new music talent list, which was compiled from the votes of 150 music critics. That same January, XL issued a new single, "Chasing Pavements," along with her debut album, 19. The title reflected Adele's age at the time of the album's release, and its popularity resulted in the release of several bonus editions throughout the year. Also in 2009, Adele won Grammy Awards for Best New Artist and Best Female Pop Vocal Performance.

Her sophomore album, 21, featuring the gospel and disco-infused single "Rolling in the Deep," was released in February of 2011. The album proved to be both a critical and commercial success, becoming one of the longest-running number one albums in history and spending over 18 weeks at the top spot. The glow of 21's success was dimmed somewhat when Adele was forced to cancel her tour after suffering a hemorrhage on her vocal chords. She underwent surgery for the hemorrhage in November of 2011. That same month, she released the concert CD/DVD Live at the Royal Albert Hall. Both Adele and 21 received many end-of-year honors, and in February 2012, as album sales began to creep closer to ten million copies, she won six major Grammy awards, one of the few artists in history to accomplish the feat in one night.

In October 2012, Adele announced that she had recorded the theme to the 23rd Bond film Skyfall. Produced by Paul Epworth and recorded at the prestigious Abbey Road Studios, the single entered the Top Ten of both the U. K. singles chart and the Billboard Hot 100 on release. By early 2013, 21 had registered sales of over 25 million copies. Although she promised she was in the early stages of creating her third album, 2013 and 2014 came and went without fresh material. In the summer of 2015, reports of an imminent third album started to surface and in October, the rumors were confirmed by Adele and her label. Preceded by the single "Hello" -- a song that debuted at number one in both the U. K. and U. S. becoming the first song to sell over a million downloads in its first week of release -- 25 debuted worldwide in late November 2015. It broke the single-week U. S. sales record previously held by *NSYNC's No Strings Attached.

David Jeffries, Rovi

Best New Videos

When the U. K. press began dubbing Adele "the next Amy Winehouse" in late 2007, the hype didn't touch upon the singer/songwriter influence found in the Londoner's music. Influenced by Roberta Flack and Suzanne Vega as much as Jill Scott, Adele soon became a phenomenon in her own right; her second album, 21, eventually sold an estimated 30 million copies worldwide, making her one of the few sales successes in an age of digital streaming. Adele first made an impression in 2006 when her demo landed her a deal with XL Recordings. She toured as an opening act for Jack Penate, and graduated to headlining status by the end of 2007, thanks to BBC Radio 1 playing her single "Daydreamer"; another song, "Hometown Glory," was also released as a single on Jamie T.'s label, Pacemaker. An appearance alongside Paul McCartney and Bjork on the BBC 2 television show Later with Jools Holland came next, and a recording contract with XL Recordings was finalized soon after. Early 2008 brought similar luck as Adele found herself atop the BBC's new music talent list, which was compiled from the votes of 150 music critics. That same January, XL issued a new single, "Chasing Pavements," along with her debut album, 19. The title reflected Adele's age at the time of the album's release, and its popularity resulted in the release of several bonus editions throughout the year. Also in 2009, Adele won Grammy Awards for Best New Artist and Best Female Pop Vocal Performance. Her sophomore album, 21, featuring the gospel and disco-infused single "Rolling in the Deep," was released in February of 2011. The album proved to be both a critical and commercial success, becoming one of the longest-running number one albums in history and spending over 18 weeks at the top spot. The glow of 21's success was dimmed somewhat when Adele was forced to cancel her tour after suffering a hemorrhage on her vocal chords. She underwent surgery for the hemorrhage in November of 2011. That same month, she released the concert CD/DVD Live at the Royal Albert Hall. Both Adele and 21 received many end-of-year honors, and in February 2012, as album sales began to creep closer to ten million copies, she won six major Grammy awards, one of the few artists in history to accomplish the feat in one night. In October 2012, Adele announced that she had recorded the theme to the 23rd Bond film Skyfall. Produced by Paul Epworth and recorded at the prestigious Abbey Road Studios, the single entered the Top Ten of both the U. K. singles chart and the Billboard Hot 100 on release. By early 2013, 21 had registered sales of over 25 million copies. Although she promised she was in the early stages of creating her third album, 2013 and 2014 came and went without fresh material. In the summer of 2015, reports of an imminent third album started to surface and in October, the rumors were confirmed by Adele and her label. Preceded by the single "Hello" -- a song that debuted at number one in both the U. K. and U. S. becoming the first song to sell over a million downloads in its first week of release -- 25 debuted worldwide in late November 2015. It broke the single-week U. S. sales record previously held by *NSYNC's No Strings Attached.

David Jeffries, Rovi

From position 0. showing 20 items, asking 20

Adele in Jenny Packham at the 2013 Academy Awards.

Adele with her award for Best Original Song, "Skyfall."

2013 Getty Images

Adele with her toddler doppelganger.

Getty Images/Tricia Messeroux/Toddlewood

Adele in Valentino at the 55th annual Grammy Awards in Los Angeles, California on February 10, 2013.

An emotional Adele thanks her new born son as she accepts the Golden Globe for Best Original Song for 'Skyfall.'

Singer Adele arrives in Burberry at the 70th Annual Golden Globe Awards held at The Beverly Hilton Hotel on January 13, 2013 in Beverly Hills, California.



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Aortobifemoral Bypass For Peripheral Arterial Disease, Bismoral

Aortobifemoral Bypass for Peripheral Arterial Disease

Surgery Overview

Aortobifemoral bypass surgery is used to bypass diseased large blood vessels in the abdomen and groin.

To bypass a narrowed or blocked blood vessel, blood is redirected through a graft made of synthetic material (such as polytetrafluoroethylene [PTFE] or Dacron). This graft is sewn above and below the diseased artery so that blood flows through the graft. These man-made grafts are more likely to be used than transplanted natural grafts for aortobifemoral surgery, because the blood vessels involved are large.

The artificial blood vessel is formed into a Y shape. The single end of the Y is sewn on the aorta. The two split ends of the Y are sewn below the blocked or narrowed areas of the femoral arteries. This allows the blood to travel around (bypass) the diseased areas.

General anesthesia is used and will cause you to sleep through the procedure.

What To Expect After Surgery

You may stay in the hospital 4 to 7 days. And you can expect your belly and groin to be sore for several weeks. You will probably feel more tired than usual for several weeks.

You may be able to do many of your usual activities after 4 to 6 weeks. But you will likely need 2 to 3 months to fully recover, especially if you typically do a lot of physical activities.

You will probably need to take at least 4 to 6 weeks off from work. It depends on the type of work you do and how you feel.

Why It Is Done

Aortobifemoral bypass surgery is for people who have narrowed or blocked blood vessels (aorta or iliac arteries) in the abdomen and pelvis. Usually the disease must be causing significant symptoms or be limb-threatening before bypass surgery is considered.

How Well It Works

Bypass surgery can restore blood flow and relieve intermittent claudication. Aortobifemoral bypass grafts stay open about 90% of the time for at least 5 years. 1

Risks

All surgeries carry a certain amount of risk. These risks include:

Specific risks for aortobifemoral bypass surgery include:

Leg swelling.

Failed or blocked grafts.

Sexual dysfunction caused by nerve damage in the pelvis.

What To Think About

Your doctor may recommend that you try an exercise program and medicine before he or she recommends that you have this surgery.

Complete the surgery information form (PDF) (What is a PDF document?) to help you prepare for this surgery.

References

Citations

Hirsch AT, et al. (2006). ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation ; National Heart. Lung. and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation, 113(11): e463-e654.

Credits

By Healthwise Staff Primary Medical Reviewer Rakesh K. Pai, MD, FACC - Cardiology, Electrophysiology Specialist Medical Reviewer David A. Szalay, MD - Vascular Surgery

Current as of November 14, 2014

WebMD Medical Reference from Healthwise

This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information. © 1995-2015 Healthwise, Incorporated. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.

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Didronel Advanced Patient Information, Anfozan

Didronel

Uses For Didronel

Etidronate is used to treat Paget's disease of the bone. It may also be used to treat or prevent a certain type of bone problem (heterotopic ossification) after hip replacement surgery or spinal injury.

Etidronate is also used to treat hypercalcemia (too much calcium in the blood) that may occur with some types of cancer.

This medicine is available only with your doctor's prescription.

Before Using Didronel

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of etidronate in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of etidronate in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving etidronate.

Pregnancy

Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

Anemia or

Blood clotting problems or

Cancer or

Dental or tooth problems or

Dental procedures (eg, tooth extraction) or

Infection or

Poor oral hygiene or

Surgery (eg, dental surgery)—May increase risk for severe jaw problems. This risk may also be increased if you use this medicine for a long time.

Enterocolitis (severe diarrhea) or

Hyperphosphatemia (high phosphate in the blood) or

Stomach or bowel problems (eg, Barrett's esophagus, difficulty with swallowing, heartburn, inflammation of the esophagus, or ulcers)—Use with caution. May make these conditions worse.

Esophagus (the tube that runs from your throat to your stomach) problems (eg, achalasia, stricture) or

Osteomalacia (soft bones) or

Trouble with swallowing—Should not be used in patients with these conditions.

Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of Didronel

Take this medicine only as directed . Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

Make sure your doctor knows if your diet includes large amounts of calcium, such as milk or other dairy products, or if you are on any special diet, such as a low-sodium or low-sugar diet. Calcium in the diet may prevent the absorption of oral etidronate.

Take etidronate with a full glass (6 to 8 ounces) of water on an empty stomach at least 2 hours before or after food (mid-morning is best) or at bedtime. Food may decrease the amount of etidronate absorbed by your body.

Do not lie down for at least 30 minutes after taking this medicine, and do not lie down until after you have eaten some food.

In some patients, etidronate takes up to 3 months to work. If you feel that the medicine is not working, do not stop taking it on your own. Instead, check with your doctor.

It is important that you eat a well-balanced diet with an adequate amount of calcium and vitamin D (found in milk or other dairy products). Too much or too little of either may increase the chance of side effects while you are taking etidronate. Your doctor can help you choose the meal plan that is best for you. However, do not take any food, especially milk, milk formulas, or other dairy products, or antacids, mineral supplements, or other medicines that are high in calcium or iron (high amounts of these minerals may also be in some vitamin preparations), magnesium, or aluminum within 2 hours of taking etidronate. To do so may keep this medicine from working properly.

If this medicine upsets your stomach, ask your doctor if you can take two smaller doses instead of one larger dose. Do not change without talking to your doctor.

For treating Paget's disease, you may need to take this medicine for up to 6 months. Then after 90 days of not taking the medicine, your doctor may want you to start another course of treatment.

If you have Paget's disease, this medicine may work slowly, so you may not feel better until you have been using it for awhile. Do not stop taking it without talking to your doctor first. Your body may continue to respond to this medicine for several months after you stop using it.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets):

For Paget's disease of bone:

Adults—Dose is based on body weight and must be determined by your doctor. At first, 5 milligrams (mg) per kilogram (kg) (2.3 mg per pound) of body weight a day, usually as a single dose, for not more than 6 months. Some people may need 6 to 10 mg per kg (2.7 to 4.6 mg per pound) of body weight a day for not more than 6 months. Others may need 11 to 20 mg per kg (5 to 9.1 mg per pound) of body weight a day for not more than 3 months. Your doctor may adjust your dose depending on your response to treatment.

Children—Use and dose must be determined by your doctor.

For treating or preventing a certain type of bone problem that may occur after hip replacement:

Adults—Dose is based on body weight and must be determined by your doctor. The dose is usually 20 milligrams (mg) per kilogram (kg) (9.1 mg per pound) of body weight a day for 1 month before surgery, and for 3 months after surgery.

Children—Use and dose must be determined by your doctor.

For treating or preventing a certain type of bone problem that may occur after spinal injury:

Adults—Dose is based on body weight and must be determined by your doctor. The dose is usually 20 milligrams (mg) per kilogram (kg) (9.1 mg per pound) of body weight a day for 2 weeks, beginning as soon as possible after your injury. Your doctor may then decrease your dose to 10 mg per kg (4.5 mg per pound) of body weight for an additional 10 weeks.

Children—Use and dose must be determined by your doctor.

For treating hypercalcemia (too much calcium in the blood):

Adults—Dose is based on body weight and must be determined by your doctor. The dose is usually 20 milligrams (mg) per kilogram (kg) (9.1 mg per pound) of body weight a day for 30 days. Treatment usually does not continue beyond 90 days.

Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Didronel

It is important that your doctor check your progress at regular visits even if you are between treatments and are not taking this medicine. If your condition has improved and your doctor has told you to stop taking etidronate, your progress must still be checked. The results of laboratory tests or the occurrence of certain symptoms will tell your doctor if more medicine must be taken. Your doctor may want you to begin another course of treatment after you have been off the medicine for at least 3 months.

This medicine can irritate your esophagus. If you think this medicine has started to damage your esophagus, stop taking this medicine and call your doctor. Some symptoms of damage to the esophagus are heartburn (either new or worse than usual), pain when swallowing, pain in the center of your chest, trouble swallowing, or feeling that food gets stuck on the way to your stomach.

It is important that you tell all of your health care providers that you are taking etidronate. If you are having dental procedures done while taking etidronate you may have an increased chance of getting a severe problem of your jaw.

Make sure you tell your doctor about any new medical problems, especially with your teeth or jaws. Tell your doctor if you have severe bone, joint, or muscle pain while using this medicine.

If this medicine causes you to have nausea or diarrhea and it continues, check with your doctor. The dose may need to be changed.

This medicine may increase your risk of developing fractures. This may be more common if you use it for a long time. Check with your doctor right away if you have dull or aching pain in the arms, legs, or thighs.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Didronel Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Bone pain or tenderness (increased, continuing, or returning—in patients with Paget's disease)

Less common

Bone fractures, especially of the thigh bone

Rare

Abdominal or stomach pain or burning

bloody, black, or tarry stools

chest pain

chills

cough or hoarseness

fever

general feeling of tiredness or weakness

hives

lower back or side pain

noisy breathing

painful or difficult urination

pale skin

skin rash or itching

sore throat

sores, ulcers, or white spots on the lips or inside the mouth

swelling of the arms, legs, face, lips, tongue, or throat

swollen glands

tightness in the chest

unusual bleeding or bruising

Incidence not known

Blistering, peeling, loosening of the skin

bone, joint, or muscle pain that is severe and occasionally disabling

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

difficulty in moving

difficulty in swallowing

discouragement

feeling sad or empty

heartburn

heavy jaw feeling

irritability

lack of appetite

large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

loosening of a tooth

loss of interest or pleasure

loss of memory

pain or burning in the throat

pain, swelling, or numbness in the mouth or jaw

problems with memory

rash with flat lesions or small raised lesions on the skin

red irritated eyes

red skin lesions, often with a purple center

redness or discoloration of the skin

seeing, hearing, or feeling things that are not there

trouble concentrating

trouble sleeping

unusual tiredness or weakness

vomiting

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

Abdominal or stomach cramps

confusion

convulsions

difficulty in breathing

irregular heartbeats

mood or mental changes

muscle cramps in the hands, arms, feet, legs, or face

numbness and tingling around the mouth, fingertips, or feet

shortness of breath

tremor

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common - at higher doses

Diarrhea

nausea

Incidence not known

Burning feeling in the chest or stomach

hair loss, thinning of hair

headache

indigestion

leg cramps

stomach upset

tenderness in the stomach area

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Truven Health Micromedex products as delivered by Drugs. com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Truven Health products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Truven Health and Drugs. com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, TRUVEN HEALTH MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Truven Health does not assume any responsibility or risk for your use of the Truven Health products.

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Orthovisc Intra-Articular Reviews And User Ratings Effectiveness, Ease Of Use, And Satisfaction, Ort

User Reviews & Ratings - ORTHOVISC intra-articular

« ORTHOVISC intra-articular Information

Current Rating: 2

Comment: I have osteoarthritis, chondromalacia and IT band pain syndrome. My knees felt better after getting the injections but as soon as I went back to mild exercising (yoga, swimming and walking long distances) the pain came back even worse than before. I don't think I would bother with the injections again.

Comment: I have osteoarthritis, chondromalacia and IT band pain syndrome. My knees felt better after getting the injections but as soon as I went back to mild exercising (yoga, swimming and walking long distances) the pain came back even worse than before. I don't think I would bother with the injections again. Hide Full Comment

1 person found this review helpful. Was this review helpful? Yes | No

Condition: Osteoarthritis of the Knee

6/4/2016 4:13:41 PM

Reviewer: gardener, 65-74 on Treatment for 1 to 6 months (Patient)

Current Rating: 1

Current Rating: 1

Current Rating: 1

Comment: Both knees injected - most recent pain due to bone spurs. Pain not only in joint but down side of calf. First injections by PA in training, and one was painful for days after. Experienced PA did last two injections with very little pain. Relief after 2nd and 3rd injections, but it did not last. Has been six weeks since last injection, and walking (sightseeing or shopping) for 1 to 1.5 hours cause. Show Full Comment

Comment: Both knees injected - most recent pain due to bone spurs. Pain not only in joint but down side of calf. First injections by PA in training, and one was painful for days after. Experienced PA did last two injections with very little pain. Relief after 2nd and 3rd injections, but it did not last. Has been six weeks since last injection, and walking (sightseeing or shopping) for 1 to 1.5 hours causes so much pain that I limp. Hide Full Comment

1 person found this review helpful. Was this review helpful? Yes | No

Condition: Osteoarthritis of the Knee

3/27/2016 1:12:49 AM

Reviewer: Marigold, 55-64 on Treatment for less than 1 month (Patient)

Current Rating: 2

Current Rating: 2

Current Rating: 2

Comment: Have had first of three rounds of shots in both knees; cortisone shots were not helpful so looking for alternatives to knee replacement surgery. Shots were extremely painful when administered, and pain continued for several days, along with severe back pain. No improvement in knee functionality or pain yet, but hoping to achieve after third round of shots are administered.

Comment: Have had first of three rounds of shots in both knees; cortisone shots were not helpful so looking for alternatives to knee replacement surgery. Shots were extremely painful when administered, and pain continued for several days, along with severe back pain. No improvement in knee functionality or pain yet, but hoping to achieve after third round of shots are administered. Hide Full Comment

5 people found this review helpful. Was this review helpful? Yes | No

Condition: Osteoarthritis of the Knee

3/14/2016 7:30:58 PM

Reviewer: Dloveslabs, 55-64 on Treatment for less than 1 month (Patient)

Current Rating: 5

Current Rating: 5

Current Rating: 5

Comment: I had #8 level pain in my left knee due to arthritis for a couple of months. Could barely get around. Cortisone and physical were not effective at all. Within a few hours of my first orthovisc injection, my knee improved. Within a few days, I didn't need NSAIDS anymore. Within a few weeks of my last injection - no pain at all and back to walking the hills with my dog. The shots are nothing in. Show Full Comment

Comment: I had #8 level pain in my left knee due to arthritis for a couple of months. Could barely get around. Cortisone and physical were not effective at all. Within a few hours of my first orthovisc injection, my knee improved. Within a few days, I didn't need NSAIDS anymore. Within a few weeks of my last injection - no pain at all and back to walking the hills with my dog. The shots are nothing in the hands of a skilled orthopedic doctor. Maybe a bit more pinch than your average flu shot. Hide Full Comment

13 people found this review helpful. Was this review helpful? Yes | No

Condition: Osteoarthritis of the Knee

2/27/2016 4:31:52 AM

Reviewer: Joykan, 35-44 on Treatment for 2 to less than 5 years (Patient)

Current Rating: 4

Current Rating: 4

Current Rating: 3

Comment: Being treated with it for the last 5 yrs, 8 bilateral sessions (3) each knee. Last 2 sessions have being very painful as the liquid is being injected. Moderate pain and discomfort last form 2-4 days. first 20 mins after injection is very painful now, not as 3 yrs ago. This treatment has postponed a bilateral TKR. Better when lidocaine is administered before the orthovysc.

Comment: Being treated with it for the last 5 yrs, 8 bilateral sessions (3) each knee. Last 2 sessions have being very painful as the liquid is being injected. Moderate pain and discomfort last form 2-4 days. first 20 mins after injection is very painful now, not as 3 yrs ago. This treatment has postponed a bilateral TKR. Better when lidocaine is administered before the orthovysc. Hide Full Comment

7 people found this review helpful. Was this review helpful? Yes | No

User Reviews & Ratings - ORTHOVISC intra-articular

« ORTHOVISC intra-articular Information

Current Rating: 5

Comment: I had severe pain in my left knee from arthritis, I'm on my second injection, so far so good no pain just a little stiffness, go for 2 more shots im feeling good about it working

Comment: I had severe pain in my left knee from arthritis, I'm on my second injection, so far so good no pain just a little stiffness, go for 2 more shots im feeling good about it working Hide Full Comment

1 person found this review helpful. Was this review helpful? Yes | No

Condition: Osteoarthritis of the Knee

7/20/2016 6:52:07 PM

Reviewer: GrandmaPink, 55-64 on Treatment for 6 months to less than 1 year (Patient)

Current Rating: 5

Current Rating: 5

Current Rating: 5

Comment: My left knee is bone on bone. My right knee is almost there as well. Tried cortisone but it did not help. Ortho Doc recommended Orthovisc but cautioned it may or may not work as it seems to work for some and not for others. We did a series of 3 weekly injections. They provided relief right away. I did not find them particularly painful at all. I've not experienced any side effects other t. Show Full Comment

Comment: My left knee is bone on bone. My right knee is almost there as well. Tried cortisone but it did not help. Ortho Doc recommended Orthovisc but cautioned it may or may not work as it seems to work for some and not for others. We did a series of 3 weekly injections. They provided relief right away. I did not find them particularly painful at all. I've not experienced any side effects other than bruised knees. They lasted me almost a full 8 months and I am an avid daily walker. They have been a Godsend for me. My knees have been pain free. I am starting the second series of 3 weekly shots tomorrow and am hoping I can go another 6-8 months on the second round. Yes, everyone is different and they may or may not work for you. But I guess you won't know until you try. In my case, I'm so happy I did this! Hide Full Comment

1 person found this review helpful. Was this review helpful? Yes | No

Condition: Osteoarthritis of the Knee

7/18/2016 10:45:36 PM

Reviewer: BG FEASTERVILLE, 45-54 on Treatment for 1 to 6 months (Patient)

Current Rating: 1

Current Rating: 1

Current Rating: 1

Comment: I have osteoarthritis of the knee from years of dance and aerobics teaching and the bounding. At only 48, I was suffering with flareups. I went to a specialist for a checkup and he recommended this Orthovisc injection. I have had a terrible experience. Severe pain for a solid 30 days straight. I refused to get the second shot but went to the doctor for the followup apt to see if that is a nor. Show Full Comment

Comment: I have osteoarthritis of the knee from years of dance and aerobics teaching and the bounding. At only 48, I was suffering with flareups. I went to a specialist for a checkup and he recommended this Orthovisc injection. I have had a terrible experience. Severe pain for a solid 30 days straight. I refused to get the second shot but went to the doctor for the followup apt to see if that is a normal reaction. Unfortunately my knee has not recovered and has been in a constant state of flare up since, it's terrible. I don't know how long this remains in the system, but it definitely 100% without a doubt caused more pain then I was in and did NOT help at all. My advice, read carefully about the side affects and efficacy. I trusted to eagerly to my doctor, and did not do any research before simply allowing to proceed with the injection. I was told it is like a "lube job for the knee cap" like an oil change for your car, provide lubrication to keep the parts from rubbing. Well, very disappointed in myself for not researching, and suffering the consequences. DO NOT TRY. Hide Full Comment

1 person found this review helpful. Was this review helpful? Yes | No

Condition: Osteoarthritis of the Knee

6/24/2016 1:45:09 PM

Reviewer: justbarb, 55-64 Female on Treatment for 6 months to less than 1 year (Patient)

Current Rating: 5

Current Rating: 3

Current Rating: 5

Comment: I had Orthovisc injections (3) 7 months ago and it's still easing my knee pain. I was told 3 years ago that I needed a new knee and now I can walk on my treadmill up to 20 minutes a day! The injections are no more painful than a cortisone injection.

Comment: I had Orthovisc injections (3) 7 months ago and it's still easing my knee pain. I was told 3 years ago that I needed a new knee and now I can walk on my treadmill up to 20 minutes a day! The injections are no more painful than a cortisone injection. Hide Full Comment

6 people found this review helpful. Was this review helpful? Yes | No

Condition: Osteoarthritis of the Knee

6/13/2016 11:10:58 AM

Reviewer: nkiflemar, 55-64 Female on Treatment for 1 to 6 months (Patient)

Current Rating: 1

Current Rating: 4

Current Rating: 1

Comment: I had the three injections and at the third one, they added cortisone to the treatment. It helped for about 4-5 weeks and now I am back to square one on pain and limping again. I am so very disappointed. (

Comment: I had the three injections and at the third one, they added cortisone to the treatment. It helped for about 4-5 weeks and now I am back to square one on pain and limping again. I am so very disappointed. ( Hide Full Comment

2 people found this review helpful. Was this review helpful? Yes | No



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Tetracycline (Antibiotics) Uses, Dosage, Side Effects, Tetraicin

Tetracycline

Tetracycline is an antibiotic that fights bacteria in the body.

Tetracycline is used to treat many different bacterial infections, such as urinary tract infections, acne, gonorrhea, chlamydia, and others.

Tetracycline may also be used for other purposes not listed in this medication guide.

Important information

Do not use tetracycline if you are pregnant. It could cause harm to the unborn baby, including permanent discoloration of the teeth later in life. Tetracycline can make birth control pills less effective. Use a second method of birth control while you are taking this medicine to keep from getting pregnant. Tetracycline passes into breast milk and may affect bone and tooth development in a nursing baby. Do not take this medication without telling your doctor if you are breast-feeding a baby. Do not give this medicine to a child younger than 8 years old. Tetracycline can cause permanent yellowing or graying of the teeth, and it can affect a child's growth.

Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Tetracycline can make your skin more sensitive to sunlight and sunburn may result. Use a sunscreen (minimum SPF 15) and wear protective clothing if you must be out in the sun.

Do not take iron supplements, multivitamins, calcium supplements, antacids, or laxatives within 2 hours before or after taking tetracycline. These products can make this medicine less effective.

Throw away any unused tetracycline when it expires or when it is no longer needed. Do not take this medicine after the expiration date on the label has passed. Expired tetracycline can cause a dangerous syndrome resulting in damage to the kidneys.

Before taking this medicine

Do not use this medication if you are allergic to tetracycline, or to similar medicines such as demeclocycline (Declomycin), doxycycline (Adoxa, Doryx, Oracea, Vibramycin), or minocycline (Dynacin, Minocin, Solodyn, Vectrin). Before taking tetracycline, tell your doctor if you have liver or kidney disease. You may not be able to take this medicine, or you may require a dosage adjustment or special monitoring during therapy.

If you are using tetracycline to treat gonorrhea, your doctor may test you to make sure you do not also have syphilis, another sexually transmitted disease.

FDA pregnancy category D. Tetracycline can cause harm to an unborn baby, including permanent discoloration of the teeth later in life. Do not use tetracycline without your doctor's consent if you are pregnant. Tell your doctor if you become pregnant during treatment. Tetracycline can make birth control pills less effective. Use a non-hormonal method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while you are taking this medicine. Tetracycline passes into breast milk and may affect bone and tooth development in a nursing infant. Do not take this medication without first talking to your doctor if you are breast-feeding a baby. Children younger than 8 years old should not take this medicine. This medicine can cause permanent tooth discoloration and can also affect a child's growth.

How should I take tetracycline?

Take tetracycline exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Take tetracycline with a full glass of water (8 ounces).

Take this medication on an empty stomach, at least 1 hour before or 2 hours after meals.

Do not take tetracycline with milk or other dairy products, unless your doctor has told you to. Dairy products can make it harder for your body to absorb the medicine.

Shake the oral suspension (liquid) well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. Take tetracycline for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated. Tetracycline will not treat a viral infection such as the common cold or flu. Do not give this medicine to another person, even if they have the same condition you have.

If you need to have any type of surgery, tell the surgeon ahead of time that you are taking tetracycline. You may need to stop using the medicine for a short time.

Throw away any unused tetracycline when it expires or when it is no longer needed. Do not take this medicine after the expiration date printed on the label. Using expired tetracycline can cause damage to your kidneys.

Store this medication at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include nausea, vomiting, and diarrhea.

What should I avoid?

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or has blood in it, call your doctor. Do not use any medicine to stop the diarrhea unless your doctor has told you to.

Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Tetracycline can make your skin more sensitive to sunlight and sunburn may result. Use a sunscreen (minimum SPF 15) and wear protective clothing if you must be out in the sun. Do not take iron supplements, multivitamins, calcium supplements, antacids, or laxatives within 2 hours before or after taking tetracycline.

Tetracycline side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using tetracycline and call your doctor at once if you have any of these serious side effects:

severe headache, dizziness, blurred vision;

fever, chills, body aches, flu symptoms;

severe blistering, peeling, and red skin rash;

urinating less than usual or not at all;

pale or yellowed skin, dark colored urine, fever, confusion or weakness;

severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;

loss of appetite, jaundice (yellowing of the skin or eyes); or

easy bruising or bleeding, unusual weakness.

Less serious tetracycline side effects may include:

sores or swelling in your rectal or genital area;

mild nausea, vomiting, diarrhea, or stomach upset;

white patches or sores inside your mouth or on your lips;

swollen tongue, trouble swallowing; or

vaginal itching or discharge.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect tetracycline?

Before taking tetracycline, tell your doctor if you are taking any of the following drugs:

cholesterol-lowering medications such as cholestyramine (Prevalite, Questran) or colestipol (Colestid);

tretinoin (Renova, Retin-A, Vesanoid);

an antacid such as Tums, Rolaids, Milk of Magnesia, Maalox, and others;

a product that contains bismuth subsalicylate such as Pepto-Bismol;

minerals such as iron, zinc, calcium, magnesium, and over-the-counter vitamin and mineral supplements;

a blood thinner such as warfarin (Coumadin); or

a penicillin antibiotic such as amoxicillin (Amoxil, Trimox, others), penicillin (BeePen-VK, Pen-Vee K, Veetids, others), dicloxacillin (Dynapen), carbenicillin (Geocillin), oxacillin (Bactocill), and others.

This list is not complete and there may be other drugs that can interact with tetracycline. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More about tetracycline

Consumer resources

Professional resources

Related treatment guides

Where can I get more information?

Your pharmacist can provide more information about tetracycline.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Disclaimer: Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2016 Cerner Multum, Inc. Version: 7.07. Revision Date: 4/12/2009 4:22:28 PM.

Everything you need to know about antibiotics:

Drug Status

Availability Rx Prescription only

Pregnancy Category D Positive evidence of risk

CSA Schedule N Not a controlled drug

Approval History Calendar Drug history at FDA

Tetracycline Rating

14 User Reviews 8.0 /10

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Vitamin B12 is used in the body in two forms: Methylcobalamin and 5-deoxyadenosyl cobalamin. The enzyme methionine synthase needs methylcobalamin as a cofactor. This enzyme is involved in the conversion of the amino acid homocysteine into methionine. Methionine in turn is required for DNA methylation. 5-Deoxyadenosyl cobalamin is a cofactor needed by the enzyme that converts L-methylmalonyl-CoA to succinyl-CoA. This conversion is an important step in the extraction of energy from proteins and fats. Furthermore, succinyl CoA is necessary for the production of hemoglobin, the substances that carries oxygen in red blood cells.

Depin for patients

Patients with pernicious anemia should be informed that they will require monthly injections of vitamin B12 for the remainder of their lives. Failure to do so will result in return of the anemia and in development of incapacitating and irreversible damage to the nerves of the spinal cord. Also, patients should be warned about the danger of taking folic acid in place of vitamin B12, because the former may prevent anemia but allow progression of subacute combined degeneration.

A vegetarian diet which contains no animal products (including milk products or eggs) does not supply any vitamin B12. Patients following such a diet, should be advised to take oral vitamin B12 regularly. The need for vitamin B12 is increased by pregnancy and lactation. Deficiency has been recognized in infants of vegetarian mothers who were breast fed, even though the mothers had no symptoms of deficiency at the time.

This description is suitable for active ingredient Cyanocobalamin

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Persons taking most antibiotics, methotrexate and pyrimethamine invalidate folic acid and vitamin B12 diagnostic blood assays. Colchicine para-aminosalicylic acid and heavy alcohol intake for longer than 2 weeks may produce malabsorption of vitamin B12.

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The Narutis hotel is located in the main street of Vilnius Old Town, which connects Town Hall and Cathedral Square. The car is not a necessity. Presidential Palace, Parliament, Ministries, Embassies as well as historical Lithuanian jewels – Gediminas Castle, the Hill of Three Crosses and other heritage sites as well as most of the institutions can easily be reached on foot.

Vilnius VNO airport – 10 km.

Bus station – 2 km.

Railway station – 2 km.

Presidential palace – 0,2 km.

Cathedral square - 0,3 km.

GediminasCastle – 0,5 km.

Town Hall – 0, 5 km.

Palace of the Grand Dukes of Lithuania – 0,3 km.

The hotel building is an architectural treasure, built in 1581 and declared a World Heritage Site by UNESCO.

The entrance of the Hotel and most of the rooms overlook the St. Johns Church and the central building of Vilnius University, which was established in 1579. In total, 12 churches, built in XIV-XIX century and representing charming Vilnius Baroque style are all located in 400 metres or less. Take a walk by narrow Old Town streets and cozy courtyards and You will in no time reach museums, galleries, Philharmonic, theatres, banks, restaurants, „Boutique“ shops and night clubs.

For those, who like to stay fit – the running trails in Bernardinai Garden and bike trails in Old Town streets are just 300 meters away from the hotel.

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The Narutis Hotel is a premier choice for a Vilnius luxury hotel. Full-service SPA, fine dining restaurant and great location in the heart of Vilnius Old Town. Enchanting and welcoming, total serenity awaits at The Narutis Hotel.

Hotel has 52 rooms and suites. You can choose a room from one of six different categories. Hotel is located in historical building therefore all the rooms differ in layout, size and design. Reconstruction and interior renovations were done in 2013-2014. For the comfort of the guest, the rooms got more spacious, marble was used for bathroom decorations. Some rooms have a bathroom with a window. Room with Disabled Access is available.

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Olanzapine Oral Uses, Side Effects, Interactions, Pictures, Warnings - Dosing, Olan

olanzapine

GENERIC NAME(S): OLANZAPINE

Warnings

There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke. heart failure. fast/irregular heartbeat. pneumonia ) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.

If you are using olanzapine in combination with other medication to treat depression. also carefully read the drug information for the other medication.

Uses

Olanzapine is used to treat certain mental/mood conditions (such as schizophrenia. bipolar disorder ). It may also be used in combination with other medication to treat depression. This medication can help to decrease hallucinations and help you to think more clearly and positively about yourself, feel less agitated, and take a more active part in everyday life.

Olanzapine belongs to a class of drugs called atypical antipsychotics. It works by helping to restore the balance of certain natural substances in the brain .

Talk to the doctor about the risks and benefits of treatment (especially when used by teenagers). See also Precautions section.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to prevent nausea and vomiting caused by cancer drug treatment (chemotherapy ).

How to use olanzapine

Read the Medication Guide provided by your pharmacist before you start taking olanzapine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth with or without food as directed by your doctor, usually once daily.

The dosage is based on your medical condition and response to treatment. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. It is important to continue taking this medication as prescribed even if you feel well. Do not stop taking this medication without consulting your doctor.

Tell your doctor if your condition persists or worsens.

Side Effects

Drowsiness, dizziness. lightheadedness, stomach upset, dry mouth. constipation. increased appetite, or weight gain may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: difficulty swallowing, shaking (tremor), signs of infection (such as fever, persistent sore throat. swollen lymph nodes ), slow heartbeat, fainting. mental/mood changes (such as confusion, restlessness), numbness/tingling of arms/legs, yellowing eyes /skin. severe stomach /abdominal pain. shortness of breath, trouble urinating.

This drug may rarely make your blood sugar level rise, which can cause or worsen diabetes. Tell your doctor right away if you develop symptoms of high blood sugar. such as increased thirst and urination. If you already have diabetes. be sure to check your blood sugars regularly. Your doctor may need to adjust your diabetes medication, exercise program. or diet.

This drug may also cause significant weight gain and a rise in your blood cholesterol (or triglyceride ) levels, especially in teenagers. These effects, along with diabetes, may increase your risk for developing heart disease. Discuss the risks and benefits of treatment with your doctor. (See also Notes section.)

Olanzapine may rarely cause a condition known as tardive dyskinesia. In some cases, this condition may be permanent. Tell your doctor right away if you develop any unusual/uncontrolled movements (especially of the face, lips, mouth. tongue. arms or legs).

This medication may increase a certain natural substance (prolactin ) made by your body. For females, this increase in prolactin may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm. or enlarged breasts. If you develop any of these symptoms, tell your doctor right away.

Get medical help right away if you have any very serious side effects, including: seizures, chest pain.

This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, signs of kidney problems (such as change in the amount of urine).

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www. fda. gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking olanzapine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems, seizures, difficulty swallowing, low white blood cell count, dementia, difficulty urinating (for example, due to enlarged prostate), glaucoma (narrow angle), stomach/intestinal disease (such as blockage, paralytic ileus), smoking, personal or family history of diabetes, heart disease, high cholesterol/triglyceride levels.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Avoid alcoholic beverages.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This medication may make you sweat less, making you more likely to get heat stroke. Avoid doing things that may cause you to overheat, such as hard work or exercise in hot weather, or using hot tubs. When the weather is hot, drink a lot of fluids and dress lightly. If you overheat, quickly look for a place to cool down and rest. Get medical help right away if you have a fever that does not go away, mental/mood changes, headache, or dizziness.

Teenagers may be more sensitive to the side effects of this drug, especially weight gain, and also increased amounts of cholesterol, triglycerides, and prolactin. See also Side Effects section for more details.

Older adults may be more sensitive to the side effects of this drug, especially drowsiness, constipation, trouble urinating, confusion, or dizziness upon standing. Drowsiness, confusion, and dizziness can increase the risk of falling.

During pregnancy, this medication should be used only when clearly needed. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop symptoms including muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice any of these symptoms in your newborn especially during their first month, tell the doctor right away.

Since untreated mental/mood problems (such as schizophrenia, bipolar disorder, depression) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss with your doctor the benefits and risks of using this medication during pregnancy.

This drug passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

A product that may interact with this drug is: metoclopramide.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and narcotic pain relievers (such as codeine).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

Overdose

If overdose is suspected, contact a poison control center or emergency room right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe drowsiness/dizziness, fast/irregular heartbeat, unusual/uncontrolled movements, seizures.

Notes

Do not share this medication with others.

Laboratory and/or medical tests (such as blood sugar, weight, blood pressure, blood cholesterol/triglyceride levels, liver function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Missed Dose

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Storage

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Information last revised May 2016. Copyright(c) 2016 First Databank, Inc.

Images

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, expect as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

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Disclaimer: The indications, uses and warnings for individual medications outside the USA are determined by local regulatory bodies in each country or region. The Drugs. com website is intended primarily for audiences in the United States and its territories. Indications, uses and warnings on Drugs. com patient information leaflets are derived from FDA product labels and may differ in countries outside the USA. Every effort has been made to ensure that the information provided on this page is accurate, up-to-date and complete, but no guarantee is made to that effect. Drugs. com does not endorse drugs, diagnose patients or recommend specific therapies. The information on this page is not a substitute for the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that a drug or drug combination is safe, effective or appropriate for any given patient. Drugs. com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided here. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Always consult your doctor or healthcare specialist for medical advice.

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Drugs. com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Data sources include Micromedex® (updated Sep 2nd, 2016), Cerner Multum™ (updated Sep 5th, 2016), Wolters Kluwer™ (updated Aug 8th, 2016) and others. To view content sources and attributions, please refer to our editorial policy .

We comply with the HONcode standard for trustworthy health information - verify here

Copyright © 2000-2016 Drugs. com. All rights reserved.



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2016-17 New, Revised, and Updated Courses Information about the new AP Computer Science Principles, revised AP World History, and updated AP Calculus courses and exams is now available on the course home pages on this site.

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Important Notice: The Drugs. com international database is in BETA release. This means it is still under development and may contain inaccuracies. It is not intended as a substitute for the expertise and judgement of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that the use of any medication in any country is safe, appropriate or effective for you. Consult with your healthcare professional before taking any medication.

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Bactrim wird zur Behandlung von Infektionen, die durch bestimmte Bakterien verursacht wurden. Bactrim ist ein Antibiotikum Kombination von Sulfonamid-Antibiotikum. Es funktioniert durch das Toten von empfindlichen Bakterien.

Verwenden Sie Bactrim, wie von Ihrem Arzt verordnet wurde.

Nehmen Bactrim durch den Mund mit oder ohne Nahrung.

Bactrim funktioniert am besten, wenn sie zur gleichen Zeit jeden Tag genommen wird.

Nehmen Sie Bactrim mit einem vollen Glas Wasser (8 oz/240 mL). Trinken extra Flussigkeiten wahrend der Einnahme Bactrim wird empfohlen. Fragen Sie Ihren Arzt fur Anweisungen.

Zur Klarung Ihrer Infektion vollstandig nehmen Bactrim fur das gesamte Verlauf der Behandlung. Halten Sie dabei, selbst wenn Sie sich besser in ein paar Tagen zu spuren.

Wenn Sie eine Dosis von Bactrim, bringen Sie es so bald wie moglich. Wenn es fast Zeit fur Ihre nachste Dosis ist, uberspringen Sie die vergessene Dosis und gehen Sie zuruck zu Ihrem regelma?igen Dosierungsschema. Nehmen Sie nicht 2 Dosen auf einmal.

Fragen Sie Ihren Arzt Fragen konnen Sie sich daruber, wie Sie Bactrim verwenden haben kann.

Shop Bactrim bei Raumtemperatur zwischen 59 und 77 Grad F (15 und 25 Grad C). Lager weg von der Hitze, Feuchtigkeit und Licht. Halten Sie in einem engen, Licht-Behaltnis. Nicht im Bad. Halten Sie Bactrim au?erhalb der Reichweite von Kindern und weg von Haustieren.

Wirkstoffe: Sulfamethoxazol und Trimethoprim.

Verwenden Sie KEINE Bactrim, wenn:

Sie sind allergisch gegen jegliche Zutaten in Bactrim oder ahnlichen Arzneimitteln

Sie hatte eine schwere allergische Reaktion auf jede andere Sulfonamid (Sulfa) Medizin (zB, Glipizid, Hydrochlorothiazid)

Sie nehmen Dofetilid

Sie haben Anamie, die durch niedrige Folsaure im Blut oder Urin Blockade verursacht

Sie sind in der Woche 38 der Schwangerschaft oder spater (full-term) oder stillen

der Patient ist ein Kind junger als 2 Monate alt

werden Sie erhalten eine Live oralen Typhus-Impfstoff.

Fragen Sie Ihren Arzt oder Ihre Arztin sofort, wenn einer dieser Punkte auf Sie zutreffen.

Einige medizinische Bedingungen konnen mit Bactrim interagieren. Informieren Sie Ihren Arzt oder Apotheker, wenn Sie irgendwelche medizinischen Bedingungen haben, vor allem, wenn einer der folgenden Punkte auf Sie zutrifft:

wenn Sie schwanger sind, planen, schwanger zu werden, oder stillen

Wenn Sie verschreibungspflichtige (insbesondere Anfall-Medikamente) oder nicht verschreibungspflichtige Arzneimittel, pflanzliche Zubereitung oder diatetische Erganzung

wenn Sie Allergien gegen Medikamente, Nahrungsmittel oder andere Substanzen,

wenn Sie eine Leber-oder Nierenerkrankungen, Blut-Probleme (zB Anamie, Porphyrie), Asthma oder HIV-Infektion

wenn Sie eine schwere Allergien, Glucose-6-Phosphat-Dehydrogenase-Mangel, oder ein Enzym-Mangel

Wenn Sie mit einem Risiko fur niedrige Folsaure im Blut sind (zB haben Sie Alkoholismus, Sie alter sind, mussen Sie nicht die Aufnahme von Nahrstoffen aus der Nahrung richtig, Sie in einem schlechten Ernahrungszustand sind, werden Sie die Einnahme von Medizin fur Anfalle).

Einige Arzneimittel konnen mit Bactrim interagieren. Informieren Sie Ihren Arzt, wenn Sie andere Arzneimittel einnehmen, vor allem einer der folgenden Eigenschaften sind:

Leucovorin weil es Bactrim die Effektivitat verringern kann

Angiotensin-Converting-Enzym (ACE)-Inhibitoren (zB Enalapril) oder Diuretika (beispielsweise Hydrochlorothiazid), weil sie das Risiko von Nebenwirkungen ist Bactrim kann

Antikoagulantien (zB Warfarin), weil das Risiko von Blutungen erhoht werden kann

Dofetilid weil das Risiko von schweren Herzproblemen kann erhoht werden

Digoxin, Methotrexat, Phenytoin, Sulfone (zB Dapson) oder Sulfonylharnstoffen (zB, Glipizid), weil das Risiko der Nebenwirkungen konnen durch Bactrim erhoht werden

BCG Impfstoff oder oralen Typhus-Impfstoff, weil ihre Wirksamkeit von Bactrim kann verringert werden

Cyclosporin, weil ihre Wirksamkeit verringert werden kann und das Risiko von Nebenwirkungen Leber gesteigert werden kann.

Dies kann nicht eine vollstandige Liste aller Interaktionen, die auftreten konnen. Fragen Sie Ihren Arzt, wenn Bactrim mit anderen Medikamenten, die Sie einnehmen. Prufen Sie mit Ihrem Arzt, bevor Sie starten, stoppen, oder andern Sie die Dosis einer Medizin.

Wichtige Sicherheitshinweise:

Bactrim kann Sie mehr leicht zu Sonnenbrand. Meiden Sie die Sonne, Hohensonne oder Solarien, bis Sie wissen, wie Sie Bactrim reagieren. Verwenden Sie einen Sonnenschutz-und Schutzkleidung tragen mussen, wenn Sie fur mehr als eine kurze Zeit au?erhalb.

Mild Durchfall ist mit einer Antibiotika-Einsatz ublich. Allerdings kann eine schwere Form von Durchfall (pseudomembranose Kolitis) selten auftreten. Dies kann zu entwickeln, wahrend Sie das Antibiotikum oder innerhalb von mehreren Monaten, nachdem Sie mit ihn zu stoppen verwenden. Fragen Sie Ihren Arzt sofort, wenn Bauchschmerzen oder Krampfe, schwerer Durchfall oder Blut im Stuhl auftreten. Behandeln Sie Durchfall nicht, ohne vorher Rucksprache mit Ihrem Arzt.

Fragen Sie Ihren Arzt sofort, wenn Bauchschmerzen oder Krampfe, schwerer Durchfall oder Blut im Stuhl wahrend der Behandlung oder innerhalb von mehreren Monaten auftreten, nachdem die Behandlung mit Bactrim. Behandeln Sie Durchfall nicht, ohne vorher Rucksprache mit Ihrem Arzt.

Achten Sie darauf, Bactrim fur das gesamte Verlauf der Behandlung zu verwenden. Wenn Sie das nicht tun, kann die Medizin nicht klar, bis Ihre Infektion vollstandig. Die Bakterien konnten auch weniger anfallig fur diese oder andere Arzneimittel. Dies konnte die Infektion schwerer zu behandeln in der Zukunft.

Bactrim funktioniert nur gegen Bakterien, es nicht zu behandeln virale Infektionen (zB eine Erkaltung).

Langfristige oder wiederholte Verwendung von Bactrim kann eine zweite Infektion. Informieren Sie Ihren Arzt, wenn Sie Anzeichen einer zweiten Infektion auftreten. Ihr Arzneimittel mussen geandert werden, um diese zu behandeln.

Diabetes-Patienten - Bactrim beeintrachtigen konnen Sie Ihren Blutzucker. Check Blutzucker eng. Fragen Sie Ihren Arzt, bevor Sie die Dosis Ihres Diabetes Medizin zu andern.

Bactrim kann mit bestimmten Labortests. Achten Sie darauf, Ihren Arzt und Labor-Mitarbeiter wissen, dass Sie nehmen Bactrim.

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Azithromycin Oral Uses, Side Effects, Interactions, Pictures, Warnings - Dosing, Azyth

azithromycin

Uses

Azithromycin is used to treat a wide variety of bacterial infections. It is a macrolide-type antibiotic. It works by stopping the growth of bacteria.

This medication will not work for viral infections (such as common cold. flu ). Unnecessary use or misuse of any antibiotic can lead to its decreased effectiveness.

How to use azithromycin

Read the Patient Information Leaflet if available from your pharmacist before you start taking azithromycin and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually once daily with or without food. You may take this medication with food if stomach upset occurs. The dosage is based on your medical condition and response to treatment.

Antibiotics work best when the amount of medicine in your body is kept at a constant level. Therefore, take this drug at the same time each day.

Continue to take this medication until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early may allow bacteria to continue to grow, which may result in a return of the infection.

Antacids containing aluminum or magnesium may decrease the absorption of azithromycin if taken at the same time. If you take an antacid that contains aluminum or magnesium, wait at least 2 hours before or after taking azithromycin.

Tell your doctor if your condition persists or worsens.

Side Effects

Stomach upset, diarrhea /loose stools, nausea. vomiting. or abdominal pain may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if any of these unlikely but serious side effects occur: hearing changes (such as decreased hearing, deafness ), eye problems (such as drooping eyelids, blurred vision ), difficulty speaking/swallowing, muscle weakness. signs of liver problems (such as unusual tiredness, persistent nausea/vomiting, severe stomach/abdominal pain, yellowing eyes /skin. dark urine).

Get medical help right away if any of these rare but serious side effects occur: fast/irregular heartbeat. severe dizziness. fainting .

This medication may rarely cause a severe intestinal condition (Clostridium difficile - associated diarrhea) due to a resistant bacteria. This condition may occur during treatment or weeks to months after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have any of the following symptoms because these products may make them worse. Tell your doctor right away if you develop: persistent diarrhea, abdominal or stomach pain/cramping, blood /mucus in your stool.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new yeast infection. Contact your doctor if you notice white patches in your mouth. a change in vaginal discharge. or other new symptoms.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction. including: rash. itching /swelling (especially of the face/tongue /throat), severe dizziness, trouble breathing .

An allergic reaction to this medication may return even if you stop the drug. If you have an allergic reaction, continue to watch for any of the above symptoms for several days after your last dose.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www. fda. gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking azithromycin, tell your doctor or pharmacist if you are allergic to it; or to other antibiotics (such as erythromycin. clarithromycin. telithromycin ); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease. a certain muscle disease (myasthenia gravis ).

Azithromycin may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.

The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using azithromycin, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure. slow heartbeat, QT prolongation in the EKG ), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using azithromycin safely.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the side effects of this drug, especially QT prolongation (see above).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This drug passes into breast milk. Consult your doctor before breast-feeding.

Interactions

See also How to Use section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: live bacterial vaccines.

Although most antibiotics are unlikely to affect hormonal birth control such as pills, patch, or ring, a few antibiotics (such as rifampin, rifabutin) can decrease their effectiveness. This could result in pregnancy. If you use hormonal birth control, ask your doctor or pharmacist for more details.

Many drugs besides azithromycin may affect the heart rhythm (QT prolongation), including amiodarone, disopyramide, dofetilide, dronedarone, ibutilide, pimozide, procainamide, quinidine, sotalol, among others.

Overdose

If overdose is suspected, contact a poison control center or emergency room right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

Notes

Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless your doctor directs you to do so. A different medication may be necessary in that case.

Missed Dose

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Storage

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Information last revised October 2015. Copyright(c) 2015 First Databank, Inc.

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Patent Ca1205031a1 - Hyaluronic Acid Fractions Having Pharmaceutical Activity, And Processes For, Hy

Hyaluronic acid fractions having pharmaceutical activity, and processes for the preparation thereof CA 1205031 A1

Abstract of the Disclosure Two pharmaceutically useful fractions of hyaluronic acid are obtained comprising a first fraction with a molecular weight between 50,000 and 100,000 which is useful for wound healing, and a second fraction having a molecular weight between 500,000 and 730,000 which is useful for intraocular and intraarticular injections. The fractions of hyaluronic acid are further useful as vehicles for opthalmic drugs, providing formulations compatible with the corneal epithelium and enhancing in vivo activity of such drugs.

Патентная формула (8)

1. A process for preparing a substantially pure, non-inflammatory, hyaluronic acid fraction comprising:

dehydrating tissue containing an available amount of hyaluronic acid;

subjecting the resulting dehydrated tissue to enzymatic digestion; and subjecting the resulting mixture to molecular filtration to obtain a hyaluronic acid fraction having an average molecular weight of from 50,000 to 100,000, from 250,000 to 350,000 or from 500,000 to 730,000.

2. A process for preparing a substantially pure, non-inflammatory hyaluronic acid fraction comprising: dehydration of tissue available for extraction of hyaluronic acid; subjecting the resulting substance to enzymatic digestion; subjecting the resulting mixture to molecular fil-tration with a membrane having a molecular weight exclusion limit of 30,000 to exclude molecules having a molecular weight of greater than 30,000; and collecting the mixture retained by said membrane; thereby obtaining a first hyaluronic acid fraction product having an average molecular weight of from 250,000 to 350,000.

3. A process for preparing a substantially pure, non-inflamma-tory hyaluronic acid fraction as claimed in claim 2, which comprises: sub-jecting said first hyaluronic fraction to further molecular ultra-filtra-tion with a membrane having a molecular weight exclusion limit of 200,000 to exclude molecules having a molecular weight greater than 200,000; con-tinuing ultra-filtration until the volume of the mixture being subjected to ultra-filtration is reduced to 10% of the initial volume; and collect-ing the mixture which passes through the membrane; thereby to obtain a second hyaluronic fraction product having an average molecular weight of from 50,000 to 100,000.

4. A process for preparing a substantially pure, non-inflamma-tory hyaluronic acid fraction comprising: collecting the mixture retained on the membrane after the ultra-filtration step with a membrane having a molecular weight exclusion limit of 200,000 as claimed in claim 3; thereby obtaining a third hyaluronic acid fraction product having an average molecular weight of from 500,000 to 730,000.

5. A substantially pure, non-inflammatory hyaluronic acid frac-tion having an average molecular weight of between 30,000 and 730,000, or the potassium or sodium salt thereof, whenever prepared by the process of claim 1 or by its obvious chemical equivalent.

6. A substantially pure, non-inflammatory hyaluronic acid frac-tion as claimed in claim 5, having an average molecular weight of between 250,000 and 350,000 or the potassium or sodium salt thereof, whenever prepared by the process of claim 2 or by its obvious chemical equivalent.

7. A substantially pure, non-inflammatory hyaluronic acid fraction as claimed in claim 5, having an average molecular weight of between 50,000 and 100,000 or the potassium or sodium salt thereof, when-ever prepared by the process of claim 3 or by its obvious chemical equiva-lent.

8. A substantially pure, non-inflammatory hyaluronic acid fraction as claimed in claim 5, having an average molecular weight of between 500,000 and 730,000 or the potassium or sodium salt thereof, whenever prepared by the process of claim 4 or by its obvious chemical equivalent.

Описание (текст распознан автоматически, поэтому в нем могут быть ошибки)

This invention relates to specific molecular weight fractions of hyaluronic acid (hereinafter r

ferred to as "HA") which have therapeutic applications and which a

e non-inflammatory when utilized. One of the HA fractions of this invention is useful for facilitating wound healing, while the second HA fraction is useful for intraocular use to substitute for endobulbar fluids or for intraarticular injection for use in treating damaged bone joints.

he HA fractions have further been found to be useful as vehicles for ophthalmic drugs providing formulations compatible with the coxneal epithelium and enhancing the activity of ophthalmic drugs. Hyaluronic acid is a naturally occurring heteropolysac-charide consisting of alternating residues of D-glucuronic acid and N-acetyl-D-glucosamine. HA is a linear polymer of high molecular weight, generally up to l8 to 13 million, and has been found in c

ll coats, the extracellular ground substance of connective tissues of vertebrates, in the syno-vial fluid in joints, in the endobulbar fluids of the eye, in human umbilicAl cord tissue, and in rooster

ions on the use of

IA are included in the wo

k of Balazs, U. S. Patent 4,141,973, directed to a fraction of HA useful for replacing endobulbar fluids7 as well as other therapeutic applica

ent, however, is specifically directed to an HA fraction having an average molecular weight greatex than 750,000, and preferably greater than 1,200,000. Balazs specifically teaches that fractions of

A having an average molecular weight of less than 750,000 are not therapeutically useul because of their inflammatory activity. These lower molecular weight fractions of HA are discarded by Balazs. However, this results in discarding 90% of the total amount of available HA obtainable from the source tissues, resulting in a use of only a small amount ( 10

) of the available HA.

As discussed above, previous investigations of HA, as exemplified by the Balazs patent, have been directed to utilizing high molecular weight fractions with an average molecular weight of greater than 750,000. The present applicant has isolated and characterized two new fractions of HA, one having a low molecular weight and another having a medium ranged average molecular weight

which are considered to be substantially pure as they are of a high degree of purity and do not have inflammatory activity. These new fractions of HA can be obtained from various connective tissues which contain extractable a

ounts of hyaluronic acid. The sp

tions of this facet of this inv

rentiated and separated according to molecular filtration techniques. The first fraction isolated by the applicant has been named HY

LASTINE, and has an average molecular weigh

000 to 100,000. This HYALASTINE fraction has been determined to be suitable for therapeutic, veterinary and human use because of its wound healing ac

ivity. The secona fraction isolated by the applicant has been labeled HYALECTIN, and has an average molecular weight of

730,000. This HYALRCTIN fraction is suitable for use in ocular surgery as a substitute for endobulbar liquids and for veterinary and human ther

umatic and degenerative diseases of the joints. HYAL

STINE can be administered either as an intradermal injection or it can be applied as a topical agent for wound healing. HYALECTIN, on the other hand, is suitable for intraocular and intraarticular injection. The present applicant has made intensive studies on the various fractions of HA and, in a significantly more precise 10 way than previously accomplished, has specifically determined the therapeu

ically useful fractions of HA and the inflammatory and non-useful fractions of HA. Contrary to the teachings of Balazs, the present applicant has discovered that lower molecular weight fractions of

A do indeed have useful pharmaceutical activity. Thus, according to the present invention, 80% of the HA obtainable from various sources is utilized. In particular, the present applicant has discovered one fraction of HA which is useful for stimulating wound healing, and a second fraction of HA 20 which is useful for intraocular injections to substitute for the endobulbar liquids in the eye and for intraarticular injections as a treatment for damaged joints.

Thus by one aspect of this invention a process is provided for pre-paring a substantially pure, non-inflammatory, hyaluronic acid fraction com-prising: dehydrating tissue containing an available amount of hyaluronic acid; subjecting the resulting dehydrated tissue to enzymatic digestion; subjecting the resulting mixture to molecular filtration to obtain a hyaluronic acid fraction having an average molecular weight of from ¦50,000 to 100,000, from 250,000 to 350,000 or from 500,000 to 730,000.

By another aspect of this i. nvention, a process is provided for preparing a substantially pure, non-inflammatory hyaluronic acid fraction compri. sing: dehydrating tissue available for extraction of hyaluronic aci. d; subjecting the resulting substance to en

ymatic digestion; subjecting the resulting mixture to molecular filtration with a membrane having a molecular weight exelusion limit of 30,000 to exclude molecules having a molecular weight of greater than 30,000; collecting the mixture retained by the mem-brane; thereby obtaining a substantially pure, non-inflammatory first hyaluronic acid fraction product having an average molecular weight of from 250,000 to 350,000. By a variant of this aspect of the invention, the firs-t sub-stantially pure, non-inflammatory hyaluronic acid fraction is subjected to further molecular ultra-filtration with a membrane having a molecular weight exclusion limit of 200,000 to exclude molecules having a molecular weight of greater than 200,000; the ultra-filtration is continued until the volume of the mixture being subjected to ultra-filtration is reduced to 10% of the initial volume; and the mixture which passes through the membrane is collected; thereby to obtain a second substantially pure, non-inflammatory hyaluronie fraetion product having an average molecular weight of from 50,000 to 100,000. By another variant thereof, the mixture retained on the membrane after the ultra-filtration with the membrane having a molecular weight exelusion limit of 200,000 (as described above) is collected thereby oh-taining a third substantially pure non-inflammatory hyalu. ronic acid frac-tion produet having an average moleeular weight of from 500,000 to 730,000.

y other aspects of this invention a substantially pure, non-inflammatory hyaluronie aeid fraetion having an averaqe moleeular weight of between 30,000 and 730,000, or the potassium or sodium salt thereof

is provided, e. g. having an average molecular weight of between 250,000 and 350,000 or the potassium or sodium salt thereof, or having an average mclecular weight of between 50,000 and 100,000 or the potassiu

n salt thereof, or having an average molecular weight of between 500,000 and 730,000 or the po-tassium or sodium salt thereof, by the various processes described above. As a result of the studies by the present applicant alluded to above, the present applicant has identified and investigated two specific characteristics of HA fractions, namely cell mobilization activity and intrinsic viscosity. The wound healing process in animals is facilitated by cellular mobilization, and particularly the mobilization of fibroblasts. On the other hand, cellular mobilization or proliferation activity (i. e. mytosis) is to be avoided in cases of surgery inside the oc

lar globe. This is particularly - true in operations to correct retinal detachment where an increased rate of healing may cause harmful affect

he intrinsic viscosity is also an important parameter - to be considered in determining the ut

lity of a fraction of HA. A fraction having a high intrinsic viscosity is useful for surgical uses, in the therapy of diseases of the joints of a traumatic and degenerative nature, and for replacing endobulbar li

uids. On the other hand, high viscosity is an undesirable characteristic for fractions to be utilized as drugs for facilitating wound healing. In fact, fractions to be utilized in wound healing should have low viscosity so as to be more easily used in practical application. The HYAL

STINE fraction identified by the present applicant has been determined to have good mobilization or cell proliferation activity, and low viscosity characteristics. Accordingly,

YALASTINE has the characteristics des, irable for a material useful in promoting wound healing. The same charac-teristics make

he IIYALASTINE fraction undesira-ble for use in intraocular or i, ntraarticular injection treatments. The HYALECTIN fraction identified by the applican-t has been determined to have negligible cell mobili

ation or proliferation activity, while at the same ti

e having high. _ _.

viscosity. These characteristics, therefore, make the HYALECTIN fraction useful for intraocular and intraarticular injection treatments. But, on the othex hand, HYALECTIN is not useful for wound healing treatments since this fraction does not exhibit cell mobilization activity. In isolating useful fractions of hyaluronic acid, it is also important to obtain those fractions which do not have inflarnrnatory activity. The Bala

s patent noted above teaches that in order to obtain hyaluronic acid fractions without lo inflammatory activity, fractions having an average molecular weight of more than 750,000 must be utilized exclusively. Thus

Balazs discards the fractions having less than 750,000 average molecular weight as being non-useful because of in-flammatory activity. Contrary to the teachings of Balazs, the presen

applicant has found that the inflarnmatory activity attributed by Balazs to fractions having an average molecular weight of less than 750,000 is actually due to impurities having an average molecular weight of less than 30,000. Thus, the present invention provides a process which comprises a series of molecular filtration

echniques associated with chemical methods by which the infla

natory fraction having a I molecular weight of less than 30

000 can be eliminated. By

the processes of facets of the invention, it is possible to obtain useful fractions of hyaluron

c acid haYing no inflam-matory activity which, when considered together, constitute a total yield of

of the total hyaluronic acid avail-able from the particular star

ing materials. This 80

yield of the available hyaluronic acid comprises a combined fraction which i

a combination of the

YALECTIN and HYALASTINE fractions and which has an average mole

ular weight of frorn 250,000 to ;350

000O More specifically, the HYALECTIN fraction is obtained in a yield of 30% of the available H

and the RYALASTINE fraction is obtained in a yield of 50

of the available HA from the starting tissues. This factor is an important improvement over the process of the Balazs patent discussed above in that the present inventors have discovered that significantly in-creased amounts of the available hyaluronic acid are pharma-ceutically usefulO By utilizing only the fraction having an average molecular weight of greater than 750,000, the Balazs process obtains a yield of only 10% of the original hyaluxonic acid available from animal organs, and discards lo 90% of the available hyaluronic acid. Thus, according to the present invention, the usefulness of the total hya-luronic extract has been greatly increased. A comparison of the relative yields of the extraction of various fractions of hyaluronic acid is presented below in Table 1.

Type of E3yaluronic g per 100 g Acid of fresh tissue

Reference Total hyaluronic 0.8 100 Swann D. A. 1968, acid from rooster Biochim, Biophys. combs. Acta I56, 17-29 HA (Balazs type) 0

08 10 U. S. Patent 4,141,973 HYALECTIN + HYALASTINE 0.6 80 present invention HYALECTIN 0.2 30 present invention HYALASTINE 0.4 50 present inven

ion Inflammatory 0.16 20 present invention fraction In the accompanying drawings,

igure 1 is a graph showing the different fractions of hyaluronic acid which have been identified by the present inv

Figure 1 graphically shows the different HA fractions which the p

esent applicant has identified. The solid bell-shaped curve of Figure 1 represents the appro

imate distribution of the HA fractions available from a starting tissue. Area "B" in Figure 1 represents the HA fraction identified by Balazs in U. S. Patent 4,141,973 as

eing pharmaceutically useful. Areas "A", I and II in Figure I are the fractions identified by the present applicant, area A being th

inflammatory raction having an average molecular o weight less than 30,000; area I being the HYAI. ASTINE fraction; and area II being the HYALE. CTIN fraction. From this graph, it can be seen that the Balazs method discards the large majority of available extractable HA by eliminating the HA fxactions having an average molecular weight of less than 750,000. The present invention, on the other hand, per-mits the pharmaceutical use of a large proportion of avail-able HA since the low molecular weight hyaluronic acid fraction having an average molecular weight of less than 30,000 causes the inflammatory activity which previous inves-20 tigators have noted with various extracts of HA. The present applicant has discovered that a laxgepercentage of available HA can, in fact, be utilized for therapeutic purposes if separated according to the teachings of this invention depending upon the particular therapeutic applicat. ion. While the Balazs patent specifically teaches the use of' only `10% of the available HA

the present invention permits the use of `;80% of the available

A either in the form of the HYALASTINE fxaction or wound healing applica

ions, or in the form of the

ECTIN fraction for intraocular and intr

or in the form of a combined HYALAST

raction which can also be used for wound healing applications.

The chemical and physical characteristics of the identi-fied fxactions have also been investigated by the present applicant, and these charac

eristics are summarized in Table 2.

cesses Of Preparation Example 1 - Process for obtaining a mixture of HYALASTINE and H

fractions without inflammatory activity: lo Hen crests, either fresh or frozen (3000 g), are minced in a meat mincer and then carefully homogenized in a mechanical homogenizer. The resulting paste is placed in an AISI 316 stainless steel container or in a glass container with 10 volumes of anhydrous acetone. The entire content is then agitated for 6 hours at a speed of 50

/minute and left to separate for 12 hours, after which the acetone is syphoned off and discarded. This extraction pxocess is repeated until the discarded acetone has reached the correct humidity level (Karl-Fischer method). The resulting substance is then centrifuged and vacuum dxied at a suitable temperature for 5-B hours. With this pxocess, approximately 500-600 g of dry powder is obtained from the hen crests

300 g of the dry powder is then submitted to an enzymatic digestion process with papain tO.2 g) through a buffered aqueous medium wi

h a phosphate buffer in th

presence of a suitabl

quantity of cysteine hydrochloride. This mixture is then agitated for 24 hours at 60 g/minute at a constant temperature of 6o-65oc

his whole mass is cooled to 25C adding 60 g o

E I and the agitation is maintalned for an additional hour.

The resulting mixture is filtered un

il a clear liquid is obtained. This clear liquid then undergoes rnolecular ultrafiltration by means of membranes

ith a molecular exclusion limit of 30, ooo to retain on the membrane those rnolecules with a molecular weight o

greater than 30,000. Five to six original volumes are ultrafiltered and, at the same time, distilled water is continually added to the product. The addition of distilled water is suspended and the product is ultrafiltered until it is reduced to one-thixd of its original volume. The residue liquid is rendered O. lM by adding sodium chloride and the temperature is brough to 50C. 45 g of cetylpyridinium chloride is added while the product is being agitated at 60 g/minute. This mixture is agitated for 60 minutes, after which 50 g of

cELITE is added. Under agitation the temperature of the product is reduced to 25C and the precipitate formed is collected by means of centri-fugation. The precipitate thus obtained is suspended in a O. OlM solution of sodium chloride (S liters) containing 0.05% cetylpyridinium chloride. It is agitated for a further 60 minutes at 50C. The temperature is lowered to 25C and the precipitate centrifuged. The washing process is then repeated three times and the precipitate finally gathered into containexs holding 3 liters of a O. OSM solution of sodium chloride containing 0.05

of cetylpyridinium chloride. This is agitated at 60 g/minute for 60 minutes and maintained at a constant temperature of 25C for a period of 2 hours. The

supernatant is elim-inated by means of centrifugation. The procedure is thus repeated sev

ral times with a 0.1 sodium chloride solution containing 0.05

of cetylpyridinium chloride. The mixture is centrifuged and the supexnatant discarded. The precipitate is dispersed in a 0.30M sodium chloride solution containing 0.05& of cetylpyridinium chloride (3 1). The mixture is agitated and both the preci-pitate and the clear liquid are gath

red. Extraction is repeated on the precipitate an additional 3 times, each time using 0.5 liters of the same aqueous solution. Finally, the residue precipitate is eliminated and the clear liquids united in a single container. The temperature of the liquid is increased to 50C while agitating. The lo liquid is then brought to 0.23M with sodium chloride. 1 g of cetylpyridinium chloride is added and agitation maintained for 12 hours. The mixture is cooled to 25C then filtered, first through CELITE packs and then through a filter (1

ture then undergoes a further molecular ultrafiltration through membranes with a molecular exclusion limit of 30,000, ultrafiltering 3 original volumes with the addition of a 0.33M sodium chloride solution. The addition of the sodium chloride solution is suspended and the volume of the liquid reduced to a quarter of its original volume. The solution thus concentrated is precipitated under agitation (60 g/minute) at a tempera

ure of 25C with three volumes of ethanol (95%). The precipitate is collected by centrifugation and the supernatant discarded. The precipi-tate is dissolved in 1 li

sodium chloride solution and the precipit

tion procedure is repeated with three volumes of 95

ethanol. The precipitate is gathered and washed, first with 75 ethanol (three times) D then with absolute ethanol

three times) and thirdly with absolute acetone (three timPs). The product thus obtained (HYALASTINE

) has an average molecular weight between

50,000 and 350, noo.

yaluronic acid yield is equal to 0.6

the original fresh tissue. Example 2 - ProceSs for obtaining the HYALASTINE fraction from the mixture obtained by the method described in Example 1 : The mixture obtained by the process described in Example 1 is dissolved in pyrogen free distilled water in proportions of lO mg of product in 1 ml of water. The solutio

thus obtained undergoes molecular ultrafiltration through membranes lo with a molecular exclusion limit of 200,000 with a concen-tration technique and without addition of water on the membrane. During the ultrafiltration process through membranes with an exclusion limit of 200,000, molecules with molecule weight greater than 200,000 will not pass, whereas smaller molecules will pass through the membrane along with the water. During the filtration process no water is added in the compartment above the membrane; therefore, the volume in

his compartment will decrease, along with an increase in the concentration of molecules with M. W. over 200,000. It is then ultrafiltered until the volume on the membrane is reduced to 10% of the initial volume. Two volumes of pyrogen free bidistilled water are added and the solution is again ultrafiltqred until the volume is reduced to one-thixd. The operation is repeated another two ti

es. The solution which passes through the membrane is brought to l. OM with sodium chloride and then precipitated with four volumes of ethanol at 95

The precipitate is washed three times with 75% ethanol and then vacuum dried. The product thu

HYALASTINE fraction) has an average molecular weight between 50,000 and lO0,000. The hyaluronic acid yield is equal to 0.4

of the original fresh tissue

Example 3 - Process of obtaining HYALECTIN fraction: The concentrated solution, gathered into a container from the ultrafiltration membrane with a molecular exclusion limit of 200,000 described in Example 2, is diluted with water until a solution containing 5 mg/ml of hyaluronic acid is obtained, as determined by quantitative analysis based upon an assay of glucuronic ac. id. The solution is brought to 0.1

in sodium chloride and then pxecipitated with 4 volumes of 95% e

hanol. The preci lo pitate is washed three times with 75% ethanol and then vacuum dried. The product thus obtain2d (HYALECTIN fraction) has an average molecular weight between 500,000 and 730,000. This corresponds to a specific hyaluronic acid fraction of defined molecular chain length of 2,500 to 3,500 saccharide units with a hi

h degree of purity. The hyaluronic acid yield is equal to 0.2% of the original fresh tissue.

ion Of Biological And Pharmaceu

ical Activity l. Biological activity oflcellular mobili

atlon of the hyaluronic acid fractions: The method, consisting of the determination of the detachment activity of fibroblasts in culture, was used as the method for evaluating the cell mobilization activity of the HA fractions. Mouse BALB 3T3 cells were grown in Dulbecco's modified Eagle medium supplemented with lO

calf serum9 penicillin (2S0 units/ml) and streptomycin (0.25 mg

ml), and were incubated in humidified 5

CO2, 95% air at 37C. For experi-mental purposes, cells were routinely inoculated in 60-mm - diameter plastic tissue culture dishes (6x105 cells

Confluent monolayers of 3T3 cells were decanted and fresh medium containing 2.0 mg/ml of different fractions of HA were added.

t fixed intervals, the cell detachment was observed both microscopically and by counting the mobilized cells in a Coulter Counter. Detachment assa

To measure detachment kinetics, cells were inoculated into plastic dishes and allowPd to grow for 2

hours. After this

ime, the culture medium was decanted and fresh medium containing 2.0 mg/ml of

A was added. Every o 24 hours, two dishes, one each of test culture and of control culture, were decanted and both the cells in the supernatant and the attached cells were counted in a Coulter Counter. Table 3

eports the results obtained with tests using the fractions obtained in the preparation Examples 1-3 above.

Results of Mobilization Studies Fraction Concentration No. of% Effectiveness

mg/ml) Detached(as compared to Cells ascontrol)

Compared to Controls . Control 2 x 106 HYALECTIN

x 106 75 HYALASTINE HYALECTIN 2 2.1 x 106 5

YALASTINE 2 5 x 1 o6 150 The data reported in Table 3 shows that the HYALASTINE fraction exhibits high cell mobilization activity making this fraction useEul for wound healing applications. This cell mobilizAtion

ctivity o HYALASTINE will stimulate migration and prolifera

ion of new cells when a pharmaceutical prepara

tion of the fraction is applied to a damaged tissue area. The HYALECTIN fraction/ on the other hand, exhibits very little cell mobilization activity and would not, therefore, be useful for wound healing. HYALECTIN, however, because of its high average molecular weight and inheren

y, is useful for ocular and intraarticular injections, and the lack of appreciable cell mobilization activity is an important characteristic of the HYALECTIN fraction making it especially useful for intraocular and intraarticular injections. 2. Biological inflammatory activity of the hyaluronic acid fractions: Fox this evaluation, the method of invasive cell count after intraocular administration in rabbits is utilized. M o Five

5) New Zealand or California rabbits, weighing 2 kg and with ascertained perfect vision, are used for this test. The outer eye of the rabbits is checked for inflammatory processes at a macroscopic level and the inner eye is checked by ophthalmoscope. If the ocular fundus is clearly visihle and normal, the test may proceed. The selected animals undergo local anaesthetic by the instillation of a few drops of a suitable sterile anesthetic for ophthalmology; a few drops of atropine in ophthalmological solution are also instilled. Th

test i5 carried out in sterile conditions. The ocular globe is made to protrude by means of pressure until it is possible to inject, through the sclera at 5--6 mm from the limbus, at the center of the vitreal cavity, 100

of the solution, using a 26 G needle. The other eye is taken as a control. T

o drops of antibiotic solution are instilled in the treated eye and the animals are then housed in single cages. After 50-60 hours the test may proceed further. The eyes are checked in the same way as above for the selection of the animals. The anim

ls are sacrificed with an intravenous injection of PEN

Then, firstly, the aqueous humor o ( 0.2 ml) is gathered by means of an insulin syringe with

26 G needle. The ocular globes are

hen enucleated, freed from all foreign matter, washed in saline, dried with bilbulous paper, and incised and opened in Petri plates, separating the main part of the vitreous humor and gathering it with a sterile syringe ( 0.7 ml). The vitreous humor is placed in small polyethylene test tubes and 50

of hyaluronidase (100 U NF/ml) is added. The mixture is then kept at a temperature of 37C for 3 hours in order to render the solution less viscous. A leukocyte count is carried out under a microscope by phase contrast

120 x) in a Burker chamber. A series of counts is effected on each sample, calculating the average values and expressing the result as the number of leukccytes per mm . The test i5 considered positive when: 1) the eyes examined show no signs of sufferingf and 2) the average number of leukocytes from at least 4 of the 5 treated eyes does not exceed 200 per mrn3 and the average nu

er of leukocytes from each control eye does not exceed 50 per mm3

le 4 reports the results obtained from this evaluation using the HA fra

tions obtained in preparation Examples 1-3 discussed above.

Results of Inflammator

Studies FractionMo. of Invasive Cells Control 25 HYALASTINE

HYALECTIN 32 lo Inflammatory Fraction (

150 Total Hyaluronic Acid fro

Rooster Combs (RF. Swann D. A. 1968, B. B.A

156, 17-29) 120 The results reported in Table 4 show that the HYALASTINE and HYALECTIN fractions exhibit no inflammato. ry acti. vity above that for the control

and the combined HYALASTINE and HYALECTIN fraction showed only a negligible increase in inflam-matory activity over the con

rol. Accordingly, the HYALASTINE and HYALECTIN fractions are pharmaceutically useful without exhibiting undesirable inflammatory side eff

ctsO These results also further confirm the applicant's discovery that it is the HA fraction having a low average molecular weight of less th

n 30,000 which is responsible for the inflam

matory activity of

A preparations. Hyaluronic acid from roos

er combs, prepared according to the method described in the literature by Swann (Swann D. A. 1968, B. B.A. 156

17-29), shows a remarkable inflammatory activity.

It has thus been shown that the HYALASTINE fract:i. on having an average molecular weiyht of 50,000 to 100;000 exhibits high cell mobilization activity and is, therefore9 useful in wound healing applications without exhibiting undesirable inflammatory reactions. The HYAL

CTIN fraction, having an average molecular weight of 500,000 to 730,000, has been shown to be useful for ocular and intraarticular injection due to its high molecular weight and inherent viscosi. y, and, at the same time, does not stimulate cell lo mobilization activity or inflammatory reactions which are undesirable side effects to be avoided in these pharma-ceutical applications. More specifically, the HYALASTINE fraction has been found to be useful as a wound healing preparation because of the following characteristics. 1. The preparation promotes a remarkably shortened healin

time, as compared to conventional therapy, with rapid clearing of the affected area, regular-ization of ulcer edges, vigorous development of granulation tissue, activation of cellular migration of macrophages and fibroblasts and early epitheliza-tion. 2. The prepar

tion promotes increased amenability to reconstructive surgery in the more severe cases. 3. The absence of keloid or retracting scar formation, with final reshaping of cicatriciai tissue yielding good cosmetic and functional results. The HYALASTINE preparation has been found to be useul for the treatment of various wounds including decubitus soxes (bed sores), trophic ulcers, burns, indolent wounds, post-tr

umatic ulcers, varicose and postphle

itic ulcers from venous blood stains, radionecroses, skin lesions, skin grafts

and skin lesions due to herpes simplex. For these wound healing treatments, the

YALASTINE preparation, or the sodium salt thereof, can be administered in various methods, such as by gauze pads, cream, spray or ampoules for intradermal injection. For the topical applications as a cream or on a gauze pad, the HYALASTINE is preferably combined with an emulsifying agent, which absorbs the exudat

from the exposed area while affording excellent diffusion of hyaluronic acid, and a water-dispersible excipient so that the wound dressing is easily removed. The HYALECTIN fraction has been found to be particularly useful for the treatment of horses, particularly race horses, suffering from joint disorders and diseases caused by acute or chronic trauma, infections or repeated intraarticular corticosteroid injections. Specific examples of disorders treatable with HYALECTIN are osteoarthroses with or without inflammatory signs, acute or chronic synoritis, degenerative processes in articular cartilage, and dry joint disease. The most fr

quent symptoms of these disorders are generally pain, impaired joint function, and reduced joint flexion. The HYAI, ECTIN fraction of the invention has been found to promote marked reduction of the healing time for such affected horses as compared with conventional therapy, to promote early and lasting improvement of joint function and to reduce pain and lameness. These clinically advantageous effects are believed to be promoted by a normalization of the viscoelasticity of the synovial fluid and by activation of tissue repair processes in the articular cartilages. Moreover, all the above advantageous effects are promoted by the HYALECTIN fraction in the absence of local and/or systemic toxic effects

Repeated administration of HYALECTIN produces no evidence of allergic r

actions nor any adverse or lasting effects.

Pharmaceutical Preparations The abo

e disclosure has shown that the HYAL

STINE and HYALECTIN fractions have good activity for pharmaceutical appllcations. The following examples are presented for exemplary purposes only to describe possible pharmaceutical preparations for actual in vivo administration of the

A fractions. A. Preparations for Woùnd Healing Example 1: ampoules for intradermal injection - lo each ampoule contains

-Hyalastine sodium salt mg 4 - Sodium Chloride mg 16 - Water for injection q. s.a. ml 2 Example 2: ampoules for intradermal injection - each ampoule contains: - Hyalastine potassium salt mg 5 - Sodium Chloride mg 8 - Water for injection q. s.a. ml Example 3: spray-bottle for topical application each bottle contains: O - llyalastine sodium salt mg 20

-Sodium Chloride mg 80 - Water for injection q. s.a. ml 10 Example 4: spray-bottle for topical application - I each bottle contains: - Hyalastine potassium salt mg 30 - Mannitol mg 100 - Water for injection q. s.a. ml 10 Example 5- cream for topical application - each tube of cream contains: - Hyalastine potassium salt mg 25

Polyethyleneglycol mono-stearate 400 mg 1000 - CETIOL

( decyl estex of 30 - oleic acid) mg 500 - L

NETTEISX (cetyl-stearyl alcohol

lauryl sulfate 9:1) mg 150 - Glycexol mg 2 n o - Sorbitol mg 150 - Na-dehydroacetate mg 10 - p-oxymethylbenzoate mg 7.5 - p-oxypropylbenzoate mg 5 - redistilled waterq. s.a. g 10 Example 6: cream for

opical application - each tube of cream contains: - Hyalastine sodium salt mg 30 - Paraffin jelly mg 3 - Polyethyleneglycol mono-stearate 400 my 1000 - CETIOL ( decyl ester o

oleic acid) mg 500 0 -.L

NETTE SX (cetyl-stearyl alcohol

lauryl sulfate 9:1) mg 150 - Glycerol mg 200 - Sorbitol mg 150 - Na-dehydroacetate mg 10 - p-oxymethylbenæoate my 7.5 - p-oxypropylbenzoate mg 5 - redistilled waterq. s.a. g 10 Example 7: medicated gauze pads for topical application - each gauze-pad measuring lOxlO cm contains

-Hyalastine sodium salt mg 3 - Glycerol g - Polyethyleneglycol g 2 - redistilled waterqOs. a. g 3 Example 8: medicated gauze

pads for topical application - each gauze-pad measuring 15x15 CM contains^ - Hyalastine potassium salt mg 6 - Paraffin jelly mg 0.5 - Glycerol g - Polyethyleneglycol g 2 - redistilled waterq. s.a. g 3 Example 9: dry powdex for wound heal. ing application - each gram of dry powder contains: - Hyalastine sodium salt mg 10

Mannitol g 0.75 - Glycine g 0.24 B. Preparations for Intraocular Use Example 10: l-ml vials - each vial contains: Hyalectin sodium salt mg 10 - Sodium Chloride mg 8 - Monobasic sodium phosphate 2H2

5 - Dibasic sodium phosphate 12H20 mg 3 - Water for injectionq. s.a. ml lo Example 11: 5-ml vials

each vial contains: - Hyalectin potassium salt mg 60 - Mannitol mg 50 - Monobasic sodium phosphate 2H20 mg 1.25 Dibasic sodium phosphate 12H20 mg 15

water for injectionq. s.a. ml 5 Example 12: preloaded syringes

each syringe contains: - Hyalectin sodium salt mg 40 - Sodi

m Chloridemg 16 - Monobasic sodium phosphate 2H20 mg 0.8 - Dibasic sodium phosphate 12H20 mg 8.16 - Water for injectionq. s.a. ml 2 C. Preparations for Intra-Articular Use Example 13: 2

each vial contains: - Hyalectin sodium salt mg 40 - Sodium Chloridemg 16 - Water for injectionq. s.aO ml 2 Example 14: 4-ml vials - each vial contains

yalectin potassium salt mg 60 - Mannitol mg 35 - Glycine mg 10 - Water or Injectionq. s.a. ml 4 3

Example 15: preloaded syringes - each syringe contains: - Hyalectin sodium salt mg 25 - Sodium Chloride mg 12 - Mannltol mg 10 Monobasic sodium phosphate 2H20 mg 0.5 - Dibasic sodium phosphate 12H20 mg 6 lo - Water for injection q. s.a. ml 2 Although the above-preparations have been described for exemplary purposes, it will be appreciated that other pharma-ceutical formulations could be prepared by combining the HYALASTINE and HYALECTIN fractions discovered by the inventors, or the potassium or sodium sal

s thexeof, with o

her pharma-ceutically accep

able carriers, diluents, or e

cipients and at various dosages depending upon the par

icular use for the formulation. For wound healing uses,

he preparations of the

IYALAS-TINE fraction are applied to the affected skin areas in one ofthe dosage forms discussed above, that is, either as a cream, a spray, on a gauze-pad, as a dry powder or as an intradermal injection. For intraarticular uses, the preparations of the HYALECTIN are generally administered at a dosage rate of 2 ml per joint taken either from a prepared vial or a preloaded syringe as described aboveO In an additional study

the capacity and efficiency of hyaluronic acid as a v

arious molecules has been investigated, in particular, use as a vehicle for opthalmic drugs, guaranteeing perfect tolerability and compatibility (i. e. absence of sensi

ization phenomena) with the corneal eplthel

m. Hyaluronic acid is considered of particular interes

as an ophthalmic vehicle. As discussed previously, HA is a glycosaminoglycan present in various connective tissues and biological liquids ( e. g. i the synovial fluid and in pal-ticular the vitreous humor) where, because of its chemical and physical nature and its striking visco-elastic characteristics, it plays a structural and biolo

ical role of fundamental impoxtance. Thus, a study was conducted to investigate the use of H

fractions having different molecular weights, particul

rly the hyalastine and hyalectin fractions, and a mixture of the same, for the preparation of different pharmaceutical forms, e. g. collyrium, gel, cream, inserts or dry powders. There-lo fore, opthalmic durgs of different types were studied in order to obtain a broad understanding of the potential use of this biological polymer in its different fractions as a vehicle. The experiments reported hereafter were aimed at deter-mining whether formulations containing hyaluronic acid as an excipient are capable of enhancing the bioavailability of vehicled drugs or producing a synergistic effect in combination with the vehicled drugs, particularly with drugs having ophthalmic activity or utility

l capacities of HA as a vehicle were inves-ti

ated in the rabbit ey

with four ophthalmic drugs ofdifferent types and actions, in particular, pilocarpine nitrate, triamcinolone, epidermal growth factor (EGF) and an antibiotic e. g. streptomycin and gentamicine. All of these drugs are known to have miotic, anti-inflammatory, healing and anti-microbial ef ficiency. Moreover evaluation of the activity of the antibiotic streptomycin, vehicled in hyaluronic acid, is very important because it is vne of the most widely used antibiotics in ocular infections

The experimental models studied and the

fected were as follows:

miotic activity of pilocarpine nitrate, vehicled in hyaluronic acid in rabbit eye; 2) anti-inflammatory activity of triamcinolone, vehicled in hyaluronic acid in the model of dextran-indueed inflammation in rabbit eye; 3) healing activity of epidermal growth factor lEGF) vehicled in hyaluronic acid in a model of epithelial lesion of rabbit cornea.

4) antimicrobial activity of streptomycin vehicled in o hyaluronie acid against Bacillus suhtilis 6633 in agar platesO I. Miotie Activity of Pilocarpine Nitrate Vehicled In Hyaluronie Acid Materials The following materials were used as excipients of pilo-carpine for the various pilocarpine nitrate formulations: -- hyaluronic acid sodium salt, hyalastine fractlon, (m. w. approximately 100,000), at a concentration of 10 mg/ml and 20 mg/ml;

hyaluronic acid sodium salt, hyalectin fraction (m. wO S00,000 - 730,000

at a concentration of 10 mg/ml and 20 mg/ml; -- 5

polyvinyl alcohol as a comparative ophthalmic excipient.

Various 2% formulations (collyrium or gel) of pilocar-pine nitrate were prepared and vehicled by adding the two different fractions of HA sodium salt at

concentration of 10 and 20 mg/ml. The following solutions were prepared: Formulation 1 - saline with pilocarpine nitrate (PiN03) (2

nce. Formulation 2

solution of PiNo3 (2%) vehicled in 5% polyvinyl alcohol (used as reference). Formulation 3 - solution of PiN03 (2%) vehicled in lo hyalastine fraction sodium salt (10 mg/ml). Formulation 4 - solution of PiNo3

2%) vehicled in hyalastine fraction sodium salt (20 mg/ml). Formulation 5 - solution of PiN03 (2

) vehicled in hyalectin fraction sodium s

lt (10 mg/ml). Formulation 6 - solution of PlN03 (2

) vehicled in hyalectin fraction sodium salt (20 mg/ml3. Method Albino New æealand rabbits were used (2 - 2.5 kg). The formulation to be tested was instilled in one eye by micro-syringe (10 1); the other eye served as a xeference. The diameter of the pupil was measured in all cases at s

itable time intervals. Each solution was tested on at least 8 rabbits. Each eye

as treated not more than three times and a rest period of at least a week was observed between each treatment. Parameters

easured The pupil diameters were measured at various intervals in order to determine the miotic activity curve in time. The following activity parameters were subsequently calculated from the miosis/time graphs:

I max = maximum difference in pupil diameter between the treated eye and the reference. Peak time = time taken to reach ImaX. Duration = time taken to restore basal conditions. Plateau = period of absolute miotic activity. AUC = area under miosis/time curve. Result The results of the tests are reported in Table 5. Ik can be seen from the data for the various parameters deter-lo mined from the miotic activity time curve for all the solutions tested that the addition of hyaluronic acid to a 2% pilocarpine nitrate solution gives rise to an increase in miotic activity of the

rug. In fact, the bioavailability of the drug may be as much as 2.7 times greater than that of the aqueous solution containing 2

pilocarpine nitrate (Formu-lation 1). It should also be noted that there is a statistically significant increase in activity when the hyalectin fraction of hyaluronic acid both at 10 and 20 mg/ml is used as a vehiclè

Formulations S-6), in contrast to the pilocarpine nitrate solution vehicled in polyvinyl alcohol (Formulation 2). The use of hyaluronic acid as a vehicle is particularly interesting because the miotic activity of pilocarpine nitrate lasts longer when it is vehicled with this substance. That is, for the hyaluronic acid containing formulations the time taken to restore pupil diameter to basal conditions is up to 190 minutes (Formulation 6) as compared to 110 minutes for pilocarpine in saline alone

IIo Anti Inflammator Activity of Triamclnolone Vehicled In Hyaluronic Acid Materials The following were used: - solution of hyaluxonic acid sodium salt-hyalectin fraction, mOw. between 500,000 and 730,000, 10 mg/ml in saline; -- solution of triamcinolone (10% in saline). lO Method The experiments were carried out on male New Zealand rabbits (average weight 1.6 kg). After an adap

ation period of 5 days

intraocular inflammation was induced in the rabbits by intraocular injection of dextran (10%, 0.1 ml). The administration was effected in both eyes under local anaesthetic with 4

NWASINA inserting the needle of the syringe by 4 mm into the anterior chamber, at a distance of 2 mm from the limbus of the cornea. The test was conducted on 10 animals.

reatment Treatment was effected in each animal both in the right and left eyes, by instillation of 3 drops 3 times a day for 6 days in all, of the following: - a solution of triamcinolone

10% in saline) in the left eye (LE); - a solution of hyaluronic acid sodium salt, hyalectin fraction, (10 mg/ml) + triamcinolone (10

) in the right eye

RE). lo Parameters The anti-inflammatory effect on the phlogistic reaction induced by dextran was evaluated by observing the eye with a slit lamp at the following intervals: 0, 1 hr, 3 hr, 24 hr, 48 hr, 3 days, 4 days, 5 days and 6 days. At the intervals, the eye examination evaluated the following observations: - the state of the cornea and conjunctiva for the possible presence of hypermia, edema, and espec-ially observation of the iris which is normally sensitive to phlogistic processes after intraocular injection of inflammatary agents; - the Tyndall effect, in which the presence of more or less intense opacity ("nubecula") is indicative of the presence of corpusculating

inflammatory) elements in the anterior chamber. The result of the observatio

was expressed in terms of subjective scoring (from 0 to 3) related to the gradualness of the effect noted.

Results It can be seen from the results as reported in Table 6 that administration of triamcinolone has an anti-inflammatory effect on the iris and causes the disappearance of opacity (Tyndall effect) in the anterior chamber. The inflammatory process which is evident from the lst-3rd hour until the 3rd to 4th day progressively decreases until almost normal conditions are restored, with perfect limpidness of the eye by the 6th day. On the other hand, administration of lo hyaluronic acid sodium sal

hyalectin fraction, together with triamcinolone reduces intraocular inflammation observed at the times discussed above relating to administration of triamcinolone alone. That is, the phlogistic process in the iris and the opacity in the anterior chamber is seen to have decreased by the 24th hour, with progressive reduction at 48 hours and with total absence of inflammatory reaction from the 4th day on. In the conjunctiva and the cornea, essentially no notable reactions were observed after intraocular injection of dextran. Thus, the administration of triamcinolone; together with the hyaluroni

resulted in enhanced activity of the drug as evidenced by the more rapid recoVery! of the rabbit eye.

aling Activity of EGF Vehicled ln Hyaluronlc Acid Materials The following were used: Formulation

- EGF (Epidermal growth factor), dissolved in saline (0.5 mg/5 ml) Formulation B - hyaluxonic acid sodium salt, hyalastine fraction, (m. w. approximately 100,000) dissolved in saline (10 mg/ml

Mèthod The experiments were carried out on male albino New Zealand rabbits (average weight 1.

kg). The animals, after a period of adaptation of about 5 days, underwent epithelial lesion of the cornea in suitable conditions of local anaesthetic with

). The lesion consisted of a monocular scarification of a circular area in the optic zone effected by a concave glass cylinder

0 3mm) with a sharp edge. Treatment . The animals were subdivided into groups, each group con-sisting of 5 animals, and subjected to pharmacological treat-ment by conjunctival instillation:as follows: Group Treatment _ . Group 1 (control) Saline Group 2 EGF solution

Formulation A) Group 3 Solution of hyaluronic acid sodium salt, hyalastine fraction, EGF solu

ion - combination of Formulation A + Formulation B at 1:1 ratio to make Formulation 3:

Treatment was effect

d on the right eye (RE) by conjunctival instillation of 2 drops every 8 hours for 3 total adminis-trations. Parameters Healing of the corneal epitheliurn was evaluated by ob-servation of the eye and photographic documentation with a slit lamp at various intervals ater scarification: 0, 8 hours, 16 hours, 24 hours, 32 hours, 40 hours, and 48 hours. Results lo Ophthalmological examination 1 as reported in Table 7, revealed that in the controls (Group 1) complete healing was achieved (5/5 animals) 48 hours after lesion. In the animals treated with EGF

Group 2) the healing process was apparent as early as 24 hours after scarification with considerable efficacy (4/5 animals). In the animals treated with the Formulation C comprising hyaluronic ac. id sodium salt, hyalas-line fraction, + EGF (Group 3) the healing process was complete in all the animals (S/5) as early as 16 hours after scari-fication. These results show that utilization of the hyalastine hyalurorlic acid fraction as a vehicle for EGF enhances the healing process by promoting more rapid effective healing of corneal lesions.

Table 7 HEALING OF LESIONS IN THE CORNEAL EPITHELIUM

Group Treatment Hours a

ication 0 8 16 24

3 Hyaluronic acid + + EGF (Formula - : tion C) + + +

+ = unhealed eye - = hea 1 ed eye IV. Antimicrobial Activity of Gentamicine Vehicled ln Hya-luronic Acid Materials The following materials were used: -- Gentamicine dissolved in saline (50 mg/ml) -- Hyaluronic acid sodium salt, hyalectin fraction

2 mg/ml) Method Septic phlogosis was callsed in both eyes of 11 rabbits lo by intraocular injection of a titered suspension of Pseudomonas aeruginosa (0.1 ml). In those rabbits showing septic phlogosis, hyaluronic acid, hyalectin fraction, in combination with gentarnicine was administered by instillation in the right eye and gentamicine in a buffered saline vehicle was administered in the left eye. The treatment (3 drops every 6 hours) was begun immediately after injection of the infecting agent and was continued until the infection had disappeared. The rabbits' eyes were observed every day under a slit lamp. Result Treatment with a combination of gen

amicine with hyaluronic acid resulted in a faster disappearance of the septic infection as compared to administration of the antibiotic alone. This conclusion is clear from the data presented in Table 8.

Table 8 EFFECT OF GENTAMICINE VEHICLED IN HYALURONIC ACID HYALECTINE FRACTION, ON INTRAOCULAR SEPTIC PHLOGOSIS

_ Treatment Days from Start of Phlogosis _. _ Gentamicine + Buffer Saline Vehicle O. O 0.0 0.0 O. O 0.0 36.3 100 Gentamicine + Hyaluronic Acid Hyalectine Fraction O. O 0.0 9.0+ 27.2

100 100 Values are expressed as percentages (number of eyes cured of phlogosis by the number of eyes tr

ated). + -- Significant difference vs buffer vehicle tless than 0

05, Fisher exact T-Test) 3

Additional samples, although not limitive, of ophthalmic drugs which can be vehicled with HA fractions according to the invention are as follows: antibiotics: chloramphenicol neomycin aureomycin myxin and polymyxin bacitracin mycetins lo hormones: nandrolone and nandrolone sulfate anesthetics (local): henoxinate and the hydrochloride thereof an

iviral: iododeoxyuridine iododeoxycytidine anti-inflammatories: dexamethasone and the phosphate thereof vasopressors and vasocontrictors: synephrine and neosynephrine On the basis of the results obtained from the experi-ments discussed above, it can be concluded that solutions of hyaluronic acid sodium salt (in both the hyalastine and hyalectin fractions) can be used as a vehicle for ophthalmic drugs and proves to be efficient as such for various types of drugs having differing biological actions. For example, drugs including anti-glaucoma agents e. g. pilocarpine nitrate, anti-allergic and anti-inflammatory agents e. g. triamcinolone, tissue healing and cell proliferation pro-o moting agents for promoting healing of eye tissue such asEGF, and antibiotics

g. streptomycin and gentamicine

whose miotic, anti-inflammatory, healing and antimicrohial activities respectively are reported, can all be administered effectively utilizing HA as a vehicle. The formulations of ophthalmic drugs vehicled in hyalu-ronic acid fractions with various molecular weights prove to be perfectly tolerated by the host, and compatible with - the corneal epithelium without, therefore, giving rise to sensitization phenomena.

O It is also possible from the data to observe how this biological product, hyaluronic acid

is an efficient vehicle, capable of enhancing the in vivo bioavailability of vehicled drugs, strengthening the pharmacological activity of such druys. The use of hyaluronic acid fractions as a drug vehicle particularly results in:

- an increase in the miotic activity of pilocarpine ni-trate while prolonging the activity time of the drug; - an increase in the anti-inflammatory activity of triam-cinolone on intraocular inflammation induced by dextran, with

regression of the phlogistic process in shorter times as compared to those obtained with triamcinolone alone; - an increase in the protective action of epidermal growth factor (EGF) on superficial lesions in the cornea with lo obvious synergism and reduction in healiny times as compared to recovery times with EGF alone; and - an increase in the in vivo biological activity of anti-biotics, such as gentamicine. The results obtained by using this biological polymert hyaluronic acid, as a vehicle for drugs with such varied natures and actions, allo

s for the extrapolation of i-ts potential as a vehi

le for numerous other ophthalmic drugs. Reported below are various examples of different formulations of ophthalmic drugs which may be in the form of powders, collyrium, gel, cre

m, or inserts, in which hya-luronic acid in its different fractions, hyalastine and hyalectin, is the only excipient used: - Example 1:a collyrium which may be used as "artificial tears", containing: - hyaluronic acid sodium salt hyalectin fraction 10 mg saline buffered with phosphate p

7.6 M 10 ml Exam

a collyxium which may be used as "artificial tears" con-taining: - hyaluronic acid sodium salt hyalectin fraction 20 mg - saline buffered with phosphate pH 7.6M 10 mg 3

Example 3. a gel containiny EGF in which 100 g contain:

hyaluronic acid sodium salt hyalastine fraction 55 g - hyaluronic acid sodium salt hyalectin fraction 30 g - EGF 0.5g - twice distilled water 23.5g Example 4: a iO0 mg insert with pilocarpine nitrate containing: - hyaluronic acid sodium salt hyalastine fraction 100 mg lo - pilocarpine nitrate 2 mg Example 5-a powder form for topical application containing streptomycin

100 g of powder contain: - hyaluronic acid sodium salt hyalastine fraction 70 g - hyaluronic acid sodium salt hyalectin fraction 28.5 g - streptomycin 1.5 g Although the above-preparations have been described for exemplary purposes, it will be appreciated that the pharma-ceutical formulations could be prepared by combining the hyaluronic fractions, particularly the hyalectin or hyalastine fractions or the combined hyalectin/hyalastine fraction, or the potassium or sodium salts thereof, with other active! drugs, and at various dosages depending upon the particular use for the formulation. Hyaluronic acid, particularly in the substantially pure hyalectin and hyalastine fractions, has, therefore, been shown to be an effective vehicle or excipient for use in combination with various drugs having ophthalmic utility or activity. Pharmaceutical compositions containing the HA fractions as the drug vehicle are particularly useful because the HA fractions exhibit a high level of tolerability to the eye and a high compatibility with the corneal epithelium.

Use of the HA fractions, moreover, provides a means for actually enhanciny the in vivo biological activity oE ophthalmic drugs. The use of the particular hyalectin and hyalastine HA fractions is further useful and important because these fractions, when administered in the eye

do not exhibit undesirable inflammatory side reactions.



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