Rosiglitazone

Brand names: Avandia®

Chemical formula:

Español:
• Maleato de Rosiglitazona, Tableta oral

Rosiglitazone Maleate Oral tablet

What is this medicine?

ROSIGLITAZONE (roe si GLI ta zone) helps to treat type 2 diabetes. It helps to control blood sugar. Treatment is combined with diet and exercise.
 
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•diabetic ketoacidosis
•heart disease
•heart failure
•kidney disease
•liver disease
•macular edema
•polycystic ovary syndrome
•swelling of the arms, legs, or feet
•taking insulin
•taking nitrates for chest pain
•an unusual or allergic reaction to rosiglitazone, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. You can take this medicine with or without food. Take your medicine at the same time each day. Do not take more often than directed. Do not stop taking except on your doctor's advice.

A special MedGuide will be given to you by the pharmacist with each prescription and refill. Be sure to read this information carefully each time.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

•gemfibrozil
•nitrates like amyl nitrite, isosorbide dinitrate, isosorbide mononitrate, nitroglycerin
•other medicines for diabetes, especially insulin
•rifampin

Many medications may cause an increase or decrease in blood sugar, these include:
•alcohol containing beverages
•aspirin and aspirin-like drugs
•chloramphenicol
•chromium
•diuretics
•female hormones, like estrogens or progestins and birth control pills
•heart medicines
•isoniazid
•male hormones or anabolic steroids
•medicines for weight loss
•medicines for allergies, asthma, cold, or cough
•medicines for mental problems
•medicines called MAO Inhibitors like Nardil, Parnate, Marplan, Eldepryl
•niacin
•NSAIDs, medicines for pain and inflammation, like ibuprofen or naproxen
•pentamidine
•phenytoin
•probenecid
•quinolone antibiotics like ciprofloxacin, levofloxacin, ofloxacin
•some herbal dietary supplements
•steroid medicines like prednisone or cortisone
•thyroid medicine

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress.

Your health care professional will have to check blood tests regularly to assess the effect of this medication on your liver.

Learn how to check your blood sugar. Learn the symptoms of low and high blood sugar and how to manage them.

If you have low blood sugar, eat or drink something that has sugar. Make sure others know to get medical help quickly if you have serious symptoms of low blood sugar, like if you become unconscious or have a seizure.

This medicine may increase your risk of having some heart problems. Get medical help right away if you have any chest pain or tightness, or pain that radiates to the jaw or down the arm, and shortness of breath. These may be signs of a serious medical condition.

This medicine may cause ovulation in premenopausal women who do not have regular monthly periods. This may increase your chances of becoming pregnant. You should not take this medicine if you become pregnant or think you may be pregnant. Talk with your doctor or health care professional about your birth control options while taking this medicine. Contact your doctor or health care professional right away if think you are pregnant.

If you need surgery or if you will need a procedure with contrast drugs, tell your doctor or health care professional that you are taking this medicine.

Wear a medical identification bracelet or chain to say you have diabetes, and carry a card that lists all your medications.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•bone or joint pain
•breathing problems
•chest pain or tightness
•dark urine
•loss of appetite, nausea
•low blood sugar (ask your doctor or healthcare professional for a list of these symptoms)
•pain that radiates to the jaw or down the arm
•redness, blistering, peeling or loosening of the skin, including inside the mouth
•sudden weight gain
•swelling of the ankles, feet, hands
•unusually weak or tired
•yellowing of the eyes or skin
 
Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•back ache
•diarrhea
•headache
•right upper belly pain
 
This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children

Store at room temperature between 20 and 25 degrees C (68 and 77 degrees F). Keep container tightly closed and protect from light. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Rosiglitazone
Systematic (IUPAC) name
(RS)-5-[4-(2-[methyl(pyridin-2-yl)amino]ethoxy)benzyl]thiazolidine-2,4-dione
Identifiers
CAS number	122320-73-4
ATC code	A10BG02
PubChem	77999
DrugBank	APRD00403
ChemSpider	70383
Chemical data
Formula	C18H19N3O3S
Mol. mass	357.428 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	99%
Protein binding	99.8%
Metabolism	Hepatic (CYP2C8-mediated)
Half life	3-4 hours
Excretion	Renal (64%) and fecal (23%)
Therapeutic considerations
Licence data	EU EMEA:link, US FDA:link
Pregnancy cat.	B3(AU) C(US)
Legal status	POM(UK) ℞-only(US)
Routes	Oral
Y(what is this?)  (verify)

Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl). Annual sales peaked at approx $2.5bn in 2006. The drug's patent expires in 2012.

Some reports have suggested that rosiglitazone is associated with a statistically significant risk of heart attacks, but other reports have disagreed, and the controversy has not been resolved. Concern about adverse effects has reduced the use of rosiglitazone despite its important and sustained effects on glycemic control.^[1]

Contents 1 Pharmacology 2 Side-effects and contraindications 3 Sales 4 References 5 External links

Pharmacology

Like other thiazolidinediones (TZDs), the mechanism of action of rosiglitazone is through activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ. Rosiglitazone is a selective ligand of PPARγ and has no PPARα-binding action.

Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFκB) levels fall and inhibitor (IκB) levels increase in patients on rosiglitazone.^[2]

Recent research has suggested that rosiglitazone may also be of benefit to a subset of patients with Alzheimer's disease not expressing the ApoE4 allele.^[3] This is the subject of a clinical trial currently underway.^[4]

The medication might also be effective in the treatment of mild to moderate Ulcerative Colitis, due to its antiinflammatory properties as a PPAR ligand.^[5]

A clinical trial has suggested that these agents may be of use in treating malaria. ^[6]

Side-effects and contraindications

A press release by GlaxoSmithKline in February 2007 noted that there is a greater incidence of fractures of the upper arms, hands and feet in female diabetics given rosiglitazone compared with those given metformin or glyburide.^[7] The information was based on data from the ADOPT trial.^[8] The same increase has been found with pioglitazone (Actos), another TZD.

A meta-analysis reported in May 2007 that the use of rosiglitazone was associated with a significantly increased risk of heart attack (odds ratio=1.43, (95% confidence interval, 1.03 to 1.98; P=0.03)), and an even higher risk of death from all cardiovascular diseases (odds ratio=1.64).^[9] The U.S. Food and Drug Administration (FDA) issued an alert on May 21, 2007.^[10] On July 30, 2007 an Advisory Committee of the Food and Drug Administration concluded that the use of rosiglitazone for the treatment of type 2 diabetes was associated with a greater risk of myocardial ischemic events (including heart attacks) than a placebo, but data from several long term, prospective clinical trials showed that when rosiglitazone was compared to metformin, or sulfonylurea, there was no difference in the risk of heart attack. This data, coupled with the meta-analysis, prompted the FDA to state that the data on the association between rosiglitazone and myocardial ischemia were inconclusive. The meta-analysis was not supported by an interim analysis of the trial designed to evaluate this, and several other reports have failed to conclude the controversy. This weak evidence for adverse effects has dramatically reduced the use of rosiglitazone, despite its important and sustained effects on glycemic control.^[1]

In 2009 the RECORD study, an open label trial published in the Lancet, found that there was no increase in cardiovascular hospitalisation or death with rosiglitazone compared to metformin plus sulfonylurea, but the rate of heart failure causing admission to hospital or death was significantly increased.^[11]

As early as September 2005, both Rosiglitazone and Pioglitazone have been suspected of causing Macular Edema, which causes partial blindness in various spots of the angle of vision. While blindness is also a possible effect of diabetes, which Rosiglitazone is intended to treat, an article in Canadian journal CMAJ has documented several occurrences and recommends discontinuation at the first sign of vision problems. Both TZD's are contraindicated in patients with NYHA Class III and IV heart failure.

Sales

US sales of $2.2 billion in 2006.^[12] Sales in 2Q 2007 down 22% compared to 2006.^[13] 4Q 2007 sales down to $252 million.^[14]

References

1. ^ ^{a b} Ajjan RA, Grant PJ (2008). "The cardiovascular safety of rosiglitazone". Expert Opin Drug Saf 7 (4): 367–76. doi:10.1517/14740338.7.4.367. PMID 18613801. 
2. ^ Mohanty P, Aljada A, Ghanim H, Hofmeyer D, Tripathy D, Syed T, Al-Haddad W, Dhindsa S, Dandona P (2004). "Evidence for a potent antiinflammatory effect of rosiglitazone". J Clin Endocrinol Metab 89 (6): 2728–35. doi:10.1210/jc.2003-032103. PMID 15181049. 
3. ^ Risner ME et al. (2006). "Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease". The Pharmacogenomics Journal 6: 246–254. 
4. ^ http://www.alzforum.org/drg/drc/detail.asp?id=116
5. ^ Lewis JD, Lichtenstein GR, Deren JJ, et al. (2008). "Rosiglitazone for Active Ulcerative Colitis: A Randomized Placebo Controlled Trials". Gastroenterology 134: 688–695. doi:10.1053/j.gastro.2008.03.030. 
6. ^ Boggild AK, Krudsood S, Patel SN, Serghides L, Tangpukdee N, Katz K, Wilairatana P, Liles WC, Looareesuwan S, Kain KC (2009). "Use of Peroxisome proliferator-activated receptor gamma agonists as adjunctive treatment for Plasmodium falciparum malaria: A randomized, double-blind, placebo-controlled trial.". Clin. Infect. Dis.. 
7. ^ Cobitz, Alexander R (February 2007). Clinical Trial Observation of an Increased Incidence of Fractures in Female Patients Who Received Long-Term Treatment with Avandia (rosiglitazone maleate) Tablets for Type 2 Diabetes MellitusPDF (49.9 KiB). GlaxoSmithKline. Retrieved on 2007-04-10.
8. ^ Kahn S, Haffner S, Heise M, Herman W, Holman R, Jones N, Kravitz B, Lachin J, O'Neill M, Zinman B, Viberti G (2006). "Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy". N Engl J Med 355 (23): 2427–43. doi:10.1056/NEJMoa066224. PMID 17145742. 
9. ^ Nissen SE, Wolski K (2007). "Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes". N Engl J Med 356 (24): 2457–71. doi:10.1056/NEJMoa072761. PMID 17517853. http://content.nejm.org/cgi/content/full/356/24/2457. Lay summary – Associated Press (2007-05-21). 
10. ^ U.S. Food and Drug Administration (May 21, 2007). "FDA Issues Safety Alert on Avandia". http://www.fda.gov/bbs/topics/NEWS/2007/NEW01636.html. 
11. ^ Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. The Lancet. In Press, Corrected Proof. Available at: http://www.sciencedirect.com/science/article/B6T1B-4WGD87Y-1/2/0efabb7eba7ca1f4f7c556bd636e19ab.
12. ^ http://www.mmm-online.com/FDA-toughens-Avandia-warnings/article/96354/
13. ^ http://www.usatoday.com/news/health/2007-07-25-avandia-fda_N.htm
14. ^ http://www.bloomberg.com/apps/news?pid=20601087&sid=aHobgoX8jyfg&refer=home

External links

• Official website
• MedlinePlus article
• Medscape
• ClinicalTrials.gov NCT00265148 Brain Imaging Study of Rosiglitazone Efficacy and Safety in Alzheimer's Disease

v • d • e GlaxoSmithKline plc Corporate Directors: Lawrence Culp · Crispin Davis · Jean-Pierre Garnier · Chris Gent · Julian Heslop · Deryck Maughan · Ian Prosser · Ronaldo Schmitz · Lucy Shapiro · Robert Wilson · Tadataka Yamada Products: Bupropion (Zyban) · Co-amoxiclav (Augmentin) · Paroxetine (Paxil, Seroxat, Aropax) · Rosiglitazone (Avandia) · Sumatriptan(Imitrex) Annual Revenue: $39.0 billion USD (▲2% FY 2004) · Employees: 100,019 · Stock Symbol: LSE: GSK NYSE: GSK · Website: www.gsk.com

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