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rosiglitazone (Avandia)

Tradename: Avandia. Medication Guide to be provided with each prescription Indications: 1) adjunct to diet & exercise to improve diabetic control in patients with diabetes mellitus type 2 2) indicated as monotherapy or for use in combination with metformin or insulin [7] 3) for patients inadequately controlled on a maximum dose of metformin, rosiglitazone should be added to rather than substituted for metformin 4) psoriasis (not FDA-approved use) [9] Contraindications: (cautions) -> heart failure (see recommendations for prescribing thiazolidinediones) Dosage: 1) 4 mg PO QD-BID 2) max dose: 4 mg if used in combination with insulin [7] 3) reduce insulin by 10-25% if hypoglycemia develops [7] Tabs: 2, 4, 8 mg Pharmacokinetics: 1) bioavailability after oral dose is 99% 2) 99.8% bound to serum proteins 3) metabolized in the liver largely by cyt P450 2C8 with cyt P450 2C9 playing a minor role 4) N-demethylation & hydroxylation followed by conjugation 5) t1/2: 103-158 hours Monitor: 1) LFTs at start, then every 2 months for 1st year, then periodically 2) discontinue if AST > 2.5 x upper limit of normal Adverse effects: 1) reversible elevations in ALT 3X (0.2%) 2) No evidence of hepatotoxicity 3) anemia: decreases in hemoglobin of 1.0 g/dL 4) fluid retention & edema a) may exacerbate heart failure [4,6,8] b) may exacerbate heart failure in patients with class 1 or 2 NYHA Heart failure [13] c) may increase risk of heart failure [18,22,32] 5) may increase serum triglycerides < 15% [10] 6) diabetic macular edema [12] - most have peripheral edema - may resolve with discontinuation 7) may increase risk of fractures (females) [14,22] 8) may increase risk of myocardial infarction in patients with type 2 diabetes (odds ratio 1.43) [15,16], - No increase risk of myocardial infarction [18,22,31] - cardiovascular risk in elderly confirmed [20] for CHF (relative risk, 1.6) or AMI (RR, 1.4) & for death (RR, 1.29) 9) risk of osteoporosis & fractures in women [23] 10) increased risk of macular edema (RR = 6.5 at 1 year) [30] Drug interactions: -> risk of heart failure increased when used in combination with insulin [4] Mechanism of action: 1) thiazolidinedione 2) PPAR-gamma agonist 3) PPAR-gamma regulates transcription of insulin-responsive genes * PPAR: peroxisome proliferator-activated receptor

Interactions

drug interactions drug adverse effects (more general classes) monitor with thiazolidinediones (glitazones)

Related

metformin/rosiglitazone (Avandamet) peroxisome proliferator-activated receptor gamma; PPAR-gamma; nuclear receptor subfamily 1 group C member 3 (PPARG, NR1C3)

General

peroxisome proliferator; PPAR agonist; PPAR gamma agonist thiazolidinedione; glitazone; TZD

Properties

MISC-INFO: elimination route LIVER 1/2life 103-158 HOURS protein-binding 99.8% pregnancy-category C safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. Kaiser Permanente Northern California Regional Drug Alert
  2. Kaiser Permanente Northern California Regional Drug Formulary, 2000
  3. Physician's Desk Reference (PDR) 54th edition, Medical Economics, 2000
  4. Prescriber's Letter 8(10):58 2001
  5. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  6. Prescriber's Letter 9(4):22 2002
  7. Prescriber's Letter 10(4):20 2003
  8. Journal Watch 23(24):189, 2003 Delea TE et al, Diabetes Care 26:2983, 2003 PMID: 14578227
  9. Prescriber's Letter 11(8):41 2004 Avandia and Actos for Psoriasis Detail-Document#: 200802 (subscription needed) http://www.prescribersletter.com
  10. Prescriber's Letter 12(8): 2005 Does Actos Improve Lipids Better than Avandia? Detail-Document#: 210310 (subscription needed) http://www.prescribersletter.com
  11. Department of Veterans Affairs, VA National Formulary
  12. FDA Medwatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#Avandia
  13. Prescriber's Letter 13(9): 2006 The Use of Glitazones in Patients with Congestive Heart Failure Detail-Document#: 220909 (subscription needed) http://www.prescribersletter.com
  14. FDA Medwatch http://www.fda.gov/medwatch/safety/2007/safety07.htm#rosiglitazone
  15. Nissen SE and Wolski K Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. N Engl J Medwww.nejm.org May 21, 2007 (10.1056/NEJMoa072761) http://content.nejm.org/cgi/content/full/NEJMoa072761 - FDA MedWatch http://www.fda.gov/medwatch/safety/2007/safety07.htm#Avandia http://www.fda.gov/medwatch/safety/2007/safety07.htm#Avandia2 http://www.fda.gov/medwatch/safety/2008/safety08.htm#Avandia
  16. Prescriber's Letter 14(6): 2007 Avandia and Risk of Heart Attack Information for Patients Detail-Document#: 230622 (subscription needed) http://www.prescribersletter.com
  17. Prescriber's Letter 14(7): 2007 Avandia and Risk of Heart Attack Information for Patients Avandia (Rosiglitazone) and the Risk of Myocardial Infarction Detail-Document#: 230718 (subscription needed) http://www.prescribersletter.com
  18. Prescriber's Letter 14(12): 2007 FDA Adds Boxed Warning for Heart-related Risks to Avandia Detail-Document#: 231202 (subscription needed) http://www.prescribersletter.com
  19. Lago RM et al. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: A meta-analysis of randomised clinical trials. Lancet 2007 Sep 29; 370:1129. PMID: 17905165 - Cleland JGF and Atkin SL. Thiazolidinediones, deadly sins, surrogates, and elephants. Lancet 2007 Sep 29; 370:1103. PMID: 17905146 - Montori VM et al. Patient-important outcomes in diabetes - time for consensus. Lancet 2007 Sep 29; 370:1104. PMID: 17905147
  20. Lipscombe LL et al Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. JAMA. 2007 Dec 12;298(22):2634-43. PMID: 18073359
  21. FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Avandia
  22. Home PD 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, Early Online Publication, 5 June 2009 doi:10.1016/S0140-6736(09)60953-3 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60953-3/fulltext
  23. Loke Y et al Long-term use of thiazolidinediones and fractures in type 2 CMAJ. 2009 Jan 6;180(1):32-9. Epub 2008 Dec 10. PMID: 19073651
  24. FDA MedWatch Avandia (rosiglitazone): Ongoing Review of Cardiovascular Safety http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm201446.htm - FDA MedWatch Avandia (rosiglitazone): REMS - Risk of Cardiovascular Events [UPDATED 02/04/2011] http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm226994.htm
  25. Prescriber's Letter 17(3): 2010 COMMENTARY: Avandia and Cardiovascular Safety: Ongoing Review PATIENT HANDOUT: Avandia and Risk of Heart Attack PATIENT HANDOUT SPANISH VERSION: Avandia y el Riesgo de un Ataque Cardiaco Detail-Document#: 260325 (subscription needed) http://www.prescribersletter.com
  26. Prescriber's Letter 17(4): 2010 Avandia and Cardiovascular Safety: Ongoing Review COMMENTARY: Avandia and Cardiovascular Safety: Ongoing Review PATIENT HANDOUT: Avandia and Risk of Heart Attack Detail-Document#: 260402 (subscription needed) http://www.prescribersletter.com
  27. Nissen SE and Wolski K Rosiglitazone Revisited: An Updated Meta-analysis of Risk for Myocardial Infarction and Cardiovascular Mortality Arch Intern Med. 2010 170(14): PMID: 20656674 doi:10.1001/archinternmed.2010.207 http://archinte.ama-assn.org/cgi/content/full/2010.207 - Graham DJ et al Risk of Acute Myocardial Infarction, Stroke, Heart Failure, and Death in Elderly Medicare Patients Treated With Rosiglitazone or Pioglitazone JAMA. 2010;304(4): PMID: 20584880 doi:10.1001/jama.2010.920 http://jama.ama-assn.org/cgi/content/full/jama.2010.920 - Juurlink DN Rosiglitazone and the Case for Safety Over Certainty JAMA. 2010;304(4): PMID: 20584879 doi:10.1001/jama.2010.954 http://jama.ama-assn.org/cgi/content/full/jama.2010.954
  28. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  29. FDA Drug Safety Communication: Updated Risk Evaluation and Mitigation Strategy (REMS) to Restrict Access to Rosiglitazone- containing Medicines including Avandia, Avandamet, and Avandaryl http://www.fda.gov/Drugs/DrugSafety/ucm255005.htm
  30. Idris I et al Association Between Thiazolidinedione Treatment and Risk of Macular Edema Among Patients With Type 2 Diabetes Arch Intern Med. 2012;():1-7, June 2012 PMID: 22688528 http://archinte.jamanetwork.com/article.aspx?articleID=1182550 - Singh S and Segal JB Thiazolidinediones and Macular Edema: Comment on "Association Between Thiazolidinedione Treatment and Risk of Macular Edema Among Patients With Type 2 Diabetes" PMID: 22688825
  31. FDA MedWatch. Nov 25, 2013 Rosiglitazone-containing Diabetes Medicines: Drug Safety Communication - Removal of Some Prescribing and Dispensing Restrictions. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm376683.htm - Tucker ME FDA Lifts Final Regulatory Restrictions on Rosiglitazone. Medscape. Dec 16, 2015 http://www.medscape.com/viewarticle/856056
  32. Wallach JD, Wang K, Zhang AD et al Updating insights into rosiglitazone and cardiovascular risk through shared data: individual patient and summary level meta-analyses. BMJ 2020;368:l7078 PMID: 32024657 Free Article https://www.bmj.com/content/368/bmj.l7078
  33. HIGHLIGHTS OF PRESCRIBING INFORMATION AVANDIA (rosiglitazone maleate) Tablets. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf

Component-of

glimepiride/rosiglitazone (Avandaryl) metformin/rosiglitazone (Avandamet)