Contents

Search

rofecoxib (Vioxx)

Tradename: Vioxx. (Merck to pull from worldwide market 9/04 because of increased risk of myocardial infarction.) [12] Indications: 1) relief of signs & symptoms of osteoarthritis [6] 2) management of acute pain in adults 3) treatment of primary dysmenorrhea 4) symptoms of rheumatoid arthritis [7] 5) migraine headache, FDA approved 2004 [8] Contraindications: 1) hypersensitivity to NSAIDs 2) avoid using late in pregnancy Caution: 1) liver dysfunction 2) hypertension 3) infection 4) history of GI ulceration 5) renal insufficiency Dosage: 1) arthritis: 12.5-25 mg PO QD 2) dysmenorrhea: 50 mg PO QD Pharmacokinetics: 1) bioavailability: 93%, not affected by food 2) time to peak serum concentration: 2-3 hours 3) serum levels of 320 ng/mL reaches after multiple doses of 25 mg QD 4) metabolized by reduction (extra vs intrahepatic reduction?) 5) protein-binding 87% 6) elimination 1/2life is 17 hours 7) elimination in urine (72%) & feces (14%) Adverse effects: 1) upper respiratory tract infection 2) nausea 3) heartburn 4) headache 5) dizziness 6) anemia (uncommon) 7) nephrotoxicity [3] -> decreased renal blood flow 8) edema (risk > NSAID or celecoxib [11]) 9) hypertension a) especially systolic hypertension b) risk > naproxen [7], other NSAID or celecoxib [11] c) < 5 mm Hg [17] increase in systolic BP [17] 10) heart failure [9,10] 11) small increased risk of myocardial infarction relative to traditional NSAIDs [5] (see APPROVe trial) also [18]; RR: 1.32 [19]; risk apparent shortly after starting drug [20] 12) GI bleeding; risk reduced 50% compared to naproxen [7] - only Cox2 inhibitor shown to have reduced risk relative to non-selective NSAIDs [16] 13) aseptic meningitis (within 2 weeks) [7]; recovery with stopping drug Drug interactions: 1) loop diuretics decreased effectiveness 2) methotrexate: increased toxicity 3) rifampin decreases effectiveness of rofecoxib 4) thiazide diuretics: decreased effectivness 5) lithium carbonate ? Mechanism of action: 1) 2nd FDA-approved cyclooxygenase-2 (COX-2) inhibitor 2) does NOT inhibit platelet aggregation 3) inhibits formation of prostacyclin

Interactions

drug interactions drug adverse effects (more general classes) monitor with non steroidal anti-inflammatory agents (NSIADs)

General

cyclooxygenase-2 (COX-2) specific inhibitor indole sulfone

Properties

INHIBITS: cyclooxygenase-2 MISC-INFO: elimination route KIDNEY LIVER 1/2life 17 HOURS protein-binding 87%

Database Correlations

PUBCHEM cid=5090

References

  1. Kaiser Permanente Northern California Regional Drug Alert
  2. Micromedex
  3. Journal Watch 20(15):117, 2000 Swann et al, Ann Intern Med 133:1-9, 2000
  4. Prescriber's Letter 7(10):55 2000
  5. Prescriber's Letter 8(9):49 2001 JAMA 286:954, 2001 NEJM 345:433, 2001
  6. Journal Watch 22(4):31-32, 2002 Geba et al, JAMA 287:64, 2002
  7. Prescriber's Letter 9(5):25 2002
  8. Prescriber's Letter 11(5):29 2004 Detail-Document#: 200514 (subscription needed) http://www.prescribersletter.com
  9. Prescriber's Letter 11(6):32 2004 Detail-Document#: 200603 (subscription needed) http://www.prescribersletter.com
  10. Journal Watch 24(14):109, 2004 Mamdani M, Juurlink DN, Lee DS, Rochon PA, Kopp A, Naglie G, Austin PC, Laupacis A, Stukel TA. Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study. Lancet. 2004 May 29;363(9423):1751-6. PMID: 15172772
  11. Journal Watch 24(14):109, 2004 Wolfe F, Zhao S, Pettitt D. Blood pressure destabilization and edema among 8538 users of celecoxib, rofecoxib, and nonselective nonsteroidal antiinflammatory drugs (NSAID) and nonusers of NSAID receiving ordinary clinical care. J Rheumatol. 2004 Jun;31(6):1143-51. PMID: 15170928
  12. Prescriber's Letter 11(10): 2004 Vioxx (rofecoxib) is now removed from the U.S. and worldwide market. Information for Patients Taking Vioxx (rofecoxib). Detail-Document#: 201050 (subscription needed) http://www.prescribersletter.com
  13. Prescriber's Letter 11(11): 2004 Safety of COX-2 Inhibitors and Their Place in Therapy Detail-Document#: 201102 (subscription needed) http://www.prescribersletter.com
  14. Journal Watch 24(21):157-58, 2004 - Topol EJ. Failing the public health--rofecoxib, Merck, and the FDA. N Engl J Med. 2004 Oct 21;351(17):1707-9. Epub 2004 Oct 06. PMID: 15470193 - Fitzgerald GA. Coxibs and cardiovascular disease. N Engl J Med. 2004 Oct 21;351(17):1709-11. Epub 2004 Oct 06. PMID: 15470192
  15. Journal Watch 25(1):2, 2005 Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet. 2004 Dec 4;364(9450):2021-9. PMID: 15582059 http://www.thelancet.com/journal/vol364/iss9450/full/llan.364.9450.primary_research.31389.1
  16. Prescriber's Letter 12(3): 2005
  17. Journal Watch 25(6):45-46, 2005 - Sowers JR, White WB, Pitt B, Whelton A, Simon LS, Winer N, Kivitz A, van Ingen H, Brabant T, Fort JG; Celecoxib Rofecoxib Efficacy and Safety in Comorbidities Evaluation Trial (CRESCENT) Investigators. The Effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Arch Intern Med. 2005 Jan 24;165(2):161-8. Erratum in: Arch Intern Med. 2005 Mar 14;165(5):551. PMID: 15668361 - Aw TJ, Haas SJ, Liew D, Krum H. Meta-analysis of cyclooxygenase-2 inhibitors and their effects on blood pressure. Arch Intern Med. 2005 Mar 14;165(5):490-6. Epub 2005 Feb 14. PMID: 15710786
  18. Journal Watch 25(7):56, 2005 - Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, Shoor S, Ray WA. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005 Feb 5;365(9458):475-81. PMID: 15705456 - Maxwell SR, Webb DJ. COX-2 selective inhibitors--important lessons learned. Lancet. 2005 Feb 5;365(9458):449-51. No abstract available. PMID: 15705439
  19. Journal Watch 25(16):126, 2005 - Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo- oxygenase-2 inhibitors or conventional non-steroidal anti- inflammatory drugs: population based nested case-control analysis. BMJ. 2005 Jun 11;330(7504):1366. PMID: 15947398 http://bmj.bmjjournals.com/cgi/content/full/330/7504/1366
  20. Prescriber's Letter 13(10): 2006 Cardiovascular Risks of NSAIDs and COX-2 Inhibitors Detail-Document#: 221003 (subscription needed) http://www.prescribersletter.com