rofecoxib (Vioxx)
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Introduction
Tradename: Vioxx. (Merck to pull from worldwide market 9/04 because of increased risk of myocardial infarction.)[12]
Indications
- relief of signs & symptoms of osteoarthritis[6]
- management of acute pain in adults
- treatment of primary dysmenorrhea
- symptoms of rheumatoid arthritis[7]
- migraine headache, FDA approved 2004[8]
Contraindications
- hypersensitivity to NSAIDs
- avoid using late in pregnancy
Caution:
- liver dysfunction
- hypertension
- infection
- history of GI ulceration
- renal insufficiency
Dosage
Pharmacokinetics
- bioavailability: 93%, not affected by food
- time to peak serum concentration: 2-3 hours
- serum levels of 320 ng/mL reaches after multiple doses of 25 mg QD
- metabolized by reduction (extra vs intrahepatic reduction?)
- protein-binding 87%
- elimination 1/2life is 17 hours
- elimination in urine (72%) & feces (14%)
elimination via kidney
elimination via liver
1/2life = 17 hours
protein binding = 87 %
Adverse effects
- upper respiratory tract infection
- nausea
- heartburn
- headache
- dizziness
- anemia (uncommon)
- nephrotoxicity[3]
- decreased renal blood flow
- edema (risk > NSAID or celecoxib[11])
- hypertension
- especially systolic hypertension
- risk > naproxen[7], other NSAID or celecoxib[11]
- < 5 mm Hg[17] increase in systolic BP[17]
- heart failure[9][10]
- 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]
- GI bleeding; risk reduced 50% compared to naproxen[7]
- only Cox2 inhibitor shown to have reduced risk relative to non-selective NSAIDs[16]
- aseptic meningitis (within 2 weeks)[7]; recovery with stopping drug
Drug interactions
- loop diuretics decreased effectiveness
- methotrexate: increased toxicity
- rifampin decreases effectiveness of rofecoxib
- thiazide diuretics: decreased effectivness
- lithium carbonate ?
- drug interaction(s) of direct oral anticoagulants (DOAC) with NSAIDs
- drug interaction(s) of cholinesterase inhibitors with NSAIDs
- drug interaction(s) of lithium carbonate with NSAIDs
- drug interaction(s) of NSAIDs with oral contraceptive
- drug interaction(s) of NSAIDs with SSRIs
- drug interaction(s) of NSAIDs with antidepressants
- drug interaction(s) of aspirin with NSAIDs
- drug interaction(s) of apixaban with NSAIDs
- drug interaction(s) of warfarin with NSAIDs
- drug interaction(s) of NSAIDs with beta blockers
- drug interaction(s) of NSAIDs with ARBs
- drug interaction(s) of coxib with SSRI
- drug interaction(s) of NSAIDs with aldosterone antagonis
- drug interaction(s) of NSAIDs with glucocorticoid
- drug interaction(s) of NSAIDs, diuretics & angiotensin II receptor antagonists
- drug interaction(s) of NSAIDs, diuretics & ACE inhibitors
- drug interaction(s) of NSAIDs with ACE inhibitors
- drug interaction(s) of NSAIDs & antihypertensives
- drug interaction(s) of NSAIDs & loop diuretics
- drug interaction(s) of NSAIDs & aspirin
Mechanism of action
- 2nd FDA-approved cyclooxygenase-2 (COX-2) inhibitor
- does NOT inhibit platelet aggregation
- inhibits formation of prostacyclin
More general terms
References
- ↑ Kaiser Permanente Northern California Regional Drug Alert
- ↑ Micromedex
- ↑ 3.0 3.1 Journal Watch 20(15):117, 2000 Swann et al, Ann Intern Med 133:1-9, 2000
- ↑ Prescriber's Letter 7(10):55 2000
- ↑ 5.0 5.1 Prescriber's Letter 8(9):49 2001 JAMA 286:954, 2001 NEJM 345:433, 2001
- ↑ 6.0 6.1 Journal Watch 22(4):31-32, 2002 Geba et al, JAMA 287:64, 2002
- ↑ 7.0 7.1 7.2 7.3 7.4 Prescriber's Letter 9(5):25 2002
- ↑ 8.0 8.1 Prescriber's Letter 11(5):29 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200514&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 Prescriber's Letter 11(6):32 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200603&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 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: https://www.ncbi.nlm.nih.gov/pubmed/15172772
- ↑ 11.0 11.1 11.2 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: https://www.ncbi.nlm.nih.gov/pubmed/15170928
- ↑ 12.0 12.1 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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=201050&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 11(11): 2004 Safety of COX-2 Inhibitors and Their Place in Therapy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=201102&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/15470193
Fitzgerald GA. Coxibs and cardiovascular disease. N Engl J Med. 2004 Oct 21;351(17):1709-11. Epub 2004 Oct 06. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15470192 - ↑ 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15582059 <Internet> http://www.thelancet.com/journal/vol364/iss9450/full/llan.364.9450.primary_research.31389.1
- ↑ 16.0 16.1 Prescriber's Letter 12(3): 2005
- ↑ 17.0 17.1 17.2 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/15710786 - ↑ 18.0 18.1 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: https://www.ncbi.nlm.nih.gov/pubmed/15705456
Maxwell SR, Webb DJ. COX-2 selective inhibitors--important lessons learned. Lancet. 2005 Feb 5;365(9458):449-51. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15705439 - ↑ 19.0 19.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15947398 <Internet> http://bmj.bmjjournals.com/cgi/content/full/330/7504/1366 - ↑ 20.0 20.1 Prescriber's Letter 13(10): 2006 Cardiovascular Risks of NSAIDs and COX-2 Inhibitors Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=221003&pb=PRL (subscription needed) http://www.prescribersletter.com