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valdecoxib (Bextra)

Tradename: Bextra. FDA approved 12/01. 4-(5-methyl-3-phenyl-3-isoxazolyl)benzenesulfonamide. * April 7, 2005: After concluding that the overall risk versus benefit profile is unfavorable, FDA has requested Pfizer, Inc. to voluntarily withdraw Bextra (valdecoxib) from the market. This request is based on: [9] * The lack of adequate data on the cardiovascular safety of long-term use of Bextra, along with the increased risk of adverse cardiovascular (CV) events in short-term coronary artery bypass surgery (CABG) trials that FDA believes may be relevant to chronic use. * Reports of serious and potentially life-threatening skin reactions, including deaths, in patients using Bextra. The risk of these reactions in individual patients is unpredictable, occurring in patients with and without a prior history of sulfa allergy, and after both short- and long-term use. * Lack of any demonstrated advantages for Bextra compared with other NSAIDs. [9] Indications: 1) osteoarthritis 2) rheumatoid arthritis 3) dysmenorrhea Contraindications: -> avoid in patients with sulfonamide allergy [4,5] Dosage: 1) 10 mg PO QD (osteoarthritis) 2) 20 mg BID PRN (dysmenorrhea) Pharmacokinetics: 1) bioavailability is 83% not affected by food or antacids 2) maximal plasma levels reached 3 hours after oral dose 3) volume of distribution 86 liters 4) metabolized by cyt P450 3A4 & 2C9 5) one active metabolite without significant role 6) metabolites excreted in urine (70%) 7) elimination 1/2life of 8-11 hours increases with age Adverse effects: 1) renal failure 2) edema 3) hypertension 4) heart failure 5) may increase risk of myocardial infarction in patient s/p CABG [8] 5) anaphylaxis [4] 6) serious skin reactions (rare) - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme Drug interactions: 1) in combination with warfarin may temporarily increase INR 2) drugs that inhibit cyt P450 3A4 or 2C9 can increase levels of valdecoxib - flucanazole, ketoconazole Mechanism of action: -> inhibition of cyclooxygenase-2 Notes: Comarketed by Pharmacia & Pfizer.

Interactions

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

General

cyclooxygenase-2 (COX-2) specific inhibitor sulfonamide

Properties

INHIBITS: cyclooxygenase-2

Database Correlations

PUBCHEM cid=119607

References

  1. Prescriber's Letter 8(11):61 2001
  2. Prescriber's Letter 8(12):72 2001
  3. Prescriber's Letter 9(1):1 2002
  4. Prescriber's Letter 9(12):70 2002
  5. Prescriber's Letter 11(7):42 2004 Detail-Document#: 200702 (subscription needed) http://www.prescribersletter.com
  6. Prescriber's Letter 11(11): 63, 2004
  7. Pfizer Drug Information
  8. Journal Watch 25(6):45, 2005 Nussmeier NA, Whelton AA, Brown MT, Langford RM, Hoeft A, Parlow JL, Boyce SW, Verburg KM. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med. 2005 Mar 17;352(11):1081-91. Epub 2005 Feb 15. PMID: 15713945 - http://content.nejm.org/cgi/reprint/NEJMoa050330.pdf
  9. FDA SafetyWalk http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#Bextra