valdecoxib (Bextra)
Introduction
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
Contraindications
- avoid in patients with sulfonamide allergy[4][5]
Dosage
- 10 mg PO QD (osteoarthritis)
- 20 mg BID PRN (dysmenorrhea)
Pharmacokinetics
- bioavailability is 83% not affected by food or antacids
- maximal plasma levels reached 3 hours after oral dose
- volume of distribution 86 liters
- metabolized by cyt P450 3A4 & 2C9
- one active metabolite without significant role
- metabolites excreted in urine (70%)
- elimination 1/2life of 8-11 hours increases with age
Adverse effects
- renal failure
- edema
- hypertension
- heart failure
- may increase risk of myocardial infarction in patient s/p CABG[8]
- anaphylaxis[4]
- serious skin reactions (rare)
- drug adverse effects of NSAIDs
- drug adverse effects of COX-2-specific inhibitors
- drug adverse effects of sulfonamides
Drug interactions
- in combination with warfarin may temporarily increase INR
- drugs that inhibit cyt P450 3A4 or 2C9 can increase levels of valdecoxib
- drug interaction(s) of direct oral anticoagulants (DOAC) with NSAIDs
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) of antibiotics with warfarin
- 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
- inhibition of cyclooxygenase-2
Notes
Comarketed by Pharmacia & Pfizer
More general terms
References
- ↑ Prescriber's Letter 8(11):61 2001
- ↑ Prescriber's Letter 8(12):72 2001
- ↑ Prescriber's Letter 9(1):1 2002
- ↑ 4.0 4.1 4.2 Prescriber's Letter 9(12):70 2002
- ↑ 5.0 5.1 Prescriber's Letter 11(7):42 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200702&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 11(11): 63, 2004
- ↑ Pfizer Drug Information
- ↑ 8.0 8.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15713945
<Internet> http://content.nejm.org/cgi/reprint/NEJMoa050330.pdf - ↑ 9.0 9.1 9.2 FDA SafetyWalk http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#Bextra