BEXTRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BEXTRA (BEXTRA).
Selective cyclooxygenase-2 (COX-2) inhibitor; reduces prostaglandin synthesis.
| Metabolism | Hepatic metabolism via CYP3A4 and CYP2C9; also undergoes glucuronidation. |
| Excretion | Renal excretion of metabolites accounts for approximately 70% of the dose, with fecal excretion of metabolites accounting for about 20%. Less than 3% is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 22-24 hours in healthy adults, supporting once-daily dosing. Half-life is prolonged in elderly patients and those with renal impairment. |
| Protein binding | Approximately 98% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is about 0.7 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral bioavailability is approximately 80% after oral administration. |
| Onset of Action | Onset of analgesic action is within 30-60 minutes after oral administration. |
| Duration of Action | Duration of analgesic effect is approximately 12-24 hours with once-daily dosing, due to long half-life and sustained COX-2 inhibition. |
| Molecular Weight | 420.5 |
10 mg orally once daily; may be increased to 20 mg once daily if needed.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if creatinine clearance <30 mL/min; no adjustment for mild to moderate impairment (CrCl ≥30 mL/min). |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C); no recommended dose for moderate impairment (Child-Pugh class B) due to increased risk; use with caution at 10 mg once daily in mild impairment (Child-Pugh class A). |
| Pediatric use | Not recommended for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Initiate at lowest recommended dose (10 mg once daily); monitor renal function and gastrointestinal bleeding risk; consider concurrent proton pump inhibitor. |
| 1st trimester | Avoid; associated with increased risk of spontaneous abortion and congenital malformations, particularly cardiac defects, due to COX-2 inhibition interfering with implantation and embryonic development. |
| 2nd trimester | Avoid; may cause oligohydramnios and fetal renal dysfunction due to effects on fetal renal blood flow. |
| 3rd trimester | Contraindicated; increases risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment. |
Clinical note
Comprehensive clinical and safety monograph for BEXTRA (BEXTRA).
| Placental transfer | Crosses placenta; detectable in fetal plasma with concentrations approximately 50-100% of maternal levels. |
| Breastfeeding | Excreted into breast milk in low amounts; however, due to potential adverse effects on infant renal function and cardiovascular system, caution is advised. Alternative analgesics are preferred. |
■ FDA Black Box Warning
Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. Bextra is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
History of allergic-type reactions to sulfonamidesHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or NSAIDsTreatment of perioperative pain in coronary artery bypass graft (CABG) surgeryThird trimester of pregnancyActive peptic ulcer disease or gastrointestinal bleedingSevere hepatic impairmentSevere renal impairment (creatinine clearance <30 mL/min)Phenylketonuria (due to aspartame content in some formulations)
| Precautions | Cardiovascular risk (serious thrombotic events), gastrointestinal effects (ulcers, bleeding), renal effects, anaphylactoid reactions, serious skin reactions (e.g., Stevens-Johnson syndrome), elevation of liver enzymes. |
| Food/Dietary | No specific food interactions reported; however, alcohol may increase risk of gastrointestinal bleeding. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C (1st and 2nd trimesters); Pregnancy Category D (3rd trimester). Avoid in late pregnancy due to risk of premature closure of ductus arteriosus and oligohydramnios. Animal studies show no teratogenicity at low doses, but increased pre- and post-implantation loss and embryofetal lethality at high doses. |
| Fetal Monitoring | Monitor maternal renal function, blood pressure, and signs of fluid retention. In late pregnancy, ultrasound monitoring for amniotic fluid volume and ductus arteriosus patency. Fetal heart rate monitoring if used near term. |
| Fertility Effects | Valdecoxib may impair female fertility through inhibition of prostaglandin synthesis, affecting ovulation. Reversible upon discontinuation. Use for long-term treatment may delay or prevent conception. |
| Clinical Pearls | BEXTRA (valdecoxib) was withdrawn from the market in 2005 due to increased cardiovascular risk. Use is contraindicated in patients with coronary artery bypass graft surgery. Monitor for signs of Stevens-Johnson syndrome, especially in the first 2 weeks of therapy. |
| Patient Advice | Do not use this medication if you have heart disease or have had recent heart surgery. · Stop taking and seek immediate medical attention if you develop skin rash, blisters, or mouth sores. · Avoid alcohol and NSAIDs to reduce risk of gastrointestinal bleeding. · Take with food or milk to minimize stomach upset. · Report any signs of stroke or heart attack (chest pain, shortness of breath, weakness on one side) immediately. |