VIOXX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIOXX (VIOXX).
Selective cyclooxygenase-2 (COX-2) inhibitor; reduces prostaglandin synthesis involved in inflammation, pain, and fever.
| Metabolism | Hepatic metabolism primarily via reduction by cytosolic enzymes; minor metabolism via CYP3A4, CYP2C9, and CYP1A2. |
| Excretion | Rofecoxib is primarily eliminated via hepatic metabolism, with <1% excreted unchanged in urine. Approximately 72% of an oral dose is excreted in urine as metabolites and 14% in feces as metabolites. Biliary excretion contributes minimally. |
| Half-life | The terminal elimination half-life is approximately 17 hours (range 12-22 hours) in healthy adults. This prolonged half-life supports once-daily dosing, but accumulation occurs with repeated doses, reaching steady state within 3-4 days. In elderly patients, half-life may increase by up to 30%. |
| Protein binding | Approximately 87% bound to plasma proteins, primarily albumin. Protein binding is concentration-independent over the therapeutic range. |
| Volume of Distribution | The apparent volume of distribution (Vd/F) is approximately 0.3-0.5 L/kg. This low Vd indicates limited extravascular distribution and suggests that rofecoxib remains predominantly in the vascular compartment. |
| Bioavailability | Oral bioavailability is approximately 93% (range 80-100%), indicating excellent absorption with minimal first-pass metabolism. Administering with a high-fat meal does not significantly alter the extent of absorption but may delay peak concentration by 1-2 hours. |
| Onset of Action | For oral administration: Analgesic effects are measurable within 45 minutes, with peak effect at 2-4 hours. Onset of anti-inflammatory action may require several days of continuous dosing. |
| Duration of Action | Duration of analgesic effect is approximately 24 hours, supporting once-daily dosing. Anti-inflammatory effects persist with continued use. The mean duration of action for pain relief in osteoarthritis is 24 hours. |
| Molecular Weight | 313.35 |
12.5 to 25 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min; no adjustment needed for GFR ≥30 mL/min. |
| Liver impairment | Child-Pugh A (mild): no adjustment; Child-Pugh B (moderate): use 12.5 mg once daily; Child-Pugh C (severe): contraindicated. |
| Pediatric use | Not recommended; safety and efficacy not established in pediatric patients. |
| Geriatric use | Initiate at lowest recommended dose (12.5 mg once daily); monitor for renal function and GI bleeding. |
| 1st trimester | Avoid. Associated with increased risk of miscarriage and congenital malformations (e.g., cardiovascular). NSAIDs should be avoided in first trimester unless absolutely necessary. |
| 2nd trimester | Avoid. Risk of oligohydramnios, premature closure of ductus arteriosus. Use only if clearly needed and benefit outweighs risk; discontinue if ductal constriction or oligohydramnios occur. |
| 3rd trimester | Contraindicated. Causes premature closure of ductus arteriosus, oligohydramnios, and potentially necrotizing enterocolitis. Should not be used after 30 weeks gestation. |
Clinical note
Comprehensive clinical and safety monograph for VIOXX (VIOXX).
| Placental transfer | Crosses the placenta extensively; detectable in fetal plasma at maternal drug levels. |
| Breastfeeding | Excreted into breast milk in low concentrations; however, due to the long half-life and potential for adverse effects in infants (e.g., renal impairment, gastrointestinal bleeding), use is generally not recommended during breastfeeding. Consider alternative analgesics. |
■ FDA Black Box Warning
Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use and in patients with cardiovascular risk factors. VIOXX is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
Hypersensitivity to rofecoxib or any component of formulationHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsThird trimester of pregnancyActive peptic ulcer or gastrointestinal bleedingAdvanced renal disease (creatinine clearance <30 mL/min)Severe hepatic impairmentCerebrovascular bleeding or history of strokeConcurrent use with another NSAID or aspirin (including low-dose) due to increased GI risk
| Precautions | Increased risk of cardiovascular thrombotic events; gastrointestinal adverse events including bleeding, ulceration, and perforation; hypertension; fluid retention and edema; serious skin reactions including Stevens-Johnson syndrome; advanced renal disease; anaphylactoid reactions; asthma exacerbation; hepatic effects. |
| Food/Dietary |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | VIOXX (rofecoxib) is a COX-2 inhibitor NSAID. Avoid during third trimester due to risk of premature closure of ductus arteriosus and oligohydramnios. Use in first and second trimesters may be associated with increased risk of spontaneous abortion and cardiac defects; contraindicated after 30 weeks gestation. |
| Fetal Monitoring | Monitor amniotic fluid volume if prolonged use in second trimester; ductal flow assessment if used beyond 30 weeks; maternal renal function and blood pressure. |
| Fertility Effects | Reversible reduction in female fertility due to interference with ovulation via prostaglandin synthesis inhibition; effects resolve upon discontinuation. |
| No specific food restrictions; however, avoid alcohol as it may increase GI irritation. Grapefruit juice may increase rofecoxib levels, but clinical significance is uncertain. |
| Clinical Pearls | Avoid in patients with established cardiovascular disease or high CV risk due to increased risk of thrombotic events (MI, stroke). Use lowest effective dose for shortest duration. Contraindicated in patients with aspirin-sensitive asthma. Monitor for hypertension and edema. Efficacy comparable to NSAIDs but with fewer GI ulcers. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose or duration. · Report chest pain, shortness of breath, leg swelling, or sudden weakness immediately. · Avoid aspirin, other NSAIDs, or anticoagulants unless directed by your doctor. · May cause stomach upset; take with food or milk. · Do not use if pregnant, planning pregnancy, or breast-feeding. |