VIOXX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VIOXX (VIOXX).

How it works

Selective cyclooxygenase-2 (COX-2) inhibitor; reduces prostaglandin synthesis involved in inflammation, pain, and fever.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VIOXX (VIOXX).

Breastfeeding	Excreted in human milk; M/P ratio 0.5. Due to potential adverse effects in nursing infants, use during breastfeeding is not recommended; alternative agents preferred.
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

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of allergic-type reactions to sulfonamides; aspirin-sensitive asthma; known hypersensitivity to rofecoxib; peri-operative pain in CABG surgery; advanced renal disease; pregnancy (third trimester).

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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VIOXX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VIOXX (VIOXX).

How it works

Selective cyclooxygenase-2 (COX-2) inhibitor; reduces prostaglandin synthesis involved in inflammation, pain, and fever.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VIOXX (VIOXX).

Breastfeeding	Excreted in human milk; M/P ratio 0.5. Due to potential adverse effects in nursing infants, use during breastfeeding is not recommended; alternative agents preferred.
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