ROXIPRIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ROXIPRIN (ROXIPRIN).

How it works

Roxiprin is a combination analgesic containing rofecoxib (a COX-2 selective NSAID) and paracetamol (acetaminophen, a centrally acting analgesic/antipyretic). Rofecoxib inhibits prostaglandin synthesis by selectively blocking cyclooxygenase-2, reducing pain and inflammation. Paracetamol inhibits cyclooxygenase in the central nervous system and modulates descending serotonergic pathways, providing analgesia and antipyresis.

What the body does with it

Metabolism	Rofecoxib is extensively metabolized in the liver primarily via reduction by cytosolic enzymes, with minor involvement of CYP3A4. Paracetamol is primarily metabolized by sulfation and glucuronidation, with a minor fraction via CYP2E1 and CYP1A2 to a toxic metabolite (NAPQI).
Excretion	Renal (70% as unchanged drug, 20% as glucuronide conjugate); biliary/fecal (10%)
Half-life	2.5 hours (prolonged to 4-6 hours in hepatic impairment; no significant change in renal impairment)
Protein binding	98% (primarily to albumin, minor binding to alpha-1-acid glycoprotein)
Volume of Distribution	0.08 L/kg (low Vd indicating minimal tissue distribution, confined primarily to plasma water)
Bioavailability	Oral: 60-70% (due to first-pass metabolism; reduced to 40% with high-fat meal); Rectal: 75%; Topical: 5-10%
Onset of Action	Oral: 30-45 minutes; Intravenous: 5-10 minutes; Topical: 2-4 hours
Duration of Action	Oral: 4-6 hours (dose-dependent; extended-release formulations provide 12-hour coverage); Intravenous: 3-4 hours

Classification & Brands

Dosing & administration

500 mg orally every 6 to 8 hours as needed for pain or fever; maximum 2000 mg per day.

Dosage form	TABLET
Renal impairment	GFR 30-59 mL/min: 500 mg every 8 hours; GFR <30 mL/min: 500 mg every 12 hours; hemodialysis: avoid use.
Liver impairment	Child-Pugh class A: no adjustment; Child-Pugh class B: 500 mg every 12 hours; Child-Pugh class C: contraindicated.
Pediatric use	Children >2 years: 10-15 mg/kg/dose orally every 6-8 hours; maximum 60 mg/kg/day.
Geriatric use	Reduce initial dose to 250 mg every 8 hours; consider maximum 1500 mg/day due to increased risk of gastrointestinal bleeding and renal impairment.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ROXIPRIN (ROXIPRIN).

Breastfeeding	ROXIPRIN is excreted into human breast milk. Milk-to-plasma ratio (M/P) is approximately 0.8. Due to potential for serious adverse reactions in nursing infants (e.g., kernicterus, gastrointestinal bleeding), breastfeeding is not recommended during therapy and for 5 days after last dose.
Teratogenic Risk	ROXIPRIN (roxiprin) is contraindicated in pregnancy. First trimester: Risk of major congenital malformations (cardiac, neural tube defects) based on animal studies and limited human data. Second and third trimesters: Associated with fetal nephrotoxicity, oligohydramnios, premature closure of the ductus arteriosus, and persistent pulmonary hypertension. Use is advised against in all trimesters.

Warnings & precautions

■ FDA Black Box Warning

Rofecoxib component: Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. Risk is dose-dependent and increases with duration of use. Contraindicated in patients undergoing coronary artery bypass graft surgery.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of serious cardiovascular events (e.g., myocardial infarction, stroke). Coronary artery bypass graft surgery (perioperative). Severe hepatic impairment. Active peptic ulcer disease or gastrointestinal bleeding. History of hypersensitivity to rofecoxib, paracetamol, or NSAIDs. Third trimester of pregnancy. Concurrent use of other NSAIDs or paracetamol overdose risk.

Clinical Precautions

Precautions

Cardiovascular risk: use lowest effective dose for shortest duration. Gastrointestinal risk: increased risk of bleeding, ulceration, perforation. Hepatotoxicity: paracetamol component may cause severe liver injury if taken in high doses or with alcohol. Renal effects: monitor renal function, especially in patients with renal impairment, heart failure, or dehydration. Anaphylactoid reactions may occur. Avoid concurrent use with other NSAIDs or paracetamol-containing products.

Clinical Tips & Counseling

Drug interactions

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ROXIPRIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ROXIPRIN (ROXIPRIN).

How it works

What the body does with it

Metabolism	Rofecoxib is extensively metabolized in the liver primarily via reduction by cytosolic enzymes, with minor involvement of CYP3A4. Paracetamol is primarily metabolized by sulfation and glucuronidation, with a minor fraction via CYP2E1 and CYP1A2 to a toxic metabolite (NAPQI).
Excretion	Renal (70% as unchanged drug, 20% as glucuronide conjugate); biliary/fecal (10%)
Half-life	2.5 hours (prolonged to 4-6 hours in hepatic impairment; no significant change in renal impairment)
Protein binding	98% (primarily to albumin, minor binding to alpha-1-acid glycoprotein)
Volume of Distribution	0.08 L/kg (low Vd indicating minimal tissue distribution, confined primarily to plasma water)
Bioavailability	Oral: 60-70% (due to first-pass metabolism; reduced to 40% with high-fat meal); Rectal: 75%; Topical: 5-10%
Onset of Action	Oral: 30-45 minutes; Intravenous: 5-10 minutes; Topical: 2-4 hours
Duration of Action	Oral: 4-6 hours (dose-dependent; extended-release formulations provide 12-hour coverage); Intravenous: 3-4 hours

Classification & Brands

Dosing & administration

500 mg orally every 6 to 8 hours as needed for pain or fever; maximum 2000 mg per day.

Dosage form	TABLET
Renal impairment	GFR 30-59 mL/min: 500 mg every 8 hours; GFR <30 mL/min: 500 mg every 12 hours; hemodialysis: avoid use.
Liver impairment	Child-Pugh class A: no adjustment; Child-Pugh class B: 500 mg every 12 hours; Child-Pugh class C: contraindicated.
Pediatric use	Children >2 years: 10-15 mg/kg/dose orally every 6-8 hours; maximum 60 mg/kg/day.
Geriatric use	Reduce initial dose to 250 mg every 8 hours; consider maximum 1500 mg/day due to increased risk of gastrointestinal bleeding and renal impairment.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ROXIPRIN (ROXIPRIN).

Breastfeeding	ROXIPRIN is excreted into human breast milk. Milk-to-plasma ratio (M/P) is approximately 0.8. Due to potential for serious adverse reactions in nursing infants (e.g., kernicterus, gastrointestinal bleeding), breastfeeding is not recommended during therapy and for 5 days after last dose.
Teratogenic Risk	ROXIPRIN (roxiprin) is contraindicated in pregnancy. First trimester: Risk of major congenital malformations (cardiac, neural tube defects) based on animal studies and limited human data. Second and third trimesters: Associated with fetal nephrotoxicity, oligohydramnios, premature closure of the ductus arteriosus, and persistent pulmonary hypertension. Use is advised against in all trimesters.