Nonsteroidal Anti-inflammatory Drug (NSAID), COX-2 Selective

Relief of the signs and symptoms of osteoarthritis; management of acute pain in adults; treatment of primary dysmenorrhea

C (D after 34 weeks gestation or close to delivery)

In late pregnancy may cause premature closure of the ductus arteriosus. In animal studies, rofecoxib has been found to be excreted in milk. It is not known whether rofecoxib is excreted in human milk. Because many drugs are excreted in milk, and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Hypersensitivity to rofecoxib or any component, aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs)

Gastrointestinal irritation, ulceration, bleeding, and perforation may occur with NSAIDs (it is unclear whether rofecoxib is associated with rates of these events which are similar to nonselective NSAIDs). Use with caution in patients with a history of GI disease (bleeding or ulcers), decreased renal function, hepatic disease, congestive heart failure, hypertension, or asthma. Anaphylactoid reactions may occur, even with no prior exposure to rofecoxib.

2% to 10%:

Cardiovascular: Peripheral edema (3.7%), hypertension (3.5%)

Central nervous system: Headache (4.7%), dizziness (3%), weakness (2.2%)

Gastrointestinal: Diarrhea (6.5%), nausea (5.2%), heartburn (4.2%), epigastric discomfort (3.8%), dyspepsia (3.5%), abdominal pain (3.4%)

Genitourinary: Urinary tract infection (2.8%)

Neuromuscular & skeletal: Back pain (2.5%)

Respiratory: Upper respiratory infection (8.5%), bronchitis (2.0%), sinusitis (2.7%)

Miscellaneous: Flu-like syndrome (2.9%)

0.1% to 2%:

Cardiovascular: Chest pain, upper extremity edema, atrial fibrillation, bradycardia, arrhythmia, palpitation, tachycardia, venous insufficiency, fluid retention

Central nervous system: Anxiety, depression, decreased mental acuity, hypesthesia, insomnia, neuropathy, migraine, paresthesia, somnolence, vertigo, fever, pain

Dermatologic: Alopecia, atopic dermatitis, basal cell carcinoma, contact dermatitis, pruritus, rash, erythema, urticaria, dry skin

Endocrine & metabolic: Weight gain, hypercholesteremia

Gastrointestinal: Reflux, abdominal distension, abdominal tenderness, constipation, dry mouth, esophagitis, flatulence, gastritis, gastroenteritis, hematochezia, hemorrhoids, oral ulceration, dental caries, aphthous stomatitis

Genitourinary: Breast mass, cystitis, dysuria, menopausal disorder, nocturia, urinary retention, vaginitis, pelvic pain

Hematologic: Hematoma

Neuromuscular & skeletal: Muscle spasm, sciatica, arthralgia, bursitis, cartilage trauma, joint swelling, muscle cramps, muscle weakness, myalgia, tendonitis, traumatic arthropathy, fracture (wrist)

Ocular: Blurred vision, conjunctivitis

Otic: Otic pain, otitis media, tinnitus

Respiratory: Asthma, cough, dyspnea, pneumonia, respiratory infection, pulmonary congestion, rhinitis, epistaxis, laryngitis, dry throat, pharyngitis, tonsillitis, diaphragmatic hernia

Miscellaneous: Allergy, fungal infection, insect bite reaction, syncope, viral syndrome, herpes simplex, herpes zoster, increased sweating

<0.1% (Limited to severe): Congestive heart failure, cerebrovascular accident, deep venous thrombosis, myocardial infarction, pulmonary embolism, unstable angina, transient ischemic attack, colitis, colonic neoplasm, cholecystitis, duodenal ulcer, duodenal perforation, gastrointestinal bleeding, gastric perforation, intestinal obstruction, pancreatitis, lymphoma, breast cancer, prostatic cancer, urolithiasis, anaphylactoid reaction, angioedema, aseptic meningitis, hallucinations, acute renal failure, interstitial nephritis

Symptoms may include epigastric pain, drowsiness, lethargy, nausea, and vomiting. Gastrointestinal bleeding may occur. Rare manifestations include hypertension, respiratory depression, coma, and acute renal failure. Treatment is symptomatic and supportive. Hemodialysis does not remove rofecoxib.

May be a mild inducer of cytochrome P-450 isoenzyme 3A4 (CYP3A4)

Increased effect: Cimetidine increases AUC of rofecoxib by 23%. Rofecoxib may increase plasma concentrations of methotrexate and lithium. Rofecoxib may be used with low-dose aspirin, however rates of gastrointestinal bleeding may be increased with coadministration. Rofecoxib may increase the INR in patients receiving warfarin and may increase the risk of bleeding complications.

Decreased effects: Efficacy of thiazide diuretics, loop diuretics (furosemide) or ACE-inhibitors may be diminished by rofecoxib. Rifampin reduces the serum concentration of rofecoxib by approximately 50%. Antacids may reduce rofecoxib absorption.

Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase-2 (COX-2), which results in decreased formation of prostaglandin precursors. Rofecoxib does not inhibit cyclooxygenase-1 (COX-1) at therapeutic concentrations.

Onset: 45 minutes

Duration: Up to >24 hours

Distribution: V_dss (apparent): 86-91 L

Protein binding: 87%

Metabolism: Hepatic (99%), minor metabolism by cytochrome P-450 isoenzyme 3A4 (CYP3A4)

Bioavailability: Absolute bioavailability has not been determined

Half-life: 17 hours

Time to peak: 2-3 hours

Elimination: In urine, as metabolites (<1% unchanged drug)

Adult: Oral:

Acute pain and management of dysmenorrhea: 50 mg once daily as needed (use for longer than 5 days has not been studied)

Dosing comment in renal impairment: Use in advanced renal disease is not recommended

Dosing adjustment in hepatic impairment: No specific dosage adjustment is recommended (AUC may be increased by 69%)

Elderly: No specific adjustment is recommended. However, the AUC in elderly patients may be increased by 34% as compared to younger subjects. Use the lowest recommended dose.

Time to peak concentrations are delayed when taken with a high-fat meal; however, peak concentration and AUC are unchanged. Rofecoxib may be taken without regard to meals.

No information available to require special precautions

In models of postoperative dental pain, rofecoxib was effective against dental pain rated as moderate to severe. The analgesic efficacy of a single 50 mg dose of rofecoxib was apparently similar to 400 mg of ibuprofen or 550 mg of naproxen sodium. The onset of analgesia for postoperative dental pain with a single 50 mg dose of rofecoxib was 45 minutes.

Do not take more than recommended dose. May be taken with food to reduce GI upset. Do not take with antacids. Avoid alcohol, aspirin, and OTC medication unless approved by prescriber. You may experience dizziness, confusion, or blurred vision (avoid driving or engaging in tasks requiring alertness until response to drug is known); anorexia, nausea, vomiting, taste disturbance, gastric distress (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). GI bleeding, ulceration, or perforation can occur with or without pain; it is unclear whether rofecoxib has rates of these events which are similar to nonselective NSAIDs. Stop taking medication and report immediately stomach pain or cramping, unusual bleeding or bruising, or blood in vomitus, stool, or urine. Report persistent insomnia; skin rash; unusual fatigue or easy bruising or bleeding; muscle pain, tremors, or weakness; sudden weight gain; changes in hearing (ringing in ears); changes in vision; changes in urination pattern; or respiratory difficulty. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Suspension, oral: 12.5 mg/5 mL, 25 mg/5 mL

Tablets: 12.5 mg, 25 mg

Ehrich EW, Dallob A, De Lepeleire I, et al, "Characterization of Rofecoxib as a Cyclooxygenase-2 Isoform Inhibitor and Demonstration of Analgesia in the Dental Pain Model," Clin Pharmacol Ther, 1999, 65(3):336-47.

Hawkey CJ, "COX-2 Inhibitors," Lancet, 1999, 353(9149):307-14.