Note: This document contains side effect information about rofecoxib. Some dosage forms listed on this page may not apply to the brand name Vioxx.

Applies to rofecoxib: oral suspension, oral tablet.

Gastrointestinal

Gastrointestinal side effects have included diarrhea, dyspepsia, epigastric discomfort, heartburn, and nausea. These were the most frequently reported gastrointestinal adverse events occurring in greater than 2% of patients. Other reported adverse events occurring in less than 2% of patients studied have included acid reflux, aphthous stomatitis, constipation, dental caries, dental pain, digestive gas symptoms, dry mouth, duodenal disorder, dysgeusia, esophagitis, flatulence, gastric disorder, gastritis, gastroenteritis, hematochezia, hemorrhoids, infectious gastroenteritis, oral infection, oral lesion, oral ulcer, vomiting, colitis, colonic malignant neoplasm, cholecystitis, duodenal ulcer, gastrointestinal bleeding, intestinal obstruction, and pancreatitis.

Rofecoxib (the active ingredient contained in Vioxx) 50 mg/day has been associated with a higher incidence of gastrointestinal symptoms (abdominal pain, epigastric pain, heartburn, nausea and vomiting) than that seen with either 12.5 or 25 mg/day dosage.^[Ref]

Serious gastrointestinal toxicity such as bleeding, ulceration, and perforation of the stomach, small or large intestine, can occur at any time, with or without symptoms, in patients treated with nonsteroidal anti-inflammatories. The incidence of upper GI adverse events (perforations, ulcers, and bleed) was shown to be significantly lower (1.3% vs 1.8%) in patients with osteoarthritis receiving rofecoxib 12.5, 25, or 50 mg/day than in those receiving ibuprofen, diclofenac, or nabumetone. Risk factors for NSAID-induced GI bleeding include a prior history of peptic ulcer disease or gastrointestinal bleeding, treatment with oral corticosteroids, anticoagulation therapy, smoking, alcoholism, older age, poor general health status, and longer duration of NSAID therapy.

Rofecoxib (50 mg a day) has also been shown to have a lower incidence of serious upper gastrointestinal adverse events such as major bleeding, perforation, and obstruction compared to naproxen (1000 mg a day). The reduction in risk was about 50% in cumulative rates for rofecoxib (0.52%) compared to naproxen (1.22%) in the Vioxx Gastrointestinal Outcomes Research (VIGOR) study.^[Ref]

General

General side effects have included asthenia, fatigue, dizziness, influenza-like disease, lower extremity edema, sinusitis and upper respiratory infection. Other general side effects have included abscess, chest pain, chills, contusion, cyst, diaphragmatic hernia, fever, fluid retention, flushing, fungal infection, infection, laceration, pain, pelvic pain, peripheral edema, postoperative pain, syncope, trauma, upper extremity edema, viral syndrome, cerumen impaction, epistaxis, dry throat, otic pain, otitis, otitis media, pharyngitis, tinnitus, and tonsillitis.^[Ref]

Hepatic

In controlled clinical trials of rofecoxib (the active ingredient contained in Vioxx) the incidence of borderline elevation of liver tests was comparable to the incidence observed with ibuprofen and lower than that observed with diclofenac. In placebo controlled trials, approximately 0.5% of patients taking rofecoxib and 0.1% of patients taking placebo had noticeable elevations of ALT or AST.^[Ref]

Hepatic side effects have included borderline elevations of one or more liver tests that may occur in up to 15% of patients taking nonsteroidal anti-inflammatory drugs (NSAIDs). In addition, elevations of ALT or AST greater than three times normal have been reported in 1% of patients in clinical trials with NSAIDs. Patients with signs and/or symptoms of liver disease or with abnormal liver tests should be monitored carefully while on rofecoxib for evidence of worsening disease. If signs and symptoms consistent with liver disease develop, rofecoxib should be discontinued. Use of rofecoxib is not recommended in patients with severe hepatic insufficiency.^[Ref]

Cardiovascular

Cardiovascular side effects have included hypertension in greater than 2% of patients. Other cardiovascular side effects have included angina pectoris, atrial fibrillation, bradycardia, hematoma, irregular heart beat, palpitation, premature ventricular contraction, tachycardia, cerebrovascular accident, congestive heart failure, deep venous thrombosis, myocardial infarction, pulmonary edema, pulmonary embolism, transient ischemic attack, unstable angina and venous insufficiency.^[Ref]

The cumulative rate of serious cardiovascular thromboembolic adverse events (heart attacks, angina pectoris, and peripheral vascular events) was reported to occur in a higher percentage of patients receiving rofecoxib (1.8%) compared to patients receiving naproxen (0.6%) in the Vioxx Gastrointestinal Outcomes Research (VIGOR) study. The relationship of the cardiovascular findings to the use of rofecoxib is not known.

Patients being treated for rheumatoid arthritis with rofecoxib at a dose of 25 mg a day have been reported to have a higher incidence of hypertension compared to patients treated with naproxen at a dose of 1000 mg a day.

Lower extremity edema and hypertension have been reported to occur less often with the 12.5 and 25 mg/day dosage than with the 50 mg/day dosage.^[Ref]

Ocular

Ocular side effects have included blurred vision, ocular injection and conjunctivitis.^[Ref]

Metabolic

Metabolic side effects have included appetite change, hypercholesterolemia, and weight gain. Hyponatremia has been reported in less than 1% of patients.^[Ref]

Renal

Renal side effects have included a decrease in glomerular filtration rate. Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Acute renal failure after a single dose of rofecoxib (the active ingredient contained in Vioxx) has been reported. Interstitial nephritis has been diagnosed in a patient 3 weeks after the start of treatment with rofecoxib.^[Ref]

In two separate studies, a similar reduction in glomerular filtration rate to nonselective nonsteroidal anti-inflammatory drugs was observed.

Sudden reduction in urine output and rise in serum creatinine levels were observed in a 65-year-old woman, with a history of mild renal failure (Clcr = 57 mL/min), hyperuricemia, mitral valve regurgitation and heart failure, after receiving a single dose of rofecoxib 25 mg because of lower back pain. Over the course of her hospital stay, her renal laboratory parameters slowly returned to her baseline levels.

Acute interstitial nephritis has been reported in a 63-year-old man diagnosed with third-degree burns, on 70% of body surface area, that had been receiving for 3 weeks rofecoxib 25 mg daily for arthritis. Patient underwent one hemodialysis treatment. Creatinine and potassium levels returned to baseline levels a month later.^[Ref]

Immunologic

Immunologic, nonspecific, side effects have included allergic reactions and insect bite reactions in less than 2% of patients receiving rofecoxib (the active ingredient contained in Vioxx) ^[Ref]

Dermatologic

Dermatologic side effects have included alopecia, atopic dermatitis, basal cell carcinoma, contact dermatitis, herpes simplex, herpes zoster, nail unit disorder, perspiration, pruritus, rash, skin erythema, urticaria, and xerosis. Acute onset of neutrophilic dermatosis has been reported shortly after initiation of rofecoxib (the active ingredient contained in Vioxx) therapy. A severe case of psoriasis has been reported to have developed 5 days after the start of treatment with rofecoxib.

Pseudoporphyria has been reported in a 60-year-old woman 2 weeks after the start of rofecoxib treatment for pain control. The skin lesions cleared within 1 month after discontinuation of therapy.^[Ref]

Cases of neutrophilic dermatosis have been reported to occur within one to two weeks of initiation of rofecoxib treatment for joint pains. Patients presented with multiple subcutaneous nodules over both legs, anterior and posterior areas, and areas of ulceration. The patient's leg lesions disappeared after discontinuation of rofecoxib.

A 46-year-old woman who had previously developed psoriasis after exposure to a nonselective NSAID developed a severe case of psoriasis 5 days after she started taking rofecoxib for neck strain. It took several months for symptoms to abate.^[Ref]

Nervous system

Nervous system side effects have included headache, hypesthesia, insomnia, median nerve neuropathy, migraine, muscular spasm, paresthesia, sciatica, somnolence, and vertigo. In the postmarketing phase of rofecoxib (the active ingredient contained in Vioxx) aseptic meningitis has been reported to the Spontaneous Reporting System of the FDA.^[Ref]

Psychiatric

Psychiatric side effects have included anxiety, depression, and decreased mental acuity.^[Ref]

Respiratory

Respiratory side effects have included bronchitis, asthma, cough, dyspnea, pneumonia, pulmonary congestion, laryngitis, pharyngitis, allergic rhinitis, and nasal congestion.^[Ref]

Musculoskeletal

Musculoskeletal side effects have included back pain, arm pain, arthralgia, bursitis, cartilage trauma, joint swelling, muscle cramps, muscle weakness, musculoskeletal pain, musculoskeletal stiffness, myalgia, osteoarthritis, tendonitis, traumatic arthropathy, and wrist fracture.^[Ref]

Genitourinary

Breast malignant neoplasm, prostate malignant neoplasm and urolithiasis have been reported in less than 0.1% of patients.^[Ref]

Genitourinary side effects have included urinary tract infections, cystitis, dysuria, menopausal symptoms, menstrual disorder, nocturia, urinary retention, vaginitis, breast mass, and urolithiasis.^[Ref]

Hematologic

Hematologic side effects have included reports of lymphoma in less than 0.1% of patients.^[Ref]