BRAND NAMES

Dolib (India); Flanax (Colombia); Rofetab (India); Sivoz (Colombia); Vioxx (Australia, New-Zealand, France, Germany, Colombia, Mexico, Peru, Hong-Kong, Philippines, Thailand, South-Africa, Israel)

DRUG CLASS

Rofecoxib is a nonsteroidal anti-inflammatory agent.

MECHANISM OF ACTION

Rofecoxib, a methylsulfonylphenyl-substituted furanone derivative, is a nonsteroidal anti-inflammatory agent (NSAIA). Rofecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) and is structurally and pharmacologically related to celecoxib (celebrex). Because the goal of selective inhibitors of COX-2 is to inhibit COX-2 but not COX-1, the drugs also have been referred to as COX-1-sparing NSAIAs. Rofecoxib differs structurally and, to some extent, pharmacologically from prototypical NSAIAs, which inhibit cyclooxygenase-1 (COX-1) and -2 (COX-2).

Although the overall structures of COX-1 and -2 are similar, an important difference between the 2 isoforms of cyclooxygenase is the presence of a much larger NSAIA binding site on COX-2 compared with the NSAIA binding site on COX-1. It has been postulated that this larger binding site gives access to a sidepocket that may be the binding site for many selective COX-2 inhibitors.

Rofecoxib is a selective inhibitor of the cyclooxygenase-2 (COX-2) isoform of prostaglandin endoperoxide synthase (prostaglandin G/H synthase, PGSH). It exhibits many of the pharmacologic actions of other NSAIAs, including anti-inflammatory, analgesic, and antipyretic activity via the inhibition of prostaglandin synthesis.

CONTRAINDICATIONS

Significant - ASA allergy, severe renal function impairment, predisposition to gastrointestinal hemorrhage, history of peptic ulcer, methotrexate*.

Possibly Significant - extrinsic asthma (allergic, childhood asthma), congestive heart failure, dehydration, edema, hepatic function impairment, hypertension, anticoagulants, lithium.

SPECIAL CONCERNS

Limited information is available on the acute toxicity of rofecoxib in humans.

There are no adequate or controlled studies to date using rofecoxib in pregnant women or during labor and delivery, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. Rofecoxib should not be used during the third trimester of pregnancy, since inhibitions of prostaglandin synthesis may have adverse effects on the fetal cardiovascular system (e.g., premature closure of the ductus arteriosus). The manufacturer maintains a registry to monitor pregnancy outcomes in women exposed to rofecoxib during pregnancy. Patients may be enrolled by calling 800-986-8999.

Additionally, because of the potential for serious adverse reactions to rofecoxib in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

SIDE EFFECTS

Less Frequent - hypertension, influenza-type disease, peripheral edema, sinusitis, upper respiratory infection, urinary tract infection, abdominal pain, asthenia/fatigue, back pain, bronchitis, diarrhea, dizziness, dyspepsia, headache, heartburn, nausea, abdominal tenderness, abscess, angina pectoris, asthma, atrial fibrillation, basal cell carcinoma, chest pain, conjunctivitis, bruising/contusion, cystitis, diaphragmatic hernia, esophagitis, fungal infection, infectious gastroenteritis, hematochezia (bloody stools), herpes zoster infection, irregular heartbeat, otitus media, palpitations, pneumonia, postoperative pain, premature ventricular contraction, syncope (fainting), tachycardia, tonsillitis, venous insufficiency, abdominal distension, acid reflux, allergic rhinitis, allergy, alopecia, anxiety, aphthous stomatitis, appetite change, arm pain, arthralgia, atopic dermatitis, blister of skin, blurred vision, bradycardia, breast mass, bursitis, chills, constipation, contact dermititis, cough, dental caries, dental pain, depression, digestive gas symptoms, dry mouth, dry throat, dysguesia, dyspnea, dysuria, epistaxis, fever, flatulence, fluid retention, flushing, gastritis, gastroenteritis, hemmoroids, herpes simplex, hypercholesterolemia, hypesthesia/paresthesia, injury/trauma, insomnia, joint swelling, laceration, laryngitis, menstrual disorder, decreased mental activity, migrane, muscle cramps, muscle weakness, muscular spasm, musculoskeletal pain, musculoskeletal stiffness, nail unit disorder, nasal congestion, nocturia, oral cavity disorders, osteoarthrosis, otic pain, pain, pelvic pain, pharyngitis, pruritus, pulmonary congestion, rash, sciatica, skin erythema, somnolence, tendonitis, tinnitus, urinary retention, urticaria, vaginitis, vertigo, vomiting, weight gain.

*Re: Methotrexate/Refecoxib Drug Interactions: Clinically important drug interactions may occur when rofecoxib is used concomitantly with methotrexate. Studies may indicate a decreased renal clearance of methotrexate in patients receiving methotrexate and refecoxib treatment concurrently. Thus, patients receiving rofecoxib and methotrexate should be monitored for possible methotrexate toxicity.

SOURCES

http://www.medscape.com
http://www.mdconsult.com; Mosby's Drug Consult

Edited by Strutsy on 03/18/02 04:19 PM (server time).