Nabumetone is a naphthylalkanone. Is is a non-selective prostaglandin G/H synthase (a.k.a. cyclooxygenase or COX) inhibitor that acts on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2). Prostaglandin G/H synthase catalyzes the conversion of arachidonic acid to prostaglandin G2 and prostaglandin G2 to prostaglandin H2. Prostaglandin H2 is the precursor to a number of prostaglandins involved in fever, pain, swelling, inflammation, and platelet aggregation. The parent compound is a prodrug that undergoes hepatic biotransformation to the active compound, 6-methoxy-2-naphthylacetic acid (6MNA). The analgesic, antipyretic and anti-inflammatory effects of NSAIDs occur as a result of decreased prostaglandin synthesis.

The parent compound is a prodrug, which undergoes hepatic biotransformation to the active component, 6-methoxy-2-naphthylacetic acid (6MNA), that is a potent inhibitor of prostaglandin synthesis, most likely through binding to the COX-2 and COX-1 receptors.

Nabumetone is indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. Carefully consider the potential benefits and risks of Nabumetone and other treatment options before deciding to use Nabumetone. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals

Osteoarthritis and Rheumatoid Arthritis: The recommended starting dose is 1,000 mg taken as a single dose with or without food. Some patients may obtain more symptomatic relief from 1,500 mg to 2,000 mg per day. Nabumetone can be given in either a single or twice-daily dose. Dosages greater than 2,000 mg per day have not been studied. The lowest effective dose should be used for chronic treatment. Patients weighing under 50 kg may be less likely to require dosages beyond 1,000 mg; therefore, after observing the response to initial therapy, the dose should be adjusted to meet individual patients’ requirements.

Nabumetone is contraindicated in patients with known hypersensitivity to nabumetone or its excipients. Nabumetone should not be given to patients who have experienced asthma, urticaria, or allergictype reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients. Nabumetone is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery

Gastrointestinal: Diarrhea (14%), dyspepsia (13%), abdominal pain (12%), constipation, flatulence, nausea, positive stool guaiac, dry mouth, gastritis, stomatitis, vomiting.

Central Nervous System: Dizziness, headache, fatigue, increased sweating, insomnia, nervousness, somnolence.

Dermatologic: Pruritus, rash

Special Senses: Tinnitus

Miscellaneous: Edema

Overdose Effects

Symptoms following acute NSAIDs overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression, and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.

Patients should be managed by symptomatic and supportive care following a NSAIDs overdose. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 g/kg in children), and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.

There have been overdoses of up to 25 grams of Nabumetone reported with no long-term sequelae following standard emergency treatment (i.e., activated charcoal, gastric lavage, IV H2-blockers, etc.).

Nabumetone cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids. The pharmacological activity of Nabumetone in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions

Use in Special Populations

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: As with any NSAIDs, caution should be exercised in treating the elderly (65 years and older).

Pregnancy & Lactation

Pregnancy Category C. Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, animal reproduction studies are not always predictive of human response. There are no adequate, well-controlled studies in pregnant women. Nabumetone should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether this drug is excreted in human milk, however 6MNA is excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Nabumetone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Labor and Delivery: In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of Nabumetone on labor and delivery in pregnant women are unknown.