Nabumetone is a long-acting non-steroidal anti-inflammatory drug (NSAID) that is available by prescription only and is used in therapy of chronic arthritis. Nabumetone has been linked to rare instances of clinically apparent, idiosyncratic drug-induced liver disease.
Nabumetone (nab ue' me tone) a naphthyl alkanone and orally available anti-inflammatory agent. Like other NSAIDs, nabumetone is a potent cyclo-oxygenase (Cox-1 and -2) inhibitor which blocks the formation of prostaglandins that are important mediators in pain and inflammatory pathways. Nabumetone is a pro-drug and exerts anti-cyclo-oxygenase activity only after absorption and activation in the liver. Like other NSAIDs, it has analgesic, anti-pyretic and anti-inflammatory activities. Nabumetone was approved in the United States in 1991 and its current indications are for treatment of chronic arthritis due to osteoarthritis or rheumatoid arthritis. Nabumetone is available by prescription only, and currently more than 4 million prescriptions are filled yearly. Generic formulations are available of 500 and 750 mg; specific commercially available names include Relafen (500 mg). The usual dose in adults is 1000 mg once daily, increasing to as much as 2000 mg daily based upon response and tolerance. As with other NSAIDs, nabumetone is generally well tolerated, but side effects can included headache, dizziness, somnolence, dyspepsia, nausea, abdominal discomfort, heartburn, peripheral edema and hypersensitivity reactions.
Prospective studies show that 1% to 5% of patients taking nabumetone experience at least transient serum aminotransferase elevations. These may resolve even with drug continuation. Marked aminotransferase elevations (>3 times ULN) occur in 0.5% of patients, a rate similar to that in placebo-treated controls. Clinically apparent liver injury with jaundice from nabumetone is rare and in large clinical trials, no instances of acute liver injury with jaundice were reported. Since its approval and release, nabumetone has been reported to cause rare instances of serious hepatic adverse events (~1.3 per million prescriptions) but there have been no cases of clinically apparent liver injury due to nabumetone published in the literature. Furthermore, nabumetone is not mentioned as a cause in large case series on drug-induced liver injury or acute liver failure. Thus, the latency, clinical features and outcome of nabumetone induced liver injury have not been described and clinically apparent hepatotoxicity due to nabumetone must be very rare.
Mechanism of Injury
The mechanism by which nabumetone causes hepatotoxicity is not known. Nabumetone is undergoes rapid biotransformation in the liver to methoxy-2-naphthylacetic acid the principal active metabolite.
Outcome and Management
The minor aminotransferase elevations
that occur in a small proportion of patients during chronic therapy with
nabumetone are usually subclinical and not progressive. The clinically apparent
liver injury from nabumetone has not been characterized, but most NSAID-related hepatotoxicity is self-limited and mild-to-moderate in severity. The cross-reactivity
in liver injury between various NSAIDs has not been well defined, but can occur. For these reasons, switching to another NSAID after clinically apparent liver injury from nabumetone should be done with caution.
REPRESENTATIVE TRADE NAMES
Relafen®, Various Generic
Anti-Inflammatory Agents, Non-Steroidal
FDA product labeling at DailyMed, National Library of Medicine, NIH
Relafen® (nabumetone) Product Labeling, GlaxoSmithKline.
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References Last Updated: 29 January 2014
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