Mefenamic acid is a nonsteroidal antiinflammatory drug (NSAID) used largely for acute treatment of pain. Mefanamic acid has been linked to rare instances of clinically apparent, acute liver injury.
Mefenamic (mef" e nam' ik) acid belongs to the anthranilic acid derivative class of NSAIDs (fenamates). Like other NSAIDs, mefenamic acid is a cyclo-oxygenase (Cox-1 and -2) inhibitor and blocks the production of intracellular prostaglandins that are important in pain and inflammatory pathways. Mefenamic acid has analgesic as well as antipyretic and antiinflammatory activities, but is used largely for treatment of pain. Mefenamic acid was approved in the United States in 1967, but is not a commonly used agent. Mefenamic acid is indicated for the treatment of mild-to-moderate acute pain or dysmenorrhea. It is available by prescription only in capsules of 250 and 500 mg in generic forms and under the brand name Ponstel. The recommended dose is 250 to 500 mg 3 to 4 times daily for periods of less than 7 days. Like most NSAIDs, mefenamic acid is generally well tolerated, but side effects can include headache, dizziness, somnolence, nausea, diarrhea, abdominal discomfort, heartburn, peripheral edema and hypersensitivity reactions.
Prospective studies show that less than 5% of patients taking mefenamic acid experience transient serum aminotransferase elevations. These may resolve even with drug continuation. Marked aminotransferase elevations (>3 fold elevated) occur in <1% of patients. There have been very rare cases of mefenamic acid induced liver injury published, and mefenamic acid is not mentioned as an etiologic agent in large case series on drug induced liver injury or acute liver failure. In one case report, the latency to onset of symptoms was short and associated with Stevens-Johnson syndrome and cholestatic liver injury. The paucity of published cases makes it impossible to characterize a typical clinical pattern of liver injury.
Mechanism of Injury
The mechanism of mefenamic acid hepatotoxicity is not known, but is likely to be idiosyncratic hypersensitivity. The absence of reports of liver injury from mefenamic acid may be due, in part, to the infrequency of its use and limited duration of treatment.
Outcome and Management
The asymptomatic elevations in serum aminotransferase levels are usually self-limited and resolve even with continuing mefenamic acid. Severe cases of mefenamic acid hepatotoxicity, but not chronic hepatitis, have been described. Cross reactivity to hepatic injury among various classes of NSAIDs has not been well characterized; however, after clinically apparent injury attributable to mefenamic acid, it would be prudent to avoid other anthranilic acid derivatives (fenamates generally not available in the United States, such as tolfenamic acid and flufenamic acid), and patients who are switched to other NSAIDs should be monitored carefully.
REPRESENTATIVE TRADE NAMES
Mefenamic Acid – Ponstel®
Nonsteroidal Antiinflammatory Drugs
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 11 February 2014
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Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. PubMed Citation (Among 300 cases of drug induced liver disease in the US collected from 2004 to 2008, NSAIDs were implicated as a sole agent in 8 cases [4 diclofenac, 2 celecoxib, 1 meloxicam and 1 oxaprozin] and as one of several agents in 3 cases [1 diclofenac, 1 celecoxib, 1 ibuprofen]; none for mefenamic acid).
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