indication

For the treatment of rheumatoid arthritis, osteoarthritis, dysmenorrhea, and mild to moderate pain, inflammation, and fever.

pharmacology

Mefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). It exhibits anti-inflammatory, analgesic, and antipyretic activities. Similar to other NSAIDs, mefenamic acid inhibits prostaglandin synthetase.

mechanism of action

Mefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced.

toxicity

Oral, rat LD₅₀: 740 mg/kg. Symptoms of overdose may include severe stomach pain, coffee ground-like vomit, dark stool, ringing in the ears, change in amount of urine, unusually fast or slow heartbeat, muscle weakness, slow or shallow breathing, confusion, severe headache or loss of consciousness.

biotransformation

Mefenamic acid undergoes metabolism by CYP2C9 to 3-hydroxymethyl mefenamic acid, and further oxidation to a 3-carboxymefenamic acid may occur. The activity of these metabolites has not been studied. Mefenamic acid is also glucuronidated directly.

absorption

Mefenamic acid is rapidly absorbed after oral administration.

half life

2 hours

route of elimination

The fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3-carboxymefenamic acid.3 The elimination half-life of mefenamic acid is approximately two hours. Mefenamic acid, its metabolites and conjugates are primarily excreted by the kidneys. Both renal and hepatic excretion are significant pathways of elimination.

drug interactions

Acenocoumarol: The NSAID, mefanamic acid, may increase the anticoagulant effect of acenocoumarol.

Alendronate: Increased risk of gastric toxicity

Anisindione: The NSAID, mefanamic acid, may increase the anticoagulant effect of anisindione.

Colesevelam: Bile acid sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Monitor for decreased serum concentrations/therapeutic effects of nonsteroidal anti-inflammatory agents (NSAID) if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.

Cyclosporine: Monitor for nephrotoxicity

Dicumarol: The NSAID, mefanamic acid, may increase the anticoagulant effect of dicumarol.

Lithium: The NSAID, mefenamic acid, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Methotrexate: The NSAID, mefenamic acid, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.

Tamoxifen: Mefenamic acid may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Mefenamic acid is initiated, discontinued or dose changed.

Tolbutamide: Mefanamic acid, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Mefanamic acid is initiated, discontinued or dose changed.

Torasemide: Mefanamic acid, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Mefanamic acid is initiated, discontinued or dose changed.

Trandolapril: The NSAID, Mefenamic acid, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Mefenamic acid is initiated, discontinued or dose changed.

Treprostinil: The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Mefenamic acid. Monitor for increased bleeding during concomitant thearpy.

Trimethoprim: The strong CYP2C9 inhibitor, Mefenamic acid, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Mefenamic acid is initiated, discontinued or dose changed.

Voriconazole: Mefanamic acid, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if mefanamic acid is initiated, discontinued or dose changed.

Warfarin: Mefenamic acid, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. The antiplatelet effect of mefenamic acid may also increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if mefenamic acid is initiated, discontinued or dose changed.