Active ingredient: Mefenamic Acid - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase Inhibitors

Dosage Forms

• Bolus
• Capsule
• Capsule (enteric-coated)
• Drops
• Liquid
• Lotion
• Powder
• Powder for solution
• Shampoo
• Soap bar
• Solution
• Stick
• Syrup
• Tablet
• Tablet (extended-release)

Brands / Synonyms

Acide Mefenamique; Bafameritin-M; Bafhameritin-M; Bonabol; Coslan; HL 1; In-M; Lysalgo; Mefacit; Mefanamic Acid; Mefenacid; Mefenaminsaeure; Mephenamic Acid; Mephenaminic Acid; Methenamic Acid; Namphen; Parkemed; Ponalar; Ponstan; Ponstan Forte; Ponstel; Ponstil; Ponstyl; Pontal; Tamany Bonsan; Tanston; Vialidon

Indications

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.

Absorption

Mefenamic acid is rapidly absorbed after oral administration.

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.

Biotrnasformation / Drug Metabolism

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.

Contraindications

Ponstel is contraindicated in patients with known hypersensitivity to mefenamic acid. Ponstel should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.

Ponstel is contraindicated in patients with active ulceration or chronic inflammation of either the upper or lower gastrointestinal tract.

Ponstel should not be used in patients with preexisting renal disease.

Drug Interactions

Aspirin: As with other NSAIDs, concomitant administration of Ponstel and aspirin is not generally recommended because of the potential of increased adverse effects.

Methotrexate: NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.

ACE inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors.

Furosemide: Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy of Ponstel with furosemide, the patient should be observed closely for signs of renal failure, as well as to assure diuretic efficacy.

Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.

Warfarin: The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.

Antacids: In a single dose study (n=6), ingestion of an antacid containing 1.7-gram of magnesium hydroxide with 500-mg of mefenamic acid increased the Cmax and AUC of mefenamic acid by 125% and 36%, respectively.¹

A number of compounds are inhibitors of CYP2C9 including fluconazole, lovastatin and trimethoprim. Drug interaction studies of mefenamic acid and these compounds have not been conducted. The possibility of altered safety and efficacy should be considered when Ponstel is used concomitantly with these drugs.