Mefenamic acid exerts its therapeutic effects through its action on the cyclooxygenase (COX) enzymes. Its key mechanisms include:

1. Inhibition of Cyclooxygenase (COX) Enzymes:
   • Mefenamic acid inhibits both COX-1 and COX-2 enzymes, which are involved in the synthesis of prostaglandins and thromboxanes.
   • COX-1 is responsible for the production of prostaglandins that protect the gastric mucosa and regulate platelet function.
   • COX-2 is induced during inflammation and is responsible for the production of prostaglandins that mediate pain, inflammation, and fever.
2. Reduction of Prostaglandin Synthesis:
   • By inhibiting COX enzymes, mefenamic acid reduces the production of prostaglandins, leading to decreased inflammation, pain, and fever.
3. Antipyretic Effects:
   • Mefenamic acid reduces fever by inhibiting prostaglandin synthesis in the hypothalamus, which regulates body temperature.

Mefenamic acid is approved for a variety of clinical conditions, including:

1. Dysmenorrhea:
   • Management of primary dysmenorrhea (painful menstrual cramps).
2. Pain Relief:
   • Management of mild to moderate pain, such as headaches, dental pain, and musculoskeletal pain.
3. Inflammation:
   • Treatment of inflammatory conditions, such as rheumatoid arthritis and osteoarthritis.
4. Off-Label Uses:
   • Management of acute gout.

Adjunctive therapy for migraine headaches

The dosage of mefenamic acid varies depending on the indication, patient age, and formulation. The following dosing guidelines are based on the British National Formulary (BNF) and clinical pharmacology references:

1. Adults:
   • Oral: 500 mg three times daily, not exceeding 1500 mg daily.
   • Dysmenorrhea: 500 mg initially, followed by 250 mg every 6 hours as needed, not exceeding 1500 mg daily.
2. Children:
   • Oral: 25 mg/kg daily in divided doses, not exceeding 1500 mg daily.

Important Considerations:

• Mefenamic acid is available in oral capsules and tablets.
• Dose adjustments may be necessary for patients with hepatic or renal impairment.
• Mefenamic acid should be taken with food or milk to minimize gastrointestinal side effects.

Mefenamic acid is generally well-tolerated, but it is associated with a range of side effects, some of which can be serious. Common side effects include:

1. Gastrointestinal:
   • Nausea, vomiting, dyspepsia, and abdominal pain.
   • Gastric ulcers and gastrointestinal bleeding (rare but serious).
2. Cardiovascular:
   • Increased risk of myocardial infarction and stroke, particularly with long-term use or high doses.
3. Renal:
   • Acute kidney injury and interstitial nephritis (rare).
4. Other:
   • Headache, dizziness, and rash.

Serious Side Effects:

• Gastrointestinal Bleeding: Particularly in elderly patients or those with a history of peptic ulcer disease.
• Hypersensitivity Reactions: Stevens-Johnson syndrome (SJS) and anaphylaxis (rare).
• Hepatotoxicity: Elevated liver enzymes and, rarely, severe liver damage.

Mefenamic acid requires careful monitoring and adherence to specific precautions to ensure patient safety:

1. Gastrointestinal Risk:
   • Use with caution in patients with a history of peptic ulcer disease or gastrointestinal bleeding. Consider concomitant use of a proton pump inhibitor (PPI) for gastroprotection.
2. Cardiovascular Risk:
   • Use with caution in patients with a history of cardiovascular disease. Regular monitoring of cardiovascular health is recommended.
3. Renal Impairment:
   • Use with caution in patients with impaired kidney function. Avoid use in severe renal impairment (CrCl <30 mL/min).
4. Pregnancy and Lactation:
   • Mefenamic acid should be avoided during the third trimester of pregnancy due to the risk of premature closure of the ductus arteriosus. It is excreted in breast milk, so breastfeeding is generally not recommended.
5. Elderly Patients:
   • Lower doses may be required due to increased sensitivity to side effects, particularly gastrointestinal and renal.

Mefenamic acid has a significant potential for drug interactions due to its effects on prostaglandin synthesis and metabolism. Key interactions include:

1. Anticoagulants:
   • Mefenamic acid may enhance the anticoagulant effects of warfarin, increasing the risk of bleeding.
2. Other NSAIDs:
   • Concurrent use with other NSAIDs increases the risk of gastrointestinal side effects.
3. Antihypertensives:
   • Mefenamic acid may reduce the efficacy of antihypertensive medications, such as ACE inhibitors and beta-blockers.
4. Diuretics:
   • Mefenamic acid may reduce the diuretic and antihypertensive effects of diuretics.
5. Lithium:
   • Mefenamic acid may increase lithium levels, increasing the risk of toxicity.

Mefenamic acid is the generic name for this medication. It is marketed under various brand names, depending on the country and manufacturer. Some examples include:

• Ponstel (a well-known brand in the United States and other regions).
• Mefenamic Acid Accord.
• Mefenamic Acid Mylan.
• Mefenamic Acid Sandoz.