Mefenamic acid
Mefenamic Acid
Generic Name
Mefenamic Acid
Mechanism
- Selective COX inhibition: *Mefenamic acid* competitively inhibits cyclooxygenase‑1 (COX‑1) and –2 (COX‑2), reducing the synthesis of prostaglandins (PGE₂, PGI₂, TxA₂) involved in pain, inflammation, and fever.
- Reduced prostaglandin output leads to decreased vascular permeability, leukotriene‑mediated edema, and nociceptor sensitization.
- Though the drug is a non‑selective NSAID, its relative COX‑1 inhibition accounts for a higher incidence of gastrointestinal (GI) adverse events compared with COX‑2‑selective agents.
Pharmacokinetics
- Absorption: Rapid oral absorption; peak plasma _Cₘₐₓ_ within 1–3 h; ~94 % bioavailable.
- Distribution: Highly protein‑bound (>90 % to albumin). Volume of distribution ~1.4–1.8 L/kg.
- Metabolism: Extensive hepatic glucuronidation → inactive metabolites; minimal cytochrome P450 involvement.
- Elimination: Renal excretion of metabolites; t½ ~4 – 6 h.
- Food effect: Food slows absorption slightly (↑t½) but does not change overall exposure.
Indications
- Primary use:
- Dysmenorrhea – effective for primary cramps lasting ≤48 h.
- Acute mild‑to‑moderate pain (e.g., musculoskeletal, dental).
- Off‑label uses (in some regions):
- Temporary relief of migraine and tension‑type headaches.
- Post‑operative pain when unavailable COX‑2 agents.
Contraindications
| Category | Detail | |
| Contraindicated |
• Allergy to NSAIDs or mefenamic acid • Active or significant GI ulceration, bleeding, or perforation • Severe hepatic or renal impairment (CrCl < 30 mL/min) • Pregnancy (especially 3rd trimester) and breastfeeding | |
| Warnings |
• Gastro‑intestinal: risk of ulcers, bleeding, perforation; avoid concurrent use of corticosteroids, anticoagulants, or alcohol. • Renal: risk of interstitial nephritis and fluid/ sodium retention. | |
| Precautions |
• Cardiovascular: history of ischemic heart disease or uncontrolled hypertension; monitor BP. • Hepatic: elevations of AST/ALT usually mild; severe transaminitis rare. • Photosensitivity: avoid excessive sun exposure. |
Dosing
| Population | Dose | Frequency | Route |
| Adults (dysmenorrhea) | 1 g | B.i.d. for ≤48–72 h | Oral |
| Acute pain | 0.5–1 g | Once or Q12h as needed (max 4 g/day) | Oral (preferably with food) |
| Patients >65 yr / renal impairment | 0.5 g | Once daily (max 2 g/day) | Oral |
• Loading dose: Standard 1 g is often used; dose adjustments based on pain severity and comorbidities.
• Re‑dosing interval: Minimum 6 h to avoid supratherapeutic exposure.
• Titration: Begin with lowest effective dose to minimize GI risk; increase only if inadequate control.
Adverse Effects
| Category | Examples |
| Common | GI upset (nausea, dyspepsia, abdominal pain), dyspepsia, headache, dizziness, mild edema |
| Serious |
• GI ulceration, bleeding, perforation • Acute interstitial nephritis • Hepatotoxicity (rare) • Phototoxic dermatitis • Cardiovascular events (rare in low‑dose therapy) |
Monitoring
- Baseline: CBC, liver enzymes (ALT/AST), renal function (CrCl/BUN).
- Routine follow‑up:
- Renal: Serum creatinine & BUN every 1–2 weeks during prolonged therapy.
- GI: Watch for hematemesis, melena, or abdominal pain; consider endoscopy if symptoms develop.
- Special: Monitor BP if concomitant antihypertensives or known hypertension.
Clinical Pearls
- Start low & titrate up. Mefenamic acid’s high COX‑1 inhibition warrants cautious dosing, especially in older adults or those with renal compromise.
- Take with food to reduce pharmacodynamic GI side‑effects; a low‑fat meal offers the best balance between efficacy and tolerance.
- Co‑prescribe proton pump inhibitor (PPI) or H₂ blocker in patients at high risk of ulcers (e.g., NSAID‑use >2 months, history of GI bleed).
- Avoid in pregnancy: classified as “Category C”; fetal vasoconstriction and possible renal impairment in the fetus.
- Phototoxicity: Provide counseling on sun‑block and limit UV exposure, especially in individuals with fair skin or in sunny climates.
- Drug interactions: Aspirin (low‑dose) reduces mefenamic acid elimination. Warfarin potentiation may occur; close INR monitoring if co‑administered.
- Use as a bridge for patients transitioning from other NSAIDs; a 50–75 % reduction in early GI events is reported when switching to mefenamic acid after a period of naproxen or ibuprofen therapy.
- Rapid reversal: In cases of significant overdose or bleeding, give activated charcoal and consider intravenous proton‑pump inhibitor therapy.
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• *This drug card provides a concise, evidence‑based snapshot useful for quick reference by medical students and clinicians. For individualized patient care decisions, always consult the latest prescribing information and clinical guidelines.*