MEFENAMIC ACID
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Reversible inhibition of cyclooxygenase (COX-1 and COX-2) leading to decreased prostaglandin synthesis; exhibits both central and peripheral analgesic effects.
| Metabolism | Hepatic metabolism via CYP2C9; primary metabolites include 3-hydroxymethyl mefenamic acid and 3-carboxyl mefenamic acid. |
| Excretion | Primarily renal (52% as glucuronide metabolites, <6% unchanged) and fecal (20-30% via biliary elimination). |
| Half-life | Terminal half-life is 2-4 hours; prolonged in hepatic impairment and overdose. |
| Protein binding | >90% bound to albumin. |
| Volume of Distribution | 0.9-1.2 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 100% (essentially complete absorption). |
| Onset of Action | Oral: 30-60 minutes; clinical effect for dysmenorrhea within 2-4 hours. |
| Duration of Action | 4-6 hours; clinical effect for dysmenorrhea may last up to 8 hours due to sustained uterine relaxation. |
500 mg orally as an initial dose, followed by 250 mg every 6 hours as needed, not to exceed 1 week.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-60 mL/min: reduce dose by 50% or extend interval; GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: contraindicated. |
| Pediatric use | Children ≥14 years: same as adult dosing; children <14 years: not recommended. |
| Geriatric use | Start at lowest effective dose; reduced renal function common; maximum 500 mg/day; avoid in patients with renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| Breastfeeding | Mefenamic acid is excreted into breast milk in small amounts; M/P ratio is approximately 0.02-0.1. Due to potential adverse effects on infant renal function and platelet aggregation, caution is advised. Use lowest effective dose for shortest duration. |
| Teratogenic Risk | First trimester: NSAIDs are associated with increased risk of miscarriage and cardiac defects. Second trimester: Avoid due to risk of oligohydramnios and fetal renal dysfunction. Third trimester: Contraindicated due to risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment. |
■ FDA Black Box Warning
NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular risk factors may be at greater risk. Mefenamic acid is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | Dyspepsia |
| Serious Effects |
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; perioperative pain in the setting of CABG surgery; active gastrointestinal bleeding; history of peptic ulcer disease or gastrointestinal perforation; advanced renal disease; hypersensitivity to mefenamic acid or any component of the formulation; concomitant use with other NSAIDs or aspirin.
| Precautions | Cardiovascular risk, gastrointestinal adverse events (bleeding, ulceration, perforation), hypertension, heart failure, renal toxicity, hepatic impairment, anaphylactoid reactions, hematologic toxicity, exacerbation of asthma, photosensitivity. |
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| Fetal Monitoring | Monitor fetal ultrasound for oligohydramnios (if used beyond 48 hours after 20 weeks gestation) and ductus arteriosus patency if used after 30 weeks. Monitor maternal blood pressure, renal function, and signs of gastrointestinal bleeding. |
| Fertility Effects | Reversible inhibition of ovulation due to suppression of prostaglandin synthesis. May delay conception. Effects resolve upon discontinuation. |