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. |
| Molecular Weight | 241.29 |
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 | Avoid due to potential teratogenic effects (risk of cardiac malformations and gastroschisis) and alternative analgesics preferred. |
| 2nd trimester | Avoid; may cause oligohydramnios, premature closure of ductus arteriosus, and renal impairment. |
| 3rd trimester | Contraindicated; risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment. |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| Placental transfer | Mefenamic acid crosses the placenta readily. Detectable levels are found in fetal circulation and amniotic fluid. |
| Breastfeeding | Mefenamic acid is excreted into breast milk in small amounts. Due to potential adverse effects on the infant's cardiovascular and renal systems, it is generally not recommended during breastfeeding. Alternative analgesics such as acetaminophen or ibuprofen are preferred. |
■ 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 |
Active peptic ulcer diseaseHistory of gastrointestinal bleeding or perforationSevere heart failure (NYHA class III-IV)Hypersensitivity to mefenamic acid or any NSAIDHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsTreatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgeryThird trimester of pregnancy
| Precautions | Cardiovascular risk, gastrointestinal adverse events (bleeding, ulceration, perforation), hypertension, heart failure, renal toxicity, hepatic impairment, anaphylactoid reactions, hematologic toxicity, exacerbation of asthma, photosensitivity. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Food/Dietary | Taking with food or milk decreases gastric irritation. Avoid high-fat meals as they may delay absorption. Do not consume alcohol as it increases risk of gastrointestinal bleeding. No other significant food interactions. |
| Clinical Pearls | Mefenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) used for mild to moderate pain, including dysmenorrhea. Use at lowest effective dose for shortest duration; avoid in patients with known coronary artery disease, cerebrovascular disease, or history of gastrointestinal bleeding. Monitor for signs of GI ulceration, bleeding, and renal impairment. Mefenamic acid may cause hemolytic anemia in prolonged use; check complete blood count periodically. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Avoid alcohol and aspirin while taking mefenamic acid to reduce risk of stomach bleeding. · Do not take more than the prescribed dose or for longer than directed. · Report any signs of gastrointestinal bleeding (e.g., black or bloody stools, coffee-ground emesis) immediately. · Seek medical attention if you experience chest pain, weakness, slurred speech, or severe abdominal pain. · Use a reliable method of birth control if you are of childbearing potential; mefenamic acid may cause fetal harm. |