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# Mefenamic Acid
## Overview
Mefenamic acid is an anthranilic acid derivative nonsteroidal anti-inflammatory drug (NSAID). It exerts analgesic, anti-inflammatory, and antipyretic effects primarily through non-selective inhibition of cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis.
## Primary Indications
* Treatment of mild to moderate pain.
* Primary dysmenorrhea.
* *Note:* Use is generally limited to short-term therapy (not exceeding 7 days).
## Adult Dosing
* **Initial Dose:** 500 mg orally as a loading dose.
* **Maintenance:** 250 mg orally every 6 hours as needed.
* **Maximum Daily Dose:** Do not exceed 1,500 mg/day.
## Pediatric Dosing
* **Children ≥14 years:** Use adult dosing regimen.
* **Children <14 years:** Safety and efficacy have not been established. Use is generally not recommended.
## Dose Adjustments
* **Renal Impairment:** Avoid in severe renal impairment (CrCl <30 mL/min). Use with caution and monitor closely in mild to moderate impairment.
* **Hepatic Impairment:** Use with caution; monitor for signs of hepatic toxicity.
* **Geriatric:** Use the lowest effective dose for the shortest duration, as older patients have an increased risk of gastrointestinal (GI) and cardiovascular (CV) adverse effects.
## Contraindications
* Known hypersensitivity to mefenamic acid or other NSAIDs (including aspirin-induced asthma/urticaria).
* History of GI bleeding or perforation related to previous NSAID therapy.
* Active peptic ulcer disease or inflammatory bowel disease.
* **Perioperative setting:** Specifically contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
* Severe heart failure or severe renal impairment.
## Adverse Effects
* **Gastrointestinal:** Nausea, vomiting, diarrhea (may be severe), abdominal pain, dyspepsia, peptic ulcer, GI bleeding.
* **Renal:** Fluid retention, edema, acute renal failure, interstitial nephritis.
* **Cardiovascular:** Hypertension, increased risk of myocardial infarction and stroke (class effect).
* **Hematologic:** Anemia, rare cases of agranulocytosis or thrombocytopenia.
* **Central Nervous System:** Dizziness, headache, nervousness.
## Key Drug Interactions
* **Anticoagulants (e.g., Warfarin):** Increased risk of bleeding due to anti-platelet effects and gastric mucosal injury.
* **Antiplatelet Agents/SSRIs:** Increased risk of GI bleeding.
* **ACE Inhibitors/ARBs/Diuretics:** May diminish the antihypertensive effect; increased risk of nephrotoxicity.
* **Lithium:** May increase serum lithium levels, potentially leading to toxicity.
* **Methotrexate:** May increase methotrexate levels and toxicity.
## Monitoring
* **Gastrointestinal:** Monitor for signs of occult blood loss, melena, or dyspepsia.
* **Renal Function:** Periodic assessment of serum creatinine and electrolytes, especially in elderly or patients on diuretics.
* **Blood Pressure:** Regular monitoring, particularly in patients with hypertension.
* **CBC:** Monitor for unexplained bruising or prolonged bleeding if used for extended periods.
## Clinical Pearls
* **Diarrhea:** Mefenamic acid is uniquely associated with a higher incidence of diarrhea compared to other NSAIDs; discontinue immediately if severe diarrhea occurs.
* **Take with food:** Administration with food or milk may reduce GI irritation.
* **Avoid in Pregnancy:** Avoid use in late pregnancy (third trimester) due to the risk of premature closure of the ductus arteriosus.
* **CV Risk:** All NSAIDs pose an increased risk of serious cardiovascular thrombotic events; this risk is independent of prior cardiovascular history but may increase with duration of use.
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**Educational Disclaimer:** This information is for educational purposes only and does not constitute medical advice. Always verify current prescribing information, contraindications, and drug interactions against the official product monograph or a reliable clinical database (e.g., Lexicomp, UpToDate) before prescribing or administering medication.
