Can mefenamic acid (Nonsteroidal Anti-Inflammatory Drug (NSAID)) be used to treat a patient with migraine symptoms, considering their medical history and potential risk of gastrointestinal issues, bleeding disorders, or impaired renal function?

Can Mefenamic Acid Be Used for Migraine?

Yes, mefenamic acid can be used for migraine treatment, but it is not a first-line option and should only be considered when preferred NSAIDs have failed or are contraindicated. 1

Evidence for Mefenamic Acid in Migraine

Efficacy Data

• Limited evidence exists showing modest benefit from mefenamic acid in single placebo-controlled trials for migraine prevention, though the data are far less robust than for other NSAIDs like naproxen or ibuprofen 1
• Controlled studies demonstrate that mefenamic acid was significantly more effective than placebo for acute migraine attacks and at least as effective as reference drugs 2
• The evidence base is substantially weaker compared to first-line NSAIDs (ibuprofen, naproxen sodium, diclofenac potassium, and aspirin), which have consistent support across multiple high-quality trials 3, 4

Recommended First-Line Alternatives

• For mild to moderate migraine: Acetaminophen and NSAIDs (specifically ibuprofen, naproxen sodium, diclofenac potassium, or aspirin) are first-line therapy 1
• For moderate to severe migraine: Triptans combined with NSAIDs are first-line, with antiemetics added as needed 1, 5
• Naproxen has the strongest evidence among NSAIDs, with a meta-analysis of five placebo-controlled trials showing modest but consistent efficacy 1

Critical Safety Considerations Before Prescribing

Gastrointestinal Risks (Most Common Concern)

• GI symptoms occur in 3-45% of NSAID users, including nausea, vomiting, gastritis, and GI bleeding 1
• Serious GI bleeding risk: Approximately 1% at 3-6 months and 2-4% at one year of continuous use 6
• Contraindications: History of peptic ulcer disease or prior NSAID-associated GI bleeding 1, 6
• High-risk patients: Age ≥60 years, history of peptic ulcer, significant alcohol use (≥2 drinks/day), concomitant use of anticoagulants, aspirin, SSRIs, or corticosteroids 1, 6

Cardiovascular Risks

• All NSAIDs increase risk of MI and stroke, which can be fatal, with risk appearing as early as the first weeks of treatment 6
• Absolute contraindication: Post-CABG surgery patients 6
• Avoid in: Patients with known cardiovascular disease, recent MI, congestive heart failure, or uncontrolled hypertension 1, 6
• Mean blood pressure increase of 5 mm Hg with NSAID use 1

Renal Impairment

• High-risk patients: Age ≥60 years, compromised fluid status, concomitant nephrotoxic drugs (including ACE inhibitors, beta blockers), or baseline renal disease 1
• Discontinue if BUN or creatinine doubles or if hypertension develops or worsens 1

Bleeding Disorders

• Avoid in: Thrombocytopenia, platelet defects, or patients on anticoagulants 1
• Risk of GI bleeding increases 3-6 fold when NSAIDs are combined with anticoagulants 1
• INR increases up to 15% with concurrent warfarin use 1

Hepatic Considerations

• Rare cases of severe hepatic injury, including fulminant hepatitis and liver necrosis, have been reported 6
• Monitor for hepatotoxicity symptoms: nausea, fatigue, jaundice, right upper quadrant tenderness 6

Practical Prescribing Algorithm

Step 1: Risk Stratification

• Low-risk patient (no GI/CV/renal/bleeding history, age <60): Consider mefenamic acid only if preferred NSAIDs have failed
• Any high-risk features present: Choose alternative therapy (acetaminophen, triptans, or antiemetics) 1

Step 2: Dosing (If Appropriate)

• Acute migraine: 500 mg initial dose, then 250 mg every 6 hours as needed, not to exceed one week 6
• Use lowest effective dose for shortest duration to minimize cardiovascular and GI risks 6

Step 3: Monitoring Requirements

• Baseline: Blood pressure, BUN, creatinine, liver function tests, CBC, fecal occult blood 1
• Repeat every 3 months if continued use 1
• Discontinue immediately if: GI bleeding, significant hepatotoxicity (transaminases >3× ULN), renal dysfunction, or cardiovascular events 1, 6

Step 4: Patient Education

• Warn about GI symptoms (most common), cardiovascular symptoms (chest pain, shortness of breath), and signs of bleeding 6
• Advise taking with food to minimize GI upset 1
• Instruct to discontinue at first sign of skin rash or hypersensitivity 6

Special Populations

Pregnancy

• Avoid after 20 weeks gestation due to risk of fetal renal dysfunction and oligohydramnios 6
• Avoid after 30 weeks gestation due to risk of premature ductus arteriosus closure 6
• Acetaminophen is the safest option during pregnancy 4

Elderly Patients

• Most postmarketing fatal GI events occurred in elderly or debilitated patients 6
• Use extreme caution and consider alternative therapies 1, 6

Bottom Line

Mefenamic acid should be reserved for patients who have failed first-line NSAIDs (ibuprofen, naproxen, diclofenac, aspirin) and have no contraindications. 1, 3 The evidence supporting its use is substantially weaker than for preferred agents, and the safety profile is similar to other NSAIDs with significant GI, cardiovascular, and renal risks. 6, 2 For most patients with migraine, better-studied alternatives exist. 1, 5