Dosing and uses of Mefenamic acid
Adult dosage forms and strengths
capsule
- 250mg
Acute Pain
Initial 500 mg PO once, THEn
250 mg PO q6hr PRN usually not to exceed 7 days
Primary Dysmenorrhea
Initial 500 mg PO once, THEn
250 mg PO q6hr PRN usually not to exceed 3 days
Administration
Take with food or 8-12 oz water to avoid GI effects
For dysmenorrhea, start with onset of bleeding & pain
Other Indications & Uses
Off-label: Vascular headache
Pediatric dosage forms and strengths
capsule
- 250mg
Acute Pain
<14 years old: Not recommended
≥14 years old: Initial 500 mg PO once, THEn
250 mg PO q6hr PRN usually not to exceed 7 days
Primary Dysmenorrhea
<14 years old: Not recommended
≥14 years old: Initial 500 mg PO once, THEn
250 mg PO q6hr PRN usually not to exceed 3 days
Geriatric dosage forms and strengths
Acute pain
Initial 500 mg PO once, THEn
250 mg PO q6hr PRN usually not to exceed 7 days
Mefenamic acid adverse (side) effects
>10%
Borderline elevations of one or more LFTs (<15%)
1-10%
Abdominal pain
Anorexia
Diarrhea
Nausea
Pyrosis
Gastritis
Flatulence
Constipation
Steatorrhea
Upper GI ulcers, gross bleeding/perforation (1% of patients treated for 3-6 mth and 2-4% of those treated for 1 yo)
<1%
Leukopenia
Eosinophilia
Thrombocytopenic purpura
Agranulocytosis
Pancytopenia
Bone marrow hypoplasia
Renal failure (including papillary necrosis & acute interstitial nephritis)
Acute interstitial nephritis has been associated with hematuria, proteinuria, & nephrotic syndrome
Warnings
Black box warnings
Cardiovascular risk
- NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), & stroke, which can be fatal
- Risk may increase with duration of use
- Patients with risk factors for or existing cardiovascular disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI & stroke)
Gastrointestinal risk
- NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, & perforation of the stomach or intestines, which can be fatal
- GI adverse events may occur at any time during use & without warning symptoms
- Elderly patients are at greater risk for serious GI events
Contraindications
Hypersensitivity, ASA allergy, history of aspirin triad, GI tract ulcer/inflammation, CABG, renal dz, late pregnancy (may cause premature closure of ductus arteriosus)
Cautions
Use caution in anemia, bronchospasm, cardiac disease, CHF, HTN, SLE, fluid retention, hepatic/renal impairment, bleeding diathesis
Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include the elderly, or those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, and individuals taking diuretics, ACE inhibitors, or ARBs
History of: peptic ulcer, GI bleeding, upper GI disease
If severe diarrhea occurs, reduce dose or temporarily discontinue drug
Risk of serious skin reactions
Heart Failure(HF) risk
- NSAIDS have the potential to trigger HF by prostaglandin inhibition that leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics
- NSAIDS should be avoided or withdrawn whenever possible
- AHA/ACC Heart Failure Guidelines; Circulation. 2016; 134
Pregnancy and lactation
Pregnancy category: C; D if used for prolonged periods, or near term (premature closure of ductus arteriosus)
The Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and in approximately 2.6% of controls. (CMAJ, September 6, 2011; DOI:10.1503/cmaj.110454)
Lactation: contraindicated; excreted in breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Mefenamic acid
Mechanism of action
Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase isoenzymes, cyclooxygenase-1 (COX-1) and -2 (COX-2)
May inhibit chemotaxis, may alter lymphocyte activity, decrease proinflammatory cytokine activity, and may inhibit neutrophil aggregation. These effects may contribute to its anti-inflammatory activity
Pharmacokinetics
Half-life: 2 hr
Onset: Rapid
Peak Plasma Time: 2-4 hr (1 g dose); reached by the second day of administration (1 g dose, 4x daily)
Peak Plasma Concentration: 10 mcg/mL (1 g dose); 20 mcg/mL (1 g dose, 4x daily)
Protein Bound: Extensive
Metabolism: Hepatic oxidation/conjugation
Metabolites: 3'-hydroxymethyl and 3'-carboxyl acid metabolites and their glucuronic acid conjugates
Enzymes inhibited: Cyclooxygenase
Excretion: urine 66% (single dose); feces 20-25%
Dialyzable: No
