Usage
Mefenamic acid is prescribed for the short-term relief of mild to moderate pain, including:
- Painful menstruation (dysmenorrhea): It reduces menstrual pain and heavy bleeding by inhibiting prostaglandin production.
- Musculoskeletal pain: Effective for pain associated with conditions like osteoarthritis and rheumatoid arthritis.
- Post-operative pain: Provides relief after surgical procedures.
- Dental pain: Offers short-term pain management.
- Fever (pyrexia): Especially in children above six months of age.
- Post-partum pain: Relieves pain after childbirth.
- Menorrhagia: Reduces excessive menstrual bleeding when organic pelvic pathology has been excluded.
It is classified pharmacologically as a Non-Steroidal Anti-Inflammatory Drug (NSAID).
Mechanism of Action: Mefenamic acid primarily works by inhibiting cyclooxygenase (COX) enzymes, thereby reducing the production of prostaglandins. Prostaglandins are involved in mediating inflammation, pain, and fever. It also displays some anti-bradykinin effects.
Alternate Names
- International Nonproprietary Name (INN): Mefenamic acid
- Brand names: Ponstan, Ponstel, Pargesic
How It Works
Pharmacodynamics: Mefenamic acid’s primary mechanism of action involves inhibiting prostaglandin synthesis by blocking both COX-1 and COX-2 enzymes. COX-2 is induced during inflammatory processes; therefore, COX-2 inhibition mainly accounts for its anti-inflammatory and analgesic properties. The inhibition of COX-1 contributes to its gastrointestinal side effects. Mefenamic acid also demonstrates some anti-bradykinin activity. It does not have a significant impact on platelet function.
Pharmacokinetics:
- Absorption: Rapidly absorbed after oral administration, with peak plasma concentrations reached within 1-4 hours. Food can slow the absorption rate but not its extent.
- Metabolism: Extensively metabolized in the liver, mainly by CYP2C9.
- Elimination: Excreted primarily in the urine (as metabolites) and to a lesser extent in the feces. The elimination half-life is approximately 2 hours.
Mode of Action: Mefenamic acid reversibly binds to COX-1 and COX-2 enzymes, preventing arachidonic acid from binding to their active sites. This subsequently inhibits the synthesis of prostaglandins, thereby reducing inflammation, pain, and fever.
Receptor Binding/Enzyme Inhibition: Mefenamic acid is a COX-1 and COX-2 inhibitor.
Elimination Pathways: Primarily renal excretion (as metabolites).
Dosage
Standard Dosage
Adults:
Initial dose: 500 mg orally, followed by 250 mg every 6 hours as needed.
Maximum daily dose: 1500 mg.
Duration: Not to exceed 7 days for pain and 3 days for dysmenorrhea.
Children:
- 6 months to <2 years: 25 mg/kg/day in divided doses three times a day, or 50mg 1-3 times daily. Use as oral suspension only.
- 2 to <5 years: 100 mg 1-3 times daily. Use as oral suspension only.
- 5 to <9 years: 150 mg 1-3 times daily. Use as oral suspension only.
- 9 to <12 years: 200 mg 1-3 times daily. Use as oral suspension only.
- ≥12 years: Same as adult dose.
Pediatric dosing should be calculated based on weight, not solely on age. Ensure accurate weight measurement for precise dosage calculations. Maximum duration of treatment in children: 7 days (except for certain chronic conditions like juvenile idiopathic arthritis).
Special Cases:
- Elderly Patients: Start with the lowest effective dose due to increased risk of adverse effects. Close monitoring is essential.
- Patients with Renal Impairment: Contraindicated in severe renal impairment. Caution advised in mild to moderate renal impairment; dosage adjustment may be necessary.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Caution is recommended in patients with mild to moderate hepatic dysfunction.
- Patients with Comorbid Conditions: Caution is advised in patients with cardiovascular disease, hypertension, asthma, or a history of gastrointestinal bleeding/ulcers.
Clinical Use Cases
Mefenamic acid is not typically recommended for the specific clinical scenarios of intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations (e.g., status epilepticus, cardiac arrest). Other analgesics or anesthetic agents are usually preferred in these contexts.
Dosage Adjustments
Dose modifications are required for patients with renal or hepatic dysfunction. Initiate therapy at the lowest effective dose and monitor closely for adverse events. No specific dosage adjustments based on genetic polymorphisms are available, but individual patient responses should be monitored.
Side Effects
Common Side Effects
- Gastrointestinal: Diarrhea, constipation, nausea, vomiting, abdominal pain, heartburn, indigestion.
- Central Nervous System: Dizziness, headache, drowsiness, nervousness.
- Dermatological: Rash, itching.
Rare but Serious Side Effects
- Gastrointestinal: Ulcers, bleeding, perforation.
- Cardiovascular: Myocardial infarction, stroke, heart failure.
- Hematological: Anemia, thrombocytopenia, neutropenia, agranulocytosis.
- Renal: Acute renal failure.
- Hepatic: Liver injury.
- Hypersensitivity reactions: Angioedema, anaphylaxis, Stevens-Johnson Syndrome.
Long-Term Effects
Chronic use may increase the risk of cardiovascular events, gastrointestinal complications, and renal damage.
Adverse Drug Reactions (ADR)
Any signs of gastrointestinal bleeding (e.g., black tarry stools, coffee-ground emesis), hepatic dysfunction (e.g., jaundice), renal impairment (e.g., decreased urine output), or hypersensitivity reactions require immediate intervention.
Contraindications
- Hypersensitivity to mefenamic acid or other NSAIDs.
- History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
- Active or history of recurrent peptic ulcer/gastrointestinal bleeding.
- Inflammatory bowel disease (Crohn’s disease, ulcerative colitis).
- Severe heart failure.
- Severe renal or hepatic impairment.
- Perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
- Third trimester of pregnancy.
Drug Interactions
- Anticoagulants/Antiplatelets: Increased risk of bleeding.
- Antihypertensives (ACE inhibitors, ARBs, beta-blockers, diuretics): Reduced antihypertensive effect.
- NSAIDs (including COX-2 inhibitors): Increased risk of gastrointestinal ulcers and bleeding.
- Lithium: Increased lithium levels.
- Methotrexate: Increased methotrexate toxicity.
- Digoxin: Elevated digoxin levels.
- Cyclosporine/Tacrolimus: Increased risk of nephrotoxicity.
- Alcohol: Increased risk of gastrointestinal bleeding.
Pregnancy and Breastfeeding
- Pregnancy: Avoid during the third trimester. Use with caution during the first and second trimesters only if potential benefits outweigh the risks. Premature closure of the ductus arteriosus is a major concern.
- Breastfeeding: Not recommended. Trace amounts may be present in breast milk, posing potential risk to the infant.
Drug Profile Summary
- Mechanism of Action: Inhibits COX-1 and COX-2 enzymes, reducing prostaglandin synthesis.
- Side Effects: Diarrhea, constipation, nausea, dizziness, headache, GI ulcers/bleeding (rare but serious).
- Contraindications: Hypersensitivity to NSAIDs, active peptic ulcer, severe renal/hepatic/heart failure, third-trimester pregnancy.
- Drug Interactions: Anticoagulants, antihypertensives, NSAIDs, lithium, methotrexate.
- Pregnancy & Breastfeeding: Avoid during the third trimester of pregnancy and while breastfeeding.
- Dosage: Adults: 500 mg initial dose, then 250 mg every 6 hours as needed (maximum 1500 mg/day for up to 7 days for pain, 3 days for dysmenorrhea). Pediatric dosing available for children above six months.
- Monitoring Parameters: Renal function, liver function, signs of GI bleeding, blood pressure.
Popular Combinations
Mefenamic acid is not commonly used in fixed-dose combinations with other drugs. It is typically prescribed alone.
Precautions
- General Precautions: Use the lowest effective dose for the shortest duration. Monitor for GI bleeding, renal function, and hepatic function.
- Pregnant Women: Avoid during the third trimester. Use with caution during the first and second trimesters if essential.
- Breastfeeding Mothers: Not recommended due to potential neonatal exposure.
- Children & Elderly: Age-specific dosing required. Increased risk of adverse reactions in the elderly.
- Lifestyle Considerations: Avoid alcohol to reduce the risk of gastrointestinal bleeding.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mefenamic Acid?
A: Adults: 500 mg initially, followed by 250 mg every 6 hours as needed (maximum 1500 mg/day). Pediatric dosing varies based on age and weight.
Q2: How does Mefenamic Acid differ from other NSAIDs?
A: Mefenamic acid is a potent inhibitor of both COX-1 and COX-2, making it effective for pain and inflammation. It’s often preferred for dysmenorrhea. Its shorter half-life (2 hours) reduces the risk of some adverse effects compared to NSAIDs with longer half-lives.
Q3: Can Mefenamic Acid be used long-term?
A: No, mefenamic acid is intended for short-term use (maximum 7 days for pain, 3 days for dysmenorrhea). Long-term use can increase the risk of serious side effects, particularly cardiovascular and gastrointestinal complications.
Q4: Is Mefenamic Acid safe during pregnancy?
A: It should be avoided during the third trimester. Use with caution and only if clearly necessary during the first and second trimesters. Consult an obstetrician for guidance.
Q5: What are the signs of a Mefenamic Acid overdose?
A: Overdose symptoms may include nausea, vomiting, abdominal pain, drowsiness, lethargy, seizures, and coma. Supportive care and symptomatic treatment are recommended.
Q6: What are the common drug interactions with Mefenamic Acid?
A: Significant interactions occur with anticoagulants, antihypertensives, NSAIDs, lithium, and methotrexate. Concomitant use should be carefully evaluated and monitored.
Q7: Can patients with asthma take Mefenamic Acid?
A: Mefenamic acid can exacerbate asthma symptoms, especially in aspirin-sensitive individuals. It’s generally contraindicated in patients with aspirin-induced asthma, urticaria, or other allergic-type reactions.
Q8: What are the key counseling points for patients taking Mefenamic Acid?
A: Take with food to minimize gastrointestinal upset. Do not exceed the recommended dosage or duration. Report any signs of GI bleeding, allergic reactions, or changes in urine output. Avoid alcohol.
Q9: What is the role of therapeutic drug monitoring with Mefenamic Acid?
A: While routine therapeutic drug monitoring is not typically required, patients with renal or hepatic impairment might benefit from closer observation of drug levels and organ function.
Q10: What is the mechanism of Mefenamic Acid-induced diarrhea?
A: The diarrhea is often attributed to the inhibition of COX-1, leading to increased intestinal motility and fluid secretion.
