1. Clinical Overview
A fixed-dose combination (FDC) analgesic, anti-inflammatory, and antifibrinolytic agent. Mefenamic acid provides NSAID-based pain relief and anti-inflammatory action. Tranexamic acid is an antifibrinolytic that reduces bleeding by inhibiting plasminogen activation. Vitamin K (as Menadione Sodium Bisulfite) supports coagulation factor synthesis. This combination is primarily indicated for the management of heavy menstrual bleeding (menorrhagia) associated with pain and dysmenorrhea, offering a synergistic approach to reduce both bleeding and pain.
| Onset | Duration | Bioavailability |
|---|---|---|
| Mefenamic Acid: 1-2 hours for analgesic effect. Tranexamic Acid: Peak plasma levels in ~3 hours; clinical reduction in bleeding may be observed within the first menstrual cycle. Vitamin K: Coagulation factor synthesis takes 6-24 hours. | Mefenamic Acid: 4-6 hours. Tranexamic Acid: 7-8 hours (dosing interval). Vitamin K: Dependent on hepatic synthesis of factors II, VII, IX, X. | Mefenamic Acid: >90% (oral). Tranexamic Acid: ~45% (oral). Vitamin K (Menadione): Variable, requires conversion to active form (Menadione is a synthetic pro-vitamin). |
2. Mechanism of Action
Mefenamic Acid: Non-steroidal anti-inflammatory drug (NSAID) that reversibly inhibits both cyclooxygenase (COX-1 and COX-2) enzymes, leading to decreased synthesis of prostaglandins, thromboxanes, and prostacyclins from arachidonic acid. This reduces inflammation, pain, and fever. It also has prostaglandin antagonist activity at receptor sites. Tranexamic Acid: A synthetic derivative of the amino acid lysine. It competitively inhibits the activation of plasminogen to plasmin by binding to the lysine-binding sites on plasminogen. At higher concentrations, it non-competitively inhibits plasmin. This stabilizes clots by preventing fibrin degradation. Vitamin K (Menadione): Acts as a cofactor for the hepatic microsomal enzyme gamma-glutamyl carboxylase, which catalyzes the post-translational carboxylation of glutamic acid residues on vitamin K-dependent clotting factors (II, VII, IX, X) and proteins C and S. This carboxylation is essential for their calcium-binding and procoagulant activity.
3. Indications & Uses
- Heavy Menstrual Bleeding (Menorrhagia) associated with primary dysmenorrhea
- Idiopathic Menorrhagia (when no structural pathology is identified)
- Menstrual pain and excessive bleeding in ovulatory cycles
4. Dosage & Administration
Adult Dosage: 1 tablet three times daily, starting at the onset of menstrual bleeding or pain. Do not exceed 3 tablets per day. Duration of treatment should not exceed 4-5 days per menstrual cycle.
Administration: Take with or immediately after food with a full glass of water to minimize gastrointestinal irritation. Do not crush or chew. Swallow whole. The tablet should be taken at the first sign of menstrual bleeding or pain. Do not use for more than the prescribed days per cycle.
5. Side Effects
Common side effects may include:
- Nausea
- Dyspepsia
- Epigastric pain
- Diarrhea (mefenamic acid can cause severe diarrhea)
- Headache
- Fatigue
- Menstrual discomfort reduction may alter cycle perception
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Anticoagulants (Warfarin, Acenocoumarol) | Vitamin K antagonizes warfarin effect. Mefenamic acid increases bleeding risk via antiplatelet effect and ulcerogenic potential. TRANEXAMIC ACID INCREASES THROMBOSIS RISK. Contraindicated. | Contraindicated |
| Anti-platelets (Aspirin, Clopidogrel) | Increased risk of GI bleeding. Avoid concomitant use. | Major |
| Other NSAIDs (Ibuprofen, Diclofenac) | Increased risk of GI toxicity and renal impairment. Avoid combination. | Major |
| ACE Inhibitors (Ramipril, Enalapril) | Mefenamic acid reduces antihypertensive effect and increases risk of renal impairment. | Moderate |
| Diuretics (Furosemide, Hydrochlorothiazide) | Reduced diuretic efficacy. Increased risk of nephrotoxicity. | Moderate |
| Lithium | Mefenamic acid can increase lithium levels to toxic range. Monitor serum lithium. | Major |
| Methotrexate | Mefenamic acid may decrease renal clearance of methotrexate, increasing toxicity. | Major |
| Corticosteroids (Prednisolone) | Markedly increased risk of GI ulceration and bleeding. | Major |
| SSRIs (Fluoxetine, Sertraline) | Increased risk of upper GI bleeding. | Moderate |
| Oral Contraceptives | No significant interaction. Often used concomitantly for cycle regulation. | Minor |
| Antacids | May reduce absorption of mefenamic acid. Separate administration by 2 hours. | Minor |
| Probenecid | May increase mefenamic acid levels. | Moderate |
7. Patient Counselling
- DO take the tablet with food or milk.
- DO start taking at the first sign of menstrual bleeding or pain.
- DO NOT take for more than 4-5 days during your period.
- DO NOT take if you are pregnant or suspect pregnancy.
- DO NOT take with other painkillers like ibuprofen, aspirin, or naproxen without consulting your doctor.
- DO NOT consume alcohol while on this medication.
- DO inform your doctor about all other medicines you are taking, including supplements.
- DO keep follow-up appointments to monitor your response and any side effects.
8. Toxicology & Storage
Overdose: Mefenamic Acid Overdose: Nausea, vomiting, epigastric pain, diarrhea (may be severe and bloody), dizziness, drowsiness, headache, tinnitus, metabolic acidosis, seizures, coma, acute renal failure, hepatotoxicity. Tranexamic Acid Overdose: Nausea, vomiting, diarrhea, orthostatic hypotension, visual disturbances, thromboembolic events, seizures (especially with rapid IV administration). Vitamin K Overdose (Menadione): Hemolytic anemia, hyperbilirubinemia, kernicterus in neonates (not relevant in adults), liver damage with very high doses.
Storage: Store below 30°C. Protect from light and moisture. Keep in the original blister pack or container. Keep out of reach of children. Do not use after the expiry date printed on the pack.