1. Clinical Overview
Mifepristone is a synthetic steroid with potent antiprogestogenic and antiglucocorticoid activity. It acts as a competitive antagonist at progesterone and glucocorticoid receptors. In India, it is primarily used for medical termination of early pregnancy (up to 63 days gestation) in combination with misoprostol, as per the MTP Act. It is also approved for the management of uterine leiomyoma (fibroids) and Cushing's syndrome secondary to ectopic ACTH secretion.
| Onset | Duration | Bioavailability |
|---|---|---|
| Progesterone antagonism begins within hours of administration. For pregnancy termination, the complete process (administration of mifepristone followed by misoprostol) typically takes 24-48 hours. | The biological effects persist for several days due to its long half-life and sustained receptor binding. The antiglucocorticoid effect can last up to 72 hours. | Approximately 69% following oral administration. |
2. Mechanism of Action
Mifepristone competitively binds to the intracellular progesterone receptor with high affinity, blocking the biological action of endogenous progesterone. Progesterone is essential for maintaining the endometrium and pregnancy. By blocking its action, mifepristone leads to decidual necrosis, detachment of the trophoblast, cervical softening, and increased uterine contractility. It also sensitizes the myometrium to the contractile effects of prostaglandins (like misoprostol).
3. Indications & Uses
- Medical Termination of Intrauterine Pregnancy (up to 63 days gestation) in combination with a prostaglandin analogue (Misoprostol)
- Pre-treatment for cervical dilatation prior to surgical termination of pregnancy
4. Dosage & Administration
Adult Dosage: For MTP (≤63 days): Single oral dose of 200 mg on Day 1, followed by 400-800 mcg misoprostol buccally/vaginally 36-48 hours later. For Cervical Ripening: 200 mg single dose 36-48 hours prior to procedure. For Uterine Leiomyoma: 5-50 mg daily for up to 3 months. For Cushing's Syndrome: 300-1200 mg daily, titrated based on response.
Administration: For MTP: The 200mg tablet should be taken orally with water, under direct supervision of the registered medical practitioner at the MTP centre. The patient must remain under observation for a short period. Must be followed by misoprostol administration as per protocol. Can be taken with or without food, but a light meal is recommended to reduce nausea.
5. Side Effects
Common side effects may include:
- Nausea, vomiting, diarrhea
- Abdominal pain/cramping (expected part of the process)
- Uterine bleeding (can be heavy and prolonged)
- Headache, dizziness, fatigue
- Fever/chills (often due to misoprostol)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Ketoconazole, Itraconazole, Ritonavir | Increase mifepristone plasma levels (CYP3A4 inhibitors) | Major |
| Rifampicin, Carbamazepine, Phenytoin, St. John's Wort | Decrease mifepristone plasma levels (CYP3A4 inducers) | Major |
| Corticosteroids (e.g., Dexamethasone, Prednisolone) | Mifepristone antagonizes glucocorticoid effect; dose adjustment of steroid may be needed | Major |
| Warfarin, NSAIDs (e.g., Ibuprofen, Aspirin) | Increased risk of bleeding due to additive effects | Moderate |
| QT-prolonging drugs (e.g., Erythromycin, certain antipsychotics) | Theoretical additive risk of QT prolongation at high doses | Moderate |
7. Patient Counselling
- DO take the misoprostol exactly as and when prescribed, 36-48 hours after mifepristone.
- DO return for ALL scheduled follow-up visits (typically 14 days later) for confirmation of complete abortion by ultrasound.
- DO use effective contraception immediately after the procedure, as ovulation can resume within 10 days.
- DONT take the medication if you have an IUD in place; it must be removed first.
- DONT use aspirin or NSAIDs for pain relief unless prescribed, as they may increase bleeding. Use paracetamol instead.
8. Toxicology & Storage
Overdose: Single acute overdose is unlikely to cause toxicity beyond an exacerbation of its known effects: severe uterine bleeding, adrenal insufficiency, fatigue, nausea, and profound hypotension. Chronic high-dose overdose can lead to severe hypokalemia, hypertension, and clinical signs of adrenal insufficiency.
Storage: Store below 30°C. Protect from light and moisture. Keep the tablet in the original blister pack until use. Keep out of reach of children. Do not use after the expiry date printed on the pack.