Usage
- Medical termination of intrauterine pregnancy: Mifepristone + Misoprostol is prescribed for the medical termination of an intrauterine pregnancy through 70 days (10 weeks) gestation. It is also used for early pregnancy loss management. Occasionally Mifepristone is used alone for the management of hyperglycemia in Cushing’s syndrome.
- Pharmacological classification: Mifepristone is an antiprogestogen (antiprogestin). Misoprostol is a prostaglandin E1 analog.
- Mechanism of action: Mifepristone blocks the action of progesterone, a hormone essential for maintaining pregnancy. This leads to the detachment of the pregnancy. Misoprostol causes uterine contractions and cervical softening, leading to expulsion of the pregnancy.
Alternate Names
- Mifepristone is also known as RU-486.
- The combination is sometimes referred to as the “abortion pill” or “medical abortion.”
- Brand names for Mifepristone: Mifeprex, Korlym
- Brand name for Misoprostol: Cytotec
- Brand name for the combined product: Mifegymiso
How It Works
- Pharmacodynamics (Mifepristone): Mifepristone binds to progesterone receptors, blocking the effects of progesterone. This leads to decidual necrosis (breakdown of the uterine lining), detachment of the implanted embryo, and increased sensitivity of the myometrium (uterine muscle) to the contractile effects of prostaglandins. Mifepristone also has antiglucocorticoid activity.
- Pharmacokinetics (Mifepristone): Mifepristone is rapidly absorbed after oral administration. It is highly protein-bound and extensively metabolized in the liver, primarily by CYP3A4. It has a long elimination half-life.
- Pharmacodynamics (Misoprostol): Misoprostol binds to prostaglandin E1 receptors in the myometrium, causing uterine contractions. It also softens the cervix.
- Pharmacokinetics (Misoprostol): Misoprostol is rapidly absorbed after oral or buccal administration. It is metabolized to misoprostol acid, its active form. It is eliminated primarily through renal excretion.
- Elimination pathways: Both drugs are primarily metabolized in the liver and eliminated through a combination of hepatic and renal pathways.
Dosage
Standard Dosage
Adults (For Medical Abortion or Early Pregnancy Loss):
- Mifepristone: 200 mg orally as a single dose on Day 1.
- Misoprostol: 800 mcg (four 200 mcg tablets) buccally (between the cheek and gum for 30 minutes, then swallowed), vaginally, or sublingually, 24 to 48 hours after mifepristone administration. A second dose of misoprostol may be considered at or after 64 days gestation to increase effectiveness.
Children:
- Mifepristone/Misoprostol is not indicated for use in children for medical abortion or early pregnancy loss.
Special Cases (For Medical Abortion or Early Pregnancy Loss):
- Elderly Patients: Dose adjustments are not typically necessary.
- Patients with Renal Impairment: Dose adjustments are not typically necessary.
- Patients with Hepatic Dysfunction: Dose adjustments are not typically necessary for mifepristone. Misoprostol dose reduction may be needed.
- Patients with Comorbid Conditions: Caution is advised in patients with bleeding disorders, adrenal insufficiency, or long-term corticosteroid use.
Clinical Use Cases for Mifepristone Only (Cushing’s Syndrome):
- Adults: Initial dose is 300 mg orally once daily with food. Dose may be increased every 2-4 weeks, as needed, up to a maximum of 1200 mg daily (or 600mg in renal or hepatic dysfunction). Should not exceed 20mg/kg/day.
- Children: Use and dose must be determined by a doctor.
Clinical Use Cases for Misoprostol Only:
- Prevention of NSAID-induced ulcers: 200 mcg orally four times daily with food, after meals and at bedtime. The last dose should be taken at bedtime.
- Other Uses: Misoprostol is also used in the induction of labor, treatment of postpartum hemorrhage, and cervical ripening. Dosing varies depending on the indication and should be determined by the prescribing physician.
Side Effects
Common Side Effects:
- Cramping
- Bleeding
- Nausea
- Vomiting
- Diarrhea
- Headache
- Weakness
- Dizziness
- Fever
- Chills
Rare but Serious Side Effects:
- Heavy or prolonged bleeding
- Infection
- Incomplete abortion
- Ruptured ectopic pregnancy (if present before treatment)
- Allergic reactions
Contraindications
- Confirmed or suspected ectopic pregnancy
- IUD in place (unless removed before treatment)
- Chronic adrenal failure
- Bleeding disorders or anticoagulant therapy
- Porphyria
- Allergy to mifepristone or misoprostol
- Long-term corticosteroid use (may reduce efficacy of mifepristone)
Drug Interactions
- Mifepristone’s metabolism can be affected by CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) and inducers (e.g., rifampin, St. John’s Wort).
- Avoid grapefruit juice as it can increase mifepristone levels.
- Misoprostol can interact with NSAIDs, increasing the risk of gastrointestinal side effects.
- Antacids may reduce misoprostol absorption.
Pregnancy and Breastfeeding
- Pregnancy: Mifepristone + Misoprostol is contraindicated in ongoing pregnancies beyond 70 days gestation as it is used to terminate pregnancy. Fetal abnormalities are a risk if termination fails and pregnancy continues.
- Breastfeeding: Limited data suggest that breastfeeding need not be interrupted after a single dose of mifepristone. A 200mg dose of mifepristone may be preferred in nursing mothers. Avoid breastfeeding during long-term mifepristone therapy for Cushing’s syndrome.
Drug Profile Summary
- Mechanism of Action: Mifepristone blocks progesterone action; Misoprostol stimulates uterine contractions.
- Side Effects: Cramping, bleeding, nausea, vomiting, diarrhea, headache.
- Contraindications: Ectopic pregnancy, IUD in place, adrenal failure, bleeding disorders, porphyria, allergy.
- Drug Interactions: CYP3A4 inhibitors/inducers, grapefruit juice, NSAIDs.
- Pregnancy & Breastfeeding: Contraindicated in ongoing pregnancies beyond 70 days; limited data suggests breastfeeding is compatible with a single 200mg dose.
- Dosage: Mifepristone 200mg followed by Misoprostol 800mcg 24-48 hours later.
- Monitoring Parameters: Bleeding, vital signs, signs of infection.
Popular Combinations
Mifepristone is typically combined with Misoprostol for medical abortion.
Precautions
- Confirm intrauterine pregnancy and gestational age before treatment.
- Ensure access to emergency medical care.
- Monitor for heavy bleeding, signs of infection, and incomplete abortion.
- Counsel patients on potential side effects and follow-up care.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mifepristone + Misoprostol for medical abortion?
A: Mifepristone 200mg orally followed by Misoprostol 800 mcg (buccally, vaginally, or sublingually) 24-48 hours later.
Q2: What are the common side effects patients experience?
A: Cramping, bleeding, nausea, vomiting, diarrhea, headache, and fever.
Q3: How effective is medical abortion with Mifepristone + Misoprostol?
A: Over 95% effective through 70 days gestation.
Q4: Who should not use this medication combination?
A: Patients with ectopic pregnancy, IUD in situ, adrenal failure, bleeding disorders or those taking anticoagulants, porphyria, or allergies to either drug.
Q5: What are the warning signs of complications?
A: Heavy or prolonged bleeding, severe abdominal pain, fever greater than 100.4°F for over 4 hours, or signs of infection.
Q6: Can Mifepristone + Misoprostol be used for pregnancies beyond 70 days?
A: The combination is FDA-approved up to 70 days gestation. Some research suggests off-label use up to 77 days, but with potentially reduced efficacy. Protocols for later gestations may exist, involving different dosages of misoprostol.
Q7: What are the drug interactions I should be aware of?
A: Mifepristone interacts with CYP3A4 inhibitors and inducers and grapefruit juice. Misoprostol can interact with NSAIDs and antacids.
Q8: Can a patient breastfeed after taking Mifepristone + Misoprostol?
A: Limited evidence suggests that a single 200mg dose of mifepristone does not require interruption of breastfeeding. However, this should be discussed with the patient. Long-term use of mifepristone for Cushing’s syndrome necessitates stopping breastfeeding.
Q9: What follow-up care is required?
A: Patients should have a follow-up visit 7-14 days after treatment to confirm complete termination.
