What is the mechanism and regimen for medical abortion using mifepristone (Mifeprex) and misoprostol (Cytotec)?

Mechanism and Regimen for Medical Abortion with Mifepristone and Misoprostol

Mifepristone blocks progesterone receptors to terminate pregnancy, followed by misoprostol which induces uterine contractions to expel the pregnancy tissue—the evidence-based regimen is 200 mg mifepristone orally followed by 800 mcg misoprostol (buccal or vaginal) 24-48 hours later, effective through 63 days gestation. 1, 2

Mechanism of Action

Mifepristone

• Acts as a selective progesterone receptor antagonist at low doses, blocking the effects of progesterone which is essential for maintaining pregnancy 3
• Blocks glucocorticoid receptors (GR-II) at higher doses, though this is not the primary mechanism for pregnancy termination 3
• Causes pregnancy loss by antagonizing progesterone's effects on the endometrium and decidua, leading to detachment of the embryo 3
• Has high affinity for the glucocorticoid receptor (100%) compared to dexamethasone (23%) or cortisol (9%) 3
• Little to no affinity for estrogen, mineralocorticoid, muscarinic, histaminic, or monoamine receptors 3

Misoprostol

• A prostaglandin E1 analogue that induces uterine contractions and cervical softening 1
• Works synergistically with mifepristone to expel pregnancy tissue after the progesterone blockade has initiated detachment 1

Evidence-Based Regimen

First Trimester (Up to 63 Days Gestation)

Standard Dosing:

• Mifepristone 200 mg orally followed by misoprostol 800 mcg buccally or vaginally 24-48 hours later 1, 2
• This regimen has 97.7% efficacy through 63 days gestation 2
• Efficacy is highest at 29-42 days (98.8%) and lowest at 57-63 days (95.5%) 2

Alternative Same-Day Dosing:

• Mifepristone 200 mg followed by misoprostol 800 mcg vaginally administered simultaneously or within 6-8 hours on the same day 4, 5
• Complete abortion rate of 95.1% when given simultaneously, which is noninferior to the 24-hour interval (96.9%) 4
• For 50-63 days gestation, same-day dosing achieved 100% success at 50-56 days and 98% at 57-63 days 5

Second Trimester (12-20 Weeks Gestation)

• Mifepristone 200 mg orally followed by misoprostol 800 mcg vaginally 36-48 hours later 6
• Repeat misoprostol 400 mcg vaginally every 3 hours (maximum 4 doses in 24 hours) until abortion occurs 6
• 97.9% abort within 24 hours and 99.5% within 36 hours 6
• Median induction-to-abortion interval is 6.7 hours (7.6 hours in nulliparous vs 6.0 hours in multiparous women) 6
• Must be performed in a facility where blood transfusion and emergency surgery are available 7

Expected Effects and Timeline

Bleeding and Cramping

• Cramping and bleeding are expected therapeutic effects, not complications 1
• Bleeding lasts an average of 9-16 days 1
• Expulsion typically occurs within hours to days after misoprostol administration 1, 2

Pharmacokinetics

• Mifepristone reaches peak plasma concentration 1-4 hours after oral administration 3
• Half-life is 85 hours following multiple doses, but longer with repeat dosing 3
• Highly protein-bound (99.2%) to alpha-1-acid glycoprotein 3
• Metabolized by CYP3A4 with active metabolites that peak 2-8 hours after dosing 3
• Must be taken with food to achieve consistent plasma concentrations 3

Critical Safety Considerations

Mandatory Pregnancy Exclusion

• Pregnancy must be excluded before initiating mifepristone due to its potent anti-progestational effects 3
• Pregnancy must also be excluded if treatment is interrupted for more than 14 days in females of reproductive potential 3

Contraception Requirements

• Non-hormonal contraception required during treatment and for one month after stopping 3
• Mifepristone interferes with hormonal contraceptive effectiveness 3

Gestational Age Determination

• Use ultrasonography or menstrual history to determine gestational age 1
• Ultrasonography is needed when dating cannot be confirmed clinically or when risk factors for ectopic pregnancy exist 1

Management of Adverse Effects

Common Side Effects

• Nausea, diarrhea, warmth/chills are more common with simultaneous dosing 4
• Low-grade fever and gastrointestinal symptoms from misoprostol 1
• Manage with NSAIDs or antiemetics 1

Rare Complications

• Ongoing pregnancy, infection, hemorrhage, undiagnosed ectopic pregnancy are rare 1
• Hospitalization rate for infection: 0.01% 2
• Transfusion rate: 0.03% 2
• Need for unplanned aspiration is low, particularly at earlier gestational ages 2

Follow-Up and Confirmation

• Use clinical history combined with serial quantitative beta-hCG levels, urine pregnancy testing, or ultrasonography to confirm complete passage 1
• Follow-up typically occurs 7±1 days after treatment initiation 4
• Women who have not aborted may be offered a second dose of misoprostol 4

Special Populations

Renal Impairment

• Maximum dose 600 mg/day in renally impaired patients 3
• Patients with end-stage renal disease should be managed in experienced centers with emergency support 8
• Baseline assessment of renal function, electrolytes, and bleeding risk required 8

Hepatic Impairment

• Maximum dose 600 mg/day in mild to moderate hepatic impairment 3
• Contraindicated in severe hepatic impairment 3

Breastfeeding

• Consider pumping and discarding milk for 18-21 days (5-6 half-lives) after last dose before resuming breastfeeding 3
• Estimated relative infant dose is 0.5% with single 600 mg dose 3

Critical Contraindications

• Misoprostol should NOT be used in women with previous cesarean delivery for cervical preparation or labor induction due to uterine rupture risk 9, 7
• Avoid prostaglandin F compounds as they increase pulmonary arterial pressure and decrease coronary perfusion 7