Mifepristone + Misoprostol

✅ Approved Indication:

Medical termination of intrauterine pregnancy up to 63 days (9 weeks) of gestation

• This is the only formally approved indication in most regulatory agencies (FDA, EMA, WHO).
• Standard regimen: Mifepristone 200 mg orally, followed 24–48 hours later by Misoprostol 800 mcg buccally, sublingually, or vaginally.

⚠️ Off-label / Guideline-Supported Indications

Although not part of official drug labeling, these uses are strongly supported by WHO (2022 Abortion Care Guideline), NICE (NG140), and other international bodies:

Termination of pregnancy beyond 9 weeks (2nd trimester, under hospital supervision)

• Used in certain cases; requires specialist monitoring due to higher risk of hemorrhage or incomplete abortion.

Management of missed abortion (missed miscarriage)

• When fetal death has occurred, but pregnancy tissue remains in the uterus.
• Medical management with Mifepristone + Misoprostol is an effective alternative to surgical evacuation.

Management of incomplete abortion

• Used to expel retained products of conception after spontaneous or induced abortion.

Induction of uterine evacuation in intrauterine fetal death (IUFD)

• For pregnancies where the fetus has died in utero, but labor has not started naturally.

Cervical ripening before surgical abortion

• Mifepristone softens the cervix, Misoprostol promotes uterine contractions, reducing surgical risk.

Labor induction in selected clinical scenarios

• Such as IUFD or when continuation of pregnancy is dangerous for maternal health.

📌 Summary:

• Approved: Medical abortion up to 9 weeks.
• Off-label (guideline-supported): Missed abortion, incomplete abortion, 2nd trimester termination, IUFD, cervical ripening, and selected cases of labor induction.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Important Notice
This medication must be taken only under the advice and supervision of a registered medical practitioner. Self-medication without proper medical consultation may be unsafe and can lead to serious health risks.

Step 1: Mifepristone

• Dose: 1 tablet (200 mg)
• How to take: Swallow whole with water
• Purpose: Stops the pregnancy from continuing by blocking progesterone
• Next step: Wait 24–48 hours before taking misoprostol

Step 2: Misoprostol

Total dose: 4 tablets (200 mcg each = 800 mcg)

Recommended method (Buccal)

1.        Place 2 tablets between the left cheek and gum

2.        Place 2 tablets between the right cheek and gum

3.        Hold in place for 30 minutes until dissolved

4.        Swallow any remaining pieces with water

What to Expect

• Onset: Cramping and bleeding usually begin 1–4 hours after misoprostol
• Peak effect: Strong cramps and heavier bleeding typically last 4–6 hours
• Completion: Most pregnancies pass within 24 hours, though lighter bleeding may continue for several days

  Common symptoms may include:

  a.        Abdominal cramping

  b.       Heavy bleeding with clots

  c.        Nausea or vomiting

  d.       Diarrhea

  e.        Chills or mild fever

When to Seek Medical Care

Seek immediate medical attention if you experience:

• Heavy bleeding: Soaking 2 or more large pads per hour for 2 consecutive hours
• High fever: Temperature above 38°C (100.4°F) starting 24 hours after the medication
• Severe pain: Intense abdominal pain not relieved by ibuprofen
• No bleeding: No bleeding within 24 hours after taking misoprostol.

রেজিস্টার্ড চিকিৎসকের নির্দেশনা অনুযায়ী ঔষধ সেবন করুন।

Mifepristone is a competitive antagonist at progesterone receptors, interrupting progesterone-mediated support of the endometrium and leading to decidual breakdown. It also increases uterine contractility and cervical softening by sensitizing the myometrium to prostaglandins. Misoprostol, a prostaglandin E₁ analog, induces uterine contractions and cervix dilation, facilitating expulsion of uterine contents. This sequential action ensures complete termination or evacuation.

Absorption:

• Mifepristone is rapidly absorbed orally (peak 1–2 h).
• Misoprostol is absorbed via buccal/vaginal routes; buccal peaks at 1 h.

Distribution:

• Mifepristone highly protein‑bound (>98%), large volume of distribution.
• Misoprostol acid (active metabolite) moderately bound.

Metabolism:

• Mifepristone metabolized by CYP3A4 to active and inactive metabolites; half-life 18–25 h.
• Misoprostol is swiftly deesterified to its active form; half-life 20–40 minutes.

Excretion:

• Mifepristone and metabolites via biliary and renal routes.
• Misoprostol metabolites eliminated in urine.

Pregnancy:

• Contraindicated when used for abortion outside approved gestational age. Use category X as per FDA for pregnancy interruption (intended).

Lactation:

• Misoprostol and mifepristone may pass into breast milk in small amounts.
• Breastfeeding may continue after abortion, but express and discard milk for 36–48 h post-mifepristone to allow elimination.
• Caution advised due to theoretical risk of uterine side effects in the infant (rare).

• Primary class: Antiprogestin (mifepristone) + Prostaglandin analog (misoprostol).
• Subclass: Abortifacient/prostaglandin E₁ analog.

• Known allergy to mifepristone, misoprostol, or prostaglandin analogs.
• Ectopic pregnancy (ruptured or suspected).
• Chronic adrenal failure (due to mifepristone’s glucocorticoid antagonism).
• Simultaneous long‑term corticosteroid therapy.
• Hemorrhagic disorders or on anticoagulants with high bleeding risk.
• Severe anemia (Hb < 9 g/dL).
• Inability to access emergency medical care.

• High-risk groups: Anemic patients, adrenal insufficiency.
• Severe risk: Heavy bleeding (occurring in 5%), including hemorrhage.
• Monitoring: Confirm completion via ultrasound/hCG tests. Watch for infection, excessive bleeding, or sepsis.
• Early warning signs: Fever >38 °C, severe abdominal pain with dizziness, hypovolemia—requires urgent care.

Common (Systemic):

• GI upset: nausea, vomiting, diarrhea, abdominal cramps (around misoprostol dosing).
• Headache, dizziness, fatigue.

Gynecologic/Reproductive:

• Heavy uterine bleeding 24–48 h post-misoprostol; cramps moderate to severe during expulsion.
• Transient spotting up to 14 days.

Rare/Serious:

• Endometrial infection, sepsis (especially with fever >37.8 °C ≥ 24 h).
• Uterine rupture in late pregnancy use (very rare).
• Hypovolemic shock due to hemorrhage.

• CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin): may reduce mifepristone levels → decreased efficacy.
• CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may increase mifepristone concentrations, raising risk of cortisol receptor antagonism/adrenal insufficiency.
• Anticoagulants/antiplatelets (e.g., warfarin): increased bleeding risk due to induced uterine bleeding.
• Alcohol: may exacerbate GI effects and dehydration—advise avoidance.

• WHO (2023): Expanded indication to ≤70 days; endorses home-based use up to 63 days.
• NICE (2024, UK): Confirms home use safe and effective for ≤10 weeks, with remote follow‑up via telehealth.
• FDA (2024): Approved buccal misoprostol route; clarified safety data.
• ACOG (2022): Recommends 200 mg mifepristone alternative (vs. 600 mg) with similar outcomes; adoption underway in some regions.

• Mifepristone tablets: Store at 20–25 °C (68–77 °F); brief excursions 15–30 °C allowed. Keep in original blister until use; protect from moisture and light.
• Misoprostol tablets: Store at ≤25 °C; tightly sealed in original container with desiccant to prevent humidity exposure; avoid freezing.
• Reconstitution not applicable. If any off-label compounding: refrigerate 2–8 °C and use within 14 days; discard if not used.