Indications:
Medical termination of intrauterine pregnancy up to 12 weeks (84 days) of gestation by the combination of mifepristone with misoprostol to cause abortion.
Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy during the first trimester.
Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (beyond the first trimester).
Labour induction in foetal death in utero: In patients where prostaglandin or oxytocin cannot be used.
Administration, dosage:
Administration: Take the tablet whole with water.
Dosage:
Medical termination of developing intra-uterine pregnancy:
The method of administration will be as follows:
- Gestation up to 63 days (9 weeks): Take 1 tablet of mifepristone 200. After 24 to 48 hours, continue to sublingual or buccal 800 mcg misoprostol at medical facility or at home depending on the gestational age and individual woman’s needs.
Gestational age from 8 to 9 weeks should use misoprostol and monitor for miscarriage at a medical facility.
- Gestational age from 64 to the end of 84 days (from 10 to 12 weeks):
Only performed at medical facility under the supervision of medical staff according to National guidelines on reproductive healthcare services specified in Decision No. 4128/QD-BYT dated July 29, 2016 of the Minister of Health.
Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy during the first trimester:
Mifepristone is taken as a single 200 mg (1 tablet) oral dose, followed 36 to 48 hours later (but not beyond) by surgical termination of pregnancy.
Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (beyond the first trimester).
Mifepristone is taken as a single 600 mg (3 tablets of 200 mg each) oral dose, 36 to 48 hours prior to scheduled prostaglandin administration which will be repeated as often as indicated.
Labour induction in foetal death in utero:
Mifepristone is taken as a single 600 mg (3 tablets of 200 mg each) oral daily dose, for two consecutive days.
Labour should be induced by the usual methods if it has not started within 72 hours following the first administration of mifepristone.
Vomiting within 45 minutes after the intake could lead to a decrease in mifepristone efficacy: Oral intake of a new mifepristone 600 mg dose (3 tablets of 200 mg each) is recommended in this case.
Some special attention on the handling of the medicine before and after use:
There are no special requirements for handling this medicine after use.
Contraindications:
This medicine should never be prescribed in the following cases:
In all indications
Chronic adrenal failure.
Hypersensitivity to mifepristone or to any of the excipients of the medicine.
Severe asthma uncontrolled by therapy.
Porphyria.
In the indication: Medical termination of developing intra-uterine pregnancy:
Absolute
- Mitral valve stenosis, embolism and history of embolism.
- Adrenal gland disease.
- Blood clotting disorders, being treated with anticoagulants.
- Moderate to severe anemia.
- Confirmed or suspected ectopic pregnancy.
- The fetus clings to the old surgical scar in the uterus.
Relative
- Long-term systemic corticosteroid therapy.
- Hypertension.
- Acute genital tract infections (in need of treatment).
- Genitourinary malformations (the drug can only be used at the central level).
- Caution should be exercised in patient with caesarean scar: Reduce the dose of misoprostol and increase the time interval between doses (only taken at provincial and national obstetric and gynecology hospitals).
In the indication: Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy during the first trimester:
Pregnancy not confirmed by ultrasound scan or biological test.
Pregnancy beyond 84 days.
Suspected extra-uterine pregnancy.
In the indication: Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (beyond the first trimester):
Contraindications to the prostaglandin analogue selected.
Warnings and precautions for use:
Self-use of abortion tablets can be life-threatening, please follow the instructions of the treating physician and National guidelines on reproductive healthcare services specified in Decision No. 4128/QD-BYT dated July 29, 2016 of the Minister of Health.
Mifepristone inhibits the activity and decreases the efficacy of corticosteroids in patients receiving long-term corticosteroid therapy. Daily dose should be adjusted temporarily within 3 – 4 days after taking mifepristone.
For patients who use inhaled corticosteroid therapy, especially those with asthma, it is recommended that the dose be doubled during the 48 hours preceding the administration of mifepristone and continued for about one week.
For young patients with diabetes, if stomach problems occur due to complications of pregnancy or this treatment, insulin dose in these patients should be adjusted.
In patients who have an intrauterine device in situ, this device should be removed before initiating the treatment with mifepristone.
Special precautions for use:
Failure rate:
Intentional use of mifepristone alone without subsequent administration of prostaglandin (misoprostol) may be associated with an increased failure rate. Based on various clinical study data and various prostaglandin uses, failure rates vary as described below:
0 – 1.5% of ongoing pregnancies.
1.3 – 4.6% of partial abortion, with incomplete expulsion.
0.1 – 1.4% of haemostatic curettage.
Bleeding: Prolonged vaginal bleeding occurs in almost all cases during the treatment procedure (about 9 days), and is not a proof of complete expulsion.
After taking misoprostol, the patient may have to stay in hospital for up to 3 hours for observation.
This medicine contains Tartrazine lake which may cause allergic reactions. Caution should be exercised when using the drug for patients allergic to coloring agents.
Pregnancy and lactation:
Pregnancy:
Women must be informed that in the event of failure and a continuing pregnancy the foetus may be exposed to a risk of malformation. Therefore, another method should be advised to terminate pregnancy on the next follow-up visit at hospital.
Lactation:
To date, there have been no studies to prove or disprove that mifepristone is excreted in breast milk. However, it is recommended that the patient should discontinue breastfeeding for 3 to 4 days after mifepristone administration for safety.
Effects on ability to drive, use machines:
There has been no evidence on the medicine effects on the ability to drive or use machines. Dizziness may occur as a side effect inherent of the abortion process. Be cautious of this side effect when driving or using machinery.
Interactions, incompatibilities of medicine:
Interaction with other medicinal products and other forms of interaction:
Ketoconazole, itraconazole, erythromycin and fruit juice (grape): May inhibit mifepristone catabolism (increasing serum levels of mifepristone).
Rifampicin, dexamethasone, St.John’s Wort and certain anticonvulsants (phenytoin, phenobarbital, carbamazepine): Increase mifepristone metabolism (lowering serum levels of mifepristone).
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin should not be used with mifepristone since they are anti-prostaglandin drugs and may reduce the effectiveness of mifepristone.
Incompatibilities:
Because there are no studies of drug incompatibility, do not mix this drug with other drugs.
Undesirable effects:
Side effects are classified according to frequency: Very common (ADR ≥ 1/10), common (1/100 ≤ ADR < 1/10), uncommon (1/1,000 ≤ ADR < 1/100), rare (1/10,000 ≤ ADR < 1/1,000), very rare (ADR < 1/10,000); can not be estimated from the available data “Not known”.
Very common
Genitourinary system: Uterine contractions or cramping usually may be experienced (10 to 50%) in the hours following prostaglandin intake.
Gastrointestinal system: Nausea, vomiting, diarrhea (these gastro intestinal effects related to prostaglandin use are frequently reported).
Common
Genitourinary system: Bleeding.
All women will experience some bleeding. The amount depends on the gestational age.
Heavy bleeding occurs in about 5% of cases and approximately 1.4% of cases require haemostasis.
Uncommon
Skin reactions: Hypersensitivity: Skin rash is uncommon (0.2%).
Cardiovascular system: In a few cases, hypotension may occur (0.25%).
Rare
Skin reactions: Single cases of urticaria, erythroderma, lupus and epidermal necrolysis have been reported.
Other cases: Very rare cases of headache, malaise, hot flushes, dizziness, chills and mild fever have been reported.
Overdose and management:
Overdose:
Clinical trials have shown that no side effects occur with a single dose of up to 2 g of mifepristone.
Management:
If acute poisoning occurs, patients should be hospitalized for monitoring and special treatment.
Pharmacodynamics:
Pharmacotherapeutic group: Genitourinary system and sex hormones – Other sex hormones and modulators of the genital system – Mifepristone
ATC code: G03XB01
Properties:
Mifepristone is an antiprogestin. The drug inhibits the effect of the hormone progesterone in maintaining the fetus.
Contraception is an action happening before a nesting of fertilized ovum. Dual effects include preventing ovulation and endometrial growth. The most important effect is to slow ovulation by disrupting the follicular growth and the endocrine function of granular cells and preventing LH peak at the middle of the cycle. It also works on the endometrium if used after ovulation and affecting the nesting. In addition, degradation of corpus luteum occurs in 50% of women, which makes endometrium to peel off easily.
Mechanism of action:
Mifepristone acts as a progesterone antagonist by competing with endogenous progesterone at on receptor binding. It has a high affinity for these receptors (2-10 times higher than that of progesterone).
Mifepristone prevents the effects of progesterone on the endometrium and peritoneum. This leads to degeneration and shedding of the uterine lining, thus prevents or disrupts the embryo attachment.
Pharmacokinetics:
Absorption: After taking, the drug is quickly absorbed. Bioavailability of mifepristone is about 70% after oral administration. Peak plasma concentrations occur within 1 to 2 hours after a single dose.
Distribution: Mifepristone is 98% bound to plasma proteins: Albumin and mainly alpha-1-acid glycoprotein (AAG), the binding is saturated. Due to this binding, the volume of distribution and plasma clearance of mifepristone is inversely proportional to the plasma AAG concentration.
Administration – elimination: Half time is about 20 to 30 hours. The unbound mifepristone is rapidly metabolized by demethylation and hydroxylation in the liver. The metabolism can be detected in plasma about 1 hour after ingestion.
Mifepristone and its metabolites are mainly excreted in feces through the biliary tract and some excreted by the kidneys.
