MIF 200 mg

INDICATIONS

Mifepristone is indicated:

As a medical alternative to surgical termination of intra-uterine pregnancy
Softening and dilatation of the cervix uteri prior to surgical pregnancy termination
Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons
Labour induction for the expulsion of a dead fetus (fetal death in utero).

PHARMACOLOGY

Mifepristone is an antiprogestin; that is, it blocks the action of progesterone, a naturally produced hormone that prepares the inner lining of the uterus for implantation of a fertilized ovum and support of a growing embryo and placenta. The drug is taken orally in a prescribed dose during the first seven to nine weeks of pregnancy, and within two days the uterine lining begins to deteriorate, usually causing bleeding similar to that experienced during normal menstruation. The Mifepristone is then followed up by a dose (taken orally or as a vaginal suppository) of the synthetic prostaglandin Misoprostol, which stimulates the uterus to undergo contractions. The embryo and other uterine contents are expelled in a process very similar to spontaneous abortion or miscarriage.

DOSAGE & ADMINISTRATION

As a medical alternative to surgical termination of intra-uterine pregnancy in early pregnancy: 600 mg Mifepristone in a single oral dose followed 36-48 hrs later, by the administration of a prostaglandin analogue Misoprostol 400 mcg orally (up to 49 days) or Gemeprost 1 mg vaginally (up to 63 days). Softening and dilatation of the cervix uteri prior to surgical pregnancy termination: 200 mg Mifepristone, followed 36-48 hrs later (but not beyond) by a surgical termination of pregnancy. Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (to reduce the doses of prostaglandin): 600 mg of Mifepristone taken in a single oral dose, 36-48 hrs prior to scheduled prostaglandin administration which will be repeated as often as indicated. Labour induction for expulsion of a dead fetus (fetal death in utero): 600 mg of Mifepristone in a single oral daily dose for 2 consecutive days. Mifepristone alone leads to expulsion in about 60%. Labour should be induced by the usual methods if it has not started within 72 hrs following the first administration of Mifepristone.Use in children: Safety and effectiveness in pediatric patients have not been established.

INTERACTION

ketoconazole, itraconazole, erythromycin and grapefruit juice may inhibit its metabolism (increasing serum levels of mifepristone). Furthermore, rifampicin, dexamethasone, St John's Wort and certain anticonvulsants (phenytoin, phenobarbital, carbamazepine) may induce mifepristone metabolism (lowering serum levels of Mifepristone). Based on invitro inhibition information, co-administration of mifepristone may lead to an increase in serum levels of drugs that are CYP3A4 substrates. Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not adversely influence the effects of Mifepristone or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medical termination of pregnancy.

SIDE EFFECTS

It is very common for women to experience uterine contractions or cramping (10-45%) in the hours following prostaglandin intake. Bleeding increases with gestational age. Heavy bleeding occurs in about 5% of cases and from 0-1.4% may require haemostatic curettage. Uterine rupture, hypotension, skin rashes, urticaria, hot flashes and dizziness have been uncommonly reported.

PREGNANCY & LACTATION

Mifepristone is indicated for use in the termination of pregnancy (through 49 days’ pregnancy) and has no other approved indication for use during pregnancy. It is not known whether Mifepristone is excreted in human milk. Many hormones with a similar chemical structure, however, are excreted in breast milk. Since the effects of Mifepristone on infants are unknown, breast-feeding women should consult with their health care provider to decide if they should discard their breast milk for a few days following administration of the medications.

PRECAUTIONS & WARNINGS

Mifepristone is available only in single dose packaging. Administration must be under the supervision of a qualified physician. There are no data on the safety and efficacy of Mifepristone in women with chronic medical conditions such as cardiovascular, hypertensive, hepatic, respiratory or renal disease; insulin-dependent diabetes mellitus; severe anemia or heavy smoking. Women who are more than 35 years of age and who also smoke 10 or more cigarettes per day should be treated with caution because such patients were generally excluded from clinical trials of Mifepristone. Although there is no clinical evidence, the effectiveness of Mifepristone may be lower if Misoprostol is administered more than two days after Mifepristone administration.

THERAPEUTIC CLASS

Drugs acting on the Uterus

STORAGE CONDITIONS

Store in a cool and dry place, protected from light, store below 25°C.