Uterine fibroids
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).
Mifepristone is a synthetic steroid which blocks the effects of progesterone by competitively binding to the intracellular progesterone receptor. It sensitises the myometrium to the contraction-inducing action of prostaglandin. At higher doses, it blocks the effect of cortisol at the glucocorticoid receptor while increasing circulating cortisol concentrations.
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.
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: Mifepristone is indicated for use in the termination of pregnancy (through 49 days’ pregnancy) and has no other approved indication for use during pregnancy.
Lactation: 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.
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.
Use in children: Safety and effectiveness in pediatric patients have not been established.
Drugs acting on the Uterus
Single doses of Mifepristone up to 2 gm caused no unwanted reaction. In the event of massive ingestion, signs of adrenal failure might occur. Acute intoxication may require admission to hospital and if relevant treatment with dexamethasone.
Store at 25° C.
