Mifepristone

A decrease of the efficacy of the method can theoretically occur due to the antiprostaglandin properties of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin (acetyl salicylic acid). Some 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.

Due to the antiglucocorticoid activity of mifepristone, the efficacy of long-term corticosteroid therapy, including inhaled corticosteroids in asthmatic patients, may be decreased during the 3 to 4 days following intake of mifepristone. Therapy should be adjusted.

Based on in vitro inhibition information, co-administration of mifepristone may lead to an increase in serum levels of drugs that are CYP3A4 substrates. Due to the slow elimination of mifepristone from the body, such interaction may be observed for a prolonged period after its administration. Therefore, caution should be exercised when mifepristone is administered with drugs that are CYP3A4 substrates and have narrow therapeutic range, including some agents used during general anaesthesia.

No interaction studies have been performed. On the basis of this drug’s metabolism by CYP3A4, it is possible that 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).

In the absence of specific studies, mifepristone is not recommended in patients with:

• Malnutrition
• Hepatic failure
• Renal failure

Rare but serious cardiovascular accidents (myocardial infarction and/or spasm of the coronary arteries and severe hypotension) have been reported following the intra vaginal and intra muscular administration of a high dose of prostaglandin analogue. Misoprostol administered orally could also constitute a potential risk factor of acute cardiovascular events. For this reason, women with risk factors for cardiovascular disease (e.g. age over 35 years with chronic smoking, hyperlipidemia, diabetes) or established cardiovascular disease should be treated with caution.

In case of suspected acute adrenal failure, dexamethasone administration is recommended. 1 mg of dexamethasone antagonises a dose of 400 mg of mifepristone.

In animals, the abortifacient effect of mifepristone precludes the proper assessment of any teratogenic effect of the molecule.

With subabortive doses, malformations were observed in rabbits, but not in rats, mice or monkeys. In clinical practice, rare cases of malformations of the extremity of lower limbs (out of them, club-foot) have been reported in case of mifepristone administered alone or associated with prostaglandins. One of the possible mechanisms might be amniotic band syndrome. However, data is too limited to determine whether the molecule is a human teratogen.

Consequently:

• Women should be informed, that due to the risk of failure of the medical method of pregnancy termination and to the risk to the foetus, the follow-up visit is mandatory.
• Should a failure of the method be diagnosed at the follow-up visit (viable ongoing pregnancy),and should the patient still agree, pregnancy termination should be completed by another method.
• Should the patient wish to continue with her pregnancy, a careful ultrasound monitoring of the pregnancy, with a special attention to the limbs, must be established in a specialised centre.

Mifepristone is excreted in mother’s milk in small amounts. Consequently, mifepristone use should be avoided during breastfeeding.

Fertility

Mifepristone does not affect fertility. It is possible that the woman becomes pregnant again as soon as the termination of pregnancy is completed. Therefore, it is important to inform the patient to start contraception immediately after the termination of the pregnancy is confirmed.

No data showing an effect on the ability to drive or using machines are known. Dizziness could occur as a side effect inherent of the abortion process. When driving or using machines one should take this possible side effect into account.