mifepristone
Regulatory sources consulted
Approved indications
- Medical termination of an ongoing intrauterine pregnancy up to 63 days of amenorrhea, sequentially with a prostaglandin analogue.
- Cervical ripening before surgical termination of pregnancy during the first trimester.
Contraindications
Absolute
- Chronic adrenal failure, severe uncontrolled asthma, hereditary porphyria, or hypersensitivity.
- For medical termination: unconfirmed pregnancy, more than 63 days of amenorrhea, suspected ectopic pregnancy, or contraindication to the selected prostaglandin analogue.
Clinical warnings
- Major warning · Use only within a protocol that ensures counseling, the prostaglandin analogue when applicable, emergency care, and follow-up to confirm complete expulsion. — CIMA/AEMPS, ficha técnica 62728
- Major warning · Seek urgent care for very heavy bleeding, persistent pain, fever, or malaise. Hemorrhage, severe infection or septic shock, and uterine rupture with prostaglandins have been reported. — CIMA/AEMPS, ficha técnica 62728
- Major warning · Stop and do not re-expose after a severe skin reaction, including toxic epidermal necrolysis or acute generalized exanthematous pustulosis. — CIMA/AEMPS, ficha técnica 62728
Drug interactions
- HighStrong or moderate CYP3A4 inducers
Mechanism: They markedly reduce mifepristone exposure and may lower effectiveness.
Recommendation: Follow the label-specific regimen for patients receiving inducers; do not improvise dosing.
CIMA/AEMPS, ficha técnica 62728https://cima.aemps.es/cima/dochtml/ft/62728/FT_62728.html
- HighNarrow-therapeutic-index CYP3A4 substrates
Mechanism: Mifepristone inhibits CYP3A4 and may increase exposure and toxicity of narrow-therapeutic-index substrates.
Recommendation: Avoid or use specialist monitoring and adjust the substrate according to its label.
CIMA/AEMPS, ficha técnica 62728https://cima.aemps.es/cima/dochtml/ft/62728/FT_62728.html
- ModerateNSAIDs, including acetylsalicylic acid
Mechanism: There is a theoretical concern about prostaglandin antagonism; evidence cited in the label did not show that same-day use reduced cervical ripening, uterine contractility, or clinical effectiveness.
Recommendation: Do not extrapolate this observation to every regimen; follow the authorized protocol and assess concomitant use individually.
CIMA/AEMPS, ficha técnica 62728https://cima.aemps.es/cima/dochtml/ft/62728/FT_62728.html
Adverse events
Common (≥1%)
Uterine bleeding · Cramping pain or uterine contractions · Nausea · Vomiting · Diarrhea · Post-abortion infection
Rare but serious
Hemorrhage requiring intervention · Septic or toxic shock · Uterine rupture · Severe skin reaction
Pregnancy and lactation
The product is used to terminate pregnancy. If the method fails and the woman decides to continue the pregnancy, specialist follow-up is required because fetal risk is uncertain. It is excreted in small amounts in milk and should be avoided while breastfeeding.
Recent literature (PubMed)
This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 μg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygrosco
Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an antipsychotic, another treatment (e.g. mifepristone), or combination of an antidepressant plus an antipsychotic. This is an update of a review first published in 2005 and last updated in 2015. 1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, mifepristone monotherapy, and the combination of an antidepressant plus an antipsychotic versus placebo and/or each other. 2. To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment. A search of the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR); Ovid MEDLINE (1950-); Embase (1974-); and PsycINFO (1960-) was conducted on 21 February 2020. Reference lists of all included studies and related reviews were screened and key study authors contacted. All randomised controlled trials (RCTs) that included participants with acute major depression with psychotic features, as well as RCTs consisting of participants with acute major depression with or without psychotic features, that reported separately on the subgroup of participants with psychotic features. Two review authors independently extracted data and assessed risk of bias in the included studies, according to criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used intention-to-treat data. Primary outcomes were clinical response for efficacy and overall dropout rate for harm/tolerance. Secondary outcome were remission of depression, change from baseline severity score, quality of life, and dropout rate due to adverse effects. For dichotomous efficacy outcomes (i.e. respon