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Clinical Review Report: Mifepristone and misoprostol (Mifegymiso) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 May.

Cover of Clinical Review Report: Mifepristone and misoprostol (Mifegymiso)

Clinical Review Report: Mifepristone and misoprostol (Mifegymiso) [Internet].

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1Introduction

1.1. Disease Prevalence and Incidence

Medical abortion is the process by which a pregnancy is voluntarily terminated through the administration of one or more medications.1 In Canada, the primary method for abortion is surgical (i.e., uterine dilation/curettage [D&C] and suction aspiration), mainly because of the lack of an approved medical intervention.1 Both medical and surgical methods are safe and effective for appropriately selected patients, and the choice of method is based upon availability, gestational age (medical abortion is less successful in late first trimester and beyond), and patient preference.2

According to data reported to the Canadian Institute for Health Information, there were 81,897 induced abortions performed in a Canadian hospital or clinic setting in 2014.3 Of these, 33,931 (41%) were performed in hospitals and 47,966 (58%) in clinics; however, these data are incomplete, as the reporting of clinic data is voluntary and abortions that may have been obtained by Canadian women elsewhere (such as in the US) are not captured.3 Medical abortion presents an opportunity to facilitate the provision of abortion care in settings that are not identified as abortion facilities and to mitigate some of the logistical challenges reported by rural and hospital-based providers.1

1.2. Standards of Therapy

Of the total number of induced abortions reported to Canadian Institute for Health Information by Canadian hospitals in 2014, approximately 96% were surgical procedures (or a combination of surgical and medical procedures) whereas 4% were medical procedures alone.3 In a 2012 survey of Canadian abortion providers, 29.2% (62 of 212 providers) offered medical abortion, with most (84%) using a regimen involving methotrexate and misoprostol.1 The 2016 clinical practice guideline of the Society of Obstetricians and Gynaecologists of Canada (SOGC) on medical abortion for first-trimester pregnancies recommends oral mifepristone 200 mg and misoprostol 800 mcg via the buccal/vaginal/sublingual (SL) routes as the regimen of choice for medical abortion up to 70 days’ gestation among eligible women.1 The use of mifepristone in combination with misoprostol for the termination of pregnancies up to 70 days’ gestation is approved in the US,16 and the mifepristone and misoprostol regimen is considered to be the gold standard for early medical abortion by the World Health Organization (WHO).17 Alternative evidence-based medical abortion regimens include mifepristone and misoprostol regimens at higher gestational age (although associated with decreased completion rates) and methotrexate and misoprostol regimens or misoprostol alone for pregnancies up to 63 days’ gestation in women with contraindications to mifepristone or methotrexate, respectively.1

The decision between medical and surgical abortion requires an understanding of both options and a review of factors that affect method selection.1 The differentiating features of medical abortion are the avoidance of surgery, longer procedure time (i.e., days or weeks compared with minutes), generally more pain, heavier bleeding, more physician visits for assessment, medication administration and follow-up, medication costs that may be borne by the patient, and increased anonymity, when compared with surgical abortion.1 There are a number of conditions for which the use of the mifepristone and misoprostol regimen is absolutely or relatively contraindicated (e.g., ectopic pregnancy, chronic adrenal failure, inherited porphyrias, uncontrolled asthma, known hypersensitivity to any of the components, ambivalence, unconfirmed gestational age, IUD, long-term corticosteroid therapy, and hemorrhagic disorders or use of anticoagulant therapy).1

1.3. Drug

Mifegymiso is a new combination product containing one 200 mg mifepristone tablet for oral administration and four 200 mcg misoprostol tablets for buccal administration, supplied in different coloured boxes that are packaged together. Mifepristone is a synthetic progesterone receptor antagonist, whereas misoprostol is a synthetic analogue of prostaglandin E1.4 When mifepristone blocks progesterone receptors, the endometrium can no longer sustain a growing embryo.4 Without the effect of progesterone, the lining of the uterus breaks down, and bleeding begins.4 Mifepristone also triggers an increase in prostaglandin levels and dilates the cervix, facilitating abortion.4 The subsequent use of misoprostol induces contractions of the smooth muscle fibres in the myometrium, relaxation of the uterine cervix, and evacuation of intrauterine contents.4

Misoprostol was previously marketed in Canada as Cytotec 100 mcg and 200 mcg tablets, and was indicated for the treatment and prevention of nonsteroidal anti-inflammatory drug–induced gastroduodenal ulcers and the treatment of duodenal ulcers caused by peptic ulcer disease.18 The market authorization of Cytotec was cancelled in 2005; however, single-entity misoprostol is currently available as various generic drug products and in combination with diclofenac (i.e., Arthrotec and various generic drug products).

The recommended dose of Mifegymiso is 200 mg of mifepristone taken orally under supervision of the prescriber, followed by 800 mcg of misoprostol (four tablets of 200 mcg each) in a single dose by the buccal route 24 to 48 hours (one to two days) later.4

Indication under reviewa
For medical termination of a developing intrauterine pregnancy with a gestational age up to 49 days as measured from the first day of the LMP in a presumed 28-day cycle
Listing criteria requested by sponsor
Not specified

LMP = last menstrual period.

a

There are insufficient data in patients less than 15 years old to establish efficacy and safety. Mifegymiso is not indicated in prepubertal or post-menopausal populations.

Before prescribing Mifegymiso, physicians must do the following:4

  • Ensure that patients have access to emergency medical care in the 14 days following administration of mifepristone.
  • Schedule follow-up seven to 14 days after patients take mifepristone to confirm complete pregnancy termination.
  • Exclude ectopic pregnancy and confirm gestational age by ultrasound.
  • Counsel each patient on the risks and benefits of Mifegymiso, including bleeding, infection, and incomplete abortion.
  • Obtain the patient’s written informed consent to take the drug.
  • Complete the mandatory Mifegymiso education and registration programs.

Table 2. Key Characteristics of Mifegymiso, Methotrexate, and Misoprostol.

Table 2

Key Characteristics of Mifegymiso, Methotrexate, and Misoprostol.

Copyright © 2017 Canadian Agency for Drugs and Technologies in Health.

The copyright and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for non-commercial purposes only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors.

Except where otherwise noted, this work is distributed under the terms of a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence (CC BY-NC-ND), a copy of which is available at http://creativecommons.org/licenses/by-nc-nd/4.0/

Bookshelf ID: NBK534596

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