Clinical Updates in Reproductive Health

Medical abortion contraindications and precautions

Recommendation:

Mifepristone and misoprostol regimen Misoprostol-only regimen
Contraindications
  • Previous allergic reaction to mifepristone or misoprostol
  • Known or suspected ectopic pregnancy
  • Inherited porphyria
  • Chronic adrenal failure
  • Previous allergic reaction to misoprostol
  • Known or suspected ectopic pregnancy
Precautions
  • Intrauterine device (IUD) in place
  • Serious/unstable health problems, including but not limited to hemorrhagic disorders, heart disease and severe anemia
  • Severe uncontrolled asthma or long-term corticosteroid therapy
  • IUD in place
  • Serious/unstable health problems, including but not limited to hemorrhagic disorders, heart disease and severe anemia

Strength of recommendation: Weak

Quality of evidence: Graded for each specific contraindication or precaution below

 

Definitions

Contraindications: If a woman has any of these specific conditions, she should not be offered medical abortion with the specified regimen. Vacuum aspiration, dilatation and evacuation or treatment for ectopic pregnancy should be offered, as appropriate.

Precautions: If a woman has any of these specific conditions, medical abortion with the specified regimen may incur higher risks than normal. The risks, benefits and alternatives to medical abortion must be considered. Medical abortion provision to women with these conditions may require a higher degree of clinical judgment, skill and monitoring. Referral to a higher-level facility or alternative treatment may be appropriate.

Contraindications

Previous allergic reaction to one of the drugs involved: Allergic reactions have been reported after use of mifepristone and misoprostol (Bene et al., 2014; Cruz et al., 2009; Hauseknecht, 2003; Sahraei, Mirabzadeh, & Eshraghi, 2016; Schoen, Campbell, Maratas, & Cheung, 2014; Zhang, Qian, Hong, & Lu, 2019). Quality of evidence: High

Known or suspected ectopic pregnancy: Mifepristone and misoprostol do not treat ectopic pregnancy and use of the medications may delay diagnosis and treatment of this life-threatening condition. Quality of evidence: High

Inherited porphyria: Porphyrias are rare metabolic disorders in which genetic mutations alter the body’s generation of heme. Theoretically, mifepristone could exacerbate the manifestation of porphyria (Ventura, Cappellini, & Rochi, 2009). Quality of evidence: Very low. No human studies exist, but animal models exhibit the effect of mifepristone (Cable, Pepe, Donohue, Lambrecht, & Bonkovsky, 1994).

Chronic adrenal failure: Mifepristone is a glucocorticoid receptor antagonist (Spitz & Bardin, 1993). Mifepristone blocks negative feedback mechanisms that control cortisol secretion. In women with adrenal insufficiency on long-term corticosteroid therapy, mifepristone exposure may exacerbate the underlying condition (Sitruk-Ware
& Spitz, 2003). Quality of evidence: Very low. There are no data on mifepristone use in pregnant women with adrenal insufficiency, but there is experimental and animal data to support the recommendation.

Precautions

IUD in place: A woman who is pregnant with an IUD is at significantly elevated risk of ectopic pregnancy (Barnhart, 2009) and must be evaluated for the presence of ectopic pregnancy. If the pregnancy is found to be intrauterine, the IUD should be removed before starting medical abortion due to the theoretical risk of uterine perforation from contractions during medical abortion and the potential risk of infection (Danco, 2016; Davey, 2006). Quality of evidence: Very low. There are no studies to verify whether having an IUD in place poses actual risks during medical abortion.

Serious medical problems: Medical abortion studies generally exclude women with severe anemia or serious medical problems (Christin-Maitre, Bouchard, & Spitz, 2000; Sitruk-Ware & Spitz, 2003). One case report (Hou, 2016) documents successful medical abortion in a patient with mild hemophilia; this patient received specialized, additional medication to minimize bleeding risk. Three case reports document misoprostol-induced acute coronary artery vasospasm, which in one case required coronary artery stent placement (Illa, Bennasar, Berge, Font, & Palacio, 2010; Mazhar, Sultana, & Akram, 2018; Munoz-Franco, Lacunza-Ruiz, Vazquez-Andres, & Rodriguez-Hernandez, 2019). Whether to provide medical abortion to women with medical conditions will depend on clinical judgment, monitoring and options available for safe abortion care. Quality of evidence: Very low.

Severe uncontrolled asthma or long-term corticosteroid therapy: Mifepristone is a glucocorticoid receptor antagonist (Spitz & Bardin, 1993). Mifepristone blocks negative endocrine feedback mechanisms that control cortisol secretion. In women on long-term corticosteroid therapy for severe or uncontrolled asthma, mifepristone may exacerbate the underlying condition (Sitruk-Ware & Spitz, 2003). There are no direct studies of medical abortion among women on corticosteroid treatment, but one review suggested that increasing the dose of the steroid medications can counteract the cortisol blunting effect of mifepristone (Davey, 2006).

Medical abortion in asthmatic women requiring systemic corticosteroids has not been studied as giving mifepristone to such women risks asthma exacerbation. One review suggests using a high level of caution when giving mifepristone to such women and only doing so if the asthma is well-controlled (Davey, 2006). The glucocorticoid dose should be increased for several days before and after mifepristone. Other experts recommend that women with severe, poorly controlled asthma who are on long-term corticosteroids not take mifepristone due to the life-threatening nature of acute asthma exacerbation (Christin-Maitre et al., 2000; Creinin & Gemzell Danielsson, 2009; Sitruk-Ware, 2006).

Inhaled corticosteroids for asthma are not systemically absorbed and are not a contraindication to mifepristone. Some experts recommend that mifepristone and misoprostol should be available to women with asthma who are not on long-term systemic steroids (Creinin & Gemzell Danielsson, 2009). Quality of evidence: Very low

References

Barnhart, K. T. (2009). Clinical practice. Ectopic pregnancy. New England Journal of Medicine, 361(4), 379-387.

Bene, J., Alarcon, P., Faucon, M., Auffret, M., Delfosse, F., Becker, T., … Gautier, S. (2014). Anaphylactic shock after misoprostol in voluntary termination pregnancy-a case report. European Journal of Obstetrics, Gynecology and Reproductive Biology, 182, 260-261.

Cable, E. E., Pepe, J. A., Donohue, S. E., Lambrecht, R. W., & Bonkovsky, H. L. (1994). Effects of mifepristone (RU-486) on heme metabolism and cytochromes P-450 in cultured chick embryo liver cells, possible implications for acute porphyria. European Journal of Biochemistry, 225(2), 651-657.

Christin-Maitre, S., Bouchard, P., & Spitz, I. M. (2000). Medical termination of pregnancy. New England Journal of Medicine, 342(13), 946-956.

Creinin, M. & Gemzell Danielsson K. (2009). Medical abortion in early pregnancy. In M. Paul, E. S. Lichtenberg, L. Borgatta, D. A. Grimes, P. G. Stubblefield & M. D. Creinin (Eds.), Management of unintended and abnormal pregnancy. West Sussex UK: Wiley-Blackwell.

Cruz, M. J., Duarte, A. F., Baudrier, T., Cunha, A. P., Barreto, F., & Azevedo, F. (2009). Lichenoid drug eruption induced by misoprostol. Contact Dermatitis, 61, 240-242.

Danco Laboratories, LLC. (2016). Mifeprex® Prescribing Information. Retrieved from: www.earlyoptionpill.com

Davey, A. (2006). Mifepristone and prostaglandin for termination of pregnancy: Contraindications for use, reasons, and rationale. Contraception, 74(1), 16-20.

Hausknecht, R. (2003). Mifepristone and misoprostol for early medical abortion: 18 months experience in the United States. Contraception, 67(6), 463-465.

Hou, M. Y. (2016). Uncomplicated abortion with mifepristone and misoprostol in hemophilia A carrier. Contraception, 94(2), 187-189.

Illa, M., Bennasar, M., Berge, R., Font, C., & Palacio, M. (2010). Acute coronary artery vasospasm associated with misoprostol for termination of pregnancy. Fetal Diagnosis and Therapy, 27, 174-177.

Mazhar, F., Sultana, J., & Akram, S. (2018). Misoprostol-induced acute coronary syndrome in a premenopausal woman: A case report with literature review. Current Drug Safety, 13(1), epub ahead of print.

Munoz-Franco, F. M., Lacunza-Ruiz, F. J., Vazquez-Andres, D. J., & Rodriguez-Hernandez, J. R. (2019). Coronary artery vasospasm after misoprostol treatment for incomplete abortion: A case report. Contraception, 100(6), 498-501.

Sahraei, Z., Mirabzadeh, M., & Eshraghi, A. (2016). Erythema multiforme associated with misoprostol: A case report. American Journal of Therapeutics, 23(5), e1230-1233.

Schoen, C., Campbell, C., Maratas, A., & Cheung, K. (2014). Anaphylaxis to buccal misoprostol for labor induction. Obstetrics & Gynecology, 124(2, Part 2, Supplement 1), 466-468.

Sitruk-Ware, R. (2006). Mifepristone and misoprostol sequential regimen side effects, complications and safety. Contraception, 74(1), 48-55.

Sitruk-Ware, R. & Spitz, I. M. (2003). Pharmacological properties of mifepristone: Toxicology and safety in animal and human studies. Contraception, 68(6), 409-20.

Spitz, I. M. & Bardin, C. W. (1993). Mifepristone (RU-486)—A modulator of progestin and glucocorticoid action. New England Journal of Medicine, 329(6), 404-12.

Ventura, P., Cappellini M. D., & Rochi, E. (2009). The acute porphyrias: A diagnostic and therapeutic challenge in internal and emergency medicine. Internal and Emergency Medicine, 4(4), 297-308.

Zhang, L., Qian, M., Hong, L., & Wu, Q. (2019). First case report of acute generalized exanthemous pustulosis (AGEP) caused by mifepristone. Contact Dermatitis,  1-2.