The standard regimen for medication abortion involves two drugs, mifepristone followed by misoprostol, which are approved by the U.S. Food and Drug Administration (FDA) to terminate pregnancies up to 10 weeks of gestation.¹⁸x18American Congress of Obstetricians and Gynecologists. Practice bulletin no. 143: medical management of first-trimester abortion. Obstet Gynecol. 2014; 123: 676–692

Crossref | PubMed | Scopus (9) | Google ScholarSee all References Mifepristone (Mifeprex®, also known as RU-486) is a progesterone antagonist, which binds without activating the progesterone receptor, thereby leading to decidual necrosis (breakdown of the lining of the uterus), cervical softening, and increased uterine prostaglandin sensitivity. Misoprostol, a prostaglandin E1 analogue, causes cervical dilation and softening and uterine contractions to promote pregnancy expulsion.

The FDA-approved labeling for Mifeprex® was updated in March 2016 and describes an evidence-based treatment,¹⁹x19Abbas, D., Chong, E., and Raymond, E.G. Outpatient medical abortion is safe and effective through 70 days gestation. Contraception. 2015; 92: 197–199

Abstract | Full Text | Full Text PDF | PubMed | Scopus (12) | Google ScholarSee all References^{, 20}x20Chen, M.J. and Creinin, M.D. Mifepristone with buccal misoprostol for medical abortion: a systematic review. Obstet Gynecol. 2015; 126: 12–21

Crossref | PubMed | Scopus (30) | Google ScholarSee all References^{, 21}x21Cleland, K. and Smith, N. Aligning mifepristone regulation with evidence: driving policy change using 15 years of excellent safety data. Contraception. 2015; 92: 179–181

Abstract | Full Text | Full Text PDF | PubMed | Scopus (6) | Google ScholarSee all References^{, 22}x22Foster, A.M., Jackson, C.B., LaRoche, K.J., Simmonds, K., and Taylor, D. From qualified physician to licensed health care professional: the time has come to change mifepristone's label. Contraception. 2015; 92: 200–202

Abstract | Full Text | Full Text PDF | PubMed | Scopus (6) | Google ScholarSee all References^{, 23}x23Grossman, D. and Grindlay, K. Alternatives to ultrasound for follow-up after medication abortion: a systematic review. Contraception. 2011; 83: 504–510

Abstract | Full Text | Full Text PDF | PubMed | Scopus (47) | Google ScholarSee all References^{, 24}x24Raymond, E.G., Shannon, C., Weaver, M.A., and Winikoff, B. First-trimester medical abortion with mifepristone 200 mg and misoprostol: a systematic review. Contraception. 2013; 87: 26–37

Abstract | Full Text | Full Text PDF | PubMed | Scopus (66) | Google ScholarSee all References^{, 25}x25Weitz, T.A., Taylor, D., Desai, S. et al. Safety of aspiration abortion performed by nurse practitioners, certified nurse midwives, and physician assistants under a California legal waiver. Am J Public Health. 2013; 103: 454–461

Crossref | PubMed | Scopus (51) | Google ScholarSee all References including 200 mg mifepristone orally, followed 24-48 hours later by 800 mcg misoprostol administered buccally. This regimen may be used up to 70 days from the last menstrual period (10 weeks' gestation).¹¹x11Mifeprex, R.E.M.S. Study Group. Sixteen years of overregulation: time to unburden Mifeprex. N Engl J Med. 2017; 376: 790–794

Crossref | PubMed | Scopus (5) | Google ScholarSee all References The efficacy of this evidence-based regimen is 93% to 99%, meaning that 1% to 7% of patients will require a vacuum aspiration procedure to complete the abortion.¹⁸x18American Congress of Obstetricians and Gynecologists. Practice bulletin no. 143: medical management of first-trimester abortion. Obstet Gynecol. 2014; 123: 676–692

Crossref | PubMed | Scopus (9) | Google ScholarSee all References The U.S. Government Accountability Office recently reviewed the process that the FDA used for updating the Mifeprex® label and found that it was appropriate and based on the best available evidence.²⁶x26Government Accountability Office. Food and Drug Administration: information on Mifeprex labeling changes and ongoing monitoring efforts. U.S. Government Accountability Office, Washington, DC; March 28, 2018 (Available at:)https://www.gao.gov/products/GAO-18-292. (Accessed May 1, 2018)

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Women seeking medication abortion first undergo standard counseling to ensure that they are certain about their decision to terminate the pregnancy, as well as their choice to have a medication abortion instead of a vacuum aspiration procedure. A clinician then screens patients for medical eligibility for medication abortion. This includes assessing gestational age with the use of ultrasound or clinical assessment of uterine size and ruling out ectopic pregnancy, because mifepristone and misoprostol do not effectively terminate or treat an ectopic pregnancy. The clinician also screens for other contraindications, including chronic adrenal failure or long-term corticosteroid therapy (because of mifepristone's antiglucocorticoid effect), hemorrhagic disorders or concurrent anticoagulant use, presence of an intrauterine device, inherited porphyria (given the possible increased risk of precipitating an attack), and allergy to mifepristone, misoprostol, or other prostaglandins.²⁷x27U.S. Food and Drug Administration. Medication guide highlights of prescribing information: Mifeprex. FDA, Silver Spring, MD; 2016 (Available at:)https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020687s020lbl.pdf. (Accessed May 1, 2018)

Google ScholarSee all References^{, 28}x28Cable, E.E., Pepe, J.A., Donohue, S.E., Lambrecht, R.W., and Bonkovsky, H.L. Effects of mifepristone (RU-486) on heme metabolism and cytochromes P-450 in cultured chick embryo liver cells, possible implications for acute porphyria. Eur J Biochem. 1994; 225: 651–657

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Pretreatment laboratory testing commonly includes hemoglobin to assess for anemia and blood type to determine Rhesus (Rh) status.¹⁸x18American Congress of Obstetricians and Gynecologists. Practice bulletin no. 143: medical management of first-trimester abortion. Obstet Gynecol. 2014; 123: 676–692

Crossref | PubMed | Scopus (9) | Google ScholarSee all References Vaginal bleeding after medication administration (discussed in detail below) is unlikely to be well tolerated by women with severe anemia. In addition, women who are Rh-negative are advised to receive RhD immunoglobulin at the time of abortion to prevent the development of anti-D antibodies and to reduce the risk of alloimmunization in subsequent pregnancies.¹⁸x18American Congress of Obstetricians and Gynecologists. Practice bulletin no. 143: medical management of first-trimester abortion. Obstet Gynecol. 2014; 123: 676–692

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After ensuring eligibility, clinicians provide counseling on medication abortion and dispense the mifepristone directly to the patient, which may be taken in the clinic or at a later time, according to the FDA-approved labeling. Misoprostol may be dispensed directly by the clinician, or it may be prescribed and dispensed at a pharmacy; women take the misoprostol dose buccally at home 24-48 hours after mifepristone. Some providers use an off-label regimen of 800 mcg misoprostol self-administered vaginally as soon as 6 hours after mifepristone.²⁹x29Creinin, M.D., Fox, M.C., Teal, S., Chen, A., Schaff, E.A., Meyn, L.A., and MOD Study Trial Group. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. Obstet Gynecol. 2004; 103: 851–859

Crossref | PubMed | Scopus (77) | Google ScholarSee all References Although mifepristone is rapidly absorbed, few patients experience bleeding or pregnancy expulsion before taking misoprostol. Bleeding may occur within 1 hour of misoprostol ingestion, and 90% expel the pregnancy within 24 hours.²⁷x27U.S. Food and Drug Administration. Medication guide highlights of prescribing information: Mifeprex. FDA, Silver Spring, MD; 2016 (Available at:)https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020687s020lbl.pdf. (Accessed May 1, 2018)

Google ScholarSee all References^{, 30}x30Spitz, I.M., Bardin, C.W., Benton, L., and Robbins, A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med. 1998; 338: 1241–1247

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Expected adverse effects of medication abortion include vaginal bleeding and uterine cramping, which almost always occur with successful pregnancy termination. Clinicians often counsel patients to expect a “crescendo-decrescendo” bleed whereby the patient’s bleeding intensifies and then decreases once the pregnancy tissue is passed. The total duration of vaginal bleeding varies, but it is approximately 8 to 17 days on average.¹⁵x15Christin-Maitre, S., Bouchard, P., and Spitz, I.M. Medical termination of pregnancy. N Engl J Med. 2000; 342: 946–956

Crossref | PubMed | Scopus (104) | Google ScholarSee all References The Mifeprex® medication guide that must be given to patients includes the recommendation that they should call or seek care if they feel lightheaded or are experiencing heavy bleeding, defined as soaking more than two large pads per hour for two consecutive hours.²⁷x27U.S. Food and Drug Administration. Medication guide highlights of prescribing information: Mifeprex. FDA, Silver Spring, MD; 2016 (Available at:)https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020687s020lbl.pdf. (Accessed May 1, 2018)

Google ScholarSee all References Cramping pain usually peaks shortly after the patient takes misoprostol, and it can often be controlled with the use of nonsteroidal anti-inflammatory drugs or, if necessary, oral opioids. Adverse effects can include gastrointestinal complaints such as nausea (34% to 72%), vomiting (12% to 41%), and diarrhea (3% to 26%).¹⁸x18American Congress of Obstetricians and Gynecologists. Practice bulletin no. 143: medical management of first-trimester abortion. Obstet Gynecol. 2014; 123: 676–692

Crossref | PubMed | Scopus (9) | Google ScholarSee all References Less common adverse effects include headache, dizziness, and thermoregulatory effects such as fever or hot flashes.²¹x21Cleland, K. and Smith, N. Aligning mifepristone regulation with evidence: driving policy change using 15 years of excellent safety data. Contraception. 2015; 92: 179–181

Abstract | Full Text | Full Text PDF | PubMed | Scopus (6) | Google ScholarSee all References

Patients are generally encouraged to have follow-up after medication abortion within 2 weeks to ensure that the pregnancy has been effectively terminated and is not ongoing, which occurs in 0.5%-3% of cases (a subset of the 1% to 7% who require vacuum aspiration to complete the abortion).²¹x21Cleland, K. and Smith, N. Aligning mifepristone regulation with evidence: driving policy change using 15 years of excellent safety data. Contraception. 2015; 92: 179–181

Abstract | Full Text | Full Text PDF | PubMed | Scopus (6) | Google ScholarSee all References Ultrasound can be performed approximately 1 week after mifepristone administration or sooner if the patient reports pregnancy expulsion. Alternatively, serum human chorionic gonadotropin (hCG) may be measured on the day of mifepristone and again 1 week later. A decline in the hCG value of less than 80% over 1 week suggests an ongoing pregnancy and requires additional follow-up.³¹x31Behnamfar, F., Mahdian, M., Rahimi, F., and Samimi, M. Misoprostol abortion: ultrasonography versus beta-hCG testing for verification of effectiveness. Pak J Med Sci. 2013; 29: 1367–1370

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Since mifepristone was approved by the FDA in 2000, there have been more than 3 million American users and 19 deaths reported, yielding an estimated mortality rate of 0.0006%.¹¹x11Mifeprex, R.E.M.S. Study Group. Sixteen years of overregulation: time to unburden Mifeprex. N Engl J Med. 2017; 376: 790–794

Crossref | PubMed | Scopus (5) | Google ScholarSee all References In comparison, the risk of death among pregnant women in the United States who have a live birth is 14 times greater, at 0.009%.³²x32Raymond, E.G. and Grimes, D.A. The comparative safety of legal induced abortion and childbirth in the United States. Obstet Gynecol. 2012; 119: 215–219

Crossref | PubMed | Scopus (95) | Google ScholarSee all References Non-fatal serious adverse events, such as hospital admission, surgery, blood transfusion, or serious infection, are also rare after mifepristone use, occurring in approximately 0.3% of cases; these are almost always treatable without permanent sequelae.³³x33Upadhyay, U.D., Desai, S., Zlidar, V. et al. Incidence of emergency department visits and complications after abortion. Obstet Gynecol. 2015; 125: 175–183

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The FDA has reported a total of eight cases of fatal toxic shock after medication abortion, likely related to ascending infection secondary to vaginal colonization of Clostridium sordellii and C. perfringens.³⁴x34U.S. Food and Drug Administration. Mifepristone U.S. postmarketing adverse events summary through 04/30/2011. FDA, Silver Spring, MD; 2011 (Available at:)https://www.minnpost.com/sites/default/files/attachments/Mifeprex_April2011_AEs.pdf. (Accessed May 1, 2018)

Google ScholarSee all References Deaths attributed to clostridial infections have also been reported after vaginal delivery, cesarean section, and miscarriage, and there is no evidence of a causal link between medication abortion and infection.²⁷x27U.S. Food and Drug Administration. Medication guide highlights of prescribing information: Mifeprex. FDA, Silver Spring, MD; 2016 (Available at:)https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020687s020lbl.pdf. (Accessed May 1, 2018)

Google ScholarSee all References^{, 35}x35Cohen, A.L., Bhatnagar, J., Reagan, S., Zane, S.B., D'Angeli, M.A., and Fischer, M. Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion. Obstet Gynecol. 2007; 110: 1027–1033

Crossref | PubMed | Scopus (78) | Google ScholarSee all References Administration of prophylactic antibiotics at the time of mifepristone administration is controversial, due in part to the lack of evidence that such treatment eliminates carriage of clostridial species and the potential risks associated with antimicrobials, including adverse effects and the development of antibiotic resistance.³⁶x36Kapp, N., Whyte, P., Tang, J., Jackson, E., and Brahmi, D. A review of evidence for safe abortion care. Contraception. 2013; 88: 350–363

Abstract | Full Text | Full Text PDF | PubMed | Scopus (14) | Google ScholarSee all References

Medication abortion in the United States is primarily offered by clinicians who were already providing aspiration or surgical abortion. Uptake of medication abortion provision among private physicians has been less than expected—especially in areas not served by providers of surgical abortion. In 2005, there were only 4 providers of medication abortion that were located more than 50 miles from any surgical abortion provider.³⁷x37Finer, L.B. and Wei, J. Effect of mifepristone on abortion access in the United States. Obstet Gynecol. 2009; 114: 623–630

Crossref | PubMed | Scopus (26) | Google ScholarSee all References Part of the limited uptake among private physicians may be related to the Mifeprex® Risk Evaluation and Mitigation Strategy (REMS) program, which states that the medication may be dispensed only in clinics, medical offices, and hospitals and not in pharmacies by prescription. The REMS also requires prescribers to complete a Prescriber Agreement Form and register with the manufacturer to order the medication, and patients are required to sign an FDA-approved Patient Agreement Form summarizing the label’s use instructions and potential risks of the drug.

The intent of REMS programs is to add additional safety measures to a small number of drugs that are suspected of causing serious adverse effects that cannot be mitigated simply by the label instructions.³⁸x38U.S. Food and Drug Administration. Approved Risk Evaluation and Mitigation Strategies (REMS). FDA, Silver Spring, MD; 2016 (Available at:)https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm?event=IndvRemsDetails.page&REMS=35. (Accessed May 1, 2018)

Google ScholarSee all References^{, 39}x39U.S. Food and Drug Administration. Approved drug products with therapeutic equivalence evaluations (Orange Book). FDA, Silver Spring, MD; 2018 (Available at:)https://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm. (Accessed May 1, 2018)

Google ScholarSee all References Given its safety record, mifepristone no longer fits the profile of a drug that requires an REMS.¹¹x11Mifeprex, R.E.M.S. Study Group. Sixteen years of overregulation: time to unburden Mifeprex. N Engl J Med. 2017; 376: 790–794

Crossref | PubMed | Scopus (5) | Google ScholarSee all References Furthermore, the opportunity for misuse of the drug is minimal owing to the fact that each woman receives only a single dose. The requirement to stock mifepristone in clinic is a possible barrier to uptake by physicians⁴⁰x40Grossman, D., Grindlay, K., and Schulkin, J. Abortion provision among a national sample of obstetrician-gynecologists. Contraception. 2017; 96: 272–273

Abstract | Full Text | Full Text PDF | Google ScholarSee all References that pharmacy dispensing could help to address. Pharmacy dispensing and counseling pursuant to a prescription would allow for an additional safety check, patient counseling opportunity, and bundling of medication dispensing (such as analgesics, antibiotics, and contraceptives).

At least 2 other countries, Australia and Canada, have shifted to pharmacy dispensing of medication abortion. In Australia, evidence indicates that pharmacy dispensing has improved access to medication abortion in rural areas and has contributed to the expansion of telemedicine services. Pharmacy dispensing of mifepristone was approved in 2012, 3 years after the drug was first registered in Australia. By May 2015, the number of certified prescribers and dispensers of mifepristone in Western Australia far exceeded the number of facilities providing abortion care.¹²x12Grossman, D. and Goldstone, P. Mifepristone by prescription: a dream in the United States but reality in Australia. Contraception. 2015; 92: 186–189

Abstract | Full Text | Full Text PDF | PubMed | Scopus (14) | Google ScholarSee all References Although only 4 facilities provided abortions and were all located in the metropolitan area of Perth, there were 62 certified prescribers and 147 certified dispensers of medication abortion, with one-third located in rural areas.¹²x12Grossman, D. and Goldstone, P. Mifepristone by prescription: a dream in the United States but reality in Australia. Contraception. 2015; 92: 186–189

Abstract | Full Text | Full Text PDF | PubMed | Scopus (14) | Google ScholarSee all References In Canada, mifepristone was approved in 2015, and regulations in some provinces now permit pharmacists to dispense it directly to patients, replacing the prior restriction to “physician-only” dispensing.¹³x13Government of Canada. MIFEGYMISO Canadian Distribution and Administration Program. Ottawa, Ontario, Canada, Health Canada; 2017 (Available at:)http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2017/63330a-eng.php.

Google ScholarSee all References^{, 41}x41Norman, W.V. and Soon, J.A. Requiring physicians to dispense mifepristone: an unnecessary limit on safety and access to medical abortion. CMAJ. 2016; 188: E429–E430

Crossref | PubMed | Scopus (1) | Google ScholarSee all References^{, 42}x42Ontario College of Pharmacists. Dispensing Mifegymiso: guidance for pharmacy professionals who are dispensing mifegymiso. Ontario College of Pharmacists, Ontario Canada; 2017 (Available at:)http://www.ocpinfo.com/library/practice-related/download/Dispensing_Mifegymiso.pdf. (Accessed May 1, 2018)

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Changes in policy may not lead to immediate widespread implementation. In the case of over-the-counter emergency contraception, women still face barriers to accessing the medication at pharmacies.⁴³x43Cleland, K., Bass, J., Doci, F., and Foster, A. Access to EC in the Over-the-Counter Era. Women's Health Issues. 2016; 26: 622–627

Abstract | Full Text | Full Text PDF | PubMed | Scopus (4) | Google ScholarSee all References Pharmacy access to medication abortion may face similar barriers to implementation. Because most U.S. pharmacists are not involved in abortion care, it is likely that they are not familiar with medication abortion regimens, follow-up protocols, and management of complications, as was found in Australia before the implementation of pharmacy dispensing.⁴⁴x44Lee, R.Y., Moles, R., and Chaar, B. Mifepristone (RU486) in Australian pharmacies: the ethical and practical challenges. Contraception. 2015; 91: 25–30

Abstract | Full Text | Full Text PDF | PubMed | Scopus (5) | Google ScholarSee all References This knowledge gap could be addressed by integrating evidence-based trainings into pharmacist education.

Some pharmacists may object to dispensing mifepristone and counseling on medication abortion for personal or ethical reasons, just as some physicians decline to provide abortion.⁴⁵x45Stulberg, D.B., Dude, A.M., Dahlquist, I., and Curlin, F.A. Abortion provision among practicing obstetrician-gynecologists. Obstet Gynecol. 2011; 118: 609–614

Crossref | PubMed | Scopus (27) | Google ScholarSee all References If the number of pharmacists who object to dispensing is significant, particularly in a geographic area with limited pharmacies and access to health care, women may have to return later to fill their prescriptions or go elsewhere, which could cause delays in treatment. Strategies that have been used to facilitate pharmacist provision of contraception can also be applied to mifepristone dispensing. These include public education and community organizing, pharmacist outreach and training, and working with state pharmacy boards to shape statewide policies to ensure timely medication access.⁴⁶x46Reynertson, S., Singh, R., and Uttley, L. Pharmacy refusal toolkit protesting women's rights at the pharmacy counter: advocacy strategies from states and localities. Merger Watch. 2006;

Google ScholarSee all References Garnering corporate support for pharmacy dispensing of mifepristone and counseling on medication abortion may facilitate implementation in chain pharmacies. Supporting both pharmacies in stocking mifepristone and prescribing clinicians in writing prescriptions for the drug could help to expand access to medication abortion.

There are important benefits to women that could be realized through pharmacy dispensing of mifepristone and counseling on medication abortion by trained pharmacists. This shift in policy would increase the number of clinicians able to provide medication abortion by enabling them to avoid the up-front costs and challenges of stocking and dispensing in their offices or clinics. Pharmacy dispensing would likely enable women to bypass certain geographic, financial, or insurance obstacles to clinic-based care and receive abortion services earlier in pregnancy.⁴⁷x47Drey, E.A., Foster, D.G., Jackson, R.A., Lee, S.J., Cardenas, L.H., and Darney, P.D. Risk factors associated with presenting for abortion in the second trimester. Obstet Gynecol. 2006; 107: 128–135

Crossref | PubMed | Scopus (100) | Google ScholarSee all References^{, 48}x48Jerman, J., Frohwirth, L., Kavanaugh, M.L., and Blades, N. Barriers to abortion care and their consequences for patients traveling for services: qualitative findings from two states. Perspect Sex Reprod Health. 2017; 49: 95–102

Crossref | PubMed | Scopus (4) | Google ScholarSee all References^{, 49}x49Grosman, D.A., Grindlay, K., Buchacker, T., Potter, J.E., and Schmertmann, C.P. Changes in service delivery patterns after introduction of telemedicine provision of medical abortion in Iowa. Am J Public Health. 2013; 103: 73–78

Crossref | PubMed | Scopus (26) | Google ScholarSee all References For example, pharmacy dispensing could reduce disparities in access to medication abortion by facilitating direct-to-patient telemedicine services for women in medically underserved areas through the use of community or mail-order pharmacies. Finally, dispensing mifepristone and counseling on medication abortion at pharmacies may help to dispel myths that mifepristone is a dangerous drug.