Mifepristone R.E.M.S.

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What is mifepristone?

Mifepristone, at low doses, is a synthetic steroid that functions as a selective antagonist of the intracellular progesterone receptor, blocking the effects of progesterone. When used for termination of pregnancy, this leads to contraction-inducing activity in the myometrium.

Mifepristone has FDA approval for medical termination of intrauterine pregnancy through 70-days gestation. It is used in combination with misoprostol, a prostaglandin analogue that causes cervical softening/dilation and uterine contractions.

Mifepristone R.E.M.S.

FDA’s Risk Evaluation and Mitigation Strategy (REMS) is required for certain medications with serious safety concerns to help ensure that the benefits outweigh the risks.

  • Previously, FDA required in-person dispensing and administration of mifepristone at a clinic, hospital, or under direct supervision of a certified provider. In response to the COVID pandemic, in April 2021, FDA allowed dispensing of mifepristone by mail under a certified provider’s supervision following a telehealth consultation.

The goal of the mifepristone REMS is to mitigate the risk of serious complications associated with mifepristone by

  • Requiring healthcare providers who prescribe mifepristone to become certified in the Mifepristone REMS Program;
  • Ensuring that mifepristone is only dispensed by or under the supervision of certified prescribers, or by certified pharmacies on prescriptions issued by certified prescribers;
  • Informing patients about the risk of serious complications associated with mifepristone.

In January 2023, FDA determined that available data supported modification of the mifepristone REMS to reduce burden on the health care delivery system and help improve patient access, leading to two primary changes:

  • Removed the “in-person dispensing requirement” that mifepristone be dispensed only in certain health care settings (i.e., clinics, medical offices, hospitals) or by mail order
  • Added the requirement that pharmacies that dispense the drug must be certified

Provider criteria under the mifepristone REMS:

  • Mifepristone must be prescribed by a health care provider that meets certain qualifications and is certified under the Mifepristone REMS Program.
  • To become certified to prescribe mifepristone, health care providers must complete a Prescriber Agreement Form.
  • The Patient Agreement Form must be reviewed with and signed by the patient and the health care provider, and the risks of the mifepristone treatment regimen must be fully explained to the patient before mifepristone is prescribed.
  • The patient must be provided with a copy of the Patient Agreement Form and mifepristone Medication Guide (FDA-approved information for patients).

Pharmacy criteria under the mifepristone REMS:

  • Mifepristone may only be dispensed by or under the supervision of a certified prescriber, or by a certified pharmacy on a prescription issued by a certified prescriber
  • To become certified to dispense mifepristone, pharmacies must complete a Pharmacy Agreement form
  • Certified pharmacies must be able to ship mifepristone using a shipping service that provides tracking information
  • Certified pharmacies must ensure mifepristone is dispensed to the patient in a timely manner

More Notes on Mifepristone

Contraindications

  • Confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass
  • Chronic adrenal failure
  • Concurrent long-term corticosteroid therapy
  • History of allergy to mifepristone, misoprostol, or other prostaglandins
  • Hemorrhagic disorders or concurrent anticoagulant therapy
  • Inherited porphyria
  • Intrauterine device (IUD) in place

Dosing & Administration

  • Day 1: mifepristone 200 mg PO
  • 24 to 48 hours after taking mifepristone: misoprostol 800 mcg taken buccally
    • Two tablets of misoprostol are placed in each cheek pouch (area between cheek and gums) for 30 minutes, followed by swish and swallow with water
  • 7-14 days after taking mifepristone: follow-up with health care provider

Counseling Points

  • Following misoprostol administration:
    • Most people respond to misoprostol within 2 to 24 hours
    • If significant discomfort or excessive vaginal bleeding occurs, patients should contact a physician or go to the emergency room
  • Day 7 to 14:
    • Follow up with healthcare provider to confirm complete termination of pregnancy and evaluate degree of bleeding
    • Expect vaginal bleeding or spotting to continue for an average of 9 to 16 days

Common Adverse Reactions

  • Nausea
  • Vomiting
  • Diarrhea
  • Weakness
  • Fever/chills
  • Headache
  • Dizziness

Black Box Warning

  • Serious and sometimes fatal infections and bleeding occur very rarely following spontaneous, surgical, and medical abortions, including following mifepristone use. No causal relationship between the use of mifepristone and misoprostol and these reactions has been established. Before prescribing mifepristone, inform the patient about the risk of these serious events. Ensure that the patient knows whom to call and what to do, including going to an emergency room, if none of the provided contacts are reachable, if they experience sustained fever, severe abdominal pain, prolonged heavy bleeding, or syncope, or if they experience abdominal pain or discomfort or general malaise (including weakness, nausea, vomiting, or diarrhea) more than 24 hours after taking misoprostol.
  • Patients with serious bacterial infections (e.g., Clostridium sordelli) and sepsis can present without fever, bacteremia, or significant findings on pelvic examination following an abortion. Very rarely, deaths have been reported in patients who presented without fever, with or without abdominal pain, but with leukocytosis with a marked left shift, tachycardia, hemoconcentration, and general malaise. A high index of suspicion is needed to rule out serious infection and sepsis.
  • Prolonged heavy bleeding may be a sign of incomplete abortion or other complications, and prompt medical or surgical intervention may be needed. Advise patients to seek immediate medical attention if they experience prolonged heavy vaginal bleeding.

Drug-Drug Interactions

  • CYP3A4 inducers lower mifepristone concentrations
    • Inducers include rifampin, dexamethasone, St. John’s Wort, and certain anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine)
  • CYP3A4 inhibitors increase mifepristone concentrations
    • Inhibitors include ketoconazole, itraconazole, erythromycin, and grapefruit juice

Take-Home Points!

  • Mifepristone, a medication used for medical termination of intrauterine pregnancy through 70-days gestation, may now be dispensed from certified pharmacies
  • Any pharmacy that meets the requirements of the Mifepristone REMS Program is eligible for certification
  • Pharmacists must be aware of the risks associated with mifepristone in order to safely dispense to patients in the community

Further Reading!

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