mifepristone

mi-fe-PRISS-tone

Therapeutic Classification: abortifacients, antidiabetics

Pharmacologic Classification: antiprogestational agents

REMS

Mifeprex

Medical termination of intrauterine pregnancy up to day 70 of pregnancy (in combination with misoprostol).

Korlym

Hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome who have type 2 diabetes or glucose intolerance and have failed or are not candidates for surgery

Antagonizes endometrial and myometrial effects of progesterone.
Sensitizes the myometrium to contraction-inducing activity of prostaglandins.
Antagonizes the glucocorticoid receptor

Therapeutic effects:

Termination of pregnancy.
Improved control of blood glucose.

Absorption: Rapidly absorbed following oral administration (69% bioavailability); absorption enhanced with food.

Distribution: Unknown.

Protein Binding: 98%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme; primarily excreted in the feces.

Half-Life: 18 hr.

(termination of pregnancy)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	within 2 days	unknown

Contraindicated in:

Hypersensitivity;
Presence of an intrauterine device (IUD) (Mifeprex);
Undiagnosed adnexal mass (Mifeprex);
Chronic adrenal failure (Mifeprex);
Concurrent long-term corticosteroid therapy;
Bleeding disorders or concurrent anticoagulant therapy (Mifeprex);
Inherited porphyrias (Mifeprex);
Severe hepatic impairment (Korlym);
Concurrent use with simvastatin, lovastatin, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, or tacrolimus (Korlym);
Vaginal bleeding;
Endometrial hyperplasia with atypia or endometrial carcinoma (Korlym);
OB: Confirmed or suspected ectopic pregnancy (Mifeprex);
OB: Pregnancy (Korlym).

Use Cautiously in:

Chronic medical conditions such as cardiovascular, hypertensive, hepatic, renal, or respiratory disease (Mifeprex);
Women >35 yrs old or who smoke ≥10 cigarettes/day (Mifeprex);
Bleeding disorders or concurrent anticoagulant therapy (Korlym).

CV: hypertension (Korlym), peripheral edema (Korlym), QT interval prolongation (Korlym)

Derm: rash (Korlym)

Endo: hypothyroidism (Korlym), ↓HDL cholesterol (Korlym), adrenal insufficiency (Korlym)

F and E: hypokalemia (Korlym)

GI: abdominal pain (Mifeprex), anorexia (Korlym), constipation (Korlym), diarrhea, dry mouth (Korlym), nausea, vomiting

GU: uterine bleeding, uterine cramping (Mifeprex), pelvic pain (Mifeprex), ruptured ectopic pregnancy (Mifeprex)

MS: arthralgia (Korlym), myalgia (Korlym)

Neuro: anxiety (Korlym), dizziness, fatigue (Korlym), headache, fainting (Mifeprex), weakness (Mifeprex)

Resp: dyspnea (Korlym), Pneumocystis jirovecipneumonia

Misc: ANGIOEDEMA

Drug-drug:

↑blood levels and risk of toxicity from dihydroergotamine, ergotamine, lovastatin, simvastatin, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, or tacrolimus; concurrent use with Korlym is contraindicated.
Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, nefazodone, ritonavir, nelfinavir, atazanavir, fosamprenavir, clarithromycin, conivaptan, lopinavir/ritonavir, posaconazole, or voriconazole may ↑ levels; adjust dose of Korlym.
Moderate CYP3A4 inhibitors, including aprepitant, diltiazem, fluconazole, imatinib, or verapamil may ↑ levels; caution with concurrent use of Korlym
Blood levels and effects may be ↓ by rifampin, rifabutin dexamethasone, phenytoin, phenobarbital, and carbamazepine; avoid concurrent use with Korlym.

Drug-Natural Products:

Levels and effects may be ↓ by St. John's wort; avoid concurrent use with Korlym.

Levels and effects may be ↑ by grapefruit juice; caution with concurrent use of Korlym.

Mifeprex

PO (Adults ): Day 1: 200 mg as a single dose, followed on Day 2 or Day 3 (within 24–48 hr of taking Mifeprex) by misoprostol 800 mcg (given as four 200–mcg tablets) given buccally.

Korlym

PO (Adults ): 300 mg once daily; may ↑ by 300 mg/day every 2–4 wk (maximum dose = 1200 mg/day or 20 mg/kg/day); Initiation of Korlym in patients already being treated with strong CYP3A4 inhibitor: 300 mg once daily; may titrate up to 900 mg once daily, if needed; Initiation of strong CYP3A4 inhibitor in patients already being treated with Korlym: Current dose of Korlym = 300 mg once daily: No change; Current dose of Korlym = 600 mg once daily: ↓ dose to 300 mg once daily (may titrate up to 600 mg once daily, if needed); Current dose of Korlym = 900 mg once daily: ↓ dose to 600 mg once daily; Current dose of Korlym = 1200 mg once daily: ↓ dose to 900 mg once daily.

Renal Impairment

PO (Adults ): 300 mg once daily; may ↑ by 300 mg/day every 2–4 wk (maximum dose = 600 mg/day).

Hepatic Impairment

PO (Adults ): 300 mg once daily; may ↑ by 300 mg/day every 2–4 wk (maximum dose = 600 mg/day).

(Generic available)

Tablets (Korlym): 300 mg
Tablets (Mifeprex): 200 mg

Mifeprex: Determine duration of pregnancy. Pregnancy is dated from the first day of the last menstrual period in a presumed 28-day cycle with ovulation occurring at mid-cycle and can be determined by menstrual history and clinical examination; use ultrasound if duration is uncertain or if ectopic pregnancy is suspected. Assess women who became pregnant with an IUD in place for ectopic pregnancy.
Assess amount of bleeding and cramping during treatment. Determine if termination is complete on day 14.
Korlym: Monitor for changes in cushingoid appearance (acne, hirsutism, striae, body weight) during therapy.
Monitor for signs and symptoms of adrenal insufficiency (weakness, nausea, increased fatigue, hypotension, hypoglycemia) during therapy. If adrenal insufficiency is suspected, discontinue Korlym and administer glucocorticoids immediately.

Lab Test Considerations:

Mifeprex: ↓hemoglobin, hematocrit, and RBCs may occur in women who bleed heavily.
- Changes in quantitative human chorionic gonadotropin (hCG) levels are not accurate until at least 10 days after mifepristone administration; complete termination of pregnancy must be confirmed by clinical examination.
Korlym: Verify negative pregnancy test in women prior to starting therapy or before restarting therapy if stopped for more than 14 days. Correct hypokalemia prior to starting therapy. Assess serum potassium 1–2 wk after starting or increasing dose of Korlym and periodically thereafter.
- Monitor A1c periodically during therapy.

Do not confuse mifepristone with misoprostol.
Mifeprex is only available through a restricted program, mifepristone REMS program. Prescribers and pharmacies that dispense mifepristone must be certified by the program and patients must sign an agreement form.
Mifeprex: Mifepristone should be administered only by health care professionals who have read and understood the prescribing information, are able to assess gestational age of an embryo and diagnose ectopic pregnancies, and who are able to provide surgical intervention in cases of incomplete abortion or severe bleeding.
- Remove any IUD prior to mifepristone administration.
- Measures to prevent rhesus immunization, similar to those of surgical abortion, should be taken.
PO: On day 1, after the patient has read the Medication Guide and signed the Patient Agreement, administer one 200–mg tablet of mifepristone as a single dose. On day 2 or 3, unless abortion has occurred and been confirmed by clinical examination or ultrasound, administer four 200-mcg tablets of misoprostol buccally between 24 and 48 hrs after taking mifepristone. Expulsion of pregnancy usually happens within 2–24 hrs of taking misoprostol. On day 7–14, confirm that termination of pregnancy has occurred by clinical examination or ultrasound. If complete expulsion has not occurred, administer another dose of misoprostil 800 mcg buccally.
Korlym: Administer with a meal. DNC: Swallow tablet whole; do not crush, break, or chew.
- If Korlym therapy is interrupted, reinitiate at lowest dose (300 mg).

Mifeprex: Advise patient of the treatment and its effects. Patients must be given a copy of the Medication Guide and Patient Agreement. Patient must understand the necessity of completing the treatment schedule of three office visits (day 1, day 2–3, and day 7–14).
Inform patient that vaginal bleeding and uterine cramping will probably occur and that prolonged or heavy vaginal bleeding is not proof of complete expulsion. Bleeding or spotting occurs for an average of 9–16 days; but may continue for more than 30 days. Advise patient that if the treatment fails, there is a risk of fetal malformation; medical abortion failures are managed by surgical termination.
Caution patient to notify health care professional immediately if heavy bleeding (soak through 2 thick full-size sanitary pads per hr for 2 consecutive hrs or are concerned about heavy bleeding); abdominal pain or feeling sick (weakness, nausea, vomiting, diarrhea, with or without abdominal pain or fever more than 24 hr after taking mifepristone); or fever (≥100.4°F that lasts >4 hrs, may indicate life-threatening sepsis) occurs.
Instruct patient in the steps to take in an emergency situation, including precise instructions and a telephone number to call if she has problems or concerns.
May cause dizziness or fainting. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional if she smokes at least 10 cigarettes a day.
Rep: Caution patient that pregnancy can occur following termination of pregnancy and before resumption of normal menses. Contraception can be initiated as soon as pregnancy termination is confirmed, or before sexual intercourse is resumed.
Korlym: Instruct patient to take Korlym as directed. Advise patient to read Medication Guide prior to starting therapy and with each refill in case of changes.
Caution patient to avoid drinking grapefruit juice during therapy; may increase risk of side effects.
Instruct patient to notify health care professional if signs and symptoms of adrenal insufficiency, abnormal vaginal bleeding, or low potassium (muscle weakness, aches, cramps, palpitations) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: May cause fetal harm. Advise female patient to use a nonhormonal form of contraception during and for at least 1 mo after last dose of therapy. Notify health care professional immediately if pregnancy is suspected. Advise female patient to avoid breastfeeding during therapy. To minimize exposure to a breastfed infant, women who discontinue or interrupt Korlym therapy may consider pumping and discarding milk during therapy and for 18–21 days (5–6 half-lives) after last dose, before breastfeeding.

Mifeprex: Termination of an intrauterine pregnancy of less than 70 days duration.
Korlym: Improved control of blood glucose.

Korlym, Mifeprex

NDC Code

43393- GenBioPro Inc
- 43393-001- Mifepristone
  - 43393-001-06- 6 CARTON in 1 PACKAGE (43393-001-06) > 1 BLISTER PACK in 1 CARTON > 1 TABLET in 1 BLISTER PACK (43393-001-01)

76346- Corcept Therapeutics
- 76346-073- Korlym
  - 76346-073-01- 28 TABLET in 1 BOTTLE (76346-073-01)

76346- Corcept Therapeutics
- 76346-073- Korlym
  - 76346-073-02- 280 TABLET in 1 BOTTLE (76346-073-02)

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