mifepristone

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 yr old or who smoke ≥10 cigarettes/day (Mifeprex);
Bleeding disorders or concurrent anticoagulant therapy (Korlym).

Adv. Reactions/Side Effects ⬆ ⬇

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

Derm: rash (Korlym)

Endo: hypothyroidism (Korlym), ↓HDL-C (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)

Misc: ANGIOEDEMA, INFECTION(MIFEPREX)

Interactions ⬆ ⬇

Drug-drug:

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

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use with Korlym.

Drug-Food:

Grapefruit juice may ↑ levels and risk of toxicity; caution with concurrent use of Korlym.

Availability ⬆ ⬇

(Generic available)

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

Route/Dosage ⬆ ⬇

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).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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.

Classifications ⬆ ⬇

Therapeutic Classification: abortifacients, antidiabetics

Pharmacologic Classification: antiprogestational agents

Pharmacokinetics ⬆ ⬇

Absorption: Rapidly absorbed following oral administration (69% bioavailability); absorption ↑ 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.

Time/Action Profile ⬆ ⬇

(termination of pregnancy)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	within 2 days	unknown

Patient/Family Teaching ⬆ ⬇

Mifeprex: Explain the purpose of medication. 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, Days 2–3, and Days 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 >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 provider immediately if heavy bleeding (soak through 2 thick full-size sanitary pads per hr for 2 consecutive hr or are concerned about heavy bleeding); abdominal pain; feeling sick (weakness, nausea, vomiting, or diarrhea with or without abdominal pain or fever more than 24 hr after taking mifepristone); or fever (≥100.4°F that lasts >4 hr; 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 they have 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 provider if they smoke ≥10 cigarettes/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: Explain the purpose and side effects of medication. Instruct patient to take 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.
Instruct patient to notify health care provider 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 provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications. Avoid St. John's wort during treatment.
Rep: May cause fetal harm. Advise women of reproductive potential to use a nonhormonal form of contraception during and for ≥1 mo after last dose of therapy. Notify health care provider immediately if pregnancy is suspected. Advise women 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.

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Indications ⬇

Contraind./Precautions ⬆ ⬇