Mifepristone

KORLYM

Open Mifepristone in the interactive console ↗

Pronunciation: mi-FE-pri-stoen (KOR-lim)

Mifepristone ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Mifepristone ballicule

What it isProgesterone- and glucocorticoid-receptor antagonist; pregnancy termination and Cushing-syndrome hyperglycemia.

Why this oneThe same receptor pharmacology enables medical abortion with misoprostol and cortisol blockade without lowering cortisol levels.

What limits itAbortion use can cause severe bleeding or infection; Cushing treatment can cause adrenal insufficiency, hypokalemia, and QT prolongation.

Mifepristone molecular structure (skeletal formula) — Molecular structure: Mifepristone

FDA-approved for

pregnancy termination (2000)
Cushing hyperglycemia (2012)

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger1 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades2 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk4 / 4

Legacy pregnancy categoryX

Defining liabilityGenerally tolerated at therapeutic doses; clinically important risks are agent-specific and increase with interactions or organ impairment.

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Termination of pregnancy: exclude pregnancy before starting and if treatment is interrupted for more than 14 days (females of reproductive potential); prevent pregnancy with non-hormonal contraception during treatment and for one month after stopping.

FDA dosing	Population	Start	Target	Max
Hyperglycemia secondary to hypercortisolism in endogenous Cushing's syndrome with type 2 diabetes or glucose intolerance, after failed surgery or not a surgical candidate	Adults	300 mg PO QD with a meal	Increase in 300 mg increments per clinical response and tolerability	1200 mg QD; not to exceed 20 mg/kg per day
Same — renal impairment	Adults, renal impairment	300 mg QD (no change in initial dose)	Titrate in 300 mg increments	600 mg QD
Same — mild to moderate hepatic impairment	Adults, mild–moderate hepatic impairment	300 mg QD (no change in initial dose)	Titrate in 300 mg increments	600 mg QD; do not use in severe hepatic impairment
Same — already on a strong CYP3A inhibitor	Adults on strong CYP3A inhibitors	300 mg QD	Titrate only if clinically indicated	900 mg QD

Titration Increase no more frequently than once every 2-4 weeks.

Renal No change in initial dose; maximum 600 mg QD.

Hepatic Mild to moderate: no change in initial dose; maximum 600 mg QD. Severe: do not use.

Serum cortisol stays elevated on KORLYM and cannot be used to assess adrenal insufficiency.

Instructions

Negative pregnancy test (females of reproductive potential) before starting and if treatment is interrupted for more than 14 days.
Single daily dose, always with a meal; swallow whole — do not split, crush, or chew.
Adding a strong CYP3A inhibitor to current KORLYM: 300 mg no change; 600 mg → 300 mg (max 600 mg); 900 mg → 600 mg (max 900 mg); 1200 mg → 900 mg.
After an interruption, restart at the lowest dose (300 mg); after interruption for adverse reactions, aim for a dose lower than the one that caused it.
Correct hypokalemia before starting; check potassium 1 to 2 weeks after starting or increasing the dose and periodically thereafter.
Wait at least 2 weeks after stopping KORLYM before starting or increasing an interacting drug.
Use non-hormonal contraception (KORLYM interferes with hormonal contraceptives).

Available strengths

tab 200, 300 mg

Contraindications

Pregnancy
Concomitant CYP3A substrates: simvastatin, lovastatin, and narrow-therapeutic-range CYP3A substrates (cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus)
Systemic corticosteroids for lifesaving purposes (e.g., immunosuppression after organ transplantation)
History of unexplained vaginal bleeding, endometrial hyperplasia with atypia, or endometrial carcinoma

Cautions

Adrenal insufficiency — monitor clinically (cortisol not reliable); stop and give glucocorticoids if suspected
Hypokalemia — correct before, monitor during
Vaginal bleeding and endometrial changes; caution with hemorrhagic disorders/anticoagulants
QT interval prolongation
Exacerbation of conditions treated with corticosteroids
Strong CYP3A inhibitors — use only when necessary, cap dose
Pneumocystis jiroveci infection
Potential effects of hypercortisolemia (heart failure, coronary disease)

Adverse reactions

Nausea (48%)
Fatigue (48%)
Headache (44%)
Endometrial hypertrophy (38%)
Blood potassium decreased (34%)
Arthralgia (30%)
Vomiting (26%)
Peripheral edema (26%)
Hypertension (24%)
Dizziness (22%)
Decreased appetite (20%)

Pregnancy Contraindicated — causes pregnancy loss; single-dose human data showed a higher rate of major birth defects; exclude pregnancy and use non-hormonal contraception.

Lactation Present in human milk (amount with long-term use unknown); weigh benefits; may pump and discard during treatment and for 18-21 days after the last dose.

Cost

Mifepristone (KORLYM)

Strength		#/mo	generic $/unit	CostPlus
200 mg	tab	per unit		not offered
300 mg	tab	per unit		not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Mifepristone is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Generic entry2019

Open Mifepristone in the interactive console ↗

Self-check

Does mifepristone’s cortisol blockade lower cortisol levels?
No.
Which companion drug is used with mifepristone for medical abortion?
Misoprostol.