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About Korlym®

Korlym is approved for use in patients with endogenous Cushing's syndrome who have1:

  • Type 2 diabetes or glucose intolerance secondary to hypercortisolism and
  • Failed surgery or are not candidates for surgery

Because hypercortisolism often leads to hyperglycemia in patients with Cushing's syndrome, the pivotal trial for Korlym was designed to measure changes in glucose levels in patients with glucose intolerance or type 2 diabetes mellitus.

By blocking the glucocorticoid receptor, Korlym is able to help control hyperglycemia associated with Cushing's syndrome.

  • In the SEISMIC pivotal trial*, 60% of patients had ≥25% reduction from baseline in AUCglucose (in the Oral Glucose Tolerance Test [OGTT])1
    • The mean hemoglobin A1c (HbA1c) was reduced from 7.4% to 6.3%1
    • All patients with above-normal HbA1c levels at baseline experienced reductions—8 of these 14 normalized their HbA1c2
    • Antidiabetic medications were reduced in half the patients with diabetes mellitus type 2 and remained constant in the others1
  • Eighty-eight percent of patients who completed the trial chose to enroll in an extension trial3
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Click here to learn about the dosing and titration of Korlym.

*The pivotal trial enrolled 50 subjects with clinically significant hypercortisolism. Forty-three patients had Cushing's disease and all except one had previously undergone pituitary surgery. Four patients had ectopic ACTH secretion, and 3 had adrenal carcinoma. The population was 26 to 71 years of age; 70% were female. Forty-six of the 50 subjects received at least 30 days of dosing during the 24-week study period and were included in a modified intent-to-treat (mITT) analysis. Pre-existing antidiabetic and antihypertensive medications were continued at the start of Korlym treatment.1,2

1. Fleseriu M, Biller BM, Findling JW, Molitch ME, Schteingart DE, Gross C; on behalf of the SEISMIC Study Investigators. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome. J Clin Endocrinol Metab. 2012;97(6):2039-2049.

2. Korlym full Prescribing Information. Corcept Therapeutics Incorporated; 2013.

3. Data on file, Corcept Therapeutics Incorporated. March 31, 2013.

INDICATIONS AND USAGE

Korlym® (mifepristone) is a cortisol receptor blocker indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery.

Important Limitations of Use

Do not use for the treatment of type 2 diabetes mellitus unrelated to endogenous Cushing's syndrome.

IMPORTANT SAFETY INFORMATION

WARNING: TERMINATION OF PREGNANCY

Mifepristone is a potent antagonist of progesterone and cortisol via the progesterone and glucocorticoid (GR-II) receptors, respectively. The antiprogestational effects will result in the termination of pregnancy. Pregnancy must therefore be excluded before the initiation of treatment with Korlym and prevented during treatment and for one month after stopping treatment by the use of a nonhormonal medically acceptable method of contraception unless the patient has had a surgical sterilization, in which case no additional contraception is needed. Pregnancy must also be excluded if treatment is interrupted for more than 14 days in females of reproductive potential.

DOSAGE AND ADMINISTRATION

Administer once daily orally with a meal. The recommended starting dose is 300 mg once daily. Renal impairment: Do not exceed 600 mg once daily. Mild-to-moderate hepatic impairment: Do not exceed 600 mg once daily. Do not use in severe hepatic impairment. Based on clinical response and tolerability, the dose may be increased in 300-mg increments to a maximum of 1200 mg once daily. Do not exceed 20 mg/kg per day.

Concomitant use of Korlym with a strong CYP3A inhibitor resulted in a 38% increase in mean plasma concentration of mifepristone. For patients already being treated with a strong CYP3A inhibitor, start with a Korlym dose of 300 mg per day and titrate to a maximum of 600 mg per day if clinically indicated. When a strong CYP3A inhibitor is administered to patients already receiving Korlym, adjust the dose as follows: For patients receiving a daily dose of 600 mg, reduce the daily dose to 300 mg. Titrate to a maximum of 600 mg per day if clinically indicated. For patients receiving a daily dose of either 900 mg or 1200 mg, reduce the daily dose to 600 mg.

CONTRAINDICATIONS

Pregnancy; use of simvastatin or lovastatin and CYP3A substrates with narrow therapeutic range; concurrent long-term corticosteroid use; women with history of unexplained vaginal bleeding; women with endometrial hyperplasia with atypia or endometrial carcinoma.

WARNINGS AND PRECAUTIONS

Adrenal insufficiency: Patients should be closely monitored for signs and symptoms of adrenal insufficiency.

Hypokalemia: Hypokalemia should be corrected prior to treatment and monitored for during treatment.

Vaginal bleeding and endometrial changes: Women may experience endometrial thickening or unexpected vaginal bleeding. Use with caution if the patient also has a hemorrhagic disorder or is on anticoagulant therapy.

QT interval prolongation: Avoid use with QT interval-prolonging drugs, or in patients with potassium channel variants resulting in a long QT interval.

Use of Strong CYP3A Inhibitors: Concomitant use increases mifepristone plasma levels. Adjust Korlym dose as described in Dosage and Administration. Use only when necessary and do not exceed a Korlym dose of 600 mg.

ADVERSE REACTIONS

Most common adverse reactions in Cushing's syndrome (≥20%): nausea, fatigue, headache, decreased blood potassium, arthralgia, vomiting, peripheral edema, hypertension, dizziness, decreased appetite, endometrial hypertrophy.

DRUG INTERACTIONS

Drugs metabolized by CYP3A: Administer drugs that are metabolized by CYP3A at the lowest dose when used with Korlym.

CYP3A inhibitors: Caution should be used when Korlym is used with strong CYP3A inhibitors. Adjust Korlym dose as described in Dosage and Administration. Use only when necessary, and do not exceed a Korlym dose of 600 mg.

CYP3A inducers: Do not use Korlym with CYP3A inducers.

Drugs metabolized by CYP2C8/2C9: Use the lowest dose of CYP2C8/2C9 substrates when used with Korlym.

Drugs metabolized by CYP2B6: Use of Korlym should be done with caution with bupropion and efavirenz.

Hormonal contraceptives: Do not use with Korlym.

USE IN SPECIFIC POPULATIONS

Nursing mothers: Discontinue drug or discontinue nursing.

Please see accompanying full Prescribing Information and Medication Guide.