PATIENT SITE

Determining the Effective Dose of Korlym for Your Patient

The recommended starting dose for Korlym is 300 mg once daily. Cortisol levels cannot be used to determine the dose of Korlym. Decisions about dose increases should be based on a clinical assessment of tolerability and degree of improvement in Cushing's syndrome manifestations, including changes in:

  • Glucose control
  • Antidiabetic medication requirements
  • Insulin levels
  • Psychiatric symptoms
  • Cushingoid appearance
  • Acne
  • Hirsutism
  • Striae
  • Body weight

The pivotal trial assessed a broad range of these symptoms. Individual patients showed varying degrees of improvement in these Cushing's syndrome manifestations.1 Because of the variability in clinical presentation and variability of response in this open-label trial, it is uncertain whether these changes could be ascribed to the effects of Korlym.2

Change in mean AUCinsulin in all patients not taking insulin

Chart Image

The data in the above chart includes patients in both the diabetes and hypertension cohorts.1

AUC = area under the concentration-time curve. ET = early termination.

Source: Fleseriu M, et al.1

Changes in weight and body composition1

By Week 24/ET in the modified intent-to-treat population (n=46), the median change in body weight was 5.7±7.4%

  • 24 patients lost ≥5% of their baseline weight (12 patients lost ≥10%)
  • Mean percent total body fat declined from 42.3% overall at baseline to 38.7% (a reduction of 3.6%)
  • Waist circumference decreased by 6.8±5.8 cm in women and by 8.4±5.9 cm in men

Changes in Cushingoid appearance1,2

Individual patients showed varying degrees of improvement in Cushingoid appearance assessments, including:

  • Moon facies
  • Plethora
  • Fat distribution
  • Acne
  • Hirsutism
  • Striae

Changes in mood and cognition

In patients with Cushing's syndrome and at least mild depression, depression was measured using the Beck Depression Inventory-II (BDI-II) scale. Median BDI-II scores improved in the modified intent-to-treat population (baseline 14.5, range 0-49; Week 24/ET 9.5, range 0-36).1

The BDI-II is a 21-question scale that measures the severity of depressive symptoms. Questions are answered on a scale of 0 (I don't feel sad) to 3 (I am so sad that I can't stand it).3,4

Cognition scores were measured by the Trail-Making Test (TMT) at Week 24/ET. There were improvements in both Trail A (a median decrease of 4 seconds) and Trail B (a median decrease of 12 seconds).1

The TMT comprises 2 parts that measure cognitive ability. Parts A and B are completed in succession. Part A requires the patient to draw a line connecting 25 numbers in numerical order. Part B requires the connection of 25 numbers and letters in sequential order.

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; May 2017.

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

4. Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck Depression Inventories-IA and-II in psychiatric outpatients. J Pers Assess. 1996;67(3):588-597.

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.