Mifepristone

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. LIMITATIONS OF USE: KORLYM should not be used in the treatment of patients with type 2 diabetes unless it is secondary to Cushing's syndrome. …

• Obtain a negative pregnancy test in females of reproductive potential prior to initiating treatment with KORLYM or if treatment is interrupted for more than 14 days
• Administer once daily orally with a meal
• The recommended starting dose is 300 mg once daily
• 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
• 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
• Concomitant administration with strong CYP3A inhibitors: Do not exceed 900 mg once daily
• Testing Prior to and During KORLYM Administration Obtain a negative pregnancy test in females of reproductive potential prior to initiating treatment with KORLYM or if treatment is interrupted for more than 14 days [see Contraindications , Warnings and Precautions , Use in Specific Populations ]
• Adult Dosage The recommended starting dose is 300 mg orally once daily
• KORLYM must be given as a single daily dose
• KORLYM should always be taken with a meal
• Patients should swallow the tablet whole

Tablets: 300 mg Oval shaped, light yellow to yellow tablets debossed with “Corcept” on one side and “300” on the other side. The tablets are not scored. Tablets: 300 mg ( 3 )

• Safety and effectiveness of KORLYM
• In pediatric patients have not been established

Clinical studies with KORLYM did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger people.

• As a part of patient counseling, doctors must review the KORLYM Medication Guide with every patient
• Importance of Preventing Pregnancy Advise patients that KORLYM will cause termination of pregnancy
• KORLYM is contraindicated in pregnant patients
• KORLYM reduces the effectiveness of hormonal contraceptives
• Counsel females of reproductive potential regarding pregnancy prevention and planning with a non-hormonal contraceptive prior to use of KORLYM and up to one month after the end of treatment
• Instruct patients to contact their physician immediately if they suspect or confirm they are pregnant

KORLYM is contraindicated in: Pregnancy [See Dosage and Administration ( 2.1 ), Use in Specific Populations ( 8.1 , 8.3 )] Patients taking drugs metabolized by CYP3A such as simvastatin, lovastatin, and CYP3A substrates with narrow therapeutic ranges, such as cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus, due to an increased risk of adverse events. …

Based on the long terminal half-life of mifepristone after reaching steady state, at least 2 weeks should elapse after cessation of KORLYM before initiating or increasing the dose of any interacting concomitant medication. Drugs metabolized by CYP3A: Administer drugs that are metabolized by CYP3A at the lowest dose when used with KORLYM ( 7.1 ). CYP3A inhibitors: Caution should be used when KORLYM is used with strong CYP3A inhibitors. Limit mifepristone dose to 900 mg per day when used with strong CYP3A inhibitors ( 7.2 ). CYP3A inducers: Do not use KORLYM with CYP3A inducers ( 7.3 ). …

Adrenal insufficiency : Patients should be closely monitored for signs and symptoms of adrenal insufficiency ( 5.1 ). Hypokalemia : Hypokalemia should be corrected prior to treatment and monitored for during treatment ( 5.2 ). Vaginal bleeding and endometrial changes : Women may experience endometrial thickening or unexpected vaginal bleeding. Use with caution if patient also has a hemorrhagic disorder or is on anti-coagulant therapy ( 5.3 ). QT interval prolongation : Avoid use with QT interval-prolonging drugs, or in patients with potassium channel variants resulting in a long QT interval ( 5.4 ). Use of Strong CYP3A Inhibitors: Concomitant use can increase mifepristone plasma levels. …

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 ( 6 ). To report suspected adverse reactions, contact Corcept Therapeutics at 1-855-844-3270 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice. …

8.1 Pregnancy Risk Summary KORLYM is contraindicated in pregnancy because the use of KORLYM results in pregnancy loss. There are no data that assess the risk of birth defects in women exposed to KORLYM during pregnancy. Available data limited to exposure following a single dose of mifepristone during pregnancy showed a higher rate of major birth defects compared to the general population comparator (See Data ) . …

There is no experience with overdosage of KORLYM.

Tome assim que lembrar, a menos que esteja quase na hora da próxima dose. Nesse caso, pule a dose esquecida. Nunca tome duas doses de uma vez para compensar. Confira a bula, pois alguns medicamentos são diferentes.