Levoketoconazole

RECORLEV is indicated for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative. Limitations of Use RECORLEV is not approved for the treatment of fungal infections. The safety and effectiveness of RECORLEV for the treatment of fungal infections have not been established. RECORLEV is a cortisol synthesis inhibitor indicated for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative.

In vitro, levoketoconazole inhibits key steps in the synthesis of cortisol and testosterone, principally those mediated by CYP11B1 (11β hydroxylase), CYP11A1 (the cholesterol side-chain cleavage enzyme, the first step in the conversion of cholesterol to pregnenolone), and CYP17A1 (17α-hydroxylase).

Obtain baseline liver and electrocardiogram tests and correct hypokalemia and hypomagnesemia before starting RECORLEV. Initiate dosage at 150 mg orally twice daily, with or without food. Titrate dosage by 150 mg daily, no more frequently than every 2-3 weeks. Maximum recommended dosage is 1200 mg daily, administered as 600 mg twice daily. For additional recommendations on titration and monitoring for efficacy, see Full Prescribing Information. For recommendations on safety monitoring and dosage modifications for hepatotoxicity, QT prolongation and hypocortisolism, see Full Prescribing Information

RECORLEV is contraindicated in patients: With cirrhosis, acute liver disease or poorly controlled chronic liver disease, baseline AST or ALT greater than 3 times the upper limit of normal, recurrent symptomatic cholelithiasis, a prior history of drug induced liver injury due to ketoconazole or any azole antifungal therapy that required discontinuation of treatment, or extensive metastatic liver disease. Taking drugs that cause QT prolongation associated with ventricular arrhythmias, including torsades de pointes.

Boxed warning (hepatotoxicity and qt prolongation): Hepatotoxicity • Cases of hepatotoxicity with a fatal outcome or requiring liver transplantation have been reported with use of oral ketoconazole. Some patients had no obvious risk factors for liver disease. Serious hepatotoxicity has been reported in patients receiving RECORLEV. Hypocortisolism: Hypocortisolism has been reported with RECORLEV. Monitor patients for hypocortisolism. Dosage reduction or interruption may be necessary. Hypersensitivity Reactions: Hypersensitivity to RECORLEV has been reported. Anaphylaxis has been reported with oral ketoconazole. Risks Related to Decreased Testosterone: RECORLEV may lower serum testosterone in men and women. Inform patients to report associated symptoms

The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatotoxicity QT Prolongation Hypocortisolism Hypersensitivity Reactions Risks related to Decreased Testosterone Most common adverse reactions (incidence > 20%) are nausea/vomiting, hypokalemia, hemorrhage/contusion, systemic hypertension, headache, hepatic injury, abnormal uterine bleeding, erythema, fatigue, abdominal pain/dyspepsia, arthritis, upper respiratory infection, myalgia, arrhythmia, back pain, insomnia/sleep disturbances, and peripheral edema.

Consult approved product labeling for drugs that are substrates of CYP3A4, P-gp, OCT2, and MATE prior to initiating RECORLEV. Sensitive CYP3A4 or CYP3A4 and P-gp Substrates: Concomitant use of RECORLEV with these substrates is contraindicated or not recommended. Atorvastatin: Use lowest atorvastatin dose possible and monitor for adverse reactions for dosages exceeding 20 mg daily. Metformin: Monitor glycemia, kidney function, and vitamin B12 and adjust metformin dosage as needed. Strong CYP3A4 Inhibitors or Inducers: Avoid use of these drugs 2 weeks before and during RECORLEV treatment. Gastric Acid Modulators: See Full Prescribing Information for recommendations regarding concomitant use with RECORLEV

Storage Store RECORLEV at 20° to 25°C (68° to 77°F), excursions permitted between 15° to 30°C (59° to 86°F).