Pituitary disorders:

Indications for: RECORLEV

To treat endogenous hypercortisolemia in adults with Cushing’s syndrome for whom surgery is not an option or has not been curative.

Limitations of Use:

Not for treatment of fungal infections.

Adult Dosage:

Initially 150mg orally twice daily. Titrate by 150mg daily every 2–3 weeks based on 24hr urine free cortisol (UFC) levels and tolerability. Max 1200mg/day (600mg twice daily). May reduce dose to 150mg once daily if needed. Dose interruptions and modifications: see full labeling.

Children Dosage:

<18yrs: not established.

RECORLEV Contraindications:

Cirrhosis. Acute or poorly controlled chronic liver disease. Baseline AST or ALT >3×ULN. Recurrent symptomatic cholelithiasis. Prior history of drug induced liver injury due to ketoconazole or any azole antifungal therapy requiring treatment discontinuation. Extensive metastatic liver disease. Prolonged QTcF interval >470msec at baseline. History of torsades de pointes, ventricular tachycardia or fibrillation, or long QT syndrome (including 1st degree family history). Hypersensitivity to ketoconazole. Concomitant drugs that cause QT prolongation associated with ventricular arrhythmias, including torsades de pointes. Concomitant certain sensitive CYP3A4 or CYP3A4/P-gp substrate drugs.

Boxed Warning:

Hepatotoxicity. QT prolongation.

RECORLEV Warnings/Precautions:

Risk of serious hepatotoxicity. Obtain baseline liver function tests. Monitor liver enzymes and bilirubin weekly for at least 6 weeks after initiation, every 2 weeks for the next 6 weeks, monthly for the next 3 months, and then as clinically indicated. Permanently discontinue if AST/ALT ≥5×ULN, or AST/ALT ≥3×ULN and total bilirubin is >2×ULN. Risk of QT prolongation. Obtain ECG prior to initiation, during therapy, and before each dose increase. Temporarily discontinue if QTcF interval >500msec. Correct electrolyte abnormalities, hypokalemia and/or hypomagnesemia prior to initiation; monitor periodically. CHF. Bradyarrhythmias. Risk of hypocortisolism, adrenal insufficiency. Evaluate for precipitating causes of hypocortisolism (infection, physical stress, others). Monitor 24hr UFC, morning serum/plasma cortisol, and patient’s signs/symptoms during therapy. Pregnancy. Labor & delivery. Nursing mothers: not recommended (during and for 1 day after the last dose).

RECORLEV Classification:

Cortisol synthesis inhibitor.

RECORLEV Interactions:

See Contraindications. Increased risk of QT prolongation with bosutinib, cisapride, clarithromycin, cobimetinib, crizotinib, disopyramide, dofetilide, dronedarone, eliglustat (in poor or intermediate CYP2D6 metabolizers and in those taking strong or moderate CYP2D6 inhibitors), ivabradine, methadone, midostaurin, nicardipine, pimozide, quinidine, ranolazine. Potentiates sensitive CYP3A4 or CYP3A4/P-gp substrates (eg, alfentanil, avanafil, buspirone, conivaptan, dabigatran etexilate, darifenacin, darunavir, digoxin, ebastine, everolimus, fexofenadine, ibrutinib, lomitapide, lovastatin, midazolam, naloxegol, nisoldipine, saquinavir, simvastatin, sirolimus, tacrolimus, tipranavir, triazolam, vardenafil). Increased risk of myopathy and rhabdomyolysis with atorvastatin; use lowest atorvastatin dose possible and monitor if >20mg/day. Potentiates metformin or may potentiate other OCT2 and MATE substrates; monitor and adjust dose as needed. Avoid concomitant strong CYP3A4 inhibitors (eg, ritonavir, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, saquinavir, mifepristone) or strong CYP3A4 inducers (eg, isoniazid, rifabutin, rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine, mitotane) 2 weeks before and during levoketoconazole therapy. Avoid excessive alcohol, hepatotoxic drugs, sucralfate, H2-receptor antagonists, PPIs. Separate dosing of acid neutralizing drugs (eg, aluminum hydroxide) by at least 2hrs after levoketoconazole.

Adverse Reactions:

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, peripheral edema; hypersensitivity reactions, decreased testosterone levels.

Generic Drug Availability:


How Supplied: