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Recorlev Generic Name & Formulations
Legal Class
Rx
General Description
Levoketoconazole 150mg; tabs.
Pharmacological Class
Cortisol synthesis inhibitor.
How Supplied
Tabs—50
Manufacturer
Generic Availability
NO
Recorlev Indications
Indications
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.
Recorlev Dosage and Administration
Adult
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
<18yrs: not established.
Recorlev Contraindications
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.
Recorlev Boxed Warnings
Boxed Warning
Hepatotoxicity. QT prolongation.
Recorlev Warnings/Precautions
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 Pharmacokinetics
See Literature
Recorlev Interactions
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.
Recorlev Adverse Reactions
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.
Recorlev Clinical Trials
See Literature
Recorlev Note
Not Applicable
Recorlev Patient Counseling
See Literature
