• Obtain ECG at baseline, before each dose ↑, and then routinely during therapy after a stable dose achieved. If QTcF interval >500 msec, interrupt therapy. Resume at ↓ dose if QTcF interval ≤500 msec and any contributing factors corrected. If QT interval prolongation recurs, permanently discontinue levoketoconazole.
• Monitor for precipitating causes of hypocortisolism (infection, physical stress).

Lab Test Considerations:

• Obtain baseline ALT, AST, and total bilirubin; then check weekly for ≥6 wk after initiating therapy and every 2 wk for next 6 wk, monthly for next 3 mo, and then as clinically indicated. After dose ↑ or interruption, monitor weekly until stable dose achieved. Consider risk and benefit of initiating levoketoconazole if enzymes >normal but ≤3 times ULN. If ALT or AST ≤3 times ULN with any total bilirubin level, consider interrupting therapy and monitor tests every 7–10 days until returned to baseline. Resume at lower dose, titrate more slowly, and address any contributing factors. Before dose ↑, monitor tests weekly for 1 mo. If ALT or AST ≥3–< 5 times ULN and total bilirubin ≤2 times ULN, interrupt therapy and monitor tests every 3 days until levels stable and then every 7–10 days until levels return to baseline. Resume at ↓ dose, titrate more slowly, and address any contributing factors. Permanently discontinue levoketoconazole if abnormalities recur. Before dose ↑, monitor tests weekly for 1 mo. If ALT or AST ≥5 times ULN or ≥3 times ULN and total bilirubin >2 times ULN, permanently discontinue levoketoconazole.
• Obtain baseline serum potassium and magnesium. Correct hypokalemia and hypomagnesemia prior to initiation of therapy.
• Monitor 24-hr urine free cortisol, serum morning, or plasma cortisol levels periodically during therapy. Once maintenance dosage is achieved, monitor ≥two 24-hr urine free cortisol collections at least every 1–2 mo or as indicated. If 24-hr urine levels >ULN after max recommended dose (1200 mg/day) or patient cannot tolerate, consider discontinuing levoketoconazole and switching to another therapy. If cortisol levels <target range, there is a rapid level ↓, or signs of hypocortisolism or adrenal insufficiency occur,↓ dose or interrupt therapy and administer exogenous glucocorticoid. If therapy interrupted due to hypocortisolism, reinitiate therapy at ↓ dose when cortisol levels in target range and signs and symptoms have resolved. May titrate dose to previous dose associated with hypocortisolism if ↓ dose well tolerated but does not achieve adequate clinical response.