What are the precautions for taking levoketoconazole?

In clinical studies of levoketoconazole for the treatment of endogenous hypercortisolism in patients with Cushing's syndrome, warnings and precautions emerged regarding hepatotoxicity, QT prolongation, hypercortisolism, allergic reactions, and risks related to testosterone reduction. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Hepatotoxicity: Cases of hepatotoxicity resulting from the use of oral ketoconazole (racemic mixture of levoketoconazole) leading to fatal consequences or requiring liver transplantation have been reported. Avoid using this product simultaneously with hepatotoxic drugs. Advise patients to avoid excessive alcohol consumption while receiving RECORLEV treatment. Prompt recognition of liver injury is critical. At baseline, a liver test was performed. Monitor liver enzymes periodically during rehabilitation and more frequently during dose titration

2. QT prolongation: QT interval prolongation may lead to life-threatening ventricular arrhythmias, such as torsade de pointes. In patients with other risk factors for QT prolongation, such as congestive heart failure, bradyarrhythmias, and uncorrected electrolyte abnormalities, RECORLEV should be used with caution and more frequent ECG monitoring should be considered.

3. Hypercortisolism: Levoketoconazole can reduce cortisol levels and may lead to hypocortisolism, which may lead to life-threatening adrenal insufficiency. Reduced cortisol levels can lead to nausea, vomiting, fatigue, abdominal pain, loss of appetite, and dizziness. Significantly reduced serum cortisol levels may lead to adrenal insufficiency manifested by hypotension, abnormal electrolyte levels, and hypoglycemia. Hypercortisolism can occur at any time during rehabilitation. Assess the patient for triggers of hypercortisolism (infection, physical stress, etc.). During rehabilitation, regularly monitor 24-hour urinary free cortisol, morning serum or plasma cortisol, and the patient's signs and symptoms.

4. Allergic reaction: It has been reported that allergic reactions may occur after a single dose of oral ketoconazole. Anaphylaxis including urticaria has also been reported with ketoconazole. This product is contraindicated in patients with known hypersensitivity to levoketoconazole, ketoconazole, or any of the excipients in this product.

5. Risks related to reduced testosterone: Levoxetonazole can reduce serum testosterone in both men and women. Potential clinical manifestations of reduced testosterone concentrations in men may include gynecomastia, impotence, and oligozoospermia. Potential clinical manifestations of reduced testosterone concentrations in women include decreased libido and mood changes.

Reference materials:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7074cb65-77b3-45d2-8e8d-da8dc0f70bfd##