Drug Interactions between levoketoconazole and quetiapine
This report displays the potential drug interactions for the following 2 drugs:
- levoketoconazole
- quetiapine
Interactions between your drugs
QUEtiapine levoketoconazole
Applies to: quetiapine and levoketoconazole
CONTRAINDICATED: Coadministration with levoketoconazole may significantly increase the plasma concentrations of drugs that are sensitive CYP450 3A4 substrates or combined CYP450 3A4 and P-glycoprotein (P-gp) substrates. Levoketoconazole is a strong inhibitor of the CYP450 3A4 isoenzyme and an inhibitor of the P-gp efflux transporter. Increased exposure to CYP450 3A4 or combined CYP450 3A4 and P-gp substrates that can prolong the QT interval may increase the risk of ventricular arrhythmias including torsade de pointes and sudden death. In addition, levoketoconazole itself can cause QT interval prolongation and may have additive effects with these agents. According to cardiac electrophysiology data provided by the prescribing information, the largest mean increase in QTc was 24 msec following administration of levoketoconazole 150 mg to 600 mg twice daily in patients with endogenous Cushing's syndrome, and the increase was dose-related. During two premarketing levoketoconazole clinical studies, 4 (2.4%) patients experienced QTcF greater than 500 msec, and 23 (14.7%) patients presented a change in QTcF greater than 60 msec from baseline. The clinical studies did not include patients with baseline QTcF interval greater than 470 msec.
MANAGEMENT: Concomitant use of levoketoconazole with sensitive CYP450 3A4 substrates or combined CYP450 3A4 and P-gp substrates that can prolong the QT interval is considered contraindicated.
References
- (2022) "Product Information. Recorlev (levoketoconazole)." Xeris Pharmaceuticals Inc
- Auchus R, Pivonello R, Fleseriu M, et al. (2022) Levoketoconazole: a novel treatment for endogenous Cushing's syndrome. https://www.tandfonline.com/doi/pdf/10.1080/17446651.2021.1945440
Drug and food interactions
levoketoconazole food
Applies to: levoketoconazole
GENERALLY AVOID: Excessive use of alcohol or products containing alcohol together with ketoconazole or levoketoconazole may potentiate the risk of liver injury. Serious hepatotoxicity has been reported with levoketoconazole. Hepatotoxicity requiring liver transplantation has been reported with the use of oral ketoconazole, of which levoketoconazole is an enantiomer. Some patients had no obvious risk factors for liver disease. In addition, use of alcohol or products containing alcohol during ketoconazole or levoketoconazole therapy may result in a disulfiram-like reaction in some patients. Symptoms of disulfiram-like reaction include flushing, rash, peripheral edema, nausea, and headache.
GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of ketoconazole or levoketoconazole. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
When administered to healthy volunteers with a high-fat meal (875 calories; 62% fat), levoketoconazole systemic exposure (AUC) increased by 30% while peak plasma concentration (Cmax) did not change and the time to reach Cmax (Tmax) was delayed from 2 to 4 hours, compared to fasted conditions.
MANAGEMENT: Levoketoconazole may be administered with or without food. Excessive consumption of alcohol should generally be avoided during ketoconazole or levoketoconazole therapy. Patients should preferably avoid or limit consumption of grapefruit, grapefruit juice, or any supplement containing grapefruit extract during ketoconazole or levoketoconazole therapy. Patients receiving ketoconazole or levoketoconazole should be instructed to contact their doctor immediately if they experience swelling, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark colored urine, light colored stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage.
References
- (2019) "Product Information. Ketoconazole (ketoconazole)." Mylan Pharmaceuticals Inc
- (2022) "Product Information. Recorlev (levoketoconazole)." Xeris Pharmaceuticals Inc
- Auchus R, Pivonello R, Fleseriu M, et al. (2022) Levoketoconazole: a novel treatment for endogenous Cushing's syndrome. https://www.tandfonline.com/doi/pdf/10.1080/17446651.2021.1945440
- (2021) "Product Information. Ketoconazole (ketoconazole)." Burel Pharmaceuticals Inc
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
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