Drug Interactions between lurasidone and Xenleta
This report displays the potential drug interactions for the following 2 drugs:
- lurasidone
- Xenleta (lefamulin)
Interactions between your drugs
lurasidone lefamulin
Applies to: lurasidone and Xenleta (lefamulin)
MONITOR: When administered orally, lefamulin may increase the plasma concentrations of drugs that are primarily metabolized by the CYP450 3A4 isoenzyme. Based on interaction with midazolam, a sensitive CYP450 3A4 substrate, lefamulin may be a moderate CYP450 3A4 inhibitor. When oral midazolam was administered concomitantly with and at 2 or 4 hours after administration of lefamulin tablets, mean midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 100% and 200%, respectively. No clinically significant differences in the pharmacokinetics of midazolam were observed when administered concomitantly with lefamulin injection.
MANAGEMENT: Caution is advised when oral lefamulin is used concomitantly with drugs that are substrates of CYP450 3A4, particularly sensitive substrates or those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever oral lefamulin is added to or withdrawn from therapy. Patients should be monitored for the development of adverse effects. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration of a moderate CYP450 3A4 inhibitor like lefamulin and for any dosage adjustments that may be required.
References
- (2019) "Product Information. Xenleta (lefamulin)." Nabriva Therapeutics US, Inc.
Drug and food interactions
lurasidone food
Applies to: lurasidone
GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of lurasidone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When a single 10 mg dose of lurasidone was administered with the potent CYP450 3A4 inhibitor ketoconazole (400 mg/day for 5 days), lurasidone peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 6.9- and 9.0-fold, respectively, compared to administration alone. The AUC of lurasidone's active metabolite increased by 6-fold. Another potent CYP450 3A4 inhibitor, posaconazole, has been reported to increase lurasidone AUC by approximately 4.5-fold. When a single 20 mg dose of lurasidone was administered with the moderate CYP450 3A4 inhibitor diltiazem (extended release formulation 240 mg/day for 5 days), lurasidone Cmax and AUC increased by 2.1- and 2.2-fold, respectively, while the AUC of the active metabolite increased by 2.4-fold. 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.
GENERALLY AVOID: Alcohol may potentiate some of the central nervous system and hypotensive effects of lurasidone. Use in combination may result in increased sedation, dizziness, hypotension, and impairment of judgment, thinking, and psychomotor skills.
ADJUST DOSING INTERVAL: Food increases the oral bioavailability of lurasidone. According to the product labeling, lurasidone mean Cmax and AUC were increased approximately 3-fold and 2-fold, respectively, when administered with food relative to under fasting conditions. Lurasidone AUC was not affected by meal size (in the range of 350 to 1000 calories) or fat content. In clinical studies, lurasidone was administered with food.
MANAGEMENT: Patients treated with lurasidone should avoid consumption of grapefruit and grapefruit juice as well as alcohol. Lurasidone should be taken with food (at least 350 calories).
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
- Cerner Multum, Inc. "Australian Product Information."
- (2010) "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc
lefamulin food
Applies to: Xenleta (lefamulin)
ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of lefamulin. When a single 600 mg oral dose of lefamulin was administered with a high-calorie, high-fat breakfast (800 to 1000 calories; approximately 50% from fat), lefamulin peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 23% and 18%, respectively.
GENERALLY AVOID: Grapefruit juice may increase the oral bioavailability of lefamulin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but pharmacokinetic data are available for the potent CYP450 3A4 inhibitor, ketoconazole. When oral lefamulin was administered with oral ketoconazole, mean lefamulin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 58% and 165%, respectively. 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. Increased exposure to lefamulin may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.
MANAGEMENT: Lefamulin tablets should be taken at least one hour before or two hours after a meal. Patients should preferably avoid or limit the consumption of grapefruit and grapefruit juice during treatment with lefamulin.
References
- (2019) "Product Information. Xenleta (lefamulin)." Nabriva Therapeutics US, 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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