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Drug Interactions between lumateperone and Prezista

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

darunavir lumateperone

Applies to: Prezista (darunavir) and lumateperone

ADJUST DOSE: Coadministration with moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of lumateperone. In vitro studies show that multiple enzymes are involved in the metabolism of lumateperone, including but not limited to uridine 5'-diphospho-glucuronosyltransferases (UGT) 1A1, 1A4, and 2B15; aldoketoreductase (AKR) 1C1, 1B10, and 1C4; and cytochrome P450 (CYP450) 3A4, 2C8, and 1A2. When coadministered with diltiazem, a moderate CYP450 3A4 inhibitor, lumateperone peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2- and 2.5-fold, respectively. High plasma levels of lumateperone may increase the risk and/or severity of serious adverse effects such as extrapyramidal symptoms, tardive dyskinesia, hyperglycemia, dyslipidemia, hyperprolactinemia, neutropenia, leukopenia, orthostatic hypotension, syncope, seizures, cognitive and motor impairment, dysphagia, and heat-related illnesses due to disruption of body temperature regulation.

MANAGEMENT: The recommended dosage of lumateperone is 21 mg once daily when coadministered with moderate CYP450 3A4 inhibitors.

References

  1. (2022) "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc., SUPPL-9

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Drug and food interactions

Moderate

darunavir food

Applies to: Prezista (darunavir)

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

References

  1. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc

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Moderate

lumateperone food

Applies to: lumateperone

GENERALLY AVOID: Grapefruit and grapefruit juice may increase the plasma concentrations of lumateperone. 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 but has been reported for other CYP450 3A4 inhibitors. In a drug interaction study, the strong CYP450 3A4 inhibitor itraconazole increased lumateperone peak plasma concentration (Cmax) and systemic exposure (AUC) approximately 3.5- and 4-fold, respectively, while diltiazem (a moderate CYP450 3A4 inhibitor) increased lumateperone Cmax and AUC approximately 2- and 2.5-fold, 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.

When administered with a high-fat meal, lumateperone Cmax decreased by 33% while its AUC increased by 9% and its median time to peak plasma concentration (Tmax) was delayed by about 1 hour.

MANAGEMENT: Lumateperone should be administered with food. Coadministration of grapefruit or grapefruit juice with lumateperone should be avoided.

References

  1. (2020) "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc.

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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

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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