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Drug Interactions between ivosidenib and lenacapavir

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

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Interactions between your drugs

Moderate

ivosidenib lenacapavir

Applies to: ivosidenib and lenacapavir

MONITOR: Coadministration with drugs that are inducers of the CYP450 3A4 isoenzyme may decrease the plasma concentrations of lenacapavir which may lead to diminished virologic response. The proposed mechanism is increased clearance due to induction of CYP450 3A4, which is partly responsible for the metabolism of lenacapavir. In pharmacokinetic studies conducted in fasted subjects without HIV, coadministration of a single oral dose of lenacapavir 300 mg with the potent CYP450 3A4 inducer rifampin 600 mg once daily decreased the systemic exposure (AUC) and peak plasma concentration (Cmax) of lenacapavir by approximately 84% and 55%, respectively. In the same studies, coadministration of a single oral dose of lenacapavir 300 mg with the moderate CYP450 3A4 inducer efavirenz 600 mg once daily decreased the AUC and Cmax of lenacapavir by approximately 56% and 36%, respectively. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels should be considered during coadministration of lenacapavir with CYP450 3A4 inducers. Alternative treatments may be considered if an interaction is suspected.

References

  1. (2022) "Product Information. Sunlenca (lenacapavir)." Gilead Sciences

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Drug and food interactions

Major

ivosidenib food

Applies to: ivosidenib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivosidenib. 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. Pharmacokinetic data are available for the potent CYP450 3A4 inhibitor, itraconazole, and the moderate inhibitor, fluconazole. When a single 250 mg dose of ivosidenib was administered with itraconazole 200 mg once daily for 18 days, ivosidenib systemic exposure (AUC) increased to 269% of control, with no change in peak plasma concentration (Cmax). Based on physiologically-based pharmacokinetic modeling, coadministration of a 500 mg dose of ivosidenib with fluconazole (dosed to steady-state) is predicted to increase ivosidenib single-dose AUC to 173% of control, while multiple-dosing of both is predicted to increase ivosidenib steady-state Cmax and AUC to 152% and 190% of control, 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 ivosidenib may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.

GENERALLY AVOID: Coadministration with a high-fat meal may increase the plasma concentrations of ivosidenib. According to the product labeling, administration of a single dose with a high-fat meal (approximately 900 to 1000 calories; 500 to 600 calories in fat, 250 calories in carbohydrate, 150 calories in protein) increased ivosidenib Cmax and AUC by 98% and 25%, respectively, in healthy study subjects.

MANAGEMENT: Ivosidenib may be administered with or without food, but should not be administered with a high-fat meal. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with ivosidenib.

References

  1. (2018) "Product Information. Tibsovo (ivosidenib)." Agios Pharmaceuticals, 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.

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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

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