Drug Interactions between enfortumab vedotin and ivosidenib
This report displays the potential drug interactions for the following 2 drugs:
- enfortumab vedotin
- ivosidenib
Interactions between your drugs
ivosidenib enfortumab vedotin
Applies to: ivosidenib and enfortumab vedotin
Coadministration with inducers of CYP450 3A4 or dual P-glycoprotein (P-gp) and CYP450 3A4 inducers may decrease the plasma concentrations and effects of unconjugated monomethyl auristatin E (MMAE), the cytotoxic component of enfortumab vedotin. Enfortumab vedotin is an antibody-drug conjugate (ADC) that releases MMAE, via proteolytic cleavage. MMAE has been shown in vitro to be primarily metabolized by CYP450 3A4 as well as being a substrate of P-gp. According to physiologically-based pharmacokinetic (PBPK) modeling, concomitant use of enfortumab vedotin with rifampin, a dual P-gp and strong CYP450 3A4 inducer, is predicted to decrease unconjugated MMAE peak plasma concentration (Cmax) by 28% and systemic exposure (AUC) by 53%, with no change in ADC exposure. Some authorities suggest that the PBPK model may underestimate the full impact of rifampin on the Cmax of MMAE. The clinical significance of the interaction is unclear, since the intact ADC is required to bind to Nectin-4, an adhesion protein found on the surface of cells, which allows for internalization and cleavage by lysosomal proteases to enable intracellular delivery of MMAE. It is not known if, and to what extent, enfortumab vedotin may interact with less potent CYP450 3A4 inducers.
References
- (2023) "Product Information. Padcev (enfortumab vedotin)." Astellas Pharma Australia Pty Ltd
- (2023) "Product Information. Padcev (enfortumab vedotin)." Seagen Inc
- (2021) "Product Information. Padcev (enfortumab vedotin)." Seagen Canada Inc
- (2022) "Product Information. Padcev (enfortumab vedotine)." ASTELLAS PHARMA
- (2022) "Product Information. Padcev (enfortumab vedotin)." Astellas Pharma Ltd
Drug and food interactions
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
- (2018) "Product Information. Tibsovo (ivosidenib)." Agios 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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