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Drug Interactions between mitotane and tisotumab vedotin

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

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Interactions between your drugs

Minor

mitotane tisotumab vedotin

Applies to: mitotane and tisotumab vedotin

Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of unconjugated monomethyl auristatin E (MMAE), the anti-mitotic and cytotoxic component of tisotumab vedotin. Tisotumab vedotin is an antibody-drug conjugate (ADC) that releases MMAE via proteolytic cleavage, and MMAE has been shown in vitro to be primarily metabolized by CYP450 3A4. Although tisotumab vedotin has not been studied with CYP450 3A4 inducers, data for another ADC that contains MMAE (brentuximab vedotin) have been reported. When brentuximab vedotin was administered with the potent CYP450 3A4 inducer rifampin, MMAE peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 44% and 46%, respectively, with no change in ADC exposure. Using a model-based approach to account for the fact that MMAE exposures are decreased after multiple doses by 20% to 50% compared to the first dose, the adjusted reduction in MMAE AUC by rifampin is predicted to be 31%. Similar effects on unconjugated MMAE and ADC are expected for tisotumab vedotin when coadministered with potent CYP450 3A4 inducers. However, the interaction is not expected to be clinically relevant, since the intact ADC containing the antibody component 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.

References (3)
  1. (2011) "Product Information. Adcetris (brentuximab vedotin)." Seattle Genetics Inc
  2. Han TH, Gopal AK, Ramchandren R, et al. (2013) "CYP3A-mediated drug-drug interaction potential and excretion of brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive hematologic malignancies." J Clin Pharmacol, 53, p. 866-77
  3. (2021) "Product Information. Tivdak (tisotumab vedotin)." Seagen Inc

Drug and food interactions

Moderate

mitotane food

Applies to: mitotane

ADJUST DOSING INTERVAL: Fat-rich food enhances the absorption of mitotane. One study evaluated blood levels of mitotane (o,p'-DDD) after subjects ingested a single dose of 2 g administered using various delivery vehicles (e.g., tablets, granules, milk, chocolate or oil emulsion). Mitotane plasma levels were significantly higher for milk, chocolate, and oil emulsion when compared to those who received tablets or granules alone. In the same study, mitotane levels were evaluated in subjects following long-term treatment (total dose of 200 g over 30 to 60 days) in tablet, oil emulsion, or milk formulations. Significantly higher mean plasma levels were recorded in subjects who received mitotane as an oil emulsion or mixed in milk, when compared to tablets alone. Additionally, the recovery of o,p'-DDD from the feces was about 5 times higher in subjects who received tablets alone, suggesting absorption was reduced when compared to subjects who received mitotane mixed with a fat-rich vehicle (e.g., oil emulsion or milk).

GENERALLY AVOID: Concomitant use of mitotane with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: According to product labeling, mitotane tablets should be taken during meals containing fat-rich food (e.g., milk, chocolate, or oil) and with a full glass of water. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.

References (4)
  1. (2023) "Product Information. Lysodren (mitotane)." HRA Pharma America
  2. (2023) "Product Information. Lysodren (mitotane)." Medunik Canada
  3. (2023) "Product Information. Lysodren (mitotane)." HRA Pharma UK & Ireland Ltd
  4. Moolenaar AJ, van Slooten H, van Seters AP, Smeenk D (2023) Blood levels of o,p-DDD following administration in various vehicles after a single dose and during long-term treatment https://link.springer.com/article/10.1007/BF00258213

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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