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Drug Interactions between Epitol and tisotumab vedotin

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

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Interactions between your drugs

Minor

carBAMazepine tisotumab vedotin

Applies to: Epitol (carbamazepine) 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

  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

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Drug and food interactions

Moderate

carBAMazepine food

Applies to: Epitol (carbamazepine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References

  1. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77

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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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