Skip to main content

Drug Interactions between enfortumab vedotin and Epitol

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

carBAMazepine enfortumab vedotin

Applies to: Epitol (carbamazepine) and enfortumab vedotin

MONITOR: Coadministration with strong inducers of CYP450 3A4 or dual P-glycoprotein (P-gp) and strong 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. However, 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.

MANAGEMENT: Patients should be monitored for a reduction in clinical efficacy if therapy with a strong CYP450 3A4 inducer or a dual P-gp and strong CYP450 3A4 inducer is initiated during therapy with enfortumab vedotin.

References

  1. 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
  2. (2023) "Product Information. Padcev (enfortumab vedotin)." Astellas Pharma Australia Pty Ltd
  3. (2023) "Product Information. Padcev (enfortumab vedotin)." Seagen Inc
  4. (2021) "Product Information. Padcev (enfortumab vedotin)." Seagen Canada Inc
  5. (2022) "Product Information. Padcev (enfortumab vedotine)." ASTELLAS PHARMA
  6. (2022) "Product Information. Padcev (enfortumab vedotin)." Astellas Pharma Ltd
View all 6 references

Switch to consumer interaction data

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

Switch to consumer interaction data

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

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer