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Drug Interactions between Adcetris and Agenerase

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

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Interactions between your drugs

Major

amprenavir brentuximab vedotin

Applies to: Agenerase (amprenavir) and Adcetris (brentuximab)

MONITOR CLOSELY: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of unconjugated monomethyl auristatin E (MMAE), the anti-mitotic and cytotoxic component of brentuximab vedotin. Brentuximab 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. When brentuximab vedotin was administered with the potent CYP450 3A4 inhibitor ketoconazole, MMAE peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 25% and 34%, 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 increase in MMAE AUC by ketoconazole is predicted to be 73%.

MANAGEMENT: Caution is advised when brentuximab vedotin is used concomitantly with potent CYP450 3A4 inhibitors. Close monitoring for adverse effects including neutropenia, infection, peripheral neuropathy, hepatotoxicity, pulmonary toxicity and hyperglycemia is recommended, and the dosing of brentuximab vedotin adjusted or withheld as necessary in accordance with the product labeling.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2011) "Product Information. Adcetris (brentuximab vedotin)." Seattle Genetics Inc
  3. 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

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Drug and food interactions

Moderate

amprenavir food

Applies to: Agenerase (amprenavir)

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.

References

  1. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  2. Demarles D, Gillotin C, Bonaventure-Paci S, Vincent I, Fosse S, Taburet AM (2002) "Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice." Antimicrob Agents Chemother, 46, p. 1589-1590

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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