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Drug Interactions between brentuximab and Nexterone

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

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Interactions between your drugs

Moderate

amiodarone brentuximab vedotin

Applies to: Nexterone (amiodarone) and brentuximab

MONITOR: Coadministration with potent CYP450 3A4 inhibitors or P-glycoprotein (P-gp) inhibitors may increase the plasma concentrations of monomethyl auristatin E (MMAE), the microtubule-disrupting component of brentuximab vedotin. MMAE is primarily metabolized by CYP450 3A4 and has been found in vitro to be a substrate of the P-gp efflux transporter. In study subjects, administration of brentuximab vedotin with the potent CYP450 3A4 and P-gp inhibitor ketoconazole resulted in an approximately 34% increase in MMAE systemic exposure (AUC).

MONITOR: Coadministration of brentuximab vedotin with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Serious cases of hepatotoxicity, some fatal, have occurred in patients treated with brentuximab vedotin. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and typically occurred after the first dose or after a rechallenge. Preexisting liver disease and elevated baseline liver enzymes may also increase the risk.

MANAGEMENT: Caution is advised when brentuximab is used with potent CYP450 3A4 inhibitors (e.g., azole antifungal agents, clarithromycin, erythromycin, nefazodone, ritonavir, telithromycin) or P-gp inhibitors (e.g., protein kinase inhibitors, abiraterone, amiodarone, azithromycin, cyclosporine, dronedarone, ivacaftor) that are also potentially hepatotoxic. Close monitoring for adverse effects including neutropenia, infection, peripheral neuropathy, and hepatotoxicity is recommended. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Liver enzymes and bilirubin should be measured before and during treatment, especially in patients with underlying hepatic disease or marked baseline transaminase elevations. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dosage, or discontinuation of brentuximab vedotin in accordance with the product labeling.

References

  1. (2011) "Product Information. Xalkori (crizotinib)." Pfizer U.S. Pharmaceuticals Group

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Drug and food interactions

Major

amiodarone food

Applies to: Nexterone (amiodarone)

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered amiodarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 11 nonsmoking, healthy volunteers, grapefruit juice (300 mL with drug administration, then 3 hours and 9 hours later) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amiodarone (17 mg/kg single dose) by 84% and 50%, respectively, compared to water. Formation of the pharmacologically active metabolite, N-desethylamiodarone (N-DEA), was completely inhibited. Clinically, this interaction can lead to altered efficacy of amiodarone, since antiarrhythmic properties of amiodarone and N-DEA appear to differ. In the study, mean increases in PR and QTc intervals of 17.9% and 11.3%, respectively, were observed 6 hours postdose with water, while increases of 10.2% and 3.3%, respectively, were observed after administration with grapefruit juice.

ADJUST DOSING INTERVAL: Food increases the rate and extent of absorption of amiodarone. The mechanism appears to involve the effect of food-induced physiologic changes on drug release from its formulation. In 30 healthy volunteers, administration of a single 600 mg dose of amiodarone following a high-fat meal resulted in a Cmax and AUC that were 3.8 and 2.4 times the respective values under fasting conditions. The time to reach peak plasma concentration (Tmax) was decreased by 37%, indicating an increased rate of absorption. Mean Cmax and AUC for the active metabolite, N-DEA, also increased by 32% and 55%, respectively, but there was no change in the Tmax.

MANAGEMENT: Patients treated with oral amiodarone should avoid consumption of grapefruits and grapefruit juice. In addition, oral amiodarone should be administered consistently with regard to meals.

References

  1. (2002) "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories
  2. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  3. Meng X, Mojaverian P, Doedee M, Lin E, Weinryb I, Chiang ST, Kowey PR (2001) "Bioavailability of Amiodarone tablets administered with and without food in healthy subjects." Am J Cardiol, 87, p. 432-5

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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

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