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Drug Interactions between amiodarone and talazoparib

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

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Interactions between your drugs

Major

amiodarone talazoparib

Applies to: amiodarone and talazoparib

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of talazoparib, which has been shown in vitro to be a substrate of the efflux transporter. In a drug-drug interaction study in patients with advanced solid tumors, compared with a single talazoparib dose (0.5 mg), multiple daily doses of the P-gp inhibitor itraconazole (100 mg twice daily) with a single dose of talazoparib (0.5 mg) increased the talazoparib total exposure and peak plasma concentration by 56% and 40%, respectively. In addition, population pharmacokinetic analysis has shown that administration of talazoparib with the P-gp inhibitors amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil resulted in an approximate 45% increase in talazoparib exposure and an increase in the rate of talazoparib dose reduction. In contrast, coadministration with the P-gp inhibitors azithromycin, atorvastatin, diltiazem, felodipine, fluvoxamine, and quercetin increased talazoparib exposure by just 8%.

MANAGEMENT: Concomitant use of talazoparib with amiodarone, carvedilol, clarithromycin, itraconazole, or verapamil should preferably be avoided. If coadministration is required, talazoparib should be initiated at a reduced dosage of 0.75 mg once daily. Patients should be closely monitored for adverse effects such as myelosuppression and myelodysplastic syndrome/acute myeloid leukemia, and further dosage adjustments made or treatment withheld as needed in accordance with the product labeling. After 3 to 5 half-lives following discontinuation of the P-gp inhibitor, the talazoparib dosage may be increased to that used prior to initiation of the P-gp inhibitor.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2018) "Product Information. Talzenna (talazoparib)." Pfizer U.S. Pharmaceuticals Group

Drug and food interactions

Major

amiodarone food

Applies to: 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 (3)
  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

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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