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Drug Interactions between dronedarone and thiotepa

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

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Interactions between your drugs

Moderate

thiotepa dronedarone

Applies to: thiotepa and dronedarone

MONITOR: Coadministration with CYP450 3A4 and/or 2B6 inhibitors may increase plasma concentrations of thiotepa and decrease concentrations of its active metabolite triethylenephosphoramide (TEPA). Thiotepa is a prodrug that is primarily converted to TEPA by these isoenzymes. A pharmacokinetic study evaluating six breast cancer patients receiving high-dose chemotherapy (cyclophosphamide 1,500 mg/m2/day, thiotepa 120 mg/m2/day, and carboplatin AUC 5 mg min/mL/day) with the moderate CYP3A4 inhibitor aprepitant (125 mg one day before chemotherapy, then 80 mg daily during and for three days after) showed a 15% increase in total thiotepa exposure, a 33% decrease in TEPA formation, and 20% reduction in TEPA exposure.

MANAGEMENT: Caution and closer monitoring for decreased efficacy and adverse effects are advised when thiotepa is used concurrently with CYP450 3A4 and/or 2B6 inhibitors. Patients should be more closely monitored for thiotepa-related toxicities such as myelosuppression, cutaneous toxicity, and neurotoxicity.

References (5)
  1. de Jonge ME, Huitema AD, Holtkamp MJ, van Dam SM, Beijnen JH, Rodenhuis S (2005) "Aprepitant inhibits cyclophosphamide bioactivation and thiotepa metabolism" Cancer Chemother Pharmacol, 56, p. 370-8
  2. (2023) "Product Information. Thiotepa (thiotepa)." Meitheal Pharmaceuticals Inc.
  3. (2023) "Product Information. Tepadina (thiotepa)." Link Medical Products Pty Ltd T/A Link Pharmaceuticals, 3
  4. (2022) "Product Information. Thiotepa (thiotepa)." MSN Laboratories Europe Ltd
  5. (2021) "Product Information. Tepadina (thiotepa)." Adienne SA

Drug and food interactions

Major

dronedarone food

Applies to: dronedarone

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of dronedarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration with grapefruit juice resulted in a 2.5-fold increase in dronedarone peak plasma concentration and a 3-fold increase in systemic exposure. Because dronedarone is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of dronedarone. The mechanism of interaction is unknown. According to the product labeling, the absolute bioavailability of dronedarone increases from about 4% when administered in the fasted state to approximately 15% when administered with a high-fat meal.

MANAGEMENT: Patients treated with dronedarone should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Dronedarone should be taken twice daily with the morning and evening meals.

References (1)
  1. (2009) "Product Information. Multaq (dronedarone)." sanofi-aventis

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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