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Drug Interactions between edoxaban and nilotinib

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

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Interactions between your drugs

Major

nilotinib edoxaban

Applies to: nilotinib and edoxaban

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of edoxaban, which is a substrate of the efflux transporter. In healthy volunteers, single-dose edoxaban systemic exposure (AUC) increased approximately 80% to 90% by erythromycin, dronedarone, and ketoconazole; 70% to 80% by cyclosporine and quinidine; 50% by verapamil; and 40% by amiodarone. The peak plasma concentration (Cmax) of edoxaban also increased by approximately 45% to 90% with these drugs.

MANAGEMENT: When used for the treatment of deep vein thrombosis and pulmonary embolism, the manufacturer recommends that edoxaban dosage be reduced to 30 mg once daily in patients receiving concomitant treatment with certain P-gp inhibitors including azithromycin, clarithromycin, erythromycin, oral itraconazole, oral ketoconazole, quinidine, and verapamil. This dosage recommendation is based on data from a clinical study, the Hokusai VTE study, and is limited to use with the specific P-gp inhibitors mentioned. Other P-gp inhibitors were not permitted in the study, and patients on antiretroviral therapy (ritonavir, nelfinavir, indinavir, saquinavir) as well as cyclosporine were excluded from the study. Following discontinuation of the P-gp inhibitor, edoxaban dosage should be returned to the regular dosage of 60 mg once daily. No dosage adjustment is recommended for edoxaban when used in the treatment of nonvalvular atrial fibrillation.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Mendell J, Zahir H, Matsushima N, et al. (2013) "Drug-Drug Interaction Studies of Cardiovascular Drugs Involving P-Glycoprotein, an Efflux Transporter, on the Pharmacokinetics of Edoxaban, an Oral Factor Xa Inhibitor." Am J Cardiovasc Drugs
  3. (2015) "Product Information. Savaysa (edoxaban)." Daiichi Sankyo, Inc.
  4. Parasrampuria DA, Mendell J, Shi M, Matsushima N, Zahir H, Truitt K (2016) "Edoxaban drug–drug interactions with ketoconazole, erythromycin, and cyclosporine." Br J Clin Pharmacol, epub
View all 4 references

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Drug and food interactions

Major

nilotinib food

Applies to: nilotinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of nilotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because nilotinib 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 nilotinib. The mechanism of interaction is unknown. Compared to the fast state, nilotinib systemic exposure (AUC) increased by 82% when the dose was given 30 minutes after a high-fat meal. Because nilotinib 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.

MANAGEMENT: Patients treated with nilotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. In addition, no food should be consumed for at least 2 hours before and 1 hour after a nilotinib dose.

References

  1. (2007) "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals

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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.