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Drug Interactions between Aponvie and dasatinib

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

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Interactions between your drugs

Moderate

aprepitant dasatinib

Applies to: Aponvie (aprepitant) and dasatinib

MONITOR: Coadministration with aprepitant or its prodrug, fosaprepitant, may increase the plasma concentrations of chemotherapeutic agents that are primarily metabolized by CYP450 3A4. The proposed mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by aprepitant. In premarketing clinical studies, aprepitant was administered commonly with etoposide, vinorelbine or paclitaxel, although dosages of these agents were not adjusted to account for potential drug interactions. In separate pharmacokinetic studies, aprepitant had no effect on the pharmacokinetics of docetaxel or vinorelbine, both of which are substrates of CYP450 3A4. However, an interaction has been demonstrated with the probe CYP450 3A4 substrate, midazolam. In general, the effect of aprepitant on the pharmacokinetics of CYP450 3A4 substrates is expected to be greater when the substrates are administered orally as opposed to intravenously and may be altered following prolonged administration.

MANAGEMENT: Caution is advised if aprepitant or fosaprepitant is administered with chemotherapeutic agents that are primarily metabolized by CYP450 3A4, particularly those that were not studied extensively in premarketing trials. The potential for increased systemic toxicities of these agents should be considered. Chronic, continuous use of aprepitant for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during long-term use.

References

  1. Kivisto KT, Kroemer HK, Eichelbaum M (1995) "The role of human cytochrome p450 enzymes in the metabolism of anticancer agents: implications for drug interactions." Br J Clin Pharmacol, 40, p. 523-30
  2. Zhou XJ, Zhou-Pan XR, Gauthier T, Placidi M, Maurel P, Rahmani R (1993) "Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions." Biochem Pharmacol, 45, p. 853-61
  3. Clarke SJ, Rivory LP (1999) "Clinical pharmacokinetics of docetaxel." Clin Pharmacokinet, 36, p. 99-114
  4. Charasson V, Haaz MC, Robert J (2002) "Determination of Drug Interactions Occurring with the Metabolic Pathways of Irinotecan." Drug Metab Dispos, 30, p. 731-733
  5. (2003) "Product Information. Emend (aprepitant)." Merck & Co., Inc
  6. (2008) "Product Information. Emend for Injection (fosaprepitant)." Merck & Co., Inc
View all 6 references

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Drug and food interactions

Major

dasatinib food

Applies to: dasatinib

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of dasatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. Because dasatinib prolongs the QT interval, high plasma levels of dasatinib may increase the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

MANAGEMENT: Patients treated with dasatinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Some authorities recommend close monitoring for toxicity (e.g., myelosuppression, bleeding complications, fluid retention, bradycardia or other conduction disturbances) and a reduction of dasatinib dosage to a range of 20 to 40 mg daily should be considered if there are no alternatives and concomitant use with a potent CYP450 3A4 inhibitor is necessary.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2006) "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb
  3. Cerner Multum, Inc. "Australian Product Information."

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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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