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Drug Interactions between fosaprepitant and trabectedin

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

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Interactions between your drugs

Moderate

fosaprepitant trabectedin

Applies to: fosaprepitant and trabectedin

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 (6)
  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

Drug and food interactions

Moderate

trabectedin food

Applies to: trabectedin

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of trabectedin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

GENERALLY AVOID: Coadministration of trabectedin with other agents known to induce hepatotoxicity such as alcohol may potentiate the risk of liver injury. Reversible, acute increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have occurred frequently in patients treated with trabectedin alone or with pegylated liposomal doxorubicin in clinical trials. In one U.S. trial with 378 patients, grade 3 or 4 elevated liver function tests (defined as elevations in ALT, AST, total bilirubin, or alkaline phosphatase) were reported in 35% of patients receiving trabectedin. ALT or AST elevations greater than eight times the upper limit of normal (ULN) occurred in 18% of patients, and drug-induced liver injury (defined as concurrent elevations in ALT or AST more than three times ULN, alkaline phosphatase less than two times ULN, and total bilirubin at least two times ULN) occurred in 1.3% of patients.

MANAGEMENT: Consumption of grapefruit or grapefruit juice during treatment with trabectedin should be avoided. Excessive use of alcohol is also not 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. Monitoring of alkaline phosphatase, bilirubin, AST, and ALT should occur regularly during trabectedin treatment in accordance with the product labeling, or as often as necessary when clinical symptoms develop. Trabectedin must not be used in patients with elevated bilirubin at the time of initiation of cycle. Elevated liver function tests should be managed with treatment interruption, dosage reduction, or permanent discontinuation depending on the severity and duration of abnormality.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2010) "Product Information. Yondelis (trabectedin)." Janssen Pharmaceuticals

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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