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Fedratinib and Trabectedin

Determining the interaction of Fedratinib and Trabectedin and the possibility of their joint administration.

Check result:
Fedratinib <> Trabectedin
Relevance: 06.08.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Consumer information for this interaction is not currently available.MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of trabectedin, which is primarily metabolized by the isoenzyme. In 9 study patients with advanced malignancies, administration of a single 1.3 mg/m2 infusion of trabectedin on day 6 of treatment with rifampin (600 mg daily for 6 days), a potent CYP450 3A4 inducer, resulted in a 22% decrease in mean trabectedin peak plasma concentration (Cmax) and 31% decrease in mean systemic exposure (AUC) compared to infusion of trabectedin alone. Results from a population pharmacokinetic analysis (n = 831) indicated that the plasma clearance of trabectedin was 19% higher in patients who received concomitant dexamethasone, a moderate CYP450 3A4 inducer, compared to those who did not. MANAGEMENT: The possibility of diminished therapeutic effects should be considered when trabectedin is prescribed with CYP450 3A4 inducers. Close clinical and laboratory monitoring is recommended whenever a CYP450 3A4 inducer is added to or withdrawn from trabectedin therapy, and the dosage adjusted if necessary. References "Product Information. Yondelis (trabectedin)." Janssen Pharmaceuticals, Titusville, NJ. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 Machiels JP, Staddon A, Herremans C, et al. "Impact of cytochrome P450 3A4 inducer and inhibitor on the pharmacokinetics of trabectedin in patients with advanced malignancies: open-label, multicenter studies." Cancer Chemother Pharmacol 74 (2014): 729-37

Professional:

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of trabectedin, which is primarily metabolized by the isoenzyme. In 9 study patients with advanced malignancies, administration of a single 1.3 mg/m2 infusion of trabectedin on day 6 of treatment with rifampin (600 mg daily for 6 days), a potent CYP450 3A4 inducer, resulted in a 22% decrease in mean trabectedin peak plasma concentration (Cmax) and 31% decrease in mean systemic exposure (AUC) compared to infusion of trabectedin alone. Results from a population pharmacokinetic analysis (n = 831) indicated that the plasma clearance of trabectedin was 19% higher in patients who received concomitant dexamethasone, a moderate CYP450 3A4 inducer, compared to those who did not.

MANAGEMENT: The possibility of diminished therapeutic effects should be considered when trabectedin is prescribed with CYP450 3A4 inducers. Close clinical and laboratory monitoring is recommended whenever a CYP450 3A4 inducer is added to or withdrawn from trabectedin therapy, and the dosage adjusted if necessary.

References
  • "Product Information. Yondelis (trabectedin)." Janssen Pharmaceuticals, Titusville, NJ.
  • Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  • Machiels JP, Staddon A, Herremans C, et al. "Impact of cytochrome P450 3A4 inducer and inhibitor on the pharmacokinetics of trabectedin in patients with advanced malignancies: open-label, multicenter studies." Cancer Chemother Pharmacol 74 (2014): 729-37
Fedratinib

Generic Name: fedratinib

Brand name: Inrebic

Synonyms: n.a.

Trabectedin

Generic Name: trabectedin

Brand name: Yondelis

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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