Pexidartinib and Valproic Acid Capsules
Determining the interaction of Pexidartinib and Valproic Acid Capsules and the possibility of their joint administration.
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.GENERALLY AVOID: Coadministration of pexidartinib with strong CYP450 3A4 inhibitors and/or uridine diphosphate glucuronosyltransferase (UGT) inhibitors may significantly increase the plasma concentrations and the incidence and severity of adverse effects of pexidartinib, including potentially fatal hepatotoxicity. The proposed mechanism is inhibition of CYP450 3A4 and/or UGT, the primary isoenzymes responsible for the metabolic clearance of pexidartinib. Concomitant administration of itraconazole, a strong CYP450 3A4 inhibitor, increased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 48% and 70%, respectively. The effect of coadministration with a moderate CYP450 3A4 inhibitor on pexidartinib pharmacokinetics is unknown. Coadministration with probenecid, a UGT inhibitor, increased pexidartinib Cmax and AUC by 5% and 60%, respectively. MANAGEMENT: The use of pexidartinib with strong CYP450 3A4 inhibitors and/or UGT inhibitors should generally be avoided. If concomitant use is required, the dose of pexidartinib should be reduced according to the manufacturer's recommendations. If concomitant use of a strong CYP450 3A4 inhibitor or UGT inhibitor is discontinued, the dose of pexidartinib may be increased, after 3 plasma half-lives of the strong CYP450 3A4 inhibitor or UGT inhibitor, to the dose that was used prior to starting the strong CYP450 3A4 inhibitor or UGT inhibitor. References "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc., Parsippany, NJ.
Professional:GENERALLY AVOID: Coadministration of pexidartinib with strong CYP450 3A4 inhibitors and/or uridine diphosphate glucuronosyltransferase (UGT) inhibitors may significantly increase the plasma concentrations and the incidence and severity of adverse effects of pexidartinib, including potentially fatal hepatotoxicity. The proposed mechanism is inhibition of CYP450 3A4 and/or UGT, the primary isoenzymes responsible for the metabolic clearance of pexidartinib. Concomitant administration of itraconazole, a strong CYP450 3A4 inhibitor, increased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 48% and 70%, respectively. The effect of coadministration with a moderate CYP450 3A4 inhibitor on pexidartinib pharmacokinetics is unknown. Coadministration with probenecid, a UGT inhibitor, increased pexidartinib Cmax and AUC by 5% and 60%, respectively.
MANAGEMENT: The use of pexidartinib with strong CYP450 3A4 inhibitors and/or UGT inhibitors should generally be avoided. If concomitant use is required, the dose of pexidartinib should be reduced according to the manufacturer's recommendations. If concomitant use of a strong CYP450 3A4 inhibitor or UGT inhibitor is discontinued, the dose of pexidartinib may be increased, after 3 plasma half-lives of the strong CYP450 3A4 inhibitor or UGT inhibitor, to the dose that was used prior to starting the strong CYP450 3A4 inhibitor or UGT inhibitor.
- "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc., Parsippany, NJ.
Generic Name: valproic acid
Brand name: Depakene, Depacon, Stavzor, Valproate Sodium
Synonyms: Valproic acid, Valproic Acid and Derivatives
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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