Apixaban and Enzalutamide

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 information for this interaction is not currently available.MONITOR: Coadministration with enzalutamide may decrease the plasma concentrations and effect of apixaban. The proposed mechanism of action is enzalutamide-mediated induction of CYP450 3A4, the main isoenzyme responsible for the metabolism of apixaban. Enzalutamide is also considered a moderate CYP450 2C9 and 2C19 inducer in vivo; however, since metabolism of apixaban via these isoenzymes is considered a minor pathway the significance this effect on the concentration of apixaban remains unclear. In addition, there is conflicting evidence regarding the clinical effect of enzalutamide and its active metabolite N-desmethyl enzalutamide on the efflux transporter, P-glycoprotein (P-gp), of which apixaban is also a substrate. Both enzalutamide and N-desmethyl enzalutamide have been described in vitro as P-gp inhibitors; however, although some sources propose that P-gp induction occurs in vivo, data from clinical studies evaluating transporter-mediated drug interactions of enzalutamide are not available. It is therefore difficult to predict which effect predominates clinically and the magnitude of the effects of enzalutamide on apixaban metabolism via the CYP450 3A4 and P-gp pathways. When apixaban was coadministered with rifampin, a dual potent inducer of both CYP450 3A4 and P-gp (600 mg once a day), mean apixaban peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 42% and 54%, respectively. MANAGEMENT: Caution is advised during concomitant therapy with enzalutamide and apixaban. Therapeutic monitoring of apixaban is advised particularly when it is added to or withdrawn from treatment in patients already taking enzalutamide or when enzalutamide is added to or withdrawn from treatment in patients already taking apixaban. References Weiss J, Kocher J, Mueller C, Rosenzweig S, Theile D "Impact of enzalutamide and its main metabolite N-desmethyl enzalutamide on pharmacokinetically important drug metabolizing enzymes and drug transporters." Biopharm Drug Dispos 38 (2017): 517-25 Benoist GE, Hendriks RJ, Mulders PF, et al. "Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide." Clin Pharmacokinet (2016): "Product Information. Eliquis (apixaban)." Bristol-Myers Squibb Canada Inc, Montreal, IN. "Product Information. Xtandi (enzalutamide)." Astellas Pharma US, Inc, Deerfield, IL. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 Cerner Multum, Inc. "Australian Product Information." O 0 Shatzel JJ, Baughety MM, Olson SR, Beer TM, DeLoughery TG "Management of anticoagulation in patient with prostate cancer receiving enzalutamide." J Oncol Pract 11 (2017): 720-7 View all 7 references

MONITOR: Coadministration with enzalutamide may decrease the plasma concentrations and effect of apixaban. The proposed mechanism of action is enzalutamide-mediated induction of CYP450 3A4, the main isoenzyme responsible for the metabolism of apixaban. Enzalutamide is also considered a moderate CYP450 2C9 and 2C19 inducer in vivo; however, since metabolism of apixaban via these isoenzymes is considered a minor pathway the significance this effect on the concentration of apixaban remains unclear. In addition, there is conflicting evidence regarding the clinical effect of enzalutamide and its active metabolite N-desmethyl enzalutamide on the efflux transporter, P-glycoprotein (P-gp), of which apixaban is also a substrate. Both enzalutamide and N-desmethyl enzalutamide have been described in vitro as P-gp inhibitors; however, although some sources propose that P-gp induction occurs in vivo, data from clinical studies evaluating transporter-mediated drug interactions of enzalutamide are not available. It is therefore difficult to predict which effect predominates clinically and the magnitude of the effects of enzalutamide on apixaban metabolism via the CYP450 3A4 and P-gp pathways. When apixaban was coadministered with rifampin, a dual potent inducer of both CYP450 3A4 and P-gp (600 mg once a day), mean apixaban peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 42% and 54%, respectively.

MANAGEMENT: Caution is advised during concomitant therapy with enzalutamide and apixaban. Therapeutic monitoring of apixaban is advised particularly when it is added to or withdrawn from treatment in patients already taking enzalutamide or when enzalutamide is added to or withdrawn from treatment in patients already taking apixaban.

Apixaban

Generic Name: apixaban

Brand name: Eliquis, Eliquis Starter Pack for Treatment of DVT and PE

Synonyms: n.a.

What is Apixaban?

Enzalutamide

Generic Name: enzalutamide

Brand name: Xtandi

Synonyms: n.a.

What is Enzalutamide?