Enzalutamide & drug interactions. - Advanced Prostate...

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Enzalutamide & drug interactions.

pjoshea13 profile image
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New Dutch paper below [1]

In a recent post, I mentioned that Xtandi could cause the liver to metabolize more of certain drugs, thereby weakening the dose:

Wiki [2]: "Enzalutamide is a moderate to strong inducer of multiple cytochrome P450 enzymes including CYP3A4, CYP2C9, and CYP2C19 and hence has a high potential for clinically relevant drug interactions.

In a clinical study of enzalutamide for ER-positive breast cancer in women, enzalutamide was found to decrease serum concentrations of the aromatase inhibitors anastrozole and exemestane by 90% and 50%, respectively, which could reduce their effectiveness."

[3] " Enzalutamide is the only oral chemotherapeutic that may decrease the serum concentration of warfarin"

From the new paper:

"In 23% and 45% of all patients a potential DDI {drug-drug interactions} was found with PPIs {Proton-pump inhibitors} and CNS {Central nervous system} depressants, respectively."

[4] This link suggests a possible interaction with everything under the sun.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/288...

Br J Clin Pharmacol. 2017 Sep 7. doi: 10.1111/bcp.13425. [Epub ahead of print]

Drug-drug interaction potential in men treated with enzalutamide: Mind the gap.

Benoist GE1, van Oort IM2, Smeenk S3, Javad A1, Somford DM4, Burger DM1, Mehra N3, van Erp NP1.

Author information

1

Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.

2

Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.

3

Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.

4

Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Abstract

AIM:

Metastatic castration resistant prostate cancer (mCRPC) patients are generally older patients with several co-morbidities and are therefore more at risk for complications due to drug-drug interactions(DDIs). We assessed the prevalence of potential DDIs in a cohort of mCRPC patients treated with enzalutamide.

METHODS:

We conducted a retrospective review of pharmacy records to retrieve individual drug histories of mCRPC patients who started enzalutamide therapy in a tertiary care setting. Potential DDIs were analyzed using two international drug interaction compendia: Lexicomp® and Micromedex®, and the Dutch drug database. Two potential pharmacodynamic DDIs were analyzed.

RESULTS:

105 records were evaluated for potential DDIs with enzalutamide, 56 out of 205 different co-medications were flagged by at least one of the three compendia. Lexicomp, Micromedex and the Dutch drug database flagged for potential DDIs in 85%, 54% and 32%, respectively. 85% of DDIs were classified as major. The median number of co-medications per patient was 11(range 1-26). The median (range) number of interactions per patient was 4(0-10),1(0-5) and 0(0-2) for Lexicomp, Micromedex and the Dutch drug database, respectively. In 23% and 45% of all patients a potential DDI was found with PPIs and CNS depressants, respectively.

CONCLUSIONS:

A high prevalence of potential DDIs was found. The inclusion and grading of potential DDIs was highly variable between the three drug interaction compendia. Physicians, nurses and pharmacists should be aware of this potential problem, which might require intensive monitoring or alternative treatment strategies to prevent suboptimal treatment of the co-morbidities in patients treated with enzalutamide.

This article is protected by copyright. All rights reserved.

KEYWORDS:

anticancer drugs; cytochrome p450; drug interactions; medication safety

PMID: 28881501 DOI: 10.1111/bcp.13425

[2] en.wikipedia.org/wiki/Enzal...

[3] ascopubs.org/doi/full/10.12...

[4] uniprix.com/en/drug-lexicon...

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BigRich profile image
BigRich

Patrick,

Thank you for bring this information to the forum.

Rich

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