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

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

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Veröffentlicht in:British journal of clinical pharmacology 2018-01, Vol.84 (1), p.122-129
Hauptverfasser: Benoist, Guillemette Emma, Oort, Inge M., Smeenk, Stella, Javad, Adrian, Somford, Diederik M., Burger, David M., Mehra, Niven, Erp, Nielka P.
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Sprache:eng
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Zusammenfassung:Aims Metastatic castration‐resistant prostate cancer (mCRPC) patients are generally older patients with several co‐morbidities and are therefore at increased risk of 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 analysed using two international drug interaction compendia: Lexicomp® and Micromedex®, and the Dutch drug database. Two potential pharmacodynamic DDIs were analysed. Results A total of 105 records were evaluated for potential DDIs with enzalutamide. Of 205 different co‐medications, 56 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. Eighty‐five per cent 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. What is Already Known about this Subject Enzalutamide is an inducer of several CYP450 enzymes; a strong inducer of CYP3A4 and a moderate inducer of CYP2C19 and CYP2C9. mCRPC patients are generally older patients potentially with several co‐morbidities and therefore at increased risk of complications due to drug–drug interactions. What this Study Adds There is limited awareness of the drug interaction potential of enzalutamide. This is the first study that describes the high prevalence (85%) of potential major DDIs for patients treated with enzalutamide in a real live cohort. The high prevalence (45%) of CNS interactions in this cohort requires attention, especially as the use of CNS depressants in combination with enza
ISSN:0306-5251
1365-2125
DOI:10.1111/bcp.13425