Background and importance Cytochrome P enzymes play a key role in drug metabolism and it is essential to understanding some interactions.
Aim and objectives Optimising pharmacotherapy in prostate cancer patients through the identification of drug interactions between anti-androgenic therapy and the patient’s usual medication.
Material and methods Patients on abiraterone, enzalutamide or apalutamide treatment were identified through the pharmacy computerised record of dispensations. Their usual medication was obtained from the pharmacotherapeutic history.
The evaluation of abiraterone and enzalutamide interactions was performed with Liverpool and Uptodate databases. For apalutamide, Micromedex and Uptodate were used because apalutamide is not registered in Liverpool. Clinically relevant interactions were reported to the urologist, performing the pertinent pharmaceutical interventions.
Results 32 prostate cancer patients were identified; 21 (65.6%) were treated with abiraterone, 8 (25%) with enzalutamide and 3 (9.4%) with apalutamide. The median of age was 79 (53–90) years and the median of concomitant treatments was 7 (3–13).
18 relevant interactions were detected; 2 (11.1%) with abiraterone, 10 (55.6%) with enzalutamide and 6 (33.3%) with apalutamide. The drugs with relevant interactions belonged to the following therapeutic groups:
Cardiovascular system (61.1%). In the co-administration of bisoprolol with abiraterone or apalutamide we recommended reducing the bisoprolol doses. In treatments with enzalutamide and doxazosin, lecardipine, torasemide or nevibolol we advised changing the therapy to hydralazine, angiotensin-converting enzyme inhibitors, furosemide or atenolol. Statins should be replaced by ezetimibe or fibrates in enzalutamide or apalutamide treatment.
Antithrombotics (16.7%). Dabigatran, apixaban or acenocoumarol are contraindicated with anti-androgenic therapy.We proposed the use of heparins or oral anticoagulants with strict international normalised ratio (INR) control.
Proton pump inhibitors (PPIs) (11.1%). In patients treated with enzalutamide, pantoprazole or ??? changing to an anti-H2 was suggested.
Analgesics (11.1%). Metamizole and tramadol are not recommended in cases of concomitant administration with abiraterone or apalutamide.
In the consulted databases a discrepancy of 25% was found, which illustrates the need to compare at least two databases to obtain an optimal review of interactions.
Conclusion and relevance Abiraterone, apalutamide and, mainly, enzalutamide suffer a large number of interactions, which may modify a treatment’s efficacy and/or its safety. The use of multiple concomitant medications is a risk factor that increases the possibility of hospitalisation and mortality. The pharmacist must achieve the correct review of drug interactions with reference to at least two databases.
Conflict of interest No conflict of interest
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