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4CPS-099 Clinically relevant drug–drug interaction events in patients with abiraterone, enzalutamide or apalutamide treatment

2022· article· en· W4293230230 on OpenAlexfundno aff
Julia Bodega-Azuara, Esther Vicente‐Escrig, T Cebolla-Beltrán, V Bosó-Ribelles, Josep Edo-Peñarrocha, M Fortanet-García, Raúl Ferrando‐Piqueres

Bibliographic record

VenueSection 4: Clinical pharmacy services · 2022
Typearticle
Languageen
FieldMedicine
TopicProstate Cancer Treatment and Research
Canadian institutionsnot available
FundersRio Tinto
KeywordsEnzalutamideMedicinePharmacologyProstate cancerDrug interactionInternal medicineDrugCancerAndrogen receptor

Abstract

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<h3>Background and importance</h3> Cytochrome P enzymes play a key role in drug metabolism and it is essential to understanding some interactions. <h3>Aim and objectives</h3> Optimising pharmacotherapy in prostate cancer patients through the identification of drug interactions between anti-androgenic therapy and the patient’s usual medication. <h3>Material and methods</h3> 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. <h3>Results</h3> 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. <h3>Conclusion and relevance</h3> 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. <h3>References and/or acknowledgements</h3> <h3>Conflict of interest</h3> No conflict of interest

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.078
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.053
GPT teacher head0.417
Teacher spread0.364 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2022
Admission routes1
Has abstractyes

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