Abstract
Purpose
Abiraterone acetate combined with prednisone improves survival in metastatic castration-resistant prostate cancer (mCRPC) patients. This oral anticancer agent may result in drug–drug interactions (DDI). We aimed to evaluate the prevalence of DDI with abiraterone and the possible determinants for the occurrence of these DDI.
Methods
We performed a single centre retrospective review from electronic medical records of mCRPC patients treated with abiraterone from 2011 to 2015. Potential DDI with abiraterone were identified using Micromedex and were categorized by a 4-point scale severity.
Results
Seventy-two out of ninety-five mCRPC pts (median age: 77 years [68–82]) had comorbidities. The median number of drugs used per patient was 7 [5–9]. 66 potential DDI with abiraterone were detected in 49 patients (52%): 39 and 61% were classified as major and moderate DDI, respectively. In the univariate analysis, pain (p < 0.0001), hypo-albuminemia (p = 0.032), and higher ECOG performance status (PS) (p = 0.013) were significantly associated with a higher risk of DDI with abiraterone. Pain (p < 0.0001) and PS (p = 0.018) remained significant in the multivariate analysis.
Conclusions
Polypharmacy is an issue among mCRPC patients. In our study, half of the patients have potential DDI with abiraterone. Patients with pain and poor PS are at higher risk of DDI with abiraterone. A medication review by a pharmacist is of crucial importance to prevent DDI with abiraterone.
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References
Lees J, Chan A (2011) Polypharmacy in elderly patients with cancer : clinical implications and management. Lancet Oncol 12:1249–1257
De Bono JS, Logothetis CJ, Molina A et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364(21): 1995–2005
Ryan CJ, Smith MR, de Bono JS et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368(2):138–48
Thomas-Schoemann A, Blanchet B, Bardin C et al (2014) Drug interactions with solid tumour-targeted therapies. Crit Rev Oncol Hematol 89(1):179–196
Chan A, Tan SH, Wong CM (2009) Clinically significant drug-drug interactions between oral anticancer agents and nonanticancer agents: a Delphi survey of oncology pharmacists. Clin Ther 31(2):2379–2386
Chi KN, Tolcher A, Lee P et al (2013) Effect of abiraterone acetate plus prednisone on the pharmacokinetics of dextromethorphan and theophylline in patients with metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol 71(1):237–244
Graff JN, Beer TN (2014) Pharmacotherapeutic management of metastatic, castration-resistant prostate cancer in the elderly: focus on non-chemotherapy agents. Drugs Aging 31(12):873–882
Monbaliu J, Gonzalez M, Bernard A et al (2016 Oct) In vitro and in vivo drug–drug interaction studies to assess the effect of abiraterone acetate, abiraterone, and metabolites of abiraterone on CYP2C8 Activity. Drug Metab Dispos 44(10):1682–1691
Bernard A, Vaccaro N, Acharya M et al (2015) Impact on abiraterone pharmacokinetics and safety: open-label drug-drug interaction studies with ketoconazole and rifampicin. Clin Pharmacol Drug Dev 4(1):63–73
Extermann M, Hurria A (2007) Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol 25(14):1824–31
Hovstadius B, Petersson G (2012) Factors leading to excessive polypharmacy. Clin Geriatr Med 28:159–172
Chi KN, Spratlin J, Kollmannsberger C, North S et al (2015) Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration-resistant prostate cancer. J Clin Pharmacol 55(12):1406–1414
Benoist GE, Hendriks RJ, Mulders PF et al (2016) Pharmacokinetic aspects of the two novel oral drugs used for metastatic castration-resistant prostate cancer: abiraterone acetate and enzalutamide. Clin Pharmacokinet [Epub ahead of print]
Jamani R, Lee EK, Berry SR et al (2016) High prevalence of potential drug drug interactions in patients with castration-resistant prostate cancer treated with abiraterone acetate. Eur J Clin Pharmacol [Epub ahead of print]
Fongemie J, Felix-Getzik E (2015) A review of nebivolol pharmacology and clinical evidence. Drugs 75(12):1349–1371
Saarikoski T, Saari TI, Hagelberg NM et al (2015) Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol. Eur J Clin Pharmacol 71(3):321–327
Ing Lorenzini K, Daali Y, Dayer P et al (2012) Pharmacokinetic-pharmacodynamic modelling of opioids in healthy human volunteers. a minireview. Basic Clin Pharmacol Toxicol 110(3):219–226
Prithviraj GK, Koroukian S, Margevicius S et al (2012) Patient characteristics associated with polypharmacy and inappropriate prescribing of medications among older adults with cancer. J Geriatr Oncol. 3(3):228–237
Tod M, Goutelle S, Clavel-Grabit F et al (2011 Aug) Quantitative prediction of cytochrome P450 (CYP) 2D6-mediated drug interactions. Clin Pharmacokinet 50(8):519–530
Acknowledgements
The authors thank Pr Michel Tod for “ddi predictor” tool.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Bonnet, C., Boudou-Rouquette, P., Azoulay-Rutman, E. et al. Potential drug–drug interactions with abiraterone in metastatic castration-resistant prostate cancer patients: a prevalence study in France. Cancer Chemother Pharmacol 79, 1051–1055 (2017). https://doi.org/10.1007/s00280-017-3291-z
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DOI: https://doi.org/10.1007/s00280-017-3291-z