Skip to main content
SpringerLink
Log in

High prevalence of potential drug-drug interactions in patients with castration-resistant prostate cancer treated with abiraterone acetate

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Abiraterone acetate (AA), used to treat metastatic castration-resistant prostate cancer (mCRPC), inhibits androgen biosynthesis by blocking cytochrome P450 (CYP) 17A1. It also inhibits other cytochromes involved in the metabolism of various widely used medications. As such, there is presumably a high potential for drug-drug interactions (DDIs) that can diminish the efficacy of AA or concurrent medications, or increase the risk of DDI-related adverse events (AEs). However, the scale of AA-associated DDIs is currently unknown.

Methods

We conducted a retrospective review of pharmacy records and electronic patient charts to retrieve individual drug histories and on-treatment AEs of mCRPC patients beginning AA therapy in a tertiary care setting. Potential DDIs were analyzed using two commercial databases, Lexicomp and Micromedex.

Results

Eighty-four informative patients were identified. Sixty-five patients (77 %) and 44 patients (52 %) were flagged for one or more potential DDIs by the Lexicomp and Micromedex databases, respectively. One hundred eighty-four potential DDIs were identified overall, with a median of 1 DDI per patient in both databases. Possibly due to rigorous DDI screening before AA treatment initiation, we did not identify a definite instance of DDI-related AEs.

Conclusions

The use of commercial DDI databases suggests a substantial risk of potentially consequential DDIs in mCRPC patients undergoing AA therapy. However, prospective investigations with larger patient populations are required to better establish the clinical relevance of these DDIs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108. doi:10.3322/caac.21262

    Article  PubMed  Google Scholar 

  2. Basch E, Loblaw DA, Oliver TK, Carducci M, Chen RC, Frame JN, Garrels K, Hotte S, Kattan MW, Raghavan D, Saad F, Taplin ME, Walker-Dilks C, Williams J, Winquist E, Bennett CL, Wootton T, Rumble RB, Dusetzina SB, Virgo KS (2014) Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol 32(30):3436–3448. doi:10.1200/JCO.2013.54.8404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI, Investigators C-A (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364(21):1995–2005. doi:10.1056/NEJMoa1014618

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368(2):138–148. doi:10.1056/NEJMoa1209096

    Article  CAS  PubMed  Google Scholar 

  5. Hoy SM (2013) Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. Drugs 73(18):2077–2091. doi:10.1007/s40265-013-0150-z

    Article  CAS  PubMed  Google Scholar 

  6. Han CS, Patel R, Kim IY (2015) Pharmacokinetics, pharmacodynamics and clinical efficacy of abiraterone acetate for treating metastatic castration-resistant prostate cancer. Expert Opin Drug Metab Toxicol 11(6):967–975. doi:10.1517/17425255.2015.1041918

    Article  CAS  PubMed  Google Scholar 

  7. Benoist GE, Hendriks RJ, Mulders PF, Gerritsen WR, Somford DM, Schalken JA, van Oort IM, Burger DM, van Erp NP (2016) Pharmacokinetic aspects of the two novel oral drugs used for metastatic castration-resistant prostate cancer: abiraterone acetate and enzalutamide. Clin Pharmacokinet DOI. doi:10.1007/s40262-016-0403-6

    Google Scholar 

  8. Bernard A, Vaccaro N, Acharya M, Jiao J, Monbaliu J, De Vries R, Stieltjes H, Yu M, Tran N, Chien C (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. doi:10.1002/cpdd.132

    Article  CAS  PubMed  Google Scholar 

  9. Marbury T, Lawitz E, Stonerock R, Gonzalez M, Jiao J, Breeding J, Haqq C, Verboven P, Stieltjes H, Yu M, Molina A, Acharya M, Chien C, Tran N (2014) Single-dose pharmacokinetic studies of abiraterone acetate in men with hepatic or renal impairment. J Clin Pharmacol 54(7):732–741. doi:10.1002/jcph.253

    Article  CAS  PubMed  Google Scholar 

  10. Chi KN, Tolcher A, Lee P, Rosen PJ, Kollmannsberger CK, Papadopoulos KP, Patnaik A, Molina A, Jiao J, Pankras C, Kaiser B, Bernard A, Tran N, Acharya M (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. doi:10.1007/s00280-012-2001-0

    Article  CAS  PubMed  Google Scholar 

  11. Buajordet I, Ebbesen J, Erikssen J, Brors O, Hilberg T (2001) Fatal adverse drug events: the paradox of drug treatment. J Intern Med 250(4):327–341

    Article  CAS  PubMed  Google Scholar 

  12. Segal EM, Flood MR, Mancini RS, Whiteman RT, Friedt GA, Kramer AR, Hofstetter MA (2014) Oral chemotherapy food and drug interactions: a comprehensive review of the literature. Journal of oncology practice / American Society of Clinical Oncology 10(4):e255–e268. doi:10.1200/JOP.2013.001183

    Article  Google Scholar 

  13. Shi S, Klotz U (2011) Age-related changes in pharmacokinetics. Curr Drug Metab 12(7):601–610

    Article  CAS  PubMed  Google Scholar 

  14. Hubbard RE, O’Mahony MS, Woodhouse KW (2013) Medication prescribing in frail older people. Eur J Clin Pharmacol 69(3):319–326. doi:10.1007/s00228-012-1387-2

    Article  PubMed  Google Scholar 

  15. Droz JP, Aapro M, Balducci L, Boyle H, Van den Broeck T, Cathcart P, Dickinson L, Efstathiou E, Emberton M, Fitzpatrick JM, Heidenreich A, Hughes S, Joniau S, Kattan M, Mottet N, Oudard S, Payne H, Saad F, Sugihara T (2014) Management of prostate cancer in older patients: updated recommendations of a working group of the International Society of Geriatric Oncology. Lancet Oncol 15(9):e404–e414. doi:10.1016/S1470-2045(14)70018-X

    Article  PubMed  Google Scholar 

  16. Lorente D, Omlin A, Ferraldeschi R, Pezaro C, Perez R, Mateo J, Altavilla A, Zafeirou Z, Tunariu N, Parker C, Dearnaley D, Gillessen S, de Bono J, Attard G (2014) Tumour responses following a steroid switch from prednisone to dexamethasone in castration-resistant prostate cancer patients progressing on abiraterone. Br J Cancer 111(12):2248–2253. doi:10.1038/bjc.2014.531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE, Investigators C-A (2015) Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 16(2):152–160. doi:10.1016/S1470-2045(14)71205-7

    Article  CAS  PubMed  Google Scholar 

  18. Carcelero E, Anglada H, Tuset M, Creus N (2013) Interactions between oral antineoplastic agents and concomitant medication: a systematic review. Expert Opin Drug Saf 12(3):403–420. doi:10.1517/14740338.2013.784268

    Article  CAS  PubMed  Google Scholar 

  19. Ranchon F, Vial T, Rioufol C, Henin E, Falandry C, Freyer G, Trillet-Lenoir V, Le Tourneau C, You B (2015) Concomitant drugs with low risks of drug-drug interactions for use in oncology clinical trials. Crit Rev Oncol Hematol 94(2):189–200. doi:10.1016/j.critrevonc.2014.12.014

    Article  PubMed  Google Scholar 

  20. van Leeuwen RW, Swart EL, Boven E, Boom FA, Schuitenmaker MG, Hugtenburg JG (2011) Potential drug interactions in cancer therapy: a prevalence study using an advanced screening method. Ann Oncol 22(10):2334–2341. doi:10.1093/annonc/mdq761

    Article  PubMed  Google Scholar 

  21. van Leeuwen RW, Brundel DH, Neef C, van Gelder T, Mathijssen RH, Burger DM, Jansman FG (2013) Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs. Br J Cancer 108(5):1071–1078. doi:10.1038/bjc.2013.48

    Article  PubMed  PubMed Central  Google Scholar 

  22. van Leeuwen RW, Jansman FG, van den Bemt PM, de Man F, Piran F, Vincenten I, Jager A, Rijneveld AW, Brugma JD, Mathijssen RH, van Gelder T (2015) Drug-drug interactions in patients treated for cancer: a prospective study on clinical interventions. Ann Oncol 26(5):992–997. doi:10.1093/annonc/mdv029

    Article  PubMed  Google Scholar 

  23. Voll ML, Yap KD, Terpstra WE, Crul M (2010) Potential drug-drug interactions between anti-cancer agents and community pharmacy dispensed drugs. Pharmacy world & science : PWS 32(5):575–580. doi:10.1007/s11096-010-9410-0

    Article  CAS  Google Scholar 

  24. Ko Y, Tan SL, Chan A, Wong YP, Yong WP, Ng RC, Lim SW, Salim A (2012) Prevalence of the coprescription of clinically important interacting drug combinations involving oral anticancer agents in Singapore: a retrospective database study. Clin Ther 34(8):1696–1704. doi:10.1016/j.clinthera.2012.06.025

    Article  PubMed  Google Scholar 

  25. Nightingale G, Hajjar E, Swartz K, Andrel-Sendecki J, Chapman A (2015) Evaluation of a pharmacist-led medication assessment used to identify prevalence of and associations with polypharmacy and potentially inappropriate medication use among ambulatory senior adults with cancer. J Clin Oncol 33(13):1453–1459. doi:10.1200/JCO.2014.58.7550

    Article  PubMed  Google Scholar 

  26. Wienkers LC, Heath TG (2005) Predicting in vivo drug interactions from in vitro drug discovery data. Nat Rev Drug Discov 4(10):825–833. doi:10.1038/nrd1851

    Article  CAS  PubMed  Google Scholar 

  27. Camenisch G, Umehara K (2012) Predicting human hepatic clearance from in vitro drug metabolism and transport data: a scientific and pharmaceutical perspective for assessing drug-drug interactions. Biopharm Drug Dispos 33(4):179–194. doi:10.1002/bdd.1784

    Article  CAS  PubMed  Google Scholar 

  28. Jaiswal S, Sharma A, Shukla M, Vaghasiya K, Rangaraj N, Lal J (2014) Novel pre-clinical methodologies for pharmacokinetic drug-drug interaction studies: spotlight on “humanized” animal models. Drug Metab Rev 46(4):475–493. doi:10.3109/03602532.2014.967866

    Article  CAS  PubMed  Google Scholar 

  29. Olvey EL, Clauschee S, Malone DC (2010) Comparison of critical drug-drug interaction listings: the Department of Veterans Affairs medical system and standard reference compendia. Clin Pharmacol Ther 87(1):48–51. doi:10.1038/clpt.2009.198

    Article  CAS  PubMed  Google Scholar 

  30. Vitry AI (2007) Comparative assessment of four drug interaction compendia. Br J Clin Pharmacol 63(6):709–714. doi:10.1111/j.1365-2125.2006.02809.x

    Article  CAS  PubMed  Google Scholar 

  31. Wong CM, Ko Y, Chan A (2008) Clinically significant drug-drug interactions between oral anticancer agents and nonanticancer agents: profiling and comparison of two drug compendia. Ann Pharmacother 42(12):1737–1748. doi:10.1345/aph.1L255

    Article  CAS  PubMed  Google Scholar 

  32. Scheife RT, Hines LE, Boyce RD, Chung SP, Momper JD, Sommer CD, Abernethy DR, Horn JR, Sklar SJ, Wong SK, Jones G, Brown ML, Grizzle AJ, Comes S, Wilkins TL, Borst C, Wittie MA, Malone DC (2015) Consensus recommendations for systematic evaluation of drug-drug interaction evidence for clinical decision support. Drug Saf 38(2):197–206. doi:10.1007/s40264-014-0262-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Krzyzanowska MK, Powis M (2015) Extending the quality and safety agenda from parenteral to oral chemotherapy. Journal of oncology practice / American Society of Clinical Oncology 11(3):198–201. doi:10.1200/JOP.2015.004002

    Article  Google Scholar 

Download references

Acknowledgments

The authors would like to thank for the generous support from the TELUS Ride For Dad & The Prostate Cancer Fight Foundation (Durham/ON) and from the Joseph and Silvana Melara Cancer Research Fund that have made this study possible.

Author contributions

Conception and design: Carlo DeAngelis, Angie Giotis, Urban Emmenegger.

Collection and assembly of data: Rehana Jamani, Esther K. Lee, Ronak Saluja, Angie Giotis, Urban Emmenegger.

Data analysis and interpretation: All authors.

Manuscript writing: All authors.

Final approval of manuscript: All authors.

Author information

Authors and Affiliations

  1. Sunnybrook Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    Rehana Jamani, Esther K. Lee, Scott R. Berry, Ronak Saluja, Carlo DeAngelis, Angie Giotis & Urban Emmenegger

  2. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    Rehana Jamani, Esther K. Lee & Urban Emmenegger

  3. Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada

    Carlo DeAngelis

  4. Institute of Medical Science, University of Toronto, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada

    Urban Emmenegger

Authors
  1. Rehana Jamani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Esther K. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Scott R. Berry
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ronak Saluja
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carlo DeAngelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Angie Giotis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Urban Emmenegger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Urban Emmenegger.

Ethics declarations

Competing interests

Drs. Berry and Emmenegger provided past paid consultancy services for Janssen Inc., producer of abiraterone acetate. Of note, Janssen Inc. was not involved in any aspect of the submitted study. The other authors do not have any competing interests to declare.

Electronic supplementary material

Table S1

(DOCX 17 kb)

Table S2

(DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jamani, R., Lee, E.K., Berry, S.R. et al. High prevalence of potential drug-drug interactions in patients with castration-resistant prostate cancer treated with abiraterone acetate. Eur J Clin Pharmacol 72, 1391–1399 (2016). https://doi.org/10.1007/s00228-016-2120-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-016-2120-3

Keywords

Search

Navigation