Drug-drug interactions in patients with castration-resistant prostate cancer undergoing abiraterone therapy: Characterizing the scale of the problem.

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269 Background: Abiraterone acetate (AA), used to treat CRPC, inhibits androgen biosynthesis by blocking cytochrome P450 (CYP) 17. It also inhibits other cytochromes involved in the metabolism of various widely-used medications (strong inhibition of CYP1A2, CYP2D6, and CYP2C8; moderate inhibition of CYP2C9, CYP2C19 and CYP3A4/5). Hence, there is presumably a high potential for drug-drug interactions (DDI) that can either diminish the efficacy of AA or concurrent medications, or increase the risk of DDI-related adverse events (AE); however, the scale of AA-associated DDI is currently unknown. Methods: We conducted a retrospective review of pharmacy records and electronic pt charts to retrieve individual drug histories, comorbidities, and AE of CRPC pts beginning AA treatment between Jan 2010 and Apr 2014. Individual drug histories were analyzed for DDI using two commercial databases, Lexicomp and Micromedex. Results: 91 informative pts were identified. Using Lexicomp, the most common drugs flagged for potential DDI of high clinical significance (i.e., “avoid combination”, or “consider therapy modification”) with AA were dexamethasone, metoprolol, clopidogrel, oxycodone, and citalopram. They were administered to 12 (13%), 10 (11%), 6 (7%), 4 (4%), and 4 (4%) pts respectively. Micromedex assigned a major risk of DDI to oxycodone and a moderate risk to metoprolol. At least 1 potentially significant DDI was found in 38/91 pts (42%) with Lexicomp, and in 42/91 pts (46%) with Micromedex. Most common AE were fluid retention seen in 19 pts (21%), fatigue in 15 (16%), liver-function test abnormalities in 13 (14%), hypertension in 13 (14%), and pain in 11 (12%), all corresponding to AE typically associated with the use of AA. We did not find unequivocal evidence for DDI-related AE. Conclusions: The use of commercial DDI databases reveals a substantial risk of potentially consequential DDI in CRPC pts undergoing AA therapy, although some of the flagged DDI (e.g., between AA and dexamethasone) may be of theoretical rather than practical concern. Further investigation with larger patient populations is required to better establish the clinical relevance of these DDI.