abiraterone-acetate and Rhabdomyolysis

Abiraterone acetate is an inhibitor of androgens biosynthesis, approved as first-line treatment in castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. Abiraterone has been rarely associated with severe rhabdomyolysis, but the mechanism of muscle toxicity is unknown.. We hereby present a case of severe rhabdomyolysis resulting in acute on chronic kidney injury following abiraterone initiation in a patient previously under rosuvastatin.. Rhabdomyolysis was resolutive after rosuvastatin and abiraterone discontinuation, and kidney function recovered. There was no recurrence of muscle toxicity after re-initiation of abiraterone alone.. Abiraterone selectively inhibits CYP17 as well as the hepatic transporter OATP1B1. OATP1B1 is an efflux transporter, whose function is to extract several drugs from the portal blood, allowing them to undergo hepatic metabolism. We hypothesize that abiraterone-induced inhibition of plasmatic uptake of rosuvastatin by OATP1B1 increased plasmatic concentration of rosuvastatin, leading to toxicity on muscle cells. We therefore suggest that the association between rosuvastatin and abiraterone should be avoided.

Topics: Abiraterone Acetate; Acute Kidney Injury; Aged; Humans; Liver-Specific Organic Anion Transporter 1; Male; Prostatic Neoplasms, Castration-Resistant; Rhabdomyolysis; Rosuvastatin Calcium