Drug Interactions between Akeega and radium 223 dichloride

GENERALLY AVOID: The concomitant use of radium Ra 223 dichloride and abiraterone acetate plus a corticosteroid may increase the risk of death and fractures in patients with castration-resistant prostate cancer who have bone metastases. At the primary analysis of the ERA-223 trial (n=806), an increased incidence of mortality (39% vs 36%) and fractures (29% vs 11%) was observed in patients who received abiraterone acetate plus prednisone/prednisolone in combination with radium Ra 223 dichloride compared to patients who received placebo in combination with abiraterone acetate plus prednisone.

MANAGEMENT: The use of abiraterone acetate plus a corticosteroid in combination with radium Ra 223 dichloride is not recommended. Some authorities consider this combination to be contraindicated. It has been recommended that radium Ra 223 dichloride not be initiated for at least 5 days following the last administration of abiraterone acetate in combination with a corticosteroid. Continued monitoring for fractures should be considered in patients previously treated with this combination.

MONITOR CLOSELY: Coadministration of radium Ra 223 dichloride (Ra-223 dichloride) with other agents that can cause bone marrow suppression or myelosuppression may result in additive toxicity. Ra-223 dichloride alone is associated with thrombocytopenia, neutropenia, pancytopenia, and leukopenia; death from bone marrow failure has also been reported. In a randomized clinical trial in patients with metastatic castration-resistant prostate cancer with bone metastases, 2% of the patients on Ra-223 dichloride experienced bone marrow failure or ongoing pancytopenia compared to no patients in the placebo group. Grade 3-4 adverse reactions of thrombocytopenia and neutropenia were more commonly reported in patients who had received prior docetaxel. However, data from clinical drug interaction studies are lacking.

MANAGEMENT: Caution and close monitoring for additive hematologic toxicity are recommended if concomitant use of Ra-223 dichloride with other agents that can cause bone marrow suppression or myelosuppression is required. The manufacturer advises that Ra-223 dichloride be discontinued in patients requiring administration of chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy. If concomitant use is required, the manufacturer's product labeling should be consulted for specific hematologic monitoring and dose adjustment recommendations. Some authorities recommend not initiating subsequent systemic cancer treatment for at least 30 days after the last administration of Ra-223 dichloride. Patients should be advised to contact their physician if they develop signs or symptoms of myelosuppression or infection including but not limited to pallor, dizziness, fatigue, lethargy, fainting, easy bruising or bleeding, fever, chills, sore throat, body aches, and/or other influenza-like symptoms.