Drug Interaction Report

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 prostrate 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.

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GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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