Objective: To report a case of a possible drug interaction between warfarin, carboplatin, and etoposide resulting in a marked increase in a patient's response to warfarin, and to outline monitoring strategies for this interaction.
Case summary: A 74-year-old white man receiving warfarin (average dose 42.5 mg/wk) for atrial fibrillation was diagnosed with a right testicular non-seminoma mixed germ cell tumor. Mediastinal metastases were subsequently discovered, and the patient was treated with a chemotherapy regimen including carboplatin and etoposide. Sixteen days after the first course of chemotherapy, the international normalized ratio (INR) was increased to 12.6 from a baseline range of 1.15-2.11 that was observed over the previous 8 months of therapy, indicating a clinically significant alteration in the pharmacodynamic response to warfarin.
Discussion: This patient had no concomitant disease or dietary changes to explain the altered response to warfarin. Carboplatin and etoposide have not been reported to inhibit warfarin metabolism. However, previous reports have suggested that etoposide may displace warfarin from its protein binding sites, resulting in an early elevation in prothrombin time following chemotherapy. The late elevation of INR observed in our patient suggests that his response to warfarin may have been due to the displacement of warfarin by elemental platinum, which has a long plasma half-life.
Conclusions: This case report suggests a possible drug interaction between carboplatin, etoposide, and warfarin. Because of the risk associated with an increased response to warfarin, we recommend close monitoring of the INR, perhaps twice weekly, early and later in the time course following chemotherapy with these agents. Appropriate dosage adjustments of warfarin should be performed if an altered response to warfarin is observed.