etopophos and warfarin Interactions
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Interaction(s) found:
warfarin and etoposide phosphate (Moderate Drug-Drug)
MONITOR: The combination of etoposide and carboplatin has been reported to potentiate the hypoprothrombinemic effect of warfarin in a patient stabilized on the anticoagulant. The patient presented 16 days after initiation of chemotherapy with suspected gastrointestinal bleeding and an INR of 12.6, compared to a baseline range of 1.15 to 2.11 over the previous 8 months. The exact mechanism of the interaction is unknown but may be related to protein binding displacement of warfarin. Etoposide is highly protein-bound in the plasma and has previously been reported to cause an increase in the INR within 24 hours of administration that lasted for approximately 3 days, consistent with the drug's relatively short half-life. The intermediate active platinum derived from carboplatin also binds to plasma proteins and has an elimination half-life of 4.9 to 5.8 days, which the investigators suggest may account for the delayed nature of the interaction in the reported case.
MANAGEMENT: Based on these observations, appropriate monitoring for excessive hypoprothrombinemia is recommended early on and later in time course following the addition of etoposide and carboplatin to a stabilized regimen of warfarin. The same precaution may be applicable during therapy with other oral anticoagulants, since these agents are all highly protein-bound in the plasma. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.
