Interactions between unipen(nafcillin) and Warfarin (warfarin)
warfarin and nafcillin (Major Drug-Drug)
MONITOR CLOSELY: Dicloxacillin and nafcillin may diminish the hypoprothrombinemic effect of warfarin. The exact mechanism of interaction is unknown but may involve induction of hepatic warfarin metabolism by these penicillins. There have been case reports of patients who developed warfarin resistance following dicloxacillin or high-dose nafcillin therapy, resulting in increased warfarin requirement. In one case report, a 29-year-old male on long-term, stable anticoagulant therapy developed resistance to warfarin while receiving IV nafcillin 12 gm/day. His prothrombin time (PT) fell from 20 to 25 seconds down to 14 to 17 seconds despite doubling of his warfarin dosage. The warfarin half-life was 11 hours during nafcillin therapy and 44 hours eight months after discontinuation of nafcillin. In a retrospective review of patients enrolled in an anticoagulant clinic, investigators identified seven patients who had been stabilized on their warfarin regimen for at least 2 weeks prior to starting dicloxacillin therapy. A decrease in PT occurred approximately 4 to 5 days following initiation of dicloxacillin. The mean number of days from the initiation of dicloxacillin to the lowest recorded PT was 11.4 and the mean number of days from the last day of dicloxacillin therapy to the return of the PT to baseline was 22. The mean of the baseline and lowest recorded PTs were 18.2 and 15.1 seconds, respectively, representing a 17% decrease. Five patients required supplemental doses and/or dosage increases of warfarin. Another study found that dicloxacillin treatment led to a mean decline in PT of 9.1% (range 2% to 24%) in seven patients stabilized on warfarin for at least 2 weeks. No data are available for other oral anticoagulants.
MANAGEMENT: Coagulation parameters should be monitored more closely during coadministration of warfarin with dicloxacillin or nafcillin and for several weeks after discontinuation of the antibiotic. The same precaution may be applicable during therapy with other oral anticoagulants.
