Drug interactions between fosamprenavir and Miradon

anisindione ↔ fosamprenavir

Applies to:Miradon (anisindione) and fosamprenavir

MONITOR: Coadministration with protease inhibitors may alter the plasma concentrations and/or pharmacologic effects of oral anticoagulants. Both increases and decreases in INR have been reported. The exact mechanism of interaction is unknown. In a couple of cases, dramatic decreases in INR occurred following the addition of ritonavir. In one case, warfarin dosage had to almost double in order to maintain a therapeutic INR, and when ritonavir was discontinued months later, the INR rose rapidly and the warfarin dosage was significantly reduced. In the other, acenocoumarol dosage was progressively increased to 3 times the original dosage but failure to achieve the desired INR led to eventual withdrawal of ritonavir, whereupon INR returned to the previous level in 4 days. Nelfinavir was then substituted for ritonavir and also resulted in an interaction, but a therapeutic INR was achieved after a 210% increase in the acenocoumarol dosage. Another case report implicated indinavir in a similar interaction of a lesser magnitude. In contrast, a significant increase in INR occurred in one patient following a switch from efavirenz and abacavir to a regimen containing ritonavir, nelfinavir, zidovudine, and lamivudine. The patient's INR was low on days he skipped or lowered the ritonavir dosage and high on days in which he was compliant. In another instance, an interaction with saquinavir was thought to have caused the hypoprothrombinemia in a patient stabilized on warfarin, and a reduction of warfarin dosage by 20% was required.

MANAGEMENT: Caution is advised if oral anticoagulants must be used with protease inhibitors. The INR should be checked frequently and anticoagulant dosage adjusted accordingly, particularly following initiation, discontinuation or change of dosage of the protease inhibitor(s) in patients who are stabilized on their anticoagulant regimen.