The Clinical Effect of Atovaquone/Proguanil on Warfarin Therapy in Adults

Introduction:  

Warfarin is notorious for its many drug-drug interactions. Warfarin and atovaquone/proguanil is one of these drug interactions. Tertiary references suggest an interaction but there is no specific literature regarding atovaquone/proguanil in combination or in doses used for malaria prophylaxis.

Objectives:  

Evaluate if there is a clinically significant interaction between atovaquone/proguanil at doses used for malaria prophylaxis with warfarin.

Study Design:

This study was a retrospective descriptive analysis of all patients from March 2009 to October 2014 who picked up an atovaquone/proguanil prescription from the pharmacy while on warfarin.

Methods:

The following data were included in the analysis: warfarin and atovaquone/proguanil indication, atovaquone/proguanil dose and duration, Time in Therapeutic Range for 1 year prior to patient’s atovaquone/proguanil presecription or since date of warfarin initiation, and the INRs prior, during and after completion of atovaquone/proguanil therapy.   Also, cases were evaluated for any warfarin adverse events including any minor or major bleeding. Other possible confounding factors such as other drug interactions, drug disease interactions were also included.

Results:

A total of 27 cases were reviewed. In 17 of 27 patient cases, warfarin dose was not adjusted prior to travel. Of those 17 cases, there were no supratherapeutic INRs upon return from patient travel.  For the 10 patients who did have their warfarin doses reduced prior to travel, there was only 1 patient who had a supratherapeutic INR upon return from travel. All patients post travel remained on the same weekly dose they were on immediately prior to travel. Only three patients had a supratherapeutic INR after completion of atovaquone/proguanil.

Conclusions:

Based on this limited data we recommend against empirically reducing a patient’s weekly dose of warfarin due to this possible drug-drug interaction.