Describing the Profile of Patients on Concurrent Rifampin and Warfarin Therapy in Western Kenya: A Case Series

Abstract

BackgroundRifampicin’s ability to induce hepatic enzymes is responsible for causing a clinically significant drug interaction with warfarin. Little data exists to guide clinicians on managing this interaction, especially in Sub-Saharan Africa where many patients are exposed to this combination due to a higher burden of tuberculosis.ObjectiveThe objective of the case series is to provide insight to practicing clinicians of the unique dynamics of this drug interaction in resource-constrained settings. The case series will provide details on commonly encountered scenarios and the dosage adjustments required to maintain a therapeutic INR.MethodsA retrospective chart review was conducted of patients attending the Moi Teaching and Referral Hospital anticoagulation clinic in Eldoret, Kenya. Patients were included if they had a history of concurrent rifampicin and warfarin therapy and a minimum follow up of 2 months. Descriptive statistics were used to explain the demographic characteristics, time to therapeutic INR and average weekly warfarin dose. The inference on proportions test was conducted to compare the time in the therapeutic range (TTR) for patients on concurrent rifampicin to the rest of the patients not receiving rifampicin in the clinic.ResultsOf the 350 patient charts evaluated, 10 met the inclusion criteria. The median percentage increase of the weekly warfarin dose from baseline was 15.7 %. For the patients in this analysis, the median TTR was 47 %.DiscussionPatients on concurrent therapy should be rigorously monitored with regular INR checks and warfarin dosage adjustments. Empiric dosage adjustments of warfarin should be avoided but patient characteristics can aid in understanding the alterations seen in INR.

Improving anticoagulation in sub-Saharan Africa -- what are the challenges, and how can we overcome them?

“…In a Kenyan case series of patients on concurrent rifampicin and warfarin, the median warfarin dose increase with rifampicin was 16%, but some patients required dose increases up to +441%. [106] In a Ugandan case series, patients concomitantly prescribed rifampicin, antiretroviral therapy, and warfarin had highly labile INRs and warfarin dose requirements, and it was not possible to predict the course of INR results in any individual patient. [107] In Kenya, VTE patients with advanced HIV and tuberculosis required a median 8 additional clinic visits to achieve or maintain a therapeutic INR.…”

Diffuse Alveolar Hemorrhage Caused by Warfarin after Rifampicin Discontinuation

“…Therefore, rifampicin suppresses the anticoagulant activity of warfarin, which can cause a need to increase the warfarin dose to achieve and maintain a therapeutic INR [9]. In fact, several reports describe that warfarin dose is increased among patients administered with concurrent rifampin [6, 10, 11]. A two-to three-fold increase in the warfarin dose might be necessary during concurrent therapy to account for this drug-drug interaction [12].…”

Rifampin-warfarin interaction in a mitral valve replacement patient receiving rifampin for infective endocarditis: a case report

“…Several reports have previously described the interaction between rifampin and warfarin and the effect of rifampin on the anticoagulation effect of warfarin during concomitant use of both medications (Lee and Thrasher 2001 ; Martins et al 2013 ; Krajewski 2010 ; Maina et al 2013 ). Lee et al described a case for a patient who was started on rifampin for active tuberculosis and was started on warfarin 4 months later for left ventricular thrombus.…”

“…This interaction leads to accelerated warfarin’s clearance and ultimately a reduction in its anticoagulant effect (Strayhorn et al 1997 ; Baciewicz et al 2008 ). There are several, well-documented cases of potential interactions during concurrent rifampin-warfarin use (Lee and Thrasher 2001 ; Martins et al 2013 ; Krajewski 2010 ; Maina et al 2013 ). This interaction affects warfarin dose required to achieve and maintain therapeutic INR and may increase this dose up to six times to reach target therapeutic INR.…”