Rifampicin-warfarin interaction leading to macroscopic hematuria: a case report and review of the literature

Abstract

BackgroundRifampicin remains one of the first-line drugs used in tuberculosis therapy. This drug´s potential to induce the hepatic cytochrome P450 oxidative enzyme system increases the risk of drug-drug interactions. Thus, although the presence of comorbidities typically necessitates the use of multiple drugs, the co-administration of rifampicin and warfarin may lead to adverse drug events. We report a bleeding episode after termination of the co-administration of rifampicin and warfarin and detail the challenges related to international normalized ratio (INR) monitoring.Case presentationA 59-year-old Brazilian woman chronically treated with warfarin for atrial fibrillation (therapeutic INR range: 2.0-3.0) was referred to a multidisciplinary anticoagulation clinic at a university hospital. She showed anticoagulation resistance at the beginning of rifampicin therapy, as demonstrated by repeated subtherapeutic INR values. Three months of sequential increases in the warfarin dosage were necessary to reach a therapeutic INR, and frequent visits to the anticoagulation clinic were needed to educate the patient about her pharmacotherapy and to perform the warfarin dosage adjustments. The warfarin dosage also had to be doubled at the beginning of rifampicin therapy. However, four weeks after rifampicin discontinuation, an excessively high INR was observed (7.22), with three-day macroscopic hematuria and the need for an immediate reduction in the warfarin dosage. A therapeutic and stable INR was eventually attained at 50% of the warfarin dosage used by the patient during tuberculosis therapy.ConclusionsThe present case exemplifies the influence of rifampicin therapy on warfarin dosage requirements and the increased risk of bleeding after rifampicin discontinuation. Additionally, this case highlights the need for warfarin weekly monitoring after stopping rifampicin until the maintenance dose of warfarin has decreased to the amount administered before rifampicin use. In particular, patients with cardiovascular diseases and active tuberculosis represent a group with a substantial risk of drug-drug interactions. Learning how to predict and monitor drug-drug interactions may help reduce the incidence of clinically significant adverse drug events.

A cross-sectional evaluation of five warfarin anticoagulation services in Uganda and South Africa

“…In addition, high HIV prevalence may further complicate warfarin dosing due to drug-drug interactions with non-nucleoside reverse transcriptase inhibitors and protease inhibitors [19,20]. Although our sample included few TB patients, it is important to consider that rifampicin, which is used in first-line TB treatment, induces warfarin metabolism, which further complicates warfarin dosing [21].…”

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

“…Other reports have described the interaction between warfarin and rifampin in patients already on chronic warfarin therapy (Martins et al 2013 ; Tong et al 2014 ; Kim et al 2007 ). Similar to our case report, these reports described the interaction resulting from the addition of rifampin in patients already receiving chronic warfarin therapy.…”

“…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.…”

“…This interaction remains clinically significant during, and weeks after discontinuation of rifampin. Additionally, risk of bleeding after rifampin discontinuation has been reported (Martins et al 2013 ).…”