To achieve target international normalized ratio with concurrent warfarin and rifampicin therapy is a challenge: a case report and review of literature

Abstract

<p>A 60-year-old man with a history of deep vein thrombosis put on anticoagulation therapy with warfarin 2 mg daily. Achieving a therapeutic level of anticoagulation was difficult despite escalating doses of warfarin, because of the interaction with rifampicin. A 5 to 6 fold increase in warfarin dose was prescribed to reach therapeutic international normalized ratios (INRs), but even these increases were insufficient to maintain his INR in the therapeutic range. After rifampicin was discontinued, warfarin doses were gradually reduced over the next 2 months. When concurrent warfarin-rifampicin therapy is necessary, vigilant monitoring of INR is imperative and rifampicin should be stopped. Warfarin is an oral anticoagulant used to get target INR to prevent thrombosis in various cardiovascular diseases. Its metabolism is affected by dugs, diet and individual characteristics. It is metabolized in liver by microsomal cytochrome P450 enzyme. Rifampicin is an essential component of first line antitubercular regimen. It induces enzyme P450, responsible for metabolism of warfarin. So to get target INR 2.5 to 3.5 is very difficult even with maximum possible dose of warfarin when patient taking simultaneously both drugs. In this case, rifampicin was stopped to achieve target INR. Tuberculosis patient on warfarin should not take rifampicin as component of first line antitubercular regimen.</p>

Time course of enzyme induction in rifampicin-warfarin interaction: A case report

“…It is challenging to predict a patient's response to warfarin and the dosage adjustment required when pulmonary tuberculosis medications especially rifampicin is initiated or discontinued. There are few studies publishing the magnitude of dosage adjustment required when there is drug-drug interaction involving rifampicin and warfarin and majority of the studies showed challenges in anticoagulation management [4][5][6][7][8].…”

“…Therefore warfarin remains the drug of choice for patient with atrial fibrillation and requiring rifampicin. Several case reports showed challenges and difficulty to achieve therapeutic INR when rifampicin was co-administered with warfarin [4][5][6][7][8]. In addition, there is no published case report in Singapore to show the time course for enzyme induction and de-induction in Asian patient.…”