Update on the Interaction of Rifampin and Warfarin

Abstract

A 79-year-old man with a history of deep vein thrombosis and pulmonary embolism received anticoagulation therapy with warfarin 5 mg daily for 8 months. He was diagnosed with osteomyelitis and underwent partial metatarsal resection of his right foot. After surgery, antibiotics were initiated, including ertapenem sodium 1 g intravenously every 24 hours, vancomycin 1400 mg intravenously every 24 hours, and rifampin 300 mg by mouth twice daily. Achieving a therapeutic level of anticoagulation was difficult despite escalating doses of warfarin, because of the interaction with rifampin. 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 rifampin was discontinued, warfarin doses were gradually reduced over the next 2 months. When concurrent warfarin-rifampin therapy is necessary, vigilant monitoring is imperative and significant increases in warfarin doses are likely.

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

“…In the case presented here, it was necessary to double the warfarin dose at the beginning of rifampicin therapy and to reduce the warfarin dose by approximately 50% after discontinuing rifampicin to attain a therapeutic INR. Other recent case reports have demonstrated an increased sensitivity to warfarin after stopping rifampicin therapy and the need for more than four weeks to achieve a therapeutic INR, until the drug-drug interaction dissipated [16-18]. However, supratherapeutic INR values were not associated with bleeding in these studies (Table 1).…”

“…This drug-drug interaction has been described in individual case reports [12-18] and pharmacokinetic studies [19-21]. The effect of the rifampicin-warfarin interaction on the anticoagulant response can be tested using the international normalized ratio (INR), which is the current standard for monitoring warfarin responses.…”

Dental implants in patients affected by systemic diseases

“…It is also important to remember that several medications commonly used by dental practitioners (like metronidazole, erythromycin, clarithromycin) may increase the anticoagulant effect of warfarin. [79][80][81][82][83] …”

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

“…7 After cessation of rifampicin, prothrombin time was maintained within the same range by a 50% reduction of warfarin dose. 8 This rise in warfarin concentrations can be explained by the known mechanism by which rifampin increases warfarin clearance. 9 The proposed mechanism for the rifampicin-warfarin interaction involves the induction of the isoenzymes CYP2C9, CYP3A4, CYP1A2 and CYP2C19, accelerating the clearance of both the R and the S enantiomers of warfarin.…”

“…The target INR level varies from case to case depending on the clinical indicators, but tends to be 2-3 in most conditions. 7,8 In addition, for the first three days of "warfarinization", the levels of protein C and protein S decrease faster than procoagulation proteins such as factor II, VII, IX, and X. Warfarin is a coumarin derivative. Racemic warfarin accumulates in the liver, in which both the R and the S enantiomers are metabolized by different pathways.…”