Multiple Drugs Interaction with Warfarin in a Single Patient: The Role of Rifampicin and Trimethoprim-Sulfamethoxazole (TMP-SMX)

Introduction: Warfarin is the only anticoagulant proven for use after mechanical heart valve surgery. Rifampicin has been reported to increase the warfarin requirement, while the use of Trimethoprim–Sulfamethoxazole (TMP-SMX) may increase the risk of bleeding when used together with warfarin. Due to its narrow therapeutic index and numerous interactions with drugs and foods, it is crucial to closely monitor INR levels in patients taking warfarin with both rifampicin and TMP-SMX. Case Presentation: We reported a case of a 58-year-old gentleman with severe aortic stenosis who underwent mechanical aortic valve surgery. The patient was discharged with a stable dose of warfarin (5mg daily) and INR levels. However, due to poor hygiene, limited ambulation, and poorly controlled diabetes, he was readmitted with an infected sacral sore, requiring the initiation of both rifampicin and TMP-SMX alongside warfarin. Results: The commencement of both TMP-SMX and rifampicin in the patient caused a sudden increase in INR levels to 6 on day 4 of antibiotics, necessitating transfusion of fresh frozen plasma (FFP). Subsequently, the INR level became sub-therapeutic, requiring escalation of the warfarin dose to three times the baseline (15mg compared with the usual 5mg daily). The patient required treatment with TMP-SMX and rifampicin for a prolonged period of three weeks. However, the enzyme induction effect of rifampicin on warfarin metabolism persisted for up to three months after its discontinuation with the final warfarin dose being 7mg daily. Conclusion: This case highlights the critical need for awareness of drug interactions with warfarin. The opposing effects of TMP-SMX and rifampicin on warfarin make it crucial to closely monitor INR levels to prevent both bleeding and thromboembolic events in patients after mechanical valve surgery.