Warfarin, flu vaccine, and cotrimoxazole

Anticoagulation with warfarin requires careful monitoring. Concomitant use of medications may result in changes in the international normalized ratio (INR), which may increase the risk of bleeding or decrease the effectiveness of therapy. Two studies in the April 12 issue of Archives of Internal Medicine clarify the risk of two commonly used medications, influenza vaccine and the antibiotic trimethoprim-sulfamethoxazole. Patients on warfarin have been told that they need careful monitoring after the influenza vaccine, although the effect is not clear. Some guidelines have suggested that flu shots prolonged INRs, while others suggest the vaccine reverses the anticoagulation effect.

In this study, 104 patients on a stable warfarin regimen were randomized to receive influenza vaccine and subsequent placebo administration or vice versa. All patients were tested for coagulation variables and followed for clinical events. The influenza vaccine had no effect on anticoagulation compared to placebo. There were no fatal or major bleeding events. The authors conclude that the influenza vaccine has no significant effect on INR values or warfarin weekly doses in patients on chronic warfarin therapy and that close monitoring of INR values after influenza vaccine is not required (Arch Intern Med 2010;170:609-616).

Conversely trimethoprim-sulfamethoxazole (cotrimoxazole) may significantly prolong INRs with adverse clinical outcomes. In the population-based, nested case-controlled study using health care databases in Canada, residents 66 years or older who were treated with long-term warfarin were evaluated for upper gastrointestinal (GI) tract hemorrhage. Of the more than 134,000 patients on warfarin, 2151 patients were hospitalized for upper GI hemorrhage. Recent use of cotrimoxazole was almost four times more common in those hospitalized (adjusted odds ratio, 3.84; 95% CI, 2.33-6.33). The odds ratio for treatment with ciprofloxacin also was higher (1.94), but no significant association was observed with amoxicillin, ampicillin, nitrofurantoin, or norfloxacin. The authors conclude that among older patients receiving warfarin, cotrimoxazole is associated with a significantly higher risk of upper GI tract hemorrhage. Ciprofloxacin was also associated with risk and whenever possible clinicians should prescribe alternate antibiotics in patients receiving warfarin (Arch Intern Med 2010;170:617-621).