Content area
Full Text
Oseltamivir (Tamiflu), an antiviral drug marketed in Canada since 1999, is indicated for the treatment of acute illness due to influenza infection in patients 1 year and older who have been symptomatic for no more than 2 days.1 The drug is also indicated for the prevention of influenza illness in people over 13 years of age after close contact with an infected individual.
From Jan. 1, 1999, to Oct. 31, 2005, Health Canada received 19 reports of increased international normalized ratio (INR) suspected of being associated with the use of oseltamivir. These 19 reports involved patients aged 46 to 92 years (median age 84 years), and the indication for use of oseltamivir was either treatment or prophylaxis of influenza. All of the patients were taking warfarin. The reported onset of the adverse reaction ranged from the day treatment was started to 11 days after starting oseltamivir. The increased INR ranged from 3.2 to 10.9. Eleven of the reports were submitted by the same source and described a suspected interaction between oseltamivir and warfarin. Creatinine clearances were provided in these cases; dosage adjustments of oseltamivir were necessary in 3 cases, as recommended in patients with a creatinine clearance rate of 10-30 mL/min.1 Six patients required treatment with vitamin K. At the time of reporting, 12 patients had recovered, 2 patients had not yet recovered, and the outcome was unknown for the remaining 5 patients.
Causality assessment of these cases is difficult because some of the reports presented conflicting or insufficient clinical information, and numerous factors (e.g., diet, medical conditions, fever) are known to influence a patient's response to anticoagulants.2 In 3 cases, the warfarin dose was increased after the introduction of oseltamivir; the increases in INR occurred following these dose changes. In 3 other cases, decreases in INR occurred during the course of oseltamivir therapy without a reported change in warfarin dose. In 2 cases, clarithromycin and levofloxacin...