The possibility of an
avian flu pandemic has spurred interest in preventive treatments with
antivirals such as
oseltamivir. Combining treatment with
probenecid to delay excretion may extend limited supplies of
oseltamivir. We previously conducted a pharmacokinetic study of
oseltamivir plus
probenecid among healthy volunteers. In this article, we describe a 68-year-old woman who, during the pharmacokinetic study, developed severe
thrombocytopenia 2 weeks after starting
oseltamivir plus
probenecid. She was receiving no other
drug therapy at the time. Her platelet count decreased from 200 to 15 x 10(3)/mm(3), although no clinically evident
bleeding abnormalities were noted. The two drugs were discontinued. One week later, without any therapeutic intervention, her platelet count returned to normal. By using the Naranjo
adverse drug reaction probability scale to assess the strength of the association between the drugs and the adverse event, a score of 7 was derived for both drugs, indicating that the association was probable. We found no previous literature reports of
thrombocytopenia associated with either
drug. However, a review of the United States Food and Drug Administration's Adverse Event Reporting System database found 93 cases of
thrombocytopenia and/or decreased platelet counts associated with
oseltamivir and 24 cases associated with
probenecid administration. Signal detection analyses were significant for
oseltamivir (p=0.001), but not
probenecid. The underlying mechanism of
thrombocytopenia with these drugs is unknown. Clinicians should be aware that the use of
oseltamivir and
probenecid has been reported to be associated with
thrombocytopenia.