Oseltamivir phosphate is actually a prodrug that requires ester hydrolysis to its active form, oseltamivir carboxylate. This active form is not further metabolized but eliminated from the body via the kidneys. There is no effect on absorption if the medication is taken with food. This is a bonus as the nausea and vomiting that is described with taking this medication may be alleviated by taking oseltamivir with food. Neither the prodrug nor the active form of the drug is metabolized via cytochrome p450 enzymes so drug-drug interactions are not common. The one drug-drug effect that may occur is with coingestion of probenicid which decreases the renal clearance of oseltamivir. In addition, for patients with creatinine clearance below 30 mL/min, dosing needs to be adjusted. Oseltamivir has not been studied in infants less than 1 year of age; however, the Food and Drug Administration issued an emergency use authorization and there is an information sheet on the CDC website for dosing in this age group. http://www.cdc.gov/h1n1flu/eua/pdf/tamiflu-hcp.pdf
Side effects are usually minimal with nausea, vomiting, and headache being the most common. Severe skin reactions such as hypersensitivity reactions, Steven’s Johnson syndrome, and toxic epidermal necrolysis are reported. There are post marketing reports mostly from Japan of primarily pediatric patients exhibiting delirium and hallucinations.
There is concern about the efficacy of the live attenuated influenza vaccine (LAIV) if it is coadministered with antivirals. Patients who are on antiviral therapy should wait at least 48 hours after completion of the antiviral therapy before receiving the LAIV. In addition, if antiviral therapy is initiated within two weeks of the administration of LAIV, those patients should be revaccinated at a later date. The neuramidase inhibitors may reduce the efficacy of LAIV by reducing replication of the virus.
Question prepared by: Saralyn R. Williams, MD Medical Toxicologist
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Donna Seger, M.D.
Tennessee Poison Center
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