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Abstract
Oseltamivir is recommended for the treatment and prophylaxis of influenza in persons at higher risk for influenza complications such as individuals with diabetes, neuropsychiatric illnesses, and respiratory, cardiac, renal, hepatic or haematological diseases. However, a recent Cochrane review reported that reduction of antibody production, renal disorders, hyperglycaemia, psychiatric disorders, and QT prolongation may be related to oseltamivir use. The underlying mechanisms are reviewed. There is decisive evidence that administration of a clinically compatible dose of oseltamivir in mice challenged by a respiratory syncytial virus (RSV) that lacks a neuraminidase gene showed symptom-relieving effects and inhibition of viral clearance. These effects were accompanied by decreased level of T cell surface sialoglycosphingolipid (ganglioside) GM1 that is regulated by the endogenous neuraminidase in response to viral challenge. Clinical and non-clinical evidence supports the view that the usual dose of oseltamivir suppresses pro-inflammatory cytokines such as interferon-gamma, interleukin-6, and tumour necrosis factor-alpha almost completely with partial suppression of viral shedding in human influenza virus infection experiment. Animal toxicity tests support the clinical evidence with regard to renal and cardiac disorders (bradycardia and QT prolongation) and do not disprove the metabolic effect. Reduction of antibody production and cytokine induction and renal, metabolic, cardiac, and prolonged psychiatric disorders after oseltamivir use may be related to inhibition of the host’s endogenous neuraminidase. While the usual clinical dose of zanamivir may not have this effect, a higher dose or prolonged administration of zanamivir and other neuraminidase inhibitors may induce similar delayed reactions, including reduction of the antibody and/or cytokine production.
Disclosure statement
Rokuro Hama was a co-recipient of a UK National Institute for Health Research grant (HTA 10/80/01, Update and amalgamation of two Cochrane reviews: neuraminidase inhibitors for preventing and treating influenza in healthy adults and children (www.nets.nihr.ac.uk/projects/hta/108001). RH wrote two books published in 2008 about the harm of oseltamivir and antipyretics. He provided scientific opinions and expert testimony on 14 adverse reaction cases related to oseltamivir for the applications by their families for adverse reaction relief by PMDA (Pharmaceuticals and Medical Devices Agency) and in the lawsuits for revocation of the PMDA's decision concerning with these reactions. Most of the cases were reported in reference.[Citation6]