The NAIs oseltamivir and zanamivir were approved in the US and Europe for treatment and prevention of influenza A and B. Peramivir acts by strongly binding to the neuraminidase of the influenza viruses and inhibits activation of neuraminidase much longer than oseltamivir or zanamivir.[5] However, laninamivir in the cells is slowly released into the respiratory tract, resulting in long-lasting anti-influenza virus activity. Thus the mechanism of the long-lasting activity of laninamivir is basically different from that of peramivir.[6]
The efficacy was highly debated in recent years.[7][8][9] However, after the pandemic caused by H1N1 in 2009, the effectiveness of early treatment with neuraminidase inhibitors in reducing serious cases and deaths was reported in various countries.[10][11][12][13]
In countries where influenza-like illness is treated using NAIs on a national level, statistical reports show a low fatality record for symptomatic illness because of the universal implementation of early treatment using this class of drugs.[14] Although oseltamivir is widely used in these countries, there have been no outbreaks caused by oseltamivir-resistant viruses and also no serious illness caused by oseltamivir-resistant viruses has ever been reported.[14] The United States Centers for Disease Control and Prevention continues to recommend the use of oseltamavir treatment for people at high risk for complications and the elderly and those at lower risk who present within 48 hours of first symptoms of infection.[15]
Common side effects include nausea and vomiting. The abnormal behaviors of children after taking oseltamivir that have been reported may be an extension of delirium or hallucinations caused by influenza.[14] It occurs in the early stages of the illness, such as within 48 hours after onset of the illness. Therefore, children with influenza are advised to be observed by their parents until 48 hours after the onset of the influenza illness, regardless of whether the child is treated with NAIs.[14]
^Smith BJ, McKimm-Breshkin JL, McDonald M, Fernley RT, Varghese JN, Colman PM (May 2002). "Structural studies of the resistance of influenza virus neuramindase to inhibitors". Journal of Medicinal Chemistry. 45 (11): 2207–2212. doi:10.1021/jm010528u. PMID12014958.
^Gubareva LV (July 2004). "Molecular mechanisms of influenza virus resistance to neuraminidase inhibitors". Virus Research. 103 (1–2): 199–203. doi:10.1016/j.virusres.2004.02.034. PMID15163510.
^Bantia S, Arnold CS, Parker CD, Upshaw R, Chand P (January 2006). "Anti-influenza virus activity of peramivir in mice with single intramuscular injection". Antiviral Research. 69 (1): 39–45. doi:10.1016/j.antiviral.2005.10.002. PMID16325932.
^Ishizuka H, Yoshiba S, Okabe H, Yoshihara K (November 2010). "Clinical pharmacokinetics of laninamivir, a novel long-acting neuraminidase inhibitor, after single and multiple inhaled doses of its prodrug, CS-8958, in healthy male volunteers". Journal of Clinical Pharmacology. 50 (11): 1319–1329. doi:10.1177/0091270009356297. PMID20145259. S2CID20157230.
^Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, et al. (November 2009). "Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009". The New England Journal of Medicine. 361 (20): 1935–1944. CiteSeerX10.1.1.183.7888. doi:10.1056/NEJMoa0906695. PMID19815859.