isirv Antiviral Group
While zanamivir and oseltamivir have been licensed in many countries for therapeutic and prophylactic use, two additional neuraminidase inhibitors, peramivir and laninamivir, were licensed in Japan in 2010. Because of the short acute nature of most influenza infections, antivirals should be administered early, as soon as possible, within 48 hours of onset of symptoms.
Intravenous peramivir has been approved for the treatment of influenza A and B virus infection in Japan and Korea. Intravenous administration rapidly produces a high plasma concentration of peramivir, which exerts long-lasting anti-influenza activity following a single infusion (300 mg in adults). For high-risk patients, including elderly patients and severely ill patients, who require hospital admission, a higher dose is recommended; treatment options depend on the condition of the patient. Peramivir is, however, rapidly excreted by the kidneys, and is not suitable for prophylactic use.
Peramivir was authorized for emergency use in the USA and some other countries for treatment of severe influenza during the 2009 A(H1N1) pandemic.
Hernandez JE, Adiga R, Armstrong R, Bazan J, Bonilla H, Bradley J, et al. Clinical experience in adults and children treated with intravenous peramivir for 2009 influenza A (H1N1) under an Emergency IND program in the United States. Clin Infect Dis. 2011;52(6):695-706.
Kohno S, Kida H, Mizuguchi M, Hirotsu N, Ishida T, Kadota J, et al. Intravenous Peramivir for Treatment of Influenza A and B Virus Infection in High-Risk Patients. Antimicrob Agents Chemother. 2011;55(6):2803-12.
Sugaya N, Kohno S, Ishibashi T, Wajima T, Takahashi T. Efficacy, Safety, and Pharmacokinetics of Intravenous Peramivir in Children with 2009 Pandemic H1N1 Influenza A Virus Infection. Antimicrob Agents Chemother. 2012;56(1):369-77.
Inhaled laninamivir was approved for use in Japan in 2010. Laninamivir octanoate, the octanoyl ester prodrug of laninamivir, which is chemically similar to zanamivir, has been shown to inhibit neuraminidase activity of various influenza A and B viruses, including oseltamivir-resistant viruses, and also to be effective against A(H5N1) virus in vitro. The most important characteristic of laninamivir octanoate is its long-lasting antiviral activity, such that it is effective when administered as a single inhalation on the first day of treatment.
Following inhalation laninamivir octanoate is absorbed by the epithelial cells lining the respiratory tract where it is rapidly hydrolyzed to the active laninamivir. The slow release of laninamivir into the respiratory tract, and its slow elimination from the body over 6 days, contribute to its long-lasting anti-influenza activity.
A double-blind, randomized controlled trial revealed that a single inhalation of laninamivir was highly effective in children infected with oseltamivir-resistant seasonal influenza A(H1N1) virus possessing the H275Y mutation. No viruses resistant to laninamivir have been reported.
Sugaya N, Ohashi Y. Long-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) versus oseltamivir as treatment for children with influenza virus infection. Antimicrob Agents Chemother. 2010;54(6):2575-82.
Watanabe A, Chang SC, Kim MJ, Chu DW, Ohashi Y. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza: A double-blind, randomized, noninferiority clinical trial. Clin Infect Dis. 2010;51(10):1167-75.