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Laninamivir octanoate appears more convenient than zanamivir in pediatric patients with influenza
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Laninamivir octanoate may be a better choice for treating children with influenza, as it can be given in a single inhalation, according to a recent study.
Yoshiki Katsumi, MD, PhD, and colleagues from the department of pediatrics at Nantan General Hospital in Kyoto, Japan, examined 85 children aged 15 years and younger who were diagnosed with influenza using a rapid diagnostic test between January and May 2011. Patients were randomly assigned; 44 patients were given laninamivir octanoate (Inavir, Daiichi Sankyo) to inhale once daily at a dose of either 20 mg or 40 mg (depending on age), and 41 patients were given 20 mg of zanamivir (Relenza, GlaxoSmithKline) to inhale twice daily for 5 days.
Katsumi and colleagues said the median times to fever resolution were very close, with 36 hours for the laninamivir octanoate group and 37 for the zanamivir group. The researchers noted no differences in the frequency of asthmatic symptoms, pneumonia, gastrointestinal symptoms or abnormal behavior.
The study team said dose administration could limit effectiveness.
“Some of the patients in both groups did not inhale deeply enough to receive the entire medication dose as we and their parents wanted. We assume that these patients did not get enough medicine,” the researchers wrote, adding that additional study is needed to examine this effect. “At least for older pediatric patients with influenza, a single inhalation of [laninamivir octanoate] was sufficient and may be more convenient than 10 inhalations of zanamivir for 5 days.”
Disclosure: Dr. Katsumi reports no relevant financial disclosures.
Perspective
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Pedro A. Piedra, MD
Laninamivir octanoate, a prodrug, is a long-active neuraminidase inhibitor that is administered as a single dose by inhalation for the treatment of influenza A and influenza B infection in children and adults. After inhalation, it is converted in the respiratory tract to its active form, laninamivir. It has been shown in clinical trials in children and adults to be as effective as oseltamivir. This antiviral drug is not approved in the United States.
Laninamivir octanoate is an inhaled drug similar to zanamivir (Relenza, GlaxoSmithKline), a well-established neuraminidase inhibitor (NAI). A unique feature of laninamivir is its long half-life, achieving concentrations in the lung epithelial lining fluids that exceed inhibition of influenza for at least 5 days. This should improve compliance and reduce the likelihood of developing resistant mutant viruses during treatment. In vitro studies have shown laninamivir octanoate to be effective against oseltamivir-resistant influenza viruses, and in a clinical trial in children, it was shown to be effective against oseltamivir-resistant (H1N1) virus.
Katsumi and colleagues performed a randomized controlled study in children with influenza to evaluate the effectiveness and safety of laninamivir octanoate compared with zanamivir. A total of 112 children aged younger than 16 years were randomly assigned to one of the two groups. They observed that treatment with laninamivir octanoate was comparable to zanamivir in effectiveness and safety in influenza-infected children. Median time to fever resolution after initiation of laninamivir octanoate treatment was 36 hours compared with 37 hours for zanamivir. Both of these NAIs are administered by inhalation; however, treatment with laninamivir octanoate consists of a single inhalation dose, whereas treatment with zanamivir requires a 5-day course with twice-daily inhalations. A shortcoming of inhalation treatment is that it requires the cooperation of the child for appropriate administration. With the current inhalation device, young children might not be able to perform deep inspiration for complete delivery of the dose.
The currently approved NAIs in the United States are oseltamivir (Tamiflu, Genentech) and zanamivir. Both of these compounds require a 5-day course with twice-daily administration for influenza treatment.
Peramivir (BioCryst Pharmaceuticals) is another NAI that is not yet approved in the US. Peramivir is administered intravenously and is currently available through participation in research trials.
Laninamivir octanoate was approved for influenza treatment in Japan in September 2010 under the trade name Inavir. In March 2011, the Office of Biomedical Advanced Research and Development Authority (BARDA) at the US Department of Health and Human Services awarded a 5-year contract to Biota Scientific Management for the development of laninamivir octanoate. It is expected that phase 3 trials in children and adults will support a new drug application to the FDA.
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