Relenza therefore was not recommended for treatment or prophylaxis of seasonal influenza in individuals with asthma or chronic obstructive pulmonary disease. In 2009 the zanamivir package insert contains precautionary information regarding risk of bronchospasm in patients with respiratory disease. GlaxoSmithKline (GSK) and FDA notified healthcare professionals of a report of the death of a patient with influenza having received zanamivir inhalation powder, which was solubilized and administered by mechanical ventilation.In adults there was no increased risk of reported adverse events in trials. There was little evidence of the possible harms associated with the treatment of children with zanamivir. Zanamivir has not been known to cause toxic effects and has low systemic exposure to the human body. Mechanism of action
Zanamivir works by binding to the active site of the neuraminidase protein, rendering the influenza virus unable to escape its host cell and infect others. It is also an inhibitor of influenza virus replication in vitro and in vivo. In clinical trials, zanamivir was found to reduce the time-to-symptom resolution by 1.5 days if therapy was started within 48 hours of the onset of symptoms. The bioavailability of zanamivir is 2%. After inhalation, zanamivir is concentrated in the lungs and oropharynx, where up to 15% of the dose is absorbed and excreted in urine. History
Zanamivir was first made in 1989 by scientists led by Peter Colman and Joseph Varghese at the Australian CSIRO, in collaboration with the Victorian College of Pharmacy, and the Monash University. Zanamivir was the first of the neuraminidase inhibitors.
There is no proof that zanamivir reduced hospitalizations or pneumonia and other complications of influenza, such as bronchitis, middle ear infection, and sinusitis. Zanamivir did not reduce the risk of self reported investigator mediated pneumonia or radiologically confirmed pneumonia in adults. The effect on pneumonia in children was also not significant. Prevention
Low to moderate evidence indicates it decreases the risk of ones getting influenza by 1 to 12% in those exposed. Prophylaxis trials showed that zanamivir reduced the risk of symptomatic influenza in individuals and households, but there was no evidence of an effect on asymptomatic influenza or on other, influenza-like illnesses. Also there was no evidence of reduction of risk of person-to-person spread of the influenza virus. The evidence for a benefit in preventing influenza is weak in children, with concerns of publication bias in the literature. Resistance
As of 2009, no influenza had shown any signs of resistance in the US. A meta-analysis from 2011 found that zanamivir resistance had been rarely reported. Antiviral resistance can emerge during or after treatment with antivirals in certain people (e.g., immunosuppressed). In 2013 genes expressing resistance to zanamivir (and oseltamivir) were found in Chinese patients infected with avian influenza A H7N9. Adverse effects
Dosing is limited to the inhalation route. This restricts its usage, as treating asthmatics could induce bronchospasms. In 2006 the Food and Drug Administration (FDA) found that breathing problems (bronchospasm), including deaths, were reported in some patients after the initial approval of Relenza. Most of these patients had asthma or chronic obstructive pulmonary disease.