H1N1 swine flu drug zanamivir (Relenza) could cause death if nebulized, warn USFDA, GSK

US FDA is removing zanamivir from its approved packaging to be used for the purpose of nebulizing  by patients who are unable to take oral medications or inhale Relenza

Inhalable H1N1 swineflu drug zanamivir (Relenza) from GlaxoSmithKline could cause death death if used as liquid formulation or in any nebulizer, warns US FDA.

A zanamivir (Relenza) linked death was reported on a patient with influenza who received Relenza (zanamivir) inhalation powder which was solubilized and and administered by mechanical ventilation.

Zanamivir (Relenza) inhalation powder is not intended to be reconstituted in any liquid formulation and is not recommended for use in any nebulizer or mechanical ventilator.

Zanamivir (Relenza) inhalation powder is being removed from its FDA-approved packaging and dissolved in various solutions for the purpose of nebulizing zanamivir for inhalation by patients with influenza who are unable to take oral medications or unable to inhale Relenza Inhalation Powder using the Diskhaler.

Relenza or zanamivir for nebulization has not been approved by the FDA. The safety, effectiveness, and stability of zanamivir use by nebulization have not been established.

Relenza inhalation powder is a mixture of zanamivir active drug substance and lactose drug carrier. This formulation is not designed or intended to be administered by nebulization. There is a risk that the lactose sugar in this formulation can obstruct proper functioning of mechanical ventilator equipment, US FDA warned.

The death reported was of a pregnant woman on mechanical ventilation who received zanamivir solution made from dry powder product from Relenza Rotadisks via nebulizer for three days.

Death was attributed to obstruction of the ventilator. The obstruction in the ventilator was due to stickiness caused by Relenza’s inhalation powder lactose content in the nebulizing solution.

Relenza inhalation powder is a mixture of zanamivir (5 mg) and lactose drug carrier (20 mg). There is a risk that the lactose sugar in this formulation can obstruct proper functioning of mechanical ventilator equipment, GlaxoSmithKline said in press release.

Although an investigational aqueous formulation for nebulizer delivery was briefly explored during the early development of zanamivir and may be mentioned in some descriptions or publications of those early-phase studies, that formulation did not use the lactose-based powder contained in the marketed product, Relenza, Glaxo explained.

Zanamivir (Relenza) is indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adult and pediatric patients 7 years of age and older who have been symptomatic for no more than 2 days.

Relenza is indicated for prophylaxis of influenza in adults and pediatric patients 5 years of age and older. However, Relenza is not recommended for treatment or prophylaxis of influenza in individuals with underlying airways disease (such as asthma or chronic obstructive pulmonary disease) due to risk of serious bronchospasm.

Relenza has also not been proven effective for treatment of influenza in individuals with underlying airways disease.

Serious cases of bronchospasm, including fatalities, have been reported during treatment with zanamivir (Relenza) in patients with and without underlying airways disease.

Some patients without prior pulmonary disease may also have respiratory abnormalities from acute respiratory infection that could resemble adverse drug reactions or increase patient vulnerability to adverse drug reactions.

If use of zanamivir (Relenza) is considered for a patient with underlying airways disease, the potential risks and benefits should be carefully weighed. If a decision is made to prescribe zanamivir (Relenza) for such a patient, this should be done only under conditions of careful monitoring of respiratory function, close observation, and appropriate supportive care including availability of fast-acting bronchodilators, Glxo alerts.

Allergic-like reactions, including oropharyngeal edema, serious skin rashes, and anaphylaxis have been reported in postmarketing experience with zanamivir (Relenza). Zanamivir (Relenza) should be stopped and appropriate treatment instituted if an allergic reaction occurs or is suspected.

Safety and efficacy have not been demonstrated in patients with high-risk underlying medical conditions. No information is available regarding treatment of influenza in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring inpatient management.

Use zanamivir (Relenza) along with live attenuated influenza vaccine (LAAIV) intranasal has not been evaluated. However, because of potential interference between these products, LAIV should not be administered within 2 weeks before or 48 hours after administration of zanamivir (Relenza), unless medically indicated.

Zanamivir (Relenza) is approved for use in India.