Antiinfluenza Agents: Zanamivir

Zanamivir

Zanamivir (Relenza) is a neuraminidase inhibitor with activity against influenza A and B strains. Like os-eltamivir, zanamivir is a reversible competitive antago-nist of viral neuraminidase. It inhibits the release of progeny virus, causes viral aggregation at the cell sur-face, and impairs viral movement through respiratory secretions. Resistant variants with hemagglutinin and/or neuraminidase mutations have been produced in vivo; however, clinical resistance to zanamivir is quite rare at present.

Absorption, Metabolism, and Excretion

Zanamivir has a bioavailability of less than 5% when ab-sorbed through the gastrointestinal tract. It is adminis-tered using a breath-actuated inhaler device (Diskhaler) that delivers the drug as an aerosol in a lactose carrier. The lactose particles are large, and about 78% deposit in the oropharynx. Following oral inhalation, zanamivir has a bioavailability of 12 to 17%, with peak plasma concen-trations being reached within 1.5 hours. It is rapidly elim-inated by the kidneys without significant metabolism and has a plasma elimination half-life of 2.5 to 5 hours.

Clinical Uses

Zanamivir is indicated for treatment of uncomplicated acute influenza A and B virus in patients aged 7 and older. Treatment should be initiated no later than 2 days after the onset of symptoms. Zanamivir shortens the du-ration of illness by 1 to 1.5 days. It is also an effective prophylaxis against influenza; however, the FDA has not approved this indication at the time of publication.

Adverse Effects, Contraindications, and Drug Interactions

Zanamivir is generally well tolerated. Bronchospasm and impaired lung function have been reported in some patients taking this medication, but many of these indi-viduals had serious underlying pulmonary disease. Zanamivir should be discontinued if an individual de-velops bronchospasm or breathing difficulties; treat-ment and hospitalization may be required. Allergic re-actions, including angioedema, have been rarely reported. The efficacy of zanamivir depends upon the proper use of the inhaler device.

Zanamivir is contraindicated in individuals with se-vere or decompensated chronic obstructive lung disease or asthma because it has not been shown to be effective in these individuals and can cause serious adverse pul-monary reactions. Individuals with mild to moderate asthma may have a decline in lung function when taking zanamivir. The safety and efficacy of this medication have not been determined in individuals with severe re-nal insufficiency. No clinically significant drug interac-tions have been reported. Zanamivir does not decrease the effectiveness of the influenza vaccine.