Adults and Adolescents

The efficacy of RELENZA 10 mg inhaled twice daily for 5 days in the treatment of influenza has been evaluated in placebo-controlled trials conducted in North America, the Southern Hemisphere, and Europe during their respective influenza seasons. The magnitude of treatment effect varied between trials, with possible relationships to population-related factors including amount of symptomatic relief medication used.

Populations Studied: The principal Phase 3 trials enrolled 1,588 subjects aged 12 years and older (median age 34 years, 49% male, 91% Caucasian), with uncomplicated influenza-like illness within 2 days of symptom onset. Influenza was confirmed by culture, hemagglutination inhibition antibodies, or investigational direct tests. Of 1,164 subjects with confirmed influenza, 89% had influenza A and 11% had influenza B. These trials served as the principal basis for efficacy evaluation, with more limited Phase 2 studies providing supporting information where necessary. Following randomization to either zanamivir or placebo (inhaled lactose vehicle), all subjects received instruction and supervision by a healthcare professional for the initial dose.

Principal Results: The definition of time to improvement in major symptoms of influenza included no fever and self-assessment of “none” or “mild” for headache, myalgia, cough, and sore throat. A Phase 2 and a Phase 3 trial conducted in North America (total of over 600 influenza-positive subjects) suggested up to 1 day of shortening of median time to this defined improvement in symptoms in subjects receiving zanamivir compared with placebo, although statistical significance was not reached in either of these trials. In a trial conducted in the Southern Hemisphere (321 influenza-positive subjects), a 1.5-day difference in median time to symptom improvement was observed. Additional evidence of efficacy was provided by the European trial.

Other Findings: There was no consistent difference in treatment effect in subjects with influenza A compared with influenza B; however, these trials enrolled smaller numbers of subjects with influenza B and thus provided less evidence in support of efficacy in influenza B.

In general, subjects with lower temperature (e.g., 38.2°C or less) or investigator-rated as having less severe symptoms at entry derived less benefit from therapy.

No consistent treatment effect was demonstrated in subjects with underlying chronic medical conditions, including respiratory or cardiovascular disease [see Warnings and Precautions (5.4)].

No consistent differences in rate of development of complications were observed between treatment groups.

Some fluctuation of symptoms was observed after the primary trial endpoint in both treatment groups.

Pediatric Patients

The efficacy of RELENZA 10 mg inhaled twice daily for 5 days in the treatment of influenza in pediatric patients has been evaluated in a placebo-controlled trial conducted in North America and Europe, enrolling 471 subjects, aged 5 to 12 years (55% male, 90% Caucasian), within 36 hours of symptom onset. Of 346 subjects with confirmed influenza, 65% had influenza A and 35% had influenza B. The definition of time to improvement included no fever and parental assessment of no or mild cough and absent/minimal muscle and joint aches or pains, sore throat, chills/feverishness, and headache. Median time to symptom improvement was 1 day shorter in subjects receiving zanamivir compared with placebo. No consistent differences in rate of development of complications were observed between treatment groups. Some fluctuation of symptoms was observed after the primary trial endpoint in both treatment groups.

Although this trial was designed to enroll children aged 5 to 12 years, the product is indicated only for children aged 7 years and older. This evaluation is based on the combination of lower estimates of treatment effect in 5- and 6-year-olds compared with the overall trial population, and evidence of inadequate inhalation through the DISKHALER in a pharmacokinetic trial [see Use in Specific Populations (8.4), Clinical Pharmacology (12.3)].