Relenza Indications, Dosage, Storage, Stability - Zanamivir

Relenza Indications, Dosage, Storage, Stability - Zanamivir

INDICATIONS AND USAGE

RELENZA is indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years and older who have been symptomatic for no more than 2 days (see Description of Clinical Studies and PRECAUTIONS). RELENZA is not recommended for treatment of patients with underlying airways disease (such as asthma or chronic obstructive pulmonary disease) (see WARNINGS and PRECAUTIONS).

Description of Clinical Studies: 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 studies conducted in North America, the Southern Hemisphere, and Europe during their respective influenza seasons. The magnitude of treatment effect varied between studies, with possible relationships to population-related factors including amount of symptomatic relief medication used.

Populations Studied: The principal Phase 3 studies enrolled 1,588 patients ages 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 patients with confirmed influenza, 89% had influenza A and 11% had influenza B. These studies 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 patients 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 study conducted in North America (total of over 600 influenza-positive patients) suggested up to one day of shortening of median time to this defined improvement in symptoms in patients receiving zanamivir compared to placebo, although statistical significance was not reached in either of these studies. In a study conducted in the Southern Hemisphere (321 influenza-positive patients), a 1.5-day difference in median time to symptom improvement was observed. Additional evidence of efficacy was provided by the European study.

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

In general, patients 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 patients with underlying chronic medical conditions, including respiratory or cardiovascular disease (see WARNINGS and PRECAUTIONS).

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

Some fluctuation of symptoms was observed after the primary study 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 study conducted in North America and Europe, enrolling 471 patients, ages 5 to 12 years (55% male, 90% Caucasian), within 36 hours of symptom onset. Of 346 patients 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 one day shorter in patients 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 study endpoint in both treatment groups.

Although this study was designed to enroll children ages 5 to 12 years, the product is indicated only for children 7 years of age 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 study population, and evidence of inadequate inhalation through the DISKHALER in a pharmacokinetic study (see DESCRIPTION, CLINICAL PHARMACOLOGY: Pediatric Patients, and PRECAUTIONS: Pediatric Use).

RELENZA is for administration to the respiratory tract by oral inhalation only, using the DISKHALER device provided. Patients should be instructed in the use of the delivery system. Instructions should include a demonstration whenever possible. If RELENZA is prescribed for children, it should be used only under adult supervision and instruction, and the supervising adult should first be instructed by a healthcare professional (see PRECAUTIONS).

The recommended dose of RELENZA for treatment of influenza in adults and pediatric patients ages 7 years and older is 2 inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) twice daily (approximately 12 hours apart) for 5 days. Two doses should be taken on the first day of treatment whenever possible provided there is at least 2 hours between doses. On subsequent days, doses should be about 12 hours apart (e.g., morning and evening) at approximately the same time each day. There are no data on the effectiveness of treatment with RELENZA when initiated more than 2 days after the onset of signs or symptoms.

Patients scheduled to use an inhaled bronchodilator at the same time as RELENZA should use their bronchodilator before taking RELENZA. (See WARNINGS and PRECAUTIONS regarding patients with chronic respiratory disease and other medical conditions.)

RELENZA is supplied in a circular double-foil pack (a ROTADISK) containing 4 blisters of the drug. Five ROTADISKS are packaged in a white polypropylene tube. The tube is packaged in a carton with 1 blue and gray DISKHALER inhalation device (NDC 0173-0681-01).

Store at 25 C (77° F); excursions permitted to 15 to 30 C (59 to 86 F) (see USP Controlled Room Temperature). Keep out of reach of children. Do not puncture any RELENZA ROTADISK blister until taking a dose using the DISKHALER.

GlaxoSmithKline, Research Triangle Park, NC 27709, ©2003, GlaxoSmithKline. All rights reserved., April 2003, RL-2000