1 INDICATIONS AND USAGE RELENZA, an influenza virus neuraminidase inhibitor (NAI), is indicated for: Treatment of acute, uncomplicated influenza type A and B infections in patients aged 7 years and older who have been symptomatic for no more than 2 days.

( 1.1 ) Prophylaxis of influenza in patients aged 5 years and older.

( 1.2 ) Important Limitations of Use: Not recommended for treatment or prophylaxis of influenza in: • Individuals with underlying airways disease.

( 5.1 ) Not proven effective for: • Treatment in individuals with underlying airways disease.

( 1.3 ) • Prophylaxis in nursing home residents.

( 1.3 ) Not a substitute for annual influenza vaccination.

( 1.3 ) Consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use RELENZA.

( 1.3 ) 1.1 Treatment of Influenza RELENZA (zanamivir) inhalation powder is indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients aged 7 years and older who have been symptomatic for no more than 2 days.

1.2 Prophylaxis of Influenza RELENZA is indicated for prophylaxis of influenza in adults and pediatric patients aged 5 years and older.

1.3 Important Limitations of Use • 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 [see Warnings and Precautions ( 5.1 )] .

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

• RELENZA has not been proven effective for prophylaxis of influenza in the nursing home setting.

• RELENZA is not a substitute for early influenza vaccination on an annual basis as recommended by the Centers for Disease Control's Immunization Practices Advisory Committee.

• Influenza viruses change over time.

Emergence of resistance mutations could decrease drug effectiveness.

Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs.

Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use RELENZA.

• There is no evidence for efficacy of zanamivir in any illness caused by agents other than influenza virus A and B.

• Patients should be advised that the use of RELENZA for treatment of influenza has not been shown to reduce the risk of transmission of influenza to others.

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Bronchospasm [see Warnings and Precautions ( 5.1 )] .

• Safety information in patients with underlying airways disease [see Warnings and Precautions ( 5.1 )].

• Allergic-like reactions [see Warnings and Precautions ( 5.2 )] .

The most common adverse events reported in greater than 1.5% of subjects treated with RELENZA and more commonly than in subjects treated with placebo are: • Treatment Trials – sinusitis, dizziness.

( 6.1 ) • Prophylaxis Trials – fever and/or chills, arthralgia, and articular rheumatism.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The placebo used in clinical trials consisted of inhaled lactose powder, which is also the vehicle for the active drug; therefore, some adverse events occurring at similar frequencies in different treatment groups could be related to lactose vehicle inhalation.

Treatment of Influenza Clinical Trials in Adults and Adolescents: Adverse events that occurred with an incidence greater than or equal to 1.5% in treatment trials are listed in Table 1.

This table shows adverse events occurring in subjects aged 12 years and older receiving RELENZA 10 mg inhaled twice daily, RELENZA in all inhalation regimens, and placebo inhaled twice daily (where placebo consisted of the same lactose vehicle used in RELENZA).

Table 1.

Summary of Adverse Events ≥1.5% Incidence during Treatment in Adults and Adolescents a Includes trials where RELENZA was administered intranasally (6.4 mg 2 to 4 times per day in addition to inhaled preparation) and/or inhaled more frequently (q.i.d.) than the currently recommended dose.

Adverse Event RELENZA Placebo (Lactose Vehicle) (n = 1,520) 10 mg b.i.d.

Inhaled (n = 1,132) All Dosing Regimens a (n = 2,289) Body as a whole Headaches 2% 2% 3% Digestive Diarrhea 3% 3% 4% Nausea 3% 3% 3% Vomiting 1% 1% 2% Respiratory Nasal signs and symptoms 2% 3% 3% Bronchitis 2% 2% 3% Cough 2% 2% 3% Sinusitis 3% 2% 2% Ear, nose, and throat infections 2% 1% 2% Nervous system Dizziness 2% 1% <1% Additional adverse reactions occurring in less than 1.5% of subjects receiving RELENZA included malaise, fatigue, fever, abdominal pain, myalgia, arthralgia, and urticaria.

The most frequent laboratory abnormalities in Phase 3 treatment trials included elevations of liver enzymes and creatine phosphokinase (CPK), lymphopenia, and neutropenia.

These were reported in similar proportions of zanamivir and lactose vehicle placebo recipients with acute influenza‑like illness.

Clinical Trials in Pediatric Subjects: Adverse events that occurred with an incidence greater than or equal to 1.5% in children receiving treatment doses of RELENZA in 2 Phase 3 trials are listed in Table 2 .

This table shows adverse events occurring in pediatric subjects aged 5 to 12 years receiving RELENZA 10 mg inhaled twice daily and placebo inhaled twice daily (where placebo consisted of the same lactose vehicle used in RELENZA).

Table 2.

Summary of Adverse Events ≥1.5% Incidence during Treatment in Pediatric Subjects a a Includes a subset of subjects receiving RELENZA for treatment of influenza in a prophylaxis trial.

Adverse Event RELENZA 10 mg b.i.d.

Inhaled (n = 291) Placebo (Lactose Vehicle) (n = 318) Respiratory Ear, nose, and throat infections 5% 5% Ear, nose, and throat hemorrhage <1% 2% Asthma <1% 2% Cough <1% 2% Digestive Vomiting 2% 3% Diarrhea 2% 2% Nausea <1% 2% In 1 of the 2 trials described in Table 2 , some additional information is available from children (aged 5 to 12 years) without acute influenza-like illness who received an investigational prophylaxis regimen of RELENZA; 132 children received RELENZA and 145 children received placebo.

Among these children, nasal signs and symptoms (zanamivir 20%, placebo 9%), cough (zanamivir 16%, placebo 8%), and throat/tonsil discomfort and pain (zanamivir 11%, placebo 6%) were reported more frequently with RELENZA than placebo.

In a subset with chronic pulmonary disease, lower respiratory adverse events (described as asthma, cough, or viral respiratory infections which could include influenza-like symptoms) were reported in 7 of 7 zanamivir recipients and 5 of 12 placebo recipients.

Prophylaxis of Influenza Family/Household Prophylaxis Trials: Adverse events that occurred with an incidence of greater than or equal to 1.5% in the 2 prophylaxis trials are listed in Table 3 .

This table shows adverse events occurring in subjects aged 5 years and older receiving RELENZA 10 mg inhaled once daily for 10 days.

Table 3.

Summary of Adverse Events ≥1.5% Incidence during 10-Day Prophylaxis Trials in Adults, Adolescents, and Children a a In prophylaxis trials, symptoms associated with influenza-like illness were captured as adverse events; subjects were enrolled during a winter respiratory season during which time any symptoms that occurred were captured as adverse events.

Adverse Event Contact Cases RELENZA (n = 1,068) Placebo (n = 1,059) Lower respiratory Viral respiratory infections 13% 19% Cough 7% 9% Neurologic Headaches 13% 14% Ear, nose, and throat Nasal signs and symptoms 12% 12% Throat and tonsil discomfort and pain 8% 9% Nasal inflammation 1% 2% Musculoskeletal Muscle pain 3% 3% Endocrine and metabolic Feeding problems (decreased or increased appetite and anorexia) 2% 2% Gastrointestinal Nausea and vomiting 1% 2% Non-site specific Malaise and fatigue 5% 5% Temperature regulation disturbances (fever and/or chills) 5% 4% Community Prophylaxis Trials: Adverse events that occurred with an incidence of greater than or equal to 1.5% in 2 prophylaxis trials are listed in Table 4 .

This table shows adverse events occurring in subjects aged 5 years and older receiving RELENZA 10 mg inhaled once daily for 28 days.

Table 4.

Summary of Adverse Events ≥1.5% Incidence during 28-Day Prophylaxis Trials in Adults, Adolescents, and Children a a In prophylaxis trials, symptoms associated with influenza-like illness were captured as adverse events; subjects were enrolled during a winter respiratory season during which time any symptoms that occurred were captured as adverse events.

Adverse Event RELENZA (n = 2,231) Placebo (n = 2,239) Neurologic Headaches 24% 26% Ear, nose, and throat Throat and tonsil discomfort and pain 19% 20% Nasal signs and symptoms 12% 13% Ear, nose, and throat infections 2% 2% Lower respiratory Cough 17% 18% Viral respiratory infections 3% 4% Musculoskeletal Muscle pain 8% 8% Musculoskeletal pain 6% 6% Arthralgia and articular rheumatism 2% <1% Endocrine and metabolic Feeding problems (decreased or increased appetite and anorexia) 4% 4% Gastrointestinal Nausea and vomiting 2% 3% Diarrhea 2% 2% Non-site specific Temperature regulation disturbances (fever and/or chills) 9% 10% Malaise and fatigue 8% 8% 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of RELENZA.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Allergic Reactions Allergic or allergic-like reaction, including oropharyngeal edema [see Warnings and Precautions ( 5.2 )] .

Psychiatric Delirium, including symptoms such as altered level of consciousness, confusion, abnormal behavior, delusions, hallucinations, agitation, anxiety, nightmares [see Warnings and Precautions ( 5.3 )].

Cardiac Arrhythmias, syncope.

Neurologic Seizures.

Vasovagal-like episodes have been reported shortly following inhalation of zanamivir.

Respiratory Bronchospasm, dyspnea [see Warnings and Precautions ( 5.1 )] .

Skin Facial edema; rash, including serious cutaneous reactions (e.g., erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis); urticaria [see Warnings and Precautions ( 5.2 )] .