FDA label 342b7e19-49d6-4d0b-950a-cc00f4b79924

5 WARNINGS AND PRECAUTIONS Bronchospasm: Serious, sometimes fatal, cases have occurred. Not recommended in individuals with underlying airways disease. Discontinue RELENZA if bronchospasm or decline in respiratory function develops. (5.1) Allergic Reactions: Discontinue RELENZA and initiate appropriate treatment if an allergic reaction occurs or is suspected. (5.2) Neuropsychiatric Events: Patients with influenza, particularly pediatric patients, may be at an increased risk of seizures, confusion, or abnormal behavior early in their illness. Monitor for signs of abnormal behavior. (5.3) High-risk Underlying Medical Conditions: Safety and effectiveness have not been demonstrated in these patients. (5.4) 5.1 Bronchospasm RELENZA is not recommended for treatment or prophylaxis of influenza in individuals with underlying airways disease (such as asthma or chronic obstructive pulmonary disease). Serious cases of bronchospasm, including fatalities, have been reported during treatment with RELENZA in patients with and without underlying airways disease. Many of these cases were reported during postmarketing and causality was difficult to assess. RELENZA should be discontinued in any patient who develops bronchospasm or decline in respiratory function; immediate treatment and hospitalization may be required. 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. Bronchospasm was documented following administration of zanamivir in 1 of 13 patients with mild or moderate asthma (but without acute influenza-like illness) in a Phase I study. In a Phase III study in patients with acute influenza-like illness superimposed on underlying asthma or chronic obstructive pulmonary disease, 10% (24 of 244) of patients on zanamivir and 9% (22 of 237) on placebo experienced a greater than 20% decline in FEV 1 following treatment for 5 days. If use of 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 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. 5.2 Allergic Reactions Allergic-like reactions, including oropharyngeal edema, serious skin rashes, and anaphylaxis have been reported in postmarketing experience with RELENZA. RELENZA should be stopped and appropriate treatment instituted if an allergic reaction occurs or is suspected. 5.3 Neuropsychiatric Events Influenza can be associated with a variety of neurologic and behavioral symptoms which can include events such as seizures, hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease. There have been postmarketing reports (mostly from Japan) of delirium and abnormal behavior leading to injury in patients with influenza who were receiving neuraminidase inhibitors, including RELENZA. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made, but they appear to be uncommon based on usage data for RELENZA. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of RELENZA to these events has not been established. Patients with influenza should be closely monitored for signs of abnormal behavior. If neuropsychiatric symptoms occur, the risks and benefits of continuing treatment should be evaluated for each patient. 5.4 Limitations of Populations Studied 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. 5.5 Bacterial Infections Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. RELENZA has not been shown to prevent such complications. 5.6 Importance of Proper Use of DISKHALER Effective and safe use of RELENZA requires proper use of the DISKHALER to inhale the drug. Prescribers should carefully evaluate the ability of young children to use the delivery system if use of RELENZA is considered [see Use in Specific Populations (8.4)].

6 ADVERSE REACTIONS See Warnings and Precautions for information about risk of serious adverse events such as bronchospasm (5.1) and allergic-like reactions (5.2), and for safety information in patients with underlying airways disease (5.1). The most common adverse events reported in >1.5% of patients treated with RELENZA and more commonly than in patients treated with placebo are: Treatment Studies – sinusitis, dizziness. Prophylaxis Studies – 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 studies 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 ≥1.5% in treatment studies are listed in Table 1. This table shows adverse events occurring in patients ≥12 years of age 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 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% a Includes studies 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. Additional adverse reactions occurring in less than 1.5% of patients receiving RELENZA included malaise, fatigue, fever, abdominal pain, myalgia, arthralgia, and urticaria. The most frequent laboratory abnormalities in Phase III treatment studies included elevations of liver enzymes and 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 Patients: Adverse events that occurred with an incidence ≥1.5% in children receiving treatment doses of RELENZA in 2 Phase III studies are listed in Table 2. This table shows adverse events occurring in pediatric patients 5 to 12 years old 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 Patients a a Includes a subset of patients receiving RELENZA for treatment of influenza in a prophylaxis study. 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 studies described in Table 2, some additional information is available from children (5 to 12 years old) 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 Studies: Adverse events that occurred with an incidence of ≥1.5% in the 2 prophylaxis studies are listed in Table 3. This table shows adverse events occurring in patients ≥5 years of age receiving RELENZA 10 mg inhaled once daily for 10 days. Table 3. Summary of Adverse Events ≥1.5% Incidence During 10-Day Prophylaxis Studies in Adults, Adolescents, and Children a a In prophylaxis studies, 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 Studies: Adverse events that occurred with an incidence of ≥1.5% in 2 prophylaxis studies are listed in Table 4. This table shows adverse events occurring in patients ≥5 years of age receiving RELENZA 10 mg inhaled once daily for 28 days. Table 4. Summary of Adverse Events ≥1.5% Incidence During 28-Day Prophylaxis Studies in Adults, Adolescents, and Children a a In prophylaxis studies, 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 In addition to adverse events reported from clinical trials, the following events have been identified during postmarketing use of zanamivir (RELENZA). Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to zanamivir (RELENZA). 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. 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)] .

<table width="0.000" ID="id_f7cc2612-2798-4061-a213-42a8d71c341a"> <caption ID="id_4884ff3b-f890-4d45-a839-b9490776d627">Table 1. Summary of Adverse Events &#x2265;1.5% Incidence During Treatment in Adults and Adolescents</caption> <col/> <col/> <col/> <col/> <tbody> <tr ID="id_a28fc14e-c52f-47dc-b095-3edd3c75414f"> <td align="center" valign="bottom" rowspan="2" styleCode="Botrule Toprule Rrule Lrule">Adverse Event</td> <td align="center" valign="bottom" colspan="2" rowspan="1" styleCode="Botrule Rrule">RELENZA</td> <td align="center" valign="bottom" rowspan="2" styleCode="Rrule"> <paragraph>Placebo</paragraph> <paragraph>(Lactose Vehicle)</paragraph> (n = 1,520)</td> </tr> <tr ID="id_57d5715f-ea77-48cf-a90e-6d07a628624d"> <td align="center" valign="bottom" rowspan="1" styleCode="Lrule Botrule Rrule"> <paragraph>10 mg b.i.d.<content styleCode="bold"> Inhaled</content> </paragraph> (n = 1,132)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule"> <paragraph>All Dosing Regimens^a </paragraph> (n = 2,289)</td> </tr> <tr ID="id_9e19a0a0-116d-4add-959d-80ac1f4c08ce"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Body as a whole</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_ce9a1e8d-6577-4ee6-9d9f-0f06f187ec56"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Headaches</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> </tr> <tr ID="id_1632f196-6da8-498a-9161-75d70e3a134e"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Digestive</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_0f0e7fa4-28ee-45a1-a530-9813ec3f68d2"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Diarrhea</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">4%</td> </tr> <tr ID="id_526a3599-7be2-431f-b7a3-1b43d1dcfe0f"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Nausea</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> </tr> <tr ID="id_2641aa4b-67e3-4e66-892a-77dca99e9e75"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Vomiting</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> </tr> <tr ID="id_c60bc802-aca8-44f2-8299-42ba5cb75e2c"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Respiratory</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_bf3fd553-b593-4cd8-ae95-1e6edc0343db"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Nasal signs and symptoms</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> </tr> <tr ID="id_3ddd0276-aef1-42d6-9e44-114669687ea3"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Bronchitis</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> </tr> <tr ID="id_5f40c5d1-cdb5-4a06-aa68-759115807cbe"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Cough</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> </tr> <tr ID="id_245c3187-8503-4285-bf55-e894b01720e5"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Sinusitis</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> </tr> <tr ID="id_c201ee67-70c7-4be3-886f-27aee16a407d"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Ear, nose, and throat infections</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> </tr> <tr ID="id_14fbcd87-e7eb-48f6-81ae-52fff3f15e02"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Nervous system</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_016589a2-dc56-443d-aed8-53ba4bdac7ad"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Botrule Rrule"> Dizziness</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">&lt;1%</td> </tr> <tr ID="id_ec93227d-6ad7-42ed-975d-e445dcc94cef"> <td align="left" valign="top" colspan="4" styleCode="Lrule Botrule Rrule"> ^a Includes studies 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.</td> </tr> </tbody> </table>

<table width="555.000" ID="id_958a7e99-154e-47ca-9695-a2ff0b12e0fd"> <caption ID="id_c362245a-441e-43d8-be75-c62af3bd29e2">Table 2. Summary of Adverse Events &#x2265;1.5% Incidence During Treatment in Pediatric Patients^a </caption> <col width="47.6%"/> <col width="25.8%"/> <col width="26.7%"/> <tfoot ID="id_0009e57e-b411-4883-b185-a76b4389b2ed"> <tr> <td align="left" valign="top" colspan="3" rowspan="1" styleCode="Lrule Botrule Rrule"> ^a Includes a subset of patients receiving RELENZA for treatment of influenza in a prophylaxis study.</td> </tr> </tfoot> <tbody> <tr ID="id_545b4f03-5c2a-4522-9c39-935ceb3ef83d"> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Toprule Rrule Lrule">Adverse Event</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule"> <paragraph>RELENZA</paragraph> <paragraph>10 mg b.i.d. Inhaled</paragraph> (n = 291)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule"> <paragraph>Placebo</paragraph> <paragraph>(Lactose Vehicle)</paragraph> (n = 318)</td> </tr> <tr ID="id_5aba3972-2550-44ee-90f9-58589a4b91ba"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Respiratory</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_b67abbed-57d0-4b1b-9173-e20a5a09f799"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Ear, nose, and throat infections</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">5%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">5%</td> </tr> <tr ID="id_8064cd78-f232-4ae3-a912-a9fc9497e076"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Ear, nose, and throat hemorrhage</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">&lt;1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> </tr> <tr ID="id_0155744c-3e5a-41e7-a38f-bdd705227f5b"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Asthma</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">&lt;1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> </tr> <tr ID="id_3c9d7780-51a3-4623-98fa-593ddd17f268"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Cough</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">&lt;1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> </tr> <tr ID="id_26518851-bd56-400d-bb84-af784c09c787"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Digestive</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_80e0ff1b-bd63-4ed8-91e6-c5e17a01ddfd"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Vomiting</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> </tr> <tr ID="id_307d62e4-8f42-44f7-980d-baea35d8f992"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Diarrhea</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> </tr> <tr ID="id_4a92e92e-8ed9-415f-885d-85a8d9858521"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Botrule Rrule"> Nausea</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">&lt;1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">2%</td> </tr> </tbody> </table>

<table width="577.000" ID="id_d18496b8-fba6-4eae-8be7-6de5c28a0a62"> <caption ID="id_1e9c6dd6-84d4-42ed-a5a3-e14f4fb4bc8d">Table 3. Summary of Adverse Events &#x2265;1.5% Incidence During 10-Day Prophylaxis Studies in Adults, Adolescents, and Children^a </caption> <col width="62.9%"/> <col width="19.1%"/> <col width="18.0%"/> <tfoot ID="id_e619b15e-8345-42fe-9189-e4ece3cb7d2f"> <tr> <td align="left" valign="top" colspan="3" rowspan="1" styleCode="Lrule Botrule Rrule"> ^a In prophylaxis studies, 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.</td> </tr> </tfoot> <tbody> <tr ID="id_9cf1f031-160b-4469-aedf-b2cc39aed153"> <td align="center" valign="bottom" rowspan="2" styleCode="Botrule Toprule Rrule Lrule">Adverse Event</td> <td align="center" valign="bottom" colspan="2" rowspan="1" styleCode="Botrule Rrule">Contact Cases</td> </tr> <tr ID="id_6a6ecbac-1ead-49c0-8d15-ff9ea0128933"> <td align="center" valign="bottom" rowspan="1" styleCode="Lrule Botrule Rrule"> <paragraph>RELENZA</paragraph> (n = 1,068)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule"> <paragraph>Placebo</paragraph> (n = 1,059)</td> </tr> <tr ID="id_2e876bf0-0691-46cd-b4f8-c92276326c17"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Lower respiratory</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_e4dbb3c5-6533-4526-a109-4e1b6932443a"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Viral respiratory infections</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">13%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">19%</td> </tr> <tr ID="id_7b6018e1-9e70-43a2-983e-5bcff278b702"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Cough</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">7%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">9%</td> </tr> <tr ID="id_1e879388-c2f1-4786-a1f9-cd4983dee425"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Neurologic</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_57388c03-b5ea-42b1-b401-7a82e09e6a4d"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Headaches</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">13%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">14%</td> </tr> <tr ID="id_06025515-aeae-4488-aade-d7c022611222"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Ear, nose, and throat</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_7dfc7b0f-bc65-4ccc-9cff-d6aa0f54a2d7"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Nasal signs and symptoms</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">12%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">12%</td> </tr> <tr ID="id_25504bfc-74f9-4070-b4cb-305397b6c0b8"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Throat and tonsil discomfort and pain</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">8%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">9%</td> </tr> <tr ID="id_e447660f-0bac-41c8-a952-95116a6c880e"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Nasal inflammation</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> </tr> <tr ID="id_c1d9b14a-efd1-423e-8be4-fe28dc7ca96f"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Musculoskeletal</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_be335a3d-a1f6-4cda-a226-e9a354ec7bf4"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Muscle pain</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3%</td> </tr> <tr ID="id_ef5d2e3a-3614-4d0d-9f6f-f17b9f175718"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Endocrine and metabolic</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_b9ae97e5-e177-4eea-91f6-79443338c676"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Feeding problems (decreased or increased appetite and anorexia)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> </tr> <tr ID="id_aa8c50c1-0df3-4114-b1fe-ad1e546127c9"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Gastrointestinal</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_3861e472-3b5b-4650-993a-7b0bcf6ddb15"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Nausea and vomiting</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">2%</td> </tr> <tr ID="id_fae3b32f-1be4-4316-b53b-71876ea5e6e0"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> <content styleCode="bold">Non-site specific</content> </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_d25dff46-4d9f-4617-b27d-106534a3288e"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> Malaise and fatigue</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">5%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">5%</td> </tr> <tr ID="id_2bce0586-5844-4e08-9b0d-af6754bfe9dc"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Botrule Rrule"> Temperature regulation disturbances (fever and/or chills)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">5%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">4%</td> </tr> </tbody> </table>