SIDE EFFECTS
See WARNINGS and PRECAUTIONS for information about risk of serious adverse events such as bronchospasm and allergic-like reactions, and for safety information in patients with underlying airways disease.
Because the placebo consisted of inhaled lactose powder, which is also the vehicle for the active drug, 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 ³1.5% in treatment studies are listed in Table 1. This table shows adverse events occurring in patients ³12 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 ³.5% Incidence During Treatment in Adults and Adolescents |
| |
RELENZA |
|
Adverse Event |
10 mg b.i.d. Inhaled (n = 1,132) |
All Dosing Regimens* (n = 2,289) |
Placebo (Lactose Vehicle) (n = 1,520) |
| 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% |
| * 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 |
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 3 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 ³1.5% in children receiving treatment doses of RELENZA in two Phase 3 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 ³1.5% Incidence During Treatment in Pediatric Patients* |
|
Adverse Event |
RELENZA10 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% |
| * Includes a subset of patients receiving RELENZA for treatment of influenza in a prophylaxis study. |
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 ³1.5% in the 2 prophylaxis studies are listed in Table 3. This table shows adverse events occurring in patients ³5 years of age receiving RELENZA 10 mg inhaled once daily for 10 days.
|
Table 3. Summary of Adverse Events ³1.5% Incidence During 10-Day Prophylaxis Studies in Adults, Adolescents, and Children* |
| |
Contact Cases |
|
Adverse Event |
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% |
| * 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. |
Community Prophylaxis Studies: Adverse events that occurred with an incidence of ³1.5% in 2 prophylaxis studies are listed in Table 4. This table shows adverse events occurring in patients ³5 years of age receiving RELENZA 10 mg inhaled once daily for 28 days.
|
Table 4. Summary of Adverse Events ³1.5% Incidence During 28-Day Prophylaxis Studies in Adults, Adolescents, and Children* |
|
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 & fatigue |
8% |
8% |
| * 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. |
Observed During Clinical Practice: In addition to adverse events reported from clinical trials, the following events have been identified during post-marketing 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).
General: Allergic or allergic-like reaction, including oropharyngeal edema (see PRECAUTIONS).
Cardiac: Arrhythmias, syncope.
Neurologic: Seizures.
Respiratory: Bronchospasm, dyspnea (see WARNINGS and PRECAUTIONS).
Skin: Facial edema; rash, including serious cutaneous reactions (see PRECAUTIONS).
DRUG INTERACTIONS
No clinically significant pharmacokinetic drug interactions are predicted based on data from in vitro studies.
