RELENZA SIDE EFFECTS
SIDE EFFECTS
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.
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 Greater than or Equal to 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 Regimensa (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% |
| aIncludes 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. | |||
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 III treatment trials 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 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 III 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 Greater than or Equal to 1.5% Incidence during Treatment in Pediatric Subjectsa
| 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% |
| aIncludes a subset of subjects receiving RELENZA for treatment of influenza in a prophylaxis trial. | ||
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 Studies
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 Greater than or Equal to 1.5% Incidence during 10-Day Prophylaxis Trials in Adults, Adolescents, and Childrena
| 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 | ||
| Throat and tonsil discomfort and pain | 8% | 9% |
| Nasal signs and symptoms | 12% | 12% |
| Nasal inflammation | 1% | 2% |
| Mus culos keletal | ||
| 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% |
| aIn 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. | ||
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 Greater than or Equal to 1.5% Incidence during 28-Day Prophylaxis Trials in Adults, Adolescents, and Childrena
| 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% |
| aIn 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. | ||
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.
Psychiatric
Delirium, including symptoms such as altered level of consciousness, confusion, abnormal behavior, delusions, hallucinations, agitation, anxiety, nightmares.
Cardiac
Arrhythmias, syncope.
Neurologic
Seizures. Vasovagal-like episodes have been reported shortly following inhalation of zanamivir.
Respiratory
Bronchospasm, dyspnea.
Skin
Facial edema; rash, including serious cutaneous reactions (e.g., erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis); urticaria
SRC: NLM .