Side Effects of Relenza (zanamivir)

Relenza (zanamivir) is a flu medication and an inhaled antiviral drug used to treat and prevent influenza (the “flu”). Relenza decreases the spread of influenza A and B viruses, the viruses responsible for the flu. It does this by blocking the action of neuraminidase, an enzyme produced by the viruses that enables the viruses to spread from infected cells to healthy cells. 

By preventing the spread of virus from cell to cell, the symptoms and duration of influenza infection are reduced. On average, Relenza reduces the duration of symptoms by one day if treatment is started within forty-eight hours after symptoms begin.

Common side effects of Relenza include:

• headaches,
• diarrhea,
• nausea,
• cough,
• vomiting,
• disturbance in temperature regulation, and
• dizziness.

Serious side effects of Relenza include:

• increase or decrease in appetite,
• fever,
• chills,
• weakness,
• sinusitis,
• ear/nose/throat infections,
• skin reactions,
• muscle or joint pain,
• allergic reactions,
• bronchospasm,
• behavioral disturbances, and
• breathing problems in patients with respiratory diseases.

Drug interactions of Relenza include injections of live attenuated flu vaccine, because Relenza prevents viral replication. 

The Centers for Disease Control (CDC) states that pregnancy is not a contraindication for use of Relenza in pregnant women because the benefits outweigh the risks. 

It is unknown if Relenza is excreted in breast milk. However, the CDC recommends that nursing women who develop flu after childbirth should be treated with antiviral drugs. Consult your doctor before breastfeeding.

The most frequent side effects are:

• headaches,
• diarrhea,
• nausea,
• cough,
• vomiting,
• disturbance in temperature regulation, and
• dizziness.

Other important side effects include:

• increase or decrease in appetite,
• fever,
• chills,
• weakness,
• sinusitis, and
• ear; nose; and throat infections,
• skin reactions,
• muscle or joint pain,
• allergic reactions,
• bronchospasm, and
• behavioral disturbances.

Patients with respiratory diseases may experience breathing problems when treated with zanamivir due to irritation of the breathing tubes by the particles from the inhaler. If breathing problems occur, zanamivir should be discontinued. Patients who have asthma or other breathing problems that make them sensitive to inhaled particles should have a fast acting, inhaled bronchodilator available to treat any breathing problem that may occur when zanamivir is used.

See product 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

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 Subjects^a

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 Children^a

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 Children^a

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.

Zanamivir is not a substrate nor does it affect cytochrome P450 (CYP) isoenzymes (CYP1A1/2, 2A6, 2C9, 2C18, 2D6, 2E1, and 3A4) in human liver microsomes. No clinically significant pharmacokinetic drug interactions are predicted based on data from in vitro studies.

The concurrent use of Relenza with live attenuated influenza vaccine (LAIV) intranasal has not been evaluated. However, because of potential interference between these products, LAIV should not be administered within 2 weeks before or 48 hours after administration of Relenza, unless medically indicated. The concern about possible interference arises from the potential for antiviral drugs to inhibit replication of live vaccine virus.

Trivalent inactivated influenza vaccine can be administered at any time relative to use of Relenza.