Zanamivir

Special Alerts

CDC Health Advisory on Influenza Chemoprophylaxis and Treatment - October 19, 2004

The Centers for Disease Control and Prevention (CDC) has developed interim recommendations on the use of antiviral medications for the 2004-05 influenza season. In the United States, four antiviral medications (amantadine, rimantadine, oseltamivir, and zanamivir) are approved for treatment of influenza (only limited supplies of zanamivir are available). When used for treatment within the first 2 days of illness, all four antiviral medications are similarly effective, reducing the duration of illness by 1-2 days. Amantadine, rimantadine, and oseltamivir are approved for chemoprophylaxis of influenza.

In the 2004-05 Antiviral Medications Usage Guidelines, the CDC encourages the use of amantadine or rimantadine for chemoprophylaxis and use of oseltamivir or zanamivir for treatment (as supplies allow), in part to minimize the development of amantadine resistance among circulating influenza viruses. People who are at high risk of serious complications from influenza may benefit most from antiviral medications. Therefore, in general, people who fall into these high-risk groups should be given priority for use of influenza antiviral medications:

Treatment should be initiated in any person experiencing a potentially life-threatening influenza-related illness or any person at high risk for serious complications of influenza and who is within the first 2 days of illness onset should be treated with antiviral medications. Pregnant women should consult their primary provider regarding use of influenza antiviral medications.

Chemoprophylaxis is recommended for all persons who live or work in institutions caring for people at high risk of serious complications of influenza infection should be given antiviral medications in the event of an institutional outbreak. All persons at high risk of serious influenza complications should be given antiviral medications if they are likely to be exposed to others infected with influenza. Antiviral medications can be considered in other situations when the available supply of such medications is locally adequate. Where the supplies of both influenza vaccine and influenza antiviral medications may not be sufficient to meet demand, CDC does not recommend the use of influenza antiviral medications for chemoprophylaxis of non-high risk persons in the community.

The United States has a limited supply of influenza antiviral medications stored in the Strategic National Stockpile for emergency situations. Influenza antiviral medications in the SNS can be requested only by State or Territory Health Departments.

Complete guidelines may be viewed at: http://www.cdc.gov/flu/professionals/treatment/0405antiviralguide.htm

For further information on detection and control of influenza outbreaks in acute care facilities, see http://www.cdc.gov/ncidod/hip/INFECT/flu_acute.htm

Pronunciation

(za NA mi veer)

U.S. Brand Names

Relenza®

Generic Available

No

Canadian Brand Names

Relenza®

Use

Treatment of uncomplicated acute illness due to influenza virus in adults and children 7 years of age; should not be used in patients with underlying airway disease. Treatment should only be initiated in patients who have been symptomatic for no more than 2 days.

Use - Unlabeled/Investigational

Investigational: Prophylaxis against influenza A/B infections

Pregnancy Risk Factor

C

Pregnancy Implications

Zanamivir has been shown to cross the placenta in animal models, however, no evidence of fetal malformations has been demonstrated.

Lactation

Excretion in breast milk unknown/use caution

Contraindications

Hypersensitivity to zanamivir or any component of the formulation

Warnings/Precautions

Patients must be instructed in the use of the delivery system. No data are available to support the use of this drug in patients who begin treatment after 48 hours of symptoms, as a prophylactic treatment for influenza, or in patients with significant underlying medical conditions. Not recommended for use in patients with underlying respiratory disease, such as asthma or COPD, due to lack of efficacy and risk of serious adverse effects. Bronchospasm, decreased lung function, and other serious adverse reactions, including those with fatal outcomes, have been reported. For a patient with an underlying airway disease where a medical decision has been made to use zanamivir, a fast-acting bronchodilator should be made available, and used prior to each dose. Not a substitute for the flu shot. Consider primary or concomitant bacterial infections. Powder for oral inhalation contains lactose.

Adverse Reactions

Most adverse reactions occurred at a frequency which was equal to the control (lactose vehicle).

>1.5%:

Central nervous system: Headache (2%), dizziness (2%)

Gastrointestinal: Nausea (3%), diarrhea (3% adults, 2% children), vomiting (1% adults, 2% children)

Respiratory: Sinusitis (3%), bronchitis (2%), cough (2%), other nasal signs and symptoms (2%), infection (ear, nose, and throat; 2% adults, 5% children)

<1.5%: Malaise, fatigue, fever, abdominal pain, myalgia, arthralgia, and urticaria

In addition, the following adverse reactions have been reported during postmarketing use: Allergic or allergic-like reaction (including oropharyngeal edema), arrhythmia, syncope, seizure, bronchospasm, dyspnea, facial edema, rash (including serious cutaneous reactions)

Overdosage/Toxicology

Information is limited, and symptoms appear similar to reported adverse events from clinical studies.

Drug Interactions

No clinically significant pharmacokinetic interactions are predicted.

Stability

Store at room temperature (25°C) 77°F; do not puncture blister until taking a dose using the Diskhaler®

Mechanism of Action

Zanamivir inhibits influenza virus neuraminidase enzymes, potentially altering virus particle aggregation and release.

Pharmacodynamics/Kinetics

Absorption: Inhalation: 4% to 17%

Protein binding, plasma: <10%

Metabolism: None

Half-life elimination, serum: 2.5-5.1 hours

Excretion: Urine (as unchanged drug); feces (unabsorbed drug)

Dosage

Children 7 years and Adults: 2 inhalations (10 mg total) twice daily for 5 days. Two doses should be taken on the first day of dosing, regardless of interval, while doses should be spaced by approximately 12 hours on subsequent days.

Prophylaxis (investigational use): 2 inhalations (10 mg) once daily for duration of exposure period (6 weeks has been used in clinical trial)

Administration

Inhalation: Must be used with Diskhaler® delivery device. Patients who are scheduled to use an inhaled bronchodilator should use their bronchodilator prior to zanamivir.

Patient Education

Use delivery device exactly as directed; complete full 5-day regimen, even if symptoms improve sooner. If you have asthma or COPD you may be at risk for bronchospasm; see prescriber for appropriate bronchodilator before using zanamivir. Stop using this medication and contact your physician if you experience shortness of breath, increased wheezing, or other signs of bronchospasm. You may experience dizziness or headache (use caution when driving or engaging in hazardous tasks until response to drug is known). Report unresolved diarrhea, vomiting, or nausea; acute fever or muscle pain; or other acute and persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Additional Information

Majority of patients included in clinical trials were infected with influenza A, however, a number of patients with influenza B infections were also enrolled. Patients with lower temperature or less severe symptoms appeared to derive less benefit from therapy. No consistent treatment benefit was demonstrated in patients with chronic underlying medical conditions.

Anesthesia and Critical Care Concerns/Other Considerations

Patients with asthma or COPD should be informed of the risk of bronchospasm and should have a fast-acting bronchodilator available when treated with zanamivir. Majority of patients included in clinical trials were infected with influenza A, however, a number of patients with influenza B infections were also enrolled. Patients with lower temperature or less severe symptoms appeared to derive less benefit from therapy. No consistent treatment benefit was demonstrated in patients with chronic underlying medical conditions.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause dizziness; may rarely cause drowsiness

Mental Health: Effects on Psychiatric Treatment

None reported

Dosage Forms

Powder for oral inhalation: 5 mg/blister (20s) [4 blisters per Rotadisk® foil pack, 5 Rotadisk® per package; packaged with Diskhaler® inhalation device; contains lactose]

References

Dreitlein WB, Maratos J, and Brocavich J, "Zanamivir and Oseltamivir: Two New Options for the Treatment and Prevention of Influenza,"Clin Ther, 2001, 23(3):327-55.

International Brand Names

Relenza® (AR, AT, AU, BE, BR, CA, CH, CR, CZ, DE, DO, ES, FI, FR, GB, GT, HN, HR, HU, IE, IL, IT, NL, NO, NZ, PA, PL, PT, RO, SE, SI, SV)