Zanamivir
Class: Neuraminidase Inhibitors
VA Class: AM800
Chemical Name: 5-Acetamido-2,6-anhydro-3,4,5-trideoxy-4-guanidino-d-glycero-d-g
CAS Number: 139110-80-8
Brands: Relenza
Medically reviewed by Drugs.com. Last updated on April 20, 2020.
Warning
Special Alerts:
For information on the use of this drug in patients with coronavirus disease 2019 (COVID-19), see the document “Assessment of the Evidence for COVID-19-Related Treatments” on ASHP's COVID-19 Resource Center. To view this document, please click here: [Web]
Introduction
Antiviral; neuraminidase inhibitor; sialic acid analog.1 144
Uses for Zanamivir
Treatment of Seasonal Influenza A and B Virus Infections
Symptomatic treatment of uncomplicated acute illness caused by susceptible influenza A or B viruses in adults, adolescents, and children ≥7 years of age who have been symptomatic for ≤2 days.1 3 4 5 6 14 105 112 116 144
Efficacy for treatment of influenza not established in patients with underlying airways disease (e.g., asthma, COPD).1 Because of risk of serious bronchospasm, not recommended in those with underlying airways disease.1 (See Individuals with Asthma or COPD under Cautions.) No evidence that treatment with the drug reduces risk of transmission of influenza to others.1
CDC, US Public Health Service Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend antiviral treatment initiated as soon as possible in all individuals with suspected or confirmed influenza who require hospitalization or have severe, complicated, or progressive illness (regardless of vaccination status or underlying illness).105 112 116 137 144 Early empiric antiviral treatment also recommended in individuals with suspected or confirmed influenza of any severity if they are at high risk of developing influenza-related complications because of age or underlying medical conditions.112 116 137 144 This includes children <2 years of age, adults ≥65 years of age, individuals of any age with certain chronic medical or immunosuppressive conditions, women who are pregnant or up to 2 weeks postpartum, individuals <19 years of age who are receiving long-term aspirin therapy, American Indians or Alaskan natives, morbidly obese individuals with body mass index (BMI) ≥40, and residents of any age in nursing homes or other long-term care facilities.112 116 137
CDC, ACIP, and AAP also state empiric antiviral treatment can be considered in previously healthy, symptomatic individuals with suspected or confirmed influenza who are not known to be at increased risk of developing severe or complicated illness if such treatment can be initiated within 48 hours of illness onset.105 112 137 144 Although these individuals typically do not require treatment, early empiric antiviral treatment might provide some benefit (e.g., shortened duration of illness).144
If indicated, initiate treatment with an appropriate antiviral as early as possible since benefit is greatest if started within 48 hours of symptom onset.105 112 137 144 Because there is some evidence that antiviral treatment initiated up to 96 hours after illness onset might still be beneficial in reducing morbidity and mortality in hospitalized patients and in those with severe, complicated, or progressive illness, some experts state that antiviral treatment can be initiated >48 hours after illness onset in such patients.137 144 Do not delay initiation of treatment while waiting for laboratory confirmation.112 137 144
When treatment of seasonal influenza indicated, oseltamivir or zanamivir usually recommended.112 137 144 Oseltamivir usually preferred for hospitalized patients and patients with severe or complicated influenza since data are lacking regarding use of inhaled zanamivir in such patients.161
CDC states that use of investigational IV zanamivir† may be considered for hospitalized patients with severe influenza if they cannot tolerate or absorb oral oseltamivir (e.g., because of suspected or known gastric stasis, malabsorption, GI bleeding) or have infections caused by oseltamivir-resistant strains.161 Although safety and efficacy of IV zanamivir not established, an investigational aqueous solution for IV administration may be available either by enrollment in an ongoing clinical trial or under an emergency investigational new drug (EIND) protocol.161 (See Administration under Dosage and Administration.)
Consider viral surveillance data available from local and state health departments and the CDC when selecting an antiviral for treatment of seasonal influenza.112 137 144 Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve;144 emergence of zanamivir-resistant influenza virus may decrease effectiveness of the drug.1 Although influenza A and B viruses circulating in US during last few years generally have been susceptible to zanamivir, consult most recent information.137 144
CDC issues recommendations concerning use of antivirals for treatment of influenza, and these recommendations are updated as needed during each influenza season.137 144 Information regarding influenza surveillance and updated recommendations for treatment of seasonal influenza are available from CDC at [Web].
Prevention of Seasonal Influenza A and B Virus Infections
Prophylaxis of influenza caused by influenza A or B viruses in adults, adolescents, and children ≥5 years of age.1 2 17 18 105 112 116 137 144
Safety and efficacy established for prophylaxis of influenza in household settings and during community outbreaks;1 2 17 18 manufacturer states efficacy not established for prophylaxis of influenza in nursing home settings.1
Because of risk of serious bronchospasm, not recommended in those with underlying airways disease (e.g., asthma, COPD).1 (See Individuals with Asthma or COPD under Cautions.)
Annual vaccination with seasonal influenza virus vaccine, as recommended by ACIP, is the primary means of preventing seasonal influenza and its severe complications.100 105 112 116 144 488 Prophylaxis with an appropriate antiviral active against circulating influenza strains is considered an adjunct to vaccination for control and prevention of influenza.1 105 112 116 137 144 488
Indiscriminate use of antivirals for prophylaxis may promote resistance or reduce availability of antivirals for treatment.137 144 Base decisions regarding use of antivirals for prophylaxis of influenza on exposed person's risk for influenza complications, vaccination status, type and duration of contact, recommendations from local or public health authorities, and clinical judgment.144 Generally use postexposure prophylaxis only if it can be initiated within 48 hours of most recent exposure.137 144
When seasonal influenza viruses are circulating in the community, postexposure prophylaxis with oseltamivir or zanamivir can be considered for certain individuals, including those at high risk of developing influenza complications for whom influenza vaccine is contraindicated, unavailable, or expected to have low efficacy (e.g., immunocompromised individuals).112 116 137 144 Other possible candidates for antiviral prophylaxis include unvaccinated health care personnel, public health workers, and first responders with unprotected, close-contact exposure to a patient with confirmed, probable, or suspected influenza during the time when the patient was infectious.112 137 144 Also consider antiviral prophylaxis for controlling influenza outbreaks in nursing and long-term care facilities or other closed or semi-closed settings with large numbers of individuals at high risk for influenza complications.112 116 137 144 In individuals at high risk of influenza complications who receive parenteral inactivated influenza vaccine, prophylaxis can be considered during the 2 weeks after vaccination to provide protection until an adequate immune response develops.112 116 (See Influenza Virus Vaccines under Interactions.)
Consider viral surveillance data available from local and state health departments and the CDC when selecting an antiviral for prophylaxis of influenza.112 137 The most appropriate antiviral for prevention of influenza is based on the likelihood that the influenza strain is susceptible and the known adverse effects of the drug.137 144 Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve;137 144 emergence of zanamivir-resistant influenza virus may decrease effectiveness of the drug.1
CDC issues recommendations concerning use of antivirals for prophylaxis of influenza, and these recommendations are updated as needed during each influenza season.137 144 Information regarding influenza surveillance and updated recommendations for prevention of seasonal influenza are available from CDC at [Web].
Avian Influenza A Virus Infections
Treatment or prevention of infections caused by susceptible avian influenza A viruses†.50 94 104
CDC and WHO state that oseltamivir is drug of choice for treatment or prophylaxis of infections caused by highly pathogenic avian influenza A (H5N1);50 68 94 104 zanamivir is an alternative.50 94
Oseltamivir also is drug of choice for treatment of infections caused by avian influenza A (H7N9), especially in hospitalized patients and patients with severe or complicated illness.50 Because of limited data, zanamivir not recommended for treatment of severe avian influenza A (H7N9) infections, but may be considered in uncomplicated infections.50 Either oseltamivir or zanamivir can be used for prophylaxis in close contacts of patients with confirmed or probable avian influenza A (H7N9) infection.50
Consider use of investigational IV zanamivir† for hospitalized patients with severe influenza A (H7N9) infection who cannot tolerate or absorb oral oseltamivir (e.g., because of suspected or known gastric stasis, malabsorption, GI bleeding) or have infections caused by oseltamivir-resistant strains.50 (See Administration under Dosage and Administration.)
Pandemic Influenza
Treatment or prevention of pandemic influenza† caused by susceptible strains of influenza virus.52 151
Influenza viruses can cause pandemics, during which rates of illness and death from influenza-related complications can increase dramatically worldwide.52 104 488
Most recent influenza pandemic occurred during 2009 and was related to a novel influenza A (H1N1) strain, influenza A (H1N1)pdm09.52 100 134 144 151 488 In the US, the pandemic was characterized by a substantial increase in influenza activity that peaked in late October and early November 2009 and returned to seasonal baseline levels by January 2010.123 488 During that time, >99% of influenza viruses circulating in the US were influenza A (H1N1)pdm09.123 488 In August 2010, the WHO declared that the world was in a post-pandemic period;148 since that time, influenza A (H1N1)pdm09 has become a seasonal influenza virus and continues to circulate with other seasonal viruses.144 551 553
The spread of the highly pathogenic H5N1 strain of avian influenza A in poultry in Asia and other countries that was first identified in 2003 represents a potential future pandemic threat.28 50 54 55 56 104 147
Zanamivir Dosage and Administration
Administration
Administer commercially available powder for inhalation only by oral inhalation using the inhaler (Diskhaler) provided by the manufacturer.1
Zanamivir has been administered IV†;158 159 160 161 a parenteral dosage form not commercially available in the US.161 An investigational aqueous solution for IV administration may be available for use in hospitalized patients with severe or complicated influenza (see Treatment of Seasonal Influenza A and B Virus Infections under Uses).161 Contact manufacturer's clinical support help desk by email (gskclinicalsupportHD@gsk.com) or phone (877-626-8019 or 866-341-9160) to determine patient's eligibility for enrollment in an ongoing clinical trial of IV zanamivir or to request use of IV zanamivir under an EIND protocol.161
Do not use the powder for oral inhalation to prepare an extemporaneous solution;1 141 do not administer using a nebulizer or mechanical ventilator.1 141 (See Administration Precautions under Cautions.)
Oral Inhalation
Zanamivir powder for inhalation is commercially available in a disk containing 4 foil blisters of the drug (Rotadisk) and is provided with an inhaler (Diskhaler) that is used to deliver the drug to the respiratory tract.1
Do not remove zanamivir powder for inhalation from its foil blister packaging.141
Consult the manufacturer's instructions for information on how to load the Rotadisk onto the drug delivery system (Diskhaler) and how to use the Diskhaler to administer the drug.1
Patients should be instructed in the safe and effective use of the Diskhaler;1 instructions should include a demonstration whenever possible.1
Patients scheduled to use an inhaled bronchodilator at the same time as zanamivir should use the bronchodilator first.1
Dosage
Pediatric Patients
Treatment of Seasonal Influenza A and B Virus Infections
Oral Inhalation
Adolescents and children ≥7 years of age: 2 inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) twice daily (approximately 12 hours apart) for 5 days.1
Whenever possible, first day of treatment should include 2 doses provided there is at least 2 hours between doses; on subsequent days, doses should be given about 12 hours apart (morning and evening) at approximately the same time each day.1
Initiate treatment within 2 days after onset of symptoms.1 Although efficacy not established,1 there is some evidence that antiviral treatment initiated up to 96 hours after onset of symptoms may still be beneficial in hospitalized patients and those with severe, complicated, or progressive influenza.112 116 137 144 Although usual duration of antiviral treatment is 5 days, patients hospitalized with severe infections (e.g., those with prolonged infection or admitted into an intensive care unit) or immunosuppressed individuals may require >5 days of treatment.137 144
Prevention of Seasonal Influenza A and B Virus Infections
Household Setting
Oral InhalationAdolescents and children ≥5 years of age: 2 inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) once daily for 10 days.1
Administer at approximately same time each day.1 Efficacy in household settings not established if zanamivir prophylaxis initiated >1.5 days after onset of symptoms in index case.1
Community Outbreak
Oral InhalationAdolescents: 2 inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) once daily for 28 days.1 Administer at approximately the same time each day.1
Efficacy in community outbreaks not established if zanamivir prophylaxis initiated >5 days after the outbreak is identified in the community.1 Safety and efficacy of prophylaxis given for >28 days not evaluated.1
Avian Influenza A Virus Infections†
Treatment of Uncomplicated Avian Influenza A Virus Infections†
Oral InhalationSome experts recommend the twice-daily regimen usually recommended for treatment of seasonal influenza A and B virus infections.94 (See Treatment of Seasonal Influenza A and B Virus Infections under Dosage and Administration.)
Not recommended for treatment of severe infections.50 (See Avian Influenza A Virus Infections under Uses.)
Prophylaxis of Avian Influenza A Virus Infections†
Oral InhalationProphylaxis of highly pathogenic avian influenza virus A (H5N1) infection in close contacts†: CDC and WHO state that the once-daily dosage usually recommended for prophylaxis of seasonal influenza A and B virus infections can be used.50 94 (See Prevention of Seasonal Influenza A and B Virus Infections under Dosage and Administration.) Continue prophylaxis for 7–10 days after last known exposure.50 94
Prophylaxis of avian influenza virus A (H7N9) infection in close contacts†: CDC recommends that the twice-daily dosage usually recommended for treatment of seasonal influenza A and B virus infections be given for 5–10 days.50 (See Treatment of Seasonal Influenza A and B Virus Infections under Dosage and Administration.)
Adults
Treatment of Seasonal Influenza A and B Virus Infections
Oral Inhalation
2 inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) twice daily (approximately 12 hours apart) for 5 days.1
Whenever possible, first day of treatment should include 2 doses provided there is at least 2 hours between doses; on subsequent days, doses should be given about 12 hours apart (morning and evening) at approximately the same time each day.1
Initiate zanamivir treatment within 2 days after onset of symptoms.1 Although efficacy not established,1 there is some evidence that antiviral treatment initiated up to 96 hours after onset of symptoms may still be beneficial in hospitalized patients and those with severe, complicated, or progressive influenza.112 116 137 144 Although usual duration of antiviral treatment is 5 days, patients hospitalized with severe infections (e.g., those with prolonged infection or admitted into an intensive care unit) or immunosuppressed individuals may require >5 days of treatment.137 144
Prevention of Seasonal Influenza A and B Virus Infections
Household Setting
Oral Inhalation2 inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) once daily for 10 days.1 Administer at approximately same time each day.1
Efficacy in household settings not established if zanamivir prophylaxis initiated >1.5 days after onset of symptoms in index case.1
Community Outbreak
Oral Inhalation2 inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) once daily for 28 days.1 Administer at approximately same time each day.1
Efficacy in community outbreaks not established if zanamivir prophylaxis initiated >5 days after the outbreak is identified in the community.1 Safety and efficacy of prophylaxis given for >28 days not evaluated.1
Outbreaks in Long-term Care Facilities or Hospitals
Oral Inhalation2 inhalations (one 5-mg blister per inhalation for a total dose of 10 mg) once daily.137 CDC recommends antiviral prophylaxis be continued for minimum of 2 weeks and up to 7 days after last known case of influenza is identified.137
Avian Influenza A Virus Infections†
Treatment of Uncomplicated Avian Influenza A Virus Infections†
Oral InhalationSome experts recommend the twice-daily regimen usually recommended for treatment of seasonal influenza A and B virus infections.94 (See Treatment of Seasonal Influenza A and B Virus Infections under Dosage and Administration.)
Not recommended for treatment of severe infections.50 (See Avian Influenza A Virus Infections under Uses.)
Prophylaxis of Avian Influenza A Virus Infections†
Oral InhalationProphylaxis of highly pathogenic avian influenza virus A (H5N1) infection in close contacts†: CDC and WHO state that the once-daily dosage usually recommended for prophylaxis of seasonal influenza A and B virus infections can be used.50 94 (See Prevention of Seasonal Influenza A and B Virus Infections under Dosage and Administration.) Continue prophylaxis for 7–10 days after last known exposure.50 94
Prophylaxis of avian influenza virus A (H7N9) infection in close contacts†: CDC recommends that the twice-daily dosage usually recommended for treatment of seasonal influenza A and B virus infections be given for 5–10 days.50 (See Treatment of Seasonal Influenza A and B Virus Infections under Dosage and Administration.)
Special Populations
Renal Impairment
Dosage adjustment not needed;1 consider potential for drug accumulation.1 (See Renal Impairment under Cautions.)
Cautions for Zanamivir
Contraindications
-
History of hypersensitivity reaction to zanamivir or any ingredient in the formulation (e.g., milk protein contained in the lactose vehicle).1
Warnings/Precautions
Respiratory Effects
Serious bronchospasm, including fatalities, reported when used in patients with or without underlying airways disease.1 (See Individuals with Asthma or COPD under Cautions.) Many such cases were reported during postmarketing surveillance and causality to the drug difficult to assess.1
Some patients without prior respiratory disease also may have respiratory abnormalities from acute respiratory infection that could resemble adverse drug reactions or increase vulnerability to adverse drug reactions.1
Discontinue use if bronchospasm develops or respiratory function declines;1 immediate treatment and hospitalization may be required.1
Individuals with Asthma or COPD
Not recommended for treatment or prophylaxis of influenza in individuals with underlying airways disease (e.g., asthma, COPD) because of risk of serious bronchospasm.1
When tested in patients with mild or moderate asthma (but without acute influenza-like illness), bronchospasm documented in 1/13 patients.1 When used in patients with acute influenza-like illness superimposed on underlying asthma or COPD, a >20% decline in FEV1 occurred in more patients receiving the drug than in those receiving placebo.1
The benefits and risks should be considered carefully if use of zanamivir is considered in patients with underlying airways disease.1 If a decision is made to use the drug in such patients, monitor respiratory function carefully and have appropriate supportive care available, including short-acting β-adrenergic bronchodilators.1
Sensitivity Reactions
Hypersensitivity Reactions
Allergic-like reactions (e.g., oropharyngeal edema, serious skin rash, anaphylaxis) reported.1
Discontinue immediately and initiate appropriate treatment if an allergic reaction occurs or is suspected.1
Neuropsychiatric and CNS Effects
Postmarketing reports of delirium and abnormal behavior leading to self-injury reported mainly in Japanese children receiving neuraminidase inhibitors, including zanamivir.1 Role of zanamivir not determined.1
Influenza itself can be associated with a variety of neurologic and behavioral symptoms (e.g., seizures, hallucinations, delirium, abnormal behavior) and fatalities can occur.1 Although such events may occur in the setting of encephalitis or encephalopathy, they can occur without obvious severe disease.1
Closely monitor patients with influenza for signs of abnormal behavior.1 If neuropsychiatric symptoms develop, consider risks versus benefits of continued therapy.1
Postmarketing reports of vasovagal-like episodes shortly after oral inhalation of zanamivir.1
Concomitant Illness
Safety and efficacy for treatment or prophylaxis of influenza not established in patients with high-risk underlying medical conditions.1 (See Individuals with Asthma or COPD under Cautions.)
No data available regarding use in patients with severe or unstable medical conditions that may require inpatient care.1
Differential Diagnosis
When making treatment decisions in patients with suspected influenza, consider the possibility of primary or concomitant bacterial infection for which zanamivir would be ineffective.1
Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications of influenza.1 No evidence that zanamivir prevents such complications.1
No evidence of efficacy in illness caused by any organisms other than influenza A or B.1
Administration Precautions
Administer zanamivir powder for inhalation using only the inhaler (Diskhaler) provided by the manufacturer.1 141 Do not remove the powder from its foil blister packaging (Rotadisk).141
Mustnot be made into an extemporaneous solution for administration by nebulization or mechanical ventilation.1 Do not attempt to reconstitute or solubilize the powder in liquid;141 do not attempt to administer in a nebulizer or mechanical ventilator.141
Safety and efficacy not established for administration by nebulization or mechanical ventilation.141 Lactose in the formulation may obstruct or interfere with proper functioning of mechanical ventilator equipment.140 141 There have been reports of hospitalized patients with influenza who received extemporaneous solutions made with the powder and administered by nebulization or mechanical ventilation; at least 1 death reported when lactose in the formulation apparently obstructed proper functioning of the equipment.1 140 141
Instruct patients in the safe and effective use of the drug delivery system (Diskhaler) provided by the manufacturer.1 Instructions on use of the inhaler should include a demonstration whenever possible.1
Some geriatric patients may need assistance with the inhaler.1
Children should be under adult supervision with close attention to use of the inhaler.1 (See Pediatric Use under Cautions.)
Prior Use
No data available regarding safety and efficacy of repeated courses of zanamivir for treatment of influenza.1
Influenza Vaccination
Not a substitute for annual vaccination with a seasonal influenza vaccine (influenza virus vaccine inactivated, influenza vaccine recombinant, influenza vaccine live intranasal).1 144
Although antivirals used for treatment or prevention of influenza, including zanamivir, may be used concomitantly with or at any time before or after influenza virus vaccine inactivated,1 100 these antivirals may inhibit the vaccine virus contained in influenza vaccine live intranasal.1 100 (See Specific Drugs.)
Specific Populations
Pregnancy
Category C.1
Pregnant women are at increased risk for severe complications and death from influenza.142 144
CDC and ACIP state that pregnancy is not a contraindication to use of zanamivir for treatment or prevention of influenza; zanamivir regimens recommended in pregnant women are the same as those for other adults.142 144
CDC and ACIP state that oseltamivir may be preferred when a neuraminidase inhibitor indicated for treatment of influenza in women who are pregnant or up to 2 weeks postpartum,142 144 but the drug of choice for prophylaxis of influenza is less clear.142 Zanamivir may be preferred by some clinicians for prophylaxis in pregnant women because of its limited systemic absorption; however, consider respiratory complications that may be associated with zanamivir because of its route of administration, especially in women at risk for respiratory problems.142 144
Lactation
Use with caution.1
Distributed into milk in rats; not known whether distributed into human milk.1
Pediatric Use
Safety and efficacy for treatment of influenza not established in children <7 years of age.1 14
Safety and efficacy for prophylaxis of influenza not established in children <5 years of age.1
Safety and efficacy in adolescents and children ≥7 years of age for treatment of influenza and safety and efficacy in adolescents and children ≥5 years of age for prophylaxis of influenza similar to adults.1
Some young children may have suboptimal inspiratory flow rates through the drug delivery system (Diskhaler).1 When considering use of zanamivir in pediatric patients, clinicians should carefully evaluate the ability of the child to use the inhaler.1
Children should receive zanamivir only under adult supervision and with close attention to proper use of the inhaler.1 The supervising adult should be instructed on proper use of the inhaler.1
Geriatric Use
Safety and efficacy for treatment of influenza in those ≥65 years of age similar to younger adults.1
Safety and efficacy for prophylaxis of influenza in those ≥65 years of age in household or community settings similar to younger adults.1 Efficacy not established for prophylaxis in geriatric individuals in nursing home settings.1
Possibility exists of greater sensitivity to the drug in some older individuals.1
Some geriatric patients may need assistance with the drug delivery system (Diskhaler).1
Hepatic Impairment
Pharmacokinetics not studied in patients with hepatic impairment.1
Renal Impairment
Safety and efficacy not documented in patients with severe renal impairment.1 Although systemic exposure is limited after oral inhalation, consider potential for drug accumulation.1
Common Adverse Effects
Diarrhea, nausea, vomiting, headache, dizziness, nasal signs and symptoms, bronchitis, sinusitis, cough, and ear, nose, and throat infections.1 Some adverse effects may be related to lactose vehicle (contains milk protein) used in the powder for oral inhalation.1
Interactions for Zanamivir
Zanamivir not metabolized by and does not affect CYP enzymes, including CYP1A1, 1A2, 2A6, 2C9, 2C18, 2D6, 2E1, or 3A4.1 Drug interactions with drugs that are substrates or inhibitors of these enzymes unlikely.1
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Influenza virus vaccines |
Influenza virus vaccine inactivated: Zanamivir does not interfere with the antibody response to the vaccine1 10 144 Influenza vaccine live intranasal: Zanamivir may inhibit the vaccine virus;1 100 105 no specific studies1 100 |
Influenza virus vaccine inactivated: May be administered concomitantly with or at any time before or after zanamivir1 100 Influenza vaccine live intranasal: Do not administer the live vaccine until ≥48 hours after zanamivir is discontinued; do not administer zanamivir until ≥2 weeks after administration of the vaccine, unless medically indicated;1 100 105 if zanamivir given within 2 weeks after the vaccine, repeat vaccine dose ≥48 hours after last antiviral dose;100 alternatively, if zanamivir given 2 days before to 14 days after the vaccine, revaccinate using the parenteral inactivated vaccine or parenteral recombinant vaccine100 |
Zanamivir Pharmacokinetics
Absorption
Bioavailability
Following oral inhalation of zanamivir, approximately 4–17% of the inhaled dose is absorbed systemically.1
Absolute bioavailability averages 2% following oral inhalation;3 peak serum concentrations attained within 1–2 hours.1 3
Special Populations
In pediatric patients <12 years of age with signs and symptoms of respiratory illness, zanamivir serum concentrations may be low or undetectable following oral inhalation because of inadequate or absent inspiratory flow rates.1 (See Pediatric Use under Cautions.)
Distribution
Extent
Delivered to epithelial lining of the respiratory tract following oral inhalation.22 Amount of drug in respiratory tract depends on patient factors such as inspiratory flow rate.1 May be present in sputum and nasal washings for at least 12 hours after a dose.22
Crosses the placenta in animals.1
Distributed into milk in animals;1 not known whether distributed into human milk.1
Plasma Protein Binding
<10% bound to plasma proteins.1
Elimination
Metabolism
Not metabolized.1
Not a substrate for and does not affect CYP isoenzymes.1
Elimination Route
Following oral inhalation, absorbed drug is excreted unchanged in urine within 24 hours;1 unabsorbed drug excreted in feces.1
Half-life
Serum half-life following oral inhalation is 2.5–5.1 hours.1 23
Special Populations
Half-life prolonged in those with renal impairment;1 studies using IV zanamivir indicate half-life is 4.7 hours if mild to moderate impairment and 18.5 hours if severe impairment.1
Stability
Storage
Oral Inhalation
Powder for Inhalation
25°C (may be exposed to 15–30°C).1
Actions and Spectrum
-
Zanamivir is a potent selective competitive inhibitor of influenza virus neuraminidase, an enzyme essential for viral replication; possibly alters virus particle aggregation and release.1 2 3 4 5 6
-
Active against influenza A and B viruses, including amantadine- and rimantadine-resistant isolates.1 2 3 4 5 6 Almost all seasonal influenza A (H3N2), influenza A (H1N1)pdm09, and influenza B viruses circulating during recent influenza seasons have been susceptible to zanamivir.551 552
-
Active in vitro against some avian influenza A viruses, including influenza A H5N1, H6N1, H7N7, H7N9, and H9N2.24 30 31 50 555
-
Active against some influenza strains, including some influenza A (H1N1)pdm09 strains, resistant to oseltamivir.52 113 124 144 153 162 551 552
-
Influenza viruses with reduced susceptibility to zanamivir have been produced in vitro.1 7 10 Risk of emergence of resistant isolates with clinical use not quantified;1 seasonal influenza A (H1N1) and seasonal influenza A (H3N2) resistant to zanamivir reported rarely.153 551
-
Influenza strains cross-resistant to zanamivir and oseltamivir have been generated in cell culture;1 21 only limited data available regarding possible emergence of clinical isolates with cross-resistance to both drugs.1 21 To date, influenza A (H1N1)pdm09 isolates with the H275Y mutation144 and avian influenza A (H5N1) with the H274Y mutation94 that are resistant to oseltamivir have been susceptible to zanamivir in vitro.94 144
Advice to Patients
-
Importance of understanding proper inhalation technique and use of the drug delivery system (Diskhaler);1 importance of reading patient instructions for use.1
-
Importance of initiating zanamivir treatment as soon as possible after appearance of influenza symptoms (within 2 days after symptom onset);1 11 efficacy not established if treatment begins after 48 hours of symptoms.1
-
Advise patients that zanamivir treatment does not reduce the risk of transmission of influenza virus to others.1
-
Advise patients of the possible risk of bronchospasm, especially in those with underlying respiratory disease; importance of patients with asthma or COPD having a short-acting inhaled β-adrenergic bronchodilator readily available.1
-
Advise patients using an inhaled bronchodilator at the same time as zanamivir of the importance of using the bronchodilator first.1
-
Importance of discontinuing zanamivir and promptly contacting clinician if there is an increase in respiratory symptoms (e.g., wheezing, dyspnea, signs or symptoms of bronchospasm) or if symptoms of an allergic reaction occur.1
-
Importance of immediately contacting a clinician if patient demonstrates signs of unusual behavior.1 Influenza patients, particularly children and adolescents, may be at increased risk of seizures, confusion, or abnormal behavior early in their illness and should be closely observed for signs of unusual behavior.1 Such events are uncommon, but may occur after starting zanamivir treatment or when influenza is not treated and can result in accidental injury to the patient.1
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
-
Importance of advising patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral Inhalation |
Powder for inhalation (contained in Rotadisk foil pack) |
5 mg per inhalation |
Relenza (with Diskhaler) |
GlaxoSmithKline |
AHFS DI Essentials™. © Copyright 2021, Selected Revisions April 29, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
1. GlaxoSmithKline. Relenza (zanamivir) inhalation powder for oral inhalation prescribing information. Research Triangle Park, NC; 2013 Oct.
2. Monto AS, Robinson DP, Herlocher ML et al. Zanamivir in the prevention of influenza among healthy adults: a randomized controlled trial. JAMA. 1999; 282:31-5. http://www.ncbi.nlm.nih.gov/pubmed/10404908?dopt=AbstractPlus
3. Hayden FG, Osterhaus ADME, Treanor JJ et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. N Engl J Med. 1997; 337:874-80. http://www.ncbi.nlm.nih.gov/pubmed/9302301?dopt=AbstractPlus
4. The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections. Lancet. 1998; 352:1877-81. http://www.ncbi.nlm.nih.gov/pubmed/9863784?dopt=AbstractPlus
5. Calfee DP, Hayden FG. New approaches to influenza chemotherapy: neuraminidase inhibitors. Drugs. 1998; 56:537-53. http://www.ncbi.nlm.nih.gov/pubmed/9806102?dopt=AbstractPlus
6. Aoki FY, Hayden FG. Zanamivir: a potent and selective inhibitor of influenza A and B viruses. Clin Pharmacokinet. 1999; 36(Suppl 1):v-ix. http://www.ncbi.nlm.nih.gov/pubmed/10429834?dopt=AbstractPlus
7. Gubareva LV, Matrosivich MN, Brenner MK et al. Evidence for zanamivir resistance in an immunocompromised child infected with influenza B virus. J Infect Dis. 1998; 178:1257-62. http://www.ncbi.nlm.nih.gov/pubmed/9780244?dopt=AbstractPlus
10. Webster A, Boyce M, Edmundson S. Coadministration of orally inhaled zanamivir with inactivated trivalent influenza virus vaccine does not adversely affect the production of antihaemagglutinin antibodies in the serum of healthy volunteers. Clin Pharmacokinet. 1999; 36(Suppl 1):51-8. http://www.ncbi.nlm.nih.gov/pubmed/10429840?dopt=AbstractPlus
11. Glaxo Wellcome, Research Triangle Park, NC: Personal communication.
12. Shilling M, Povinelli L, Krause P et al. Efficacy of zanamivir for chemoprophylaxis of nursing home influenza outbreaks. Vaccine. 1998; 16:1771-4. http://www.ncbi.nlm.nih.gov/pubmed/9778755?dopt=AbstractPlus
14. Hedrick JA, Barzilai A, Behre U et al. Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: a randomized controlled trial. Pediatr Infect Dis J. 2000; 19:410-7. http://www.ncbi.nlm.nih.gov/pubmed/10819336?dopt=AbstractPlus
17. Hayden FG, Gubareva LV, Monto AS et al. Inhaled zanamivir for the prevention of influenza in families. N Engl J Med. 2000; 343:1282-9. http://www.ncbi.nlm.nih.gov/pubmed/11058672?dopt=AbstractPlus
18. Kaiser L, Henry D, Flack NP et al. Short-term treatment with zanamivir to prevent influenza: results of a placebo-controlled study. Clin Infect Dis. 2000; 30:587-9. http://www.ncbi.nlm.nih.gov/pubmed/10722450?dopt=AbstractPlus
19. Hedrick JA, Barzilai A, Behre U et al. Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: a randomized controlled trial. Pediatr Infect Dis J. 2000; 19:410-7. http://www.ncbi.nlm.nih.gov/pubmed/10819336?dopt=AbstractPlus
21. Genentech, Inc. Tamiflu (oseltamivir phosphate) capsules and for oral suspension prescribing information. South San Francisco, CA: 2013 Jan.
22. Peng AW, Milleri S, Stein DS. Direct measurement of the anti-influenza agent zanamivir in the respiratory tract following inhalation. Antimicrob Agents Chemother. 2000; 44:1974-6. http://www.ncbi.nlm.nih.gov/pubmed/10858364?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=89995&blobtype=pdf
23. Cass LM, Efthymiopoulos C, Bye A. Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers. Clin Pharmacokinet. 1999; 36(Suppl 1):1-11. http://www.ncbi.nlm.nih.gov/pubmed/10429835?dopt=AbstractPlus
24. Govorkova EA, Leneva IA, Goloubeva OG et al. Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. Antimicrob Agents Chemother. 2001;45:2723-32.
28. Hayden FG. Pandemic influenza: is an antiviral response realistic? Pediatr Infect Dis J. 2004; 23(Suppl):S262-9.
30. Koopmans M, Wilbrink B, Conyn M et al. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet. 2004; 363:587-93. http://www.ncbi.nlm.nih.gov/pubmed/14987882?dopt=AbstractPlus
31. Leneva IA, Goloubeva O, Fenton RJ et al. Efficacy of zanamivir against avian influenza A viruses that possess genes encoding H5N1 internal proteins and are pathogenic in mammals. Antimicrob Agents Chemother. 2001;45:1216-24.
32. Mai Le Q, Kiso M, Someya K et al. Isolation of drug-resistant H5N1 virus. Nature. 2005; 437.
34. Gubareva LV, Webster RG, Hayden FG. Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants. Antimicrob Agents Chemother. 2001; 45:3403-8. http://www.ncbi.nlm.nih.gov/pubmed/11709315?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=90844&blobtype=pdf
35. Yen H-L, Herlocher LM, Hoffman E et al. Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility. Antimicrob Agents Chemother. 2005: 49: 4075-84.
50. US Centers for Disease Control and Prevention. Information on avian influenza. From CDC website. Accessed 2014 Feb 4. http://www.cdc.gov/flu/avianflu/index.htm
52. World Health Organization. WHO guidelines for pharmacological management of pandemic influenza A (H1N1) 2009 and other influenza viruses. Revised February 2010. Part I. Recommendations. From WHO website. 2014 Feb 4. http://www.who.int/csr/resources/publications/swineflu/h1n1_guidelines_pharmaceutical_mngt.pdf
54. Longini IM Jr, Nizam A, Xu S et al. Containing pandemic influenza at the source. Sciencexpress. 2005 Aug 3.
55. Tsang KWT, Eng P, Liam CK et al. H5N1 influenza pandemic: contingency plans. Lancet. 2005; 366:533-4. Editorial. http://www.ncbi.nlm.nih.gov/pubmed/16099278?dopt=AbstractPlus
56. Ferguson NM, Cummings DAT, Cauchemez S et al. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. Published online at Nature.com on 3 August 2005. http://www.nature.com
68. Writing Committee of the World Health Organization (WHO) consultation on human influenza A/H5. Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005; 353:1374-85. http://www.ncbi.nlm.nih.gov/pubmed/16192482?dopt=AbstractPlus
94. World Health Organization. WHO rapid advice guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus. World Health Organization 2006. From WHO website. Accessed 2014 Feb 4. http://www.who.int/medicines/publications/WHO_PSM_PAR_2006.6.pdf
100. Influenza Division, National Center for Immunization and Respiratory Diseases, CDC. Prevention and control of seasonal influenza with vaccines. MMWR Recomm Rep. 2013; 62(RR-07):1-43.
104. World Health Organization. Avian influenza. From WHO website. Accessed 2014 Feb 4. http://www.who.int/topics/avian_influenza/en/
105. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
112. Committee on Infectious Disease. Recommendations for Prevention and Control of Influenza in Children, 2013–2014. Pediatrics. 2013; :.
113. Centers for Disease Control and Prevention (CDC). Update: influenza activity - United States, August 30, 2009-March 27, 2010, and composition of the 2010-11 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2010; 59:423-30. http://www.ncbi.nlm.nih.gov/pubmed/20395936?dopt=AbstractPlus
114. Centers for Disease Control and Prevention. Update: Swine influenza A (H1N1) infections–California and Texas, April 2009. MMWR Morb Mortal Wkly Rep. 2009; 58:435-7.
116. Harper SA, Bradley JS, Englund JA et al. Seasonal influenza in adults and children--diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2009; 48:1003-32. http://www.ncbi.nlm.nih.gov/pubmed/19281331?dopt=AbstractPlus
118. Centers for Disease Control and Prevention. Swine-origin influenza A (H1N1) virus infection in a school–New York City, April 2009. MMWR Morb Mortal Wkly Rep. 2009; 58 (Dispatch):1-3. http://www.ncbi.nlm.nih.gov/pubmed/19145219?dopt=AbstractPlus
119. Centers for Disease Control and Prevention. Outbreak of swine-origin influenza A (H1N1) virus infection–Mexico, March-April 2009. MMWR Morb Mortal Wkly Rep. 2009; 58 (Dispatch):1-3. http://www.ncbi.nlm.nih.gov/pubmed/19145219?dopt=AbstractPlus
123. Centers for Disease Control and Prevention (CDC). Update: influenza activity - United States, August 30, 2009-March 27, 2010, and composition of the 2010-11 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2010; 59:423-30. http://www.ncbi.nlm.nih.gov/pubmed/20395936?dopt=AbstractPlus
124. Centers for Disease Control and Prevention. Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. MMWR Morb Mortal Wkly Rep. 2009; 58:433-4. http://www.ncbi.nlm.nih.gov/pubmed/19407738?dopt=AbstractPlus
132. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Eng J Med. 2009; 361.
134. Centers for Disease Control and Prevention. The 2009 H1N1 pandemic: summary highlights, April 2009–April 2010. From CDC website. Accessed 28 Oct 2010. http://www.cdc.gov/h1n1flu/cdcresponse.htm
135. World Health Organization. WHO pandemic phase descriptions and main actions by phase. From WHO website. Accessed 28 Oct 2010. http://www.who.int/csr/disease/influenza/pandemic_phase_descriptions_and_actions.pdf
137. Centers for Disease Control and Prevention. Influenza antiviral medications: summary for clinicians. From CDC website. Accessed 2014 Feb 10. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
140. Kiatboonsri S, Kiatboonsri C, Theerawit P. Fatal respiratory events caused by zanamivir nebulization. Clin Infect Dis. 2010; 50:620. http://www.ncbi.nlm.nih.gov/pubmed/20095840?dopt=AbstractPlus
141. Ng-Cashin J. Dear healthcare provider letter: Relenza (zanamivir) inhalation powder must not be nebulized. Philadelphia, PA: GlaxoSmithKline; 2009 Oct 8.
142. Centers for Disease Control and Prevention. Recommendations for obstetric health care providers related to use of antiviral medications in the treatment and prevention of influenza. From CDC website. Accessed 2014 Jan 28. http://www.cdc.gov/flu/professionals/antivirals/avrec_ob.htm
144. Fiore AE, Fry A, Shay D et al. Antiviral agents for the treatment and chemoprophylaxis of influenza --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011; 60:1-24. http://www.ncbi.nlm.nih.gov/pubmed/21248682?dopt=AbstractPlus
147. . Summary of human infection with highly pathogenic avian influenza A (H5N1) virus reported to WHO, January 2003-March 2009: cluster-associated cases. Wkly Epidemiol Rec. 2010; 85:13-20. http://www.ncbi.nlm.nih.gov/pubmed/20095108?dopt=AbstractPlus
148. World Health Organization. Global alert and response (GAR). WHO recommendations for the post-pandemic period. From WHO website. Accessed Sep 29, 2010. http://www.who.int/csr/disease/swineflu/notes/briefing_20100810/en/index.html
151. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza, Bautista E, Chotpitayasunondh T et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med. 2010; 362:1708-19. http://www.ncbi.nlm.nih.gov/pubmed/20445182?dopt=AbstractPlus
153. Ujike M, Shimabukuro K, Mochizuki K et al. Oseltamivir-resistant influenza viruses A (H1N1) during 2007-2009 influenza seasons, Japan. Emerg Infect Dis. 2010; 16:926-35. http://www.ncbi.nlm.nih.gov/pubmed/20507742?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3086245&blobtype=pdf
158. Dulek DE, Williams JV, Creech CB et al. Use of intravenous zanamivir after development of oseltamivir resistance in a critically Ill immunosuppressed child infected with 2009 pandemic influenza A (H1N1) virus. Clin Infect Dis. 2010; 50:1493-6. http://www.ncbi.nlm.nih.gov/pubmed/20415572?dopt=AbstractPlus
159. Gaur AH, Bagga B, Barman S et al. Intravenous zanamivir for oseltamivir-resistant 2009 H1N1 influenza. N Engl J Med. 2010; 362:88-9. http://www.ncbi.nlm.nih.gov/pubmed/20032317?dopt=AbstractPlus
160. Härter G, Zimmermann O, Maier L et al. Intravenous zanamivir for patients with pneumonitis due to pandemic (H1N1) 2009 influenza virus. Clin Infect Dis. 2010; 50:1249-51. http://www.ncbi.nlm.nih.gov/pubmed/20367227?dopt=AbstractPlus
161. Centers for Disease Control and Prevention. Intravenous influenza antiviral medications and CDC considerations related to investigational use of intravenous zanamivir for 2013–2014 influenza season. From CDC website. Accessed 2014 Feb 3. http://www.cdc.gov/flu/professionals/antivirals/intravenous-antivirals.htm
162. . Recommended viruses for influenza vaccines for use in the 2010-2011 northern hemisphere influenza season. Wkly Epidemiol Rec. 2010; 85:81-92. http://www.ncbi.nlm.nih.gov/pubmed/20210260?dopt=AbstractPlus
488. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 12th ed. Washington DC: Public Health Foundation; 2012 May. Updates may be available at CDC website. http://www.cdc.gov/vaccines/pubs/pinkbook/flu.html
551. Centers for Disease Control and Prevention (CDC). Influenza activity--United States, 2012-13 season and composition of the 2013-14 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2013; 62:473-9. http://www.ncbi.nlm.nih.gov/pubmed/23760189?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4604847&blobtype=pdf
552. . Recommended composition of influenza virus vaccines for use in the 2013–2014 northern hemisphere influenza season. Wkly Epidemiol Rec. 2013; 88:101-14. http://www.ncbi.nlm.nih.gov/pubmed/23544236?dopt=AbstractPlus
553. World Health Organization (WHO). Standardization of terminology of the pandemic A(H1N1)2009 virus. October 2011. From WHO website. Accessed 2013 Jul. http://www.who.int/influenza/gisrs_laboratory/terminology_ah1n1pdm09/en/
555. Centers for Disease Control and Prevention (CDC). Emergence of avian influenza A(H7N9) virus causing severe human illness - China, February-April 2013. MMWR Morb Mortal Wkly Rep. 2013; 62:366-71. http://www.ncbi.nlm.nih.gov/pubmed/23657113?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4605021&blobtype=pdf
More about zanamivir
- Side Effects
- During Pregnancy or Breastfeeding
- Dosage Information
- Drug Interactions
- En Español
- 4 Reviews
- Drug class: inhaled anti-infectives
Consumer resources
Professional resources
- Other brands
- Relenza