Zanamivir (Inhalation–Systemic)
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VA CLASSIFICATION
Primary: AM809
Commonly used brand name(s): Relenza.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Antiviral (systemic).—
Indications
Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.
Accepted
Influenza A (treatment)—Zanamivir is indicated for the treatment of uncomplicated acute illness due to influenza A virus in adults and children 7 years and older1 who have been symptomatic for no more than 2 days. Zanamivir must be started within 48 hours after the onset of influenza symptoms {01}{02}{03}.
Influenza B (treatment)—Zanamivir is indicated for the treatment of uncomplicated acute illness due to influenza B virus in adults and children 7 years and older1 who have been symptomatic for no more than 2 days. Zanamivir must be started within 48 hours after the onset of influenza symptoms{01}{02}{03}.
Note: Zanamivir showed no difference in efficacy in the treatment of patients with influenza A compared with those with influenza B; however, the trials included small numbers of patients with influenza B. Therefore, less evidence exists to support the efficacy in influenza B.{01}
Safety and efficacy data in patients who initiate zanamivir after 48 hours of symptom onset have not been determined.
Safety and efficacy in patients with underlying chronic medical conditions, including respiratory and cardiovascular disease, have not been demonstrated {01}.
[Influenza A (prophylaxis) and]1
[Influenza B (prophylaxis)]1—Zanamivir is indicated for the prophylaxis of influenza A and B.{06}{07}{08}{09}{10}{11}{12} Although not a substitute for influenza virus vaccine, use of zanamivir may be considered if the vaccine is not available, in conjunction with the vaccine late in the influenza season, before the vaccine has induced an immune response, or if there is no immune response to the vaccine.{06}{07}
1 Not included in Canadian product labeling.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
Molecular weight 332.3{01}
Mechanism of action/Effect:
Zanamivir is a selective inhibitor of influenza A and B virus neuraminidase, possibly altering particle aggregation and release {01}.
Absorption:
Orally inhaled zanamivir is systemically absorbed, approximately 4% to 17%.{01}
Protein binding:
Very low (<10%). {01}
Biotransformation:
Not metabolized .{01}
Half-life:
Elimination—2.5 to 5.1 hours. {01}
Time to peak concentration:
1 to 2 hours following a 10-mg dose.{01}
Peak serum concentration:
17 to 142 nanograms/milliliter following a 10-mg dose.{01}
Time to peak effect:
72 hours. {02}
Elimination:
Renal—Excreted unchanged in the urine with excretion of a single dose completed within 24 hours. Total clearance ranges from 2.5 to 10.9 L per hour.{01}
Fecal—Unabsorbed drug is excreted in the feces.{01}
Precautions to Consider
Carcinogenicity
No carcinogenic effects were seen when zanamivir was evaluated in animals given doses up to 25 times the human dose {01}.
Tumorigenicity
An increase in lymphoma incidence over controls was seen in male rats given a high dose (30 to 50 mg per kg per day); there was no dose relationship.{03}
Mutagenicity
No mutagenic effects were seen when zanamivir was evaluated in several mutagenicity assays. {01}
Pregnancy/Reproduction
Fertility—
No impairment of fertility or mating in male or female rats and no effect on the male sperm were demonstrated{01}.
Pregnancy—
Adequate and well-controlled studies in humans have not been done No malformations, maternal toxicity, or embryotoxicity were observed in pregnant rats or rabbits and their fetuses. Zanamivir readily crosses the placenta in rats and rabbits. Fetal blood concentrations of zanamivir in rats and rabbits were significantly lower than zanamivir concentrations in the maternal blood. {01}
U.S. FDA Pregnancy Category B {01}
Breast-feeding
Zanamivir is distributed in the breast milk of rats. It is unknown if zanamivir is distributed in human breast milk. {01}
Pediatrics
Safety and efficacy have not been established in pediatric patients under 7 years of age {01}.
Note: The Canadian manufacturer states that safety and efficacy have not been established in pediatric patients under 12 years of age {03}
Adolescents
Appropriate studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of zanamivir in children older than 12 years of age. {01}
Geriatrics
Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of zanamivir in the elderly.{01}
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
The medication should not be used when the following medical problem exists:
» Hypersensitivity to zanamivir or any component of the formulation{01}
Risk-benefit should be considered when the following medical problems exist
» Respiratory disease, chronic, such as asthma or chronic obstructive pulmonary disease{01}{13} (zanamivir may cause bronchospasm or a decrease in lung function)
Cardiovascular disease (efficacy not established)
Note: Safety and efficacy of zanamivir are not established in patients with high-risk underlying medical conditions.
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for immediate medical attention
Incidence rare
Bronchospasm (wheezing)— mainly exhibited in patients with asthma or chronic obstructive pulmonary disease
Note: An increased susceptibility to bronchospasm and/or a decline in lung function has been reported in patients with chronic obstructive lung disease (COPD) and asthma. Zanamivir should be stopped if a decrease in lung function or bronchospasm is experienced. A fast-acting bronchodilator should be available when zanamivir is administered in patients with respiratory disease. {01}
Incidence not determined
—Observed during clinical practice; estimates of frequency can not be determined
Allergic or allergic type reactions, including oropharyngeal edema ( itching, pain, redness, swelling or watering of eye or eyelid; troubled breathing or wheezing; severe skin rash or hives; flushing; increased sensitivity to sunlight; joint pain; swollen glands or tightness in throat ){04}{05}
Arrythmias ( dizziness; fainting or fast, slow, or irregular heartbeat){04}{05}
Bronchospasm ( difficulty breathing; shortness of breath; tightness in chest or wheezing ){04}{05}
facial edema (swelling or puffiness of face){04}{05}
seizures ( convulsions){04}{05}
Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
Bronchitis {03}(cough producing mucus ; difficulty breathing; shortness of breath ; tightness in chest ; wheezing)
cough {03}
diarrhea {03}
dizziness
ear, nose and throat infections {03}(change in hearing; earache; pain in ear; ear drainage)
headache
nausea {03}
nasal signs and symptoms {03}
sinusitis (pain and pressure over the cheeks)
vomiting {03}
Incidence not determined
—Observed during clinical practice; estimates of frequency can not be determined
Dyspnea ( shortness of breath; difficult or labored breathing; tightness in chest or wheezing){04}{05}
rash (red, scaly, swollen, or peeling areas of skin)— including severe cutaneous reactions{04}{05}
syncope ( fainting or lightheadedness when getting up from a lying or sitting position; unusually fast heartbeat or palpitations){04}{05}
Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).
There is a lack of data on overdose of zanamivir. Adverse effects are similar between patients administered recommended doses and patients administered doses of up to 1200 milligrams per day intravenously for 5 days {01}.
There is no known specific antidote to zanamivir. Treatment is generally symptomatic and supportive.
Patients in whom an intentional overdose is confirmed or suspected should be referred for psychiatric consultation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Zanamivir (Inhalation-Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Use in children—Not recommended in pediatric patients under 7 years of age
Note: Canadian manufacturer states use is not recommended in patients under 12 years of age.
Other medical problems, especially chronic pulmonary disease such as chronic obstructive lung disease and asthma; and hypersensitivity
Proper use of this medication
» Reading patient package insert carefully
Proper administration technique for inhaler:
» Compliance with full 5-day course of therapy
Starting therapy within 2 days after the onset of signs and symptoms of influenza (weakness, headache, fever, cough, and sore throat)
» Proper dosing
Using as soon as possible; not using if almost time for the next dose; not doubling doses
Proper storage
Precautions while using this medication
The use of zanamivir has not been shown to reduce the risk of transmission of influenza to others
Fast-acting inhaled bronchodilator should be available for patients with asthma or chronic obstructive pulmonary disease
Administer inhaled bronchodilators before zanamivir for patients who take scheduled inhaled bronchodilators
Side/adverse effects
» Signs of potential side effects, especially Allergic reaction, arrythmias, bronchospasm, dyspnea, facial swelling, oropharyngeal edema, seizures
General Dosing Information
Zanamivir must be started within 2 days after the onset of signs and symptoms of influenza (weakness, headache, fever, cough, and sore throat).
Patients should be instructed on the use of the delivery system. Instructions should include a demonstration whenever possible.{01}
If zanamivir is prescribed for children, it should be used only under adult supervision and instruction, and the supervising adult should first be instructed by a healthcare professional {01}.
Patients with underlying respiratory disease should be instructed to have a fast acting inhalation bronchodilator available when treated with zanamivir. Patients scheduled to take bronchodilator at the same time as zanamivir should be advised to use their bronchodilator before using zanamivir.
Serious bacterial infections may begin with influenza-like symptoms, may co-exist with, or occur as complications during the course of this illness. Zanamivir has not been shown to prevent these complications.{03}
Inhalation Dosage Form
Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.
ZANAMIVIR POWDER FOR INHALATION
Usual adult and adolescent dose
Influenza A (treatment) or
Influenza B (treatment)
Two oral inhalations (5 milligram per inhalation) twice daily (approximately 12 hours apart in the morning and evening) for 5 days. Two doses should be taken on the first day of treatment whenever possible provided there are at least 2 hours between doses. Zanamivir must be initiated within 48 hours after the onset of signs and symptoms of influenza. Administer zanamivir with the DISKHALER.{01}
[ Influenza A (prophylaxis)]1 or
Influenza B (prophylaxis)
Two oral inhalations (5 mg per inhalation) once daily{06}{07}{08}{09}{10}{11} for 10 to 14 days until the vaccine response takes place or for the remainder of the exposure.{13}
Usual Pediatric Dose
Influenza A (treatment) or
Influenza B (treatment)
Children under 7 years of age: Safety and efficacy have not been established {01}1.
Children 7 years of age and older: See Usual adult and adolescent dose1 {01}.
[Children under 12 years of age: Safety and efficacy have not been established:]{03}
Children 12 years of age and older: See Usual adult and adolescent dose {03}.
[ Influenza A (prophylaxis)]1 or
[Influenza B (prophylaxis) ]1
Children under 7 years of age: Safety and efficacy have not been established.{06}
Children 7 years of age and older: See Usual adult and adolescent dose.{06}
Strength(s) usually available
U.S.—
5 mg per blister (delivering 4 mg) (Rx) [Relenza (lactose)]
Note: The package is supplied with 5 circular double-foil packs in a white polypropylene tube and one DISKHALER inhalation device. Each circular double-foil pack (a ROTADISK) contains 4 blisters of the drug.{01}
Canada—
5 mg per blister (Rx) [Relenza (lactose [20 mg])]
Packaging and storage:
Store at 25 °C (77 °F); excursions permitted to 15 °C to 30 °C (59 °F to 86 °F){01}.
Auxiliary labeling:
• Continue medication for full time of treatment.
Note:
• Include patient instructions when dispensing.
• Demonstrate administration technique.
Revised: 12/23/2002
References
- Product Information: Relenza(R) zanamivir for inhalation. GlaxoWellcome Inc., Research Triangle Park, NC, USA, 2000.
- 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; 337:874-880.
- Product Information: Relenza™ zanamivir. GlaxoWellcome Inc., Missisauga, Ontario, Canada. (PI revised 09/2000) reviewed 12/2000.
- Product Information: Relenza® zanamivir. GlaxoSmithKline, Research Triangle Park NC. (PI revised 3/2001) PI reviewed 9/2001
- Product Information:Pr Relenza™ zanamivir. GlaxoWellcome Inc., Mississauga, Ontario, Canada. (PI revised 12/2000) reviewed 09/2001
- Consensus on review of evidence table, 11/11/2002.
- 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.
- Kaiser L, Henry D, Flack NP, Keene O, Hayden FG. Short-term treatment with zanamivir to prevent influenza: results of a placebo-controlled study. Clin Infect Dis 2000; 30: 587-9.
- Lee C, Loeb M, Phillips A, et al. Zanamivir use during transmission of amantadine-resistant influenza A in a nursing home. Infect Control Hosp Epidemiol 2000; 21: 700-4.
- McGeer AJ, Lee W, McArthur M, et al. Use of zanamivir to control an outbreak of influenza A in a nursing home [abstract]. Clin Infect Dis 2000; 31: 318.
- 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.
- Schilling M, Povinelli L, Krause P, et al. Efficacy of zanamivir for chemoprophylaxis of nursing home influenza outbreaks. Vaccine 1998; 16: 1771-4.
- Expert Committee comment, 11/22/2002.
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