RELENZA (zanamivir inhalation powder)

RELENZA (zanamivir inhalation powder)

RELENZA (zanamivir inhalation powder)

The active component of RELENZA is zanamivir. The chemical name of zanamivir is 5(acetylamino)-4-[(aminoiminomethyl)-amino]-2,6-anhydro-3,4,5-trideoxy-D-glycero-D-galactonon-2-enonic acid. It has a molecular formula of C12H20N4O7 and a molecular weight of 332.3.

RELENZA is for administration to the respiratory tract by oral inhalation only. Each RELENZA ROTADISK contains 4 regularly spaced double-foil blisters with each blister containing a powder mixture of 5 mg of zanamivir and 20 mg of lactose (which contains milk proteins). The contents of each blister are inhaled using a specially designed breath-activated plastic device for inhaling powder called the DISKHALER. After a RELENZA ROTADISK is loaded into the DISKHALER, a blister that contains medication is pierced and the zanamivir is dispersed into the air stream created when the patient inhales through the mouthpiece. The amount of drug delivered to the respiratory tract will depend on patient factors such as inspiratory flow. Under standardized in vitro testing, RELENZA ROTADISK delivers 4 mg of zanamivir from the DISKHALER device when tested at a pressure drop of 3 kPa (corresponding to a flow rate of about 62 to 65 L/minute) for 3 seconds.

INDICATIONS AND USAGE

Treatment of Influenza

RELENZA (zanamivir) inhalation powder is indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients aged 7 years and older who have been symptomatic for no more than 2 days.

Prophylaxis of Influenza

RELENZA is indicated for prophylaxis of influenza in adults and pediatric patients aged 5 years and older.

Important Limitations of Use

  • RELENZA is not recommended for treatment or prophylaxis of influenza in individuals with underlying airways disease (such as asthma or chronic obstructive pulmonary disease) due to risk of serious bronchospasm.
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  • RELENZA has not been proven effective for treatment of influenza in individuals with underlying airways disease.
  • RELENZA has not been proven effective for prophylaxis of influenza in the nursing home setting.
  • RELENZA is not a substitute for early influenza vaccination on an annual basis as recommended by the Centers for Disease Control’s Immunization Practices Advisory Committee.
  • Influenza viruses change over time. Emergence of resistance mutations could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use RELENZA.
  • There is no evidence for efficacy of zanamivir in any illness caused by agents other than influenza virus A and B.
  • Patients should be advised that the use of RELENZA for treatment of influenza has not been shown to reduce the risk of transmission of influenza to others.

Mechanism of Action

Zanamivir is an inhibitor of influenza virus neuraminidase, an enzyme that releases viral particles from the plasma membrane of infected cells and promotes virus spread in the respiratory tract. In neuraminidase inhibition assays, zanamivir is active against all neuraminidase (NA) enzyme subtypes N1 to N9. The median baseline 50% neuraminidase inhibitory concentrations (IC50) of zanamivir for influenza type A subtype H1N1, influenza type A subtype H3N2, and influenza type B viruses were 0.85 nM (n = 31; range: 0.45 to 1.35 nM), 1.01 nM (n = 32; range: 0.33 to 2.04 nM), and 3.86 nM (n = 16; range: 2.02 to 5.77 nM), respectively, in a chemiluminescent assay. Amino acid substitutions have been found in the neuraminidase active site that reduce virus susceptibility to zanamivir

DOSAGE AND ADMINISTRATION

Treatment of Influenza

  • The recommended dose of RELENZA for treatment of influenza in adults and pediatric patients aged 7 years and older is 10 mg twice daily (approximately 12 hours apart) for 5 days.
  • Two doses should be taken on the first day of treatment whenever possible provided there is at least 2 hours between doses.
  • On subsequent days, doses should be about 12 hours apart (e.g., morning and evening) at approximately the same time each day.
  • The safety and efficacy of repeated treatment courses have not been studied.

Prophylaxis of Influenza

Household Setting

  • The recommended dose of RELENZA for prophylaxis of influenza in adults and pediatric patients aged 5 years and older in a household setting is 10 mg once daily for 10 days.
  • The dose should be administered at approximately the same time each day.
  • There are no data on the effectiveness of prophylaxis with RELENZA in a household setting when initiated more than 1.5 days after the onset of signs or symptoms in the index case.

Community Outbreaks

  • The recommended dose of RELENZA for prophylaxis of influenza in adults and adolescents in a community setting is 10 mg once daily for 28 days.
  • The dose should be administered at approximately the same time each day.
  • There are no data on the effectiveness of prophylaxis with RELENZA in a community outbreak when initiated more than 5 days after the outbreak was identified in the community.
  • The safety and effectiveness of prophylaxis with RELENZA have not been evaluated for longer than 28 days’ duration.

CONTRAINDICATIONS

RELENZA is contraindicated in patients with history of allergic reaction to any ingredient of RELENZA, including milk proteins.

WARNINGS AND PRECAUTIONS

  • Bronchospasm: Serious, sometimes fatal, cases have occurred. Not recommended in individuals with underlying airways disease. Discontinue RELENZA if bronchospasm or decline in respiratory function develops.
  • Allergic Reactions: Discontinue RELENZA and initiate appropriate treatment if an allergic reaction occurs or is suspected.
  • Neuropsychiatric Events: Patients with influenza, particularly pediatric patients, may be at an increased risk of seizures, confusion, or abnormal behavior early in their illness. Monitor for signs of abnormal behavior.
  • High-Risk Underlying Medical Conditions: Safety and effectiveness have not been demonstrated in these patients.

Adverse reactions

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

DRUG INTERACTIONS

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.

USE IN SPECIFIC POPULATIONS

Pregnancy: Available data from published studies suggest that use of RELENZA during pregnancy is not associated with an increased risk of birth defects or adverse maternal or fetal outcomes.

Pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes, including maternal death, stillbirths, birth defects, preterm delivery, low birth weight, and small for gestational age.

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Lactation: There are no data on the presence of zanamivir in human milk or the effects on milk production. There are data from adults that have shown low oral bioavailability of zanamivir. Limited data from postmarketing case reports have not suggested a safety concern in infants exposed to breast milk of mothers using RELENZA. Zanamivir was present in the milk of lactating rats without effect on nursing pups. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RELENZA and any potential adverse effects on the breastfed child from RELENZA or the underlying maternal condition.

Pediatric Use: Safety and effectiveness of RELENZA for treatment of influenza have not been assessed in pediatric patients younger than 7 years.

Renal Impairment: Safety and efficacy have not been documented in the presence of severe renal insufficiency. Due to the low systemic bioavailability of zanamivir following oral inhalation, no dosage adjustments are necessary in patients with renal impairment. However, the potential for drug accumulation should be considered.

OVERDOSAGE

Reports of overdosage from administration of RELENZA have been received during postmarketing experience. The reported clinical signs or symptoms were similar to those observed with therapeutic doses of RELENZA and the underlying disease.

As zanamivir has a low molecular weight, low protein binding, and small volume of distribution, it is expected to be removed by hemodialysis.

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