What is Relenza Diskhaler (zanamivir) and what are its dosing regimens for influenza treatment and prophylaxis?

Relenza Diskhaler: Zanamivir Inhalation Powder for Influenza

Relenza Diskhaler is an inhaled dry-powder formulation of zanamivir, a neuraminidase inhibitor antiviral medication active against both influenza A and B viruses, delivered via a proprietary breath-activated plastic inhalation device. 1

Mechanism and Formulation

• Zanamivir is a potent competitive inhibitor of the viral neuraminidase glycoprotein, which is essential for influenza A and B virus replication and spread. 2, 3
• The medication is supplied as a dry powder in 5-mg blisters that must be administered using the DISKHALER device included in the package; it cannot be nebulized or used with ventilators. 1, 4
• Each therapeutic dose consists of two inhalations (one 5-mg blister per inhalation) for a total of 10 mg. 2, 1

Pharmacokinetics

• Approximately 7–21% of the inhaled dose reaches the lungs, while 70–87% deposits in the oropharynx. 2, 4
• Only 4–17% of the total inhaled dose is absorbed systemically, with a half-life of 2.5–5.1 hours. 2, 4
• Systemically absorbed zanamivir is excreted unchanged in the urine; unabsorbed drug is eliminated in the feces. 2, 4

Treatment Dosing

• Adults and children ≥7 years: 10 mg (two 5-mg inhalations) twice daily for 5 days, with doses spaced approximately 12 hours apart. 2, 1, 4
• Two doses should be taken on the first day whenever possible, provided there is at least 2 hours between doses. 1
• Treatment must be initiated within 48 hours of symptom onset for maximum effectiveness. 2, 5
• Zanamivir is not approved for treatment in children younger than 7 years. 2, 4

Prophylaxis Dosing

• Household setting (adults and children ≥5 years): 10 mg once daily for 10 days following exposure to an infected household member. 2, 1, 4
• Community outbreak (adults and adolescents): 10 mg once daily for 28 days during community influenza activity. 1
• Prophylaxis should be initiated within 1.5 days of symptom onset in the index case for household settings, or within 5 days of outbreak identification in community settings. 1
• Zanamivir is not approved for prophylaxis in children younger than 5 years. 2, 4

Special Populations

Renal Impairment

• No dose adjustment is required for patients with mild, moderate, or severe renal dysfunction; standard dosing applies regardless of creatinine clearance. 2, 4

Elderly Patients

• No dose reduction is needed based on age alone; patients ≥65 years receive standard adult dosing. 2, 4

Hepatic Dysfunction

• No specific studies have evaluated zanamivir in patients with liver disease, and no dosing adjustments are provided. 2, 4

Critical Contraindications and Warnings

• Zanamivir is absolutely contraindicated in patients with underlying obstructive airway disease (asthma or chronic obstructive pulmonary disease) due to the risk of life-threatening bronchospasm. 2, 4
• Rare postmarketing reports have documented bronchospasm and decline in respiratory function, even in patients without known airway disease. 5, 6
• Seizure events have been reported during postmarketing surveillance, though epidemiologic studies have not demonstrated an increased seizure risk. 2, 4

Administration Technique

• Patients must receive instruction and demonstration on correct use of the DISKHALER device before initiating therapy. 2, 1, 4
• If prescribed for children, zanamivir should be used only under adult supervision, and the supervising adult must first be instructed by a healthcare professional. 1
• Patients using an inhaled bronchodilator should administer their bronchodilator before taking zanamivir. 1

Clinical Efficacy

• Zanamivir reduces the median time to alleviation of major influenza symptoms by 1 to 2.5 days compared with placebo when initiated within 48 hours of symptom onset. 5, 7, 6
• Treatment accelerates return to normal activities, reduces interference with sleep, decreases consumption of relief medication, and lowers the incidence of complications requiring antibacterial therapy. 5, 6
• For prophylaxis in household settings, zanamivir confers an approximately 80% reduction in the odds of contracting influenza. 8

Resistance Profile

• No reports of patients on acute zanamivir therapy shedding drug-resistant virus have been documented to date. 8
• All zanamivir-resistant variants selected in laboratory studies have demonstrated diminished viral viability. 8

Comparison with Oseltamivir

• Unlike oseltamivir (which is administered orally), zanamivir is delivered directly to the site of viral replication in the respiratory tract via inhalation. 7
• Zanamivir does not require dose adjustment for renal impairment, whereas oseltamivir requires dose reduction when creatinine clearance falls below 30 mL/min. 2, 4
• Zanamivir is contraindicated in patients with underlying airway disease, while oseltamivir has no such restriction. 2, 4