RELENZA ROTADISK

Indications

• Treatment of uncomplicated acute illness due to influenza A and B
• Post-exposure prophylaxis of influenza
• Prevention of influenza during an epidemic

Dosage

Children: Child 5–17 years: 10 mg twice daily for 5 days via inhalation.

Adults: 10 mg twice daily for 5 days via inhalation, or 10 mg once daily for 10 days for prophylaxis during an epidemic.

Mechanism of action

Zanamivir exerts its antiviral effect by selectively inhibiting the neuraminidase enzyme of the influenza virus. This inhibition prevents the release of newly formed virus particles from infected cells, thereby limiting the spread of the virus within the respiratory tract. By binding to neuraminidase, zanamivir also alters the virus particle aggregation and enhances the retention of the virus in respiratory secretions, making it less infectious.

Pharmacodynamics

Zanamivir has a high affinity for the influenza neuraminidase enzyme, which is critical for viral replication. By inhibiting this enzyme, zanamivir reduces the severity and duration of influenza symptoms. The drug also significantly inhibits human sialidases NEU3 and NEU2, which may contribute to some of its side effects. As a neuraminidase inhibitor, zanamivir is effective against both influenza A and B viruses.

Pharmacokinetics

Zanamivir is administered via inhalation, leading to rapid absorption in the respiratory tract. It is not significantly absorbed systemically, with minimal plasma concentrations observed after inhalation. The drug is primarily excreted unchanged in the urine. The half-life of zanamivir is approximately 2.5 to 5 hours, and it does not undergo significant metabolism. Dosing adjustments may be necessary in patients with renal impairment.

Adverse effects

• Skin reactions
• Oropharyngeal oedema
• Face oedema
• Severe cutaneous adverse reactions
• Diarrhoea
• Hepatocellular injury
• Psychiatric disorders
• Neurological disorders

Precautions

• Asthma
• Chronic pulmonary disease
• Uncontrolled chronic illness
• Risk of bronchospasm when used by inhalation; a short-acting bronchodilator should be available
• Avoid in severe asthma unless close monitoring possible and appropriate facilities available

Pregnancy

Manufacturer advises avoiding unless potential benefit outweighs risk (e.g. during a pandemic)-limited information available; animal studies do not indicate toxicity.

Breast-feeding

Manufacturer advises use only if potential benefit outweighs risk (e.g. during a pandemic)-limited information available; present in low levels in milk.

Storage

Store below 25°C. Protect from moisture.

Formulations

• Inhalation powder

Mechanism of action

The proposed mechanism of action of zanamivir is via inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release. By binding and inhibiting the neuraminidase protein, the drug renders the influenza virus unable to escape its host cell and infect others. Zanamivir is a potent selective competitive inhibitor of the influenza virus neuraminidase, an enzyme essential for viral replication. Neuraminidase cleaves terminal sialic acid residues from glycoconjugates to enable the release of virus from infected cells, prevent the formation of viral aggragates after release from host cells, and possibly decrease viral inactivation by respiratory mucous. Zanamivir is a selective inhibitor of influenza A and B virus neuraminidase, possibly altering particle aggregation and release.

Pharmacodynamics

Zanamivir, an antiviral agent, is a neuraminidase inhibitor indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years and older who have been symptomatic for no more than 2 days. Zanamivir has also been shown to significantly inhibit the human sialidases NEU3 and NEU2 in the micromolar range (Ki 3.7 +/-0.48 and 12.9+/-0.07 microM, respectively), which could account for some of the rare side effects of zanamivir.