Zanamivir (DB00558): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Zanamivir, marketed as Relenza, is an antiviral medication that holds a significant place in the history of infectious disease therapy as the first commercially developed neuraminidase inhibitor. Its development represents a landmark achievement in rational, structure-based drug design, providing a targeted mechanism for combating influenza A and B viruses. The drug functions as a potent sialic acid analogue, competitively inhibiting the viral neuraminidase enzyme, which is essential for the release of progeny virions from infected host cells. This action effectively halts the propagation of the virus within the respiratory tract.

The clinical profile of Zanamivir is fundamentally defined by its route of administration. Formulated as a dry powder for oral inhalation, it achieves high therapeutic concentrations directly at the site of infection in the respiratory epithelium while maintaining very low systemic bioavailability (4-17%). This localized activity minimizes the potential for systemic side effects and drug-drug interactions. However, this delivery method is also its primary limitation. The drug is associated with a significant risk of severe, sometimes fatal, bronchospasm and is therefore not recommended for patients with underlying airway diseases such as asthma or chronic obstructive pulmonary disease (COPD)—a population particularly vulnerable to influenza complications.

In clinical trials, Zanamivir has demonstrated a modest but statistically significant benefit in treating uncomplicated influenza, reducing the duration of symptoms by approximately 0.6 to 1.5 days when initiated within 48 hours of onset. Its efficacy in preventing major complications, hospitalizations, or death has not been clearly established. As a prophylactic agent, it is effective in reducing the incidence of symptomatic influenza in household and community settings.