Neuraminidase inhibitors

crop_square Key points

  • check_circle Sialic acid analogues active against influenza A and B
  • check_circle Prevent the release of influenza virions from infected cells
  • check_circle Need to be administered within 48h after onset of symptoms
  • check_circle Generally well-tolerated drugs

crop_square Background and biochemistry

Neuraminidase inhibitors are a class of antivirals used in the treatment of influenza A and B infections. The first commercially available agent was Zanamivir which was FDA approved in 1999. The first oral neuraminidase inhibitor was Oseltamivir (Tamiflu), also approved in 1999. All available neuraminidase inhibitors are analogues of sialic acid. Neuraminidase inhibitors efficacy has been subject to debate since they were first introduced. They are considered effective when given early, usually within the first 48h of an influenza infection.

crop_square Mechanism of action

Neuraminidase inhibitors prevent the release of influenza virions from an infected host cell. During the late stage of the influenza life cycle, newly synthesised viral envelope proteins are inserted into the infected host cell’s plasma membrane. The intracellular nucleocapsid containing the viral RNA approaches the viral envelope proteins initiating the viral budding from the host cell. The budding virion is attached to the host cell through cellular sialic acid glycoprotein and viral haemagglutinin sialic acid bonds. Viral neuraminidases cleave sialic acid which leads to the release of influenza virions from the host cell. Neuraminidase inhibitors competitively inhibit this viral enzyme preventing the release of virions. Mutations to the viral neuraminidase may reduce susceptibility to neuraminidase inhibitors but resistant strains are currently still rare.

crop_square Drugs and spectrum of activity

  • Osetal­mivir (oral)
  • Zana­mivir (inhaled)
  • Pera­mivir (intravenous)

crop_square Pharmacokinetics

Oseltamivir is a prodrug which is hepatically metabolised to its active carboxylated form. Absorption from the gastrointestinal tract is rapid and bioavailability around 80%. Roughly 20% of Zanamivir is found in the blood stream after inhalation. Elimination half-life may be as short as 2h for Zanamivir, around 8h for the active metabolite of oseltamivir and up to 20h for peramivir. Major route of elimination for all neuraminidase inhibitors is via the kidneys.

crop_square Adverse drug effects

Neuraminidase inhibitors are generally well-tolerated drugs. Gastrointestinal side effects may occur with all drugs in this class. Rare side effects include Steven-Johnson syndrome (oseltamivir), neutropenia (peramivir) and bronchospasm with inhaled zanamivir.