Zanamivir

watchedfields

changed

verifiedrevid

470635535

width

200

tradename

Relenza, others

medlineplus

a699021

dailymedid

Zanamivir

pregnancy au

routes of administration

Inhalation, intravenous

atc prefix

J05

atc suffix

AH01

legal au

legal uk

POM

legal us

Rx-only

legal us comment

‡R1R‡

legal eu

Rx-only

legal eu comment

‡R2R‡‡R3R‡‡R4R‡

bioavailability

2% (oral)

protein bound

<10%

metabolism

Negligible

elimination half-life

2.5–5.1 hours

excretion

Kidney

cas number

139110-80-8

pubchem

60855

drugbank

DB00558

chemspiderid

54842

unii

L6O3XI777I

kegg

D00902

chebi

50663

chembl

222813

pdb ligand

ZMR

iupac name

(2R,3R,4S)-4-guanidino-3-(prop-1-en-2-ylamino)-2-((1R,2R)-1,2,3-trihydroxypropyl)-3,4-dihydro-2H-pyran-6-carboxylic acid

smiles

O=C(O)C=1O[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(=O)C)[C@@H](/N=C(\N)N)C=1

stdinchi

1S/C12H20N4O7/c1-4(18)15-8-5(16-12(13)14)2-7(11(21)22)23-10(8)9(20)6(19)3-17/h2,5-6,8-10,17,19-20H,3H2,1H3,(H,15,18)(H,21,22)(H4,13,14,16)/t5-,6+,8+,9+,10+/m0/s1

stdinchikey

ARAIBEBZBOPLMB-UFGQHTETSA-N

Zanamivir, sold under the brand name Relenza among others, is an anti-viral medication used to treat and prevent influenza caused by influenza A and influenza B viruses. It is a neuraminidase inhibitor and was developed by the Australian biotech firm Biota Holdings. It was licensed to Glaxo Wellcome in 1990 and approved in the US in 1999, only for use as a treatment for influenza. In 2006, it was approved for prevention of influenza A and B. Zanamivir is the first neuraminidase inhibitor commercially developed. It was developed by GlaxoSmithKline.

Medical uses

Zanamivir is used for the treatment of infections caused by influenza A and influenza B viruses, but in otherwise-healthy individuals, benefits overall appear to be small. It decreases the risk of one contracting symptomatic, but not asymptomatic influenza. The combination of diagnostic uncertainty, the risk for virus strain resistance, possible side effects and financial cost outweigh the small benefits of zanamivir for the prophylaxis and treatment of healthy individuals.

Treatment

In otherwise-healthy individuals, benefits overall appear to be small. Zanamivir shortens the duration of symptoms of influenza-like illness (unconfirmed influenza or 'the flu') by less than a day. In children with asthma there was no clear effect on the time to first alleviation of symptoms. Whether it affects the risk of one's need to be hospitalized or the risk of death is not clear. There is no proof that zanamivir reduced hospitalizations or pneumonia and other complications of influenza, such as

History

Zanamivir was first made in 1989 by scientists led by Peter Colman[20][21] and Joseph Varghese[22] at the Australian CSIRO, in collaboration with the Victorian College of Pharmacy and Monash University. Zanamivir was the first of the neuraminidase inhibitors. The discovery was initially funded by the Australian biotechnology company Biota and was part of Biota's ongoing program to develop antiviral agents through rational drug design. Its strategy relied on the availability of the structure of influenza neuraminidase by X-ray crystallography. It was also known, as far back as 1974, that 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA), a sialic acid analogue, is an inhibitor of neuraminidase.[23]

Computational chemistry techniques were used to probe the active site of the enzyme, in an attempt to design derivatives of DANA that would bind tightly to the amino acid residues of the catalytic site, so would be potent and specific inhibitors of the enzyme. The GRID software by Molecular Discovery was used to determine energetically favourable interactions between various functional groups and residues in the catalytic site canyon. This investigation showed a negatively charged zone occurs in the neuraminidase active site that aligns with the C4 hydroxyl group of DANA. This hydroxyl is, therefore, replaced with a positively charged amino group; the 4-amino DANA was shown to be 100 times better as an inhibitor than DANA, owing to the formation of a salt bridge with a conserved glutamic acid (119) in the active site. Glu 119 was also noticed to be at the bottom of a conserved pocket in the active site that is just big enough to accommodate the larger, but more basic guanidine functional group.[24] Zanamivir, a transition-state analogue inhibitor of neuraminidase, was the result.[25]

In 1999, the zanamivir was approved in the US[26] and the European Union for the treatment of influenza A and B. The FDA advisory committee recommended by a vote 13 to 4 that it should not be approved, because it lacked efficacy and was no more effective than placebo when the patients were on other drugs such as paracetamol. But the FDA leadership overruled the committee.[27] In 2006, zanamivir was approved in the US[14] and the European Union for prevention of influenza A and B.

References

Relenza- zanamivir powder DailyMed, 19 October 2021, retrieved 30 September 2022^

List of nationally authorised medicinal products European Medicines Agency (EMA)^

Relenza European Medicines Agency (EMA), retrieved 24 March 2025^

Dectova EPAR European Medicines Agency (EMA), 26 April 2019, retrieved 24 March 2025^

Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments BMJ, April 2014^

The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews PLOS ONE, 2013^

Neuraminidase inhibitors for preventing and treating influenza in adults and children The Cochrane Database of Systematic Reviews, April 2014^

Neuraminidase inhibitors for preventing and treating influenza in children (published trials only) The Cochrane Database of Systematic Reviews, April 2012^

2008-2009 Influenza Season Week 32 ending August 15, 2009 Flu Activity & Surveillance, Centers for Disease Control and Prevention (CDC), 21 August 2009^

Systematic review of influenza resistance to the neuraminidase inhibitors BMC Infectious Diseases, May 2011^

Influenza Antiviral Medications: Summary for Clinicians CDC, 11 May 2018, retrieved 21 April 2014^

Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance Lancet, June 2013^

Perspectives on antiviral use during pandemic influenza Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, December 2001^

FDA Approves a Second Drug for the Prevention of Influenza A and B in Adults and Children U.S. Food and Drug Administration (FDA)^

Safe and Appropriate Use of Influenza Drugs U.S. Food and Drug Administration (FDA), 30 April 2009, retrieved 11 November 2009^

Relenza (zanamivir) Inhalation Powder U.S. Food and Drug Administration (FDA)^

Zanamivir: a review of clinical safety Drug Safety, October 1999^

Threat of pandemic brings flu drug back to life Nature Medicine, September 2005^

Neuraminidase inhibitors for influenza The New England Journal of Medicine, September 2005^

Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution Nature, 1983^

Colman, Peter Malcolm - CSIROpedia retrieved 2 October 2013^

Varghese, Joseph Noozhumurry - CSIROpedia retrieved 2 October 2013^

Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid Virology, April 1974^

Flu drugs - pathway to discovery Education in Chemistry, Royal Society of Chemistry, 1 March 2007, retrieved 19 June 2018^

Rational design of potent sialidase-based inhibitors of influenza virus replication Nature, June 1993^

Drug Approval Package: Relenza (Zanamivir) NDA# 21036 U.S. Food and Drug Administration (FDA), 30 March 2001, retrieved 24 March 2025^

Conflicts of interest. WHO and the pandemic flu "conspiracies" BMJ, June 2010^

Medical uses

Treatment

Prevention

Resistance

Adverse effects

Mechanism of action

History

References