PharmacologyTier 1Medical Sciences concept

Evidence base for neuraminidase inhibitors (oseltamivir) in influenza

Core concept

Neuraminidase cleaves sialic acid, releasing budding virions from the infected cell surface and preventing self-aggregation
- Inhibition -> progeny virions stay tethered -> dec spread within the respiratory tract
- Oseltamivir, zanamivir (inhaled), peramivir (IV) - all NA inhibitors
Baloxavir is a different mechanism - cap-dependent endonuclease (PA subunit) inhibitor, single oral dose, blocks transcription initiation
Mechanism dictates the timing: the drug stops new rounds of replication, so it must be given while replication is still happening - within 48 h

Efficacy in otherwise healthy outpatients is modest and contested
- Symptom duration reduced by roughly half a day to one day when started within 48 h
- Cochrane review found no reliable reduction in hospitalisation or complications, and criticised the incompleteness of the manufacturer trial data
- NNT for symptom benefit is high; adverse effects (nausea, vomiting) are common
The evidence is stronger, though observational, in high-risk and hospitalised patients
- Meta-analyses of hospitalised patients suggest dec mortality when started early, particularly in severe influenza and pregnancy
- Guidelines therefore recommend treatment regardless of duration of symptoms in hospitalised, severe, progressive or high-risk disease
Dose: oseltamivir 75 mg bd for 5 days (renal dose adjustment); prophylaxis 75 mg daily
Resistance - H275Y neuraminidase mutation confers oseltamivir (not zanamivir) resistance; baloxavir selects PA I38X variants, especially in children
Adverse effects - nausea and vomiting (commonest), rarely neuropsychiatric events in adolescents
Zanamivir is inhaled - avoid in asthma and COPD (bronchospasm); peramivir is a single IV dose

Treat, do not swab-and-wait, in the high-risk patient - start empirically while awaiting PCR
- Indications: hospitalised, severe or progressive illness, pregnancy and 2 weeks postpartum, age >=65, chronic cardiac/respiratory/renal/liver/neurological disease, immunosuppression, obesity, Aboriginal and Torres Strait Islander people, children under 5, residential care
Vaccination is the far more effective intervention - annual, and the honest answer to "what should we do about influenza"
Post-exposure prophylaxis in outbreak control (aged care facilities) and for unvaccinated high-risk contacts
Bacterial superinfection (Streptococcus pneumoniae, Staphylococcus aureus including MRSA) drives much of influenza mortality - antivirals do not treat it
The examinable tension: a widely prescribed drug with a real mechanism, marginal outpatient evidence, and a guideline recommendation resting on observational high-risk data

3 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.