What is the efficacy of flu antivirals, such as oseltamivir (Tamiflu) and zanamivir (Relenza), in treating and preventing influenza?

Efficacy of Flu Antivirals

Flu antivirals are moderately effective medications that reduce illness duration by approximately 1-1.5 days when started within 48 hours of symptom onset, but their most important benefit is a 50% reduction in serious complications like pneumonia and significant mortality reduction in hospitalized patients, making them most valuable for high-risk and severely ill individuals rather than routine use in otherwise healthy people. 1, 2

Treatment Efficacy: Symptom Reduction

When initiated within 48 hours of symptom onset, both oseltamivir (Tamiflu) and zanamivir (Relenza) demonstrate the following benefits:

• Reduce illness duration by 0.7-1.5 days in otherwise healthy adults 3, 2, 4
• Shorten symptoms by 17.6 hours in children (29.9 hours when excluding children with asthma) 1
• Reduce illness severity by up to 38% compared to placebo when started early 2, 5
• Greatest benefit occurs when treatment begins within 30-36 hours of symptom onset, with diminishing returns after 48 hours 3, 5

The modest symptom reduction in otherwise healthy individuals is why general use for uncomplicated influenza is not strongly recommended. 3, 6

Most Important Benefit: Reduction in Serious Complications

The critical value of antivirals lies in preventing severe outcomes, not just shortening symptoms:

• 50% reduction in pneumonia risk in patients with laboratory-confirmed influenza 3, 1, 2
• 34% reduction in otitis media in children 1, 2
• Significant mortality benefit in hospitalized patients (odds ratio 0.21 for death within 15 days), even when treatment starts beyond 48 hours 1, 2
• Reduced hospital length of stay: 4 days when treated within 48 hours versus 6 days when treated after 48 hours 3

Prophylaxis Efficacy

When used preventively, antivirals demonstrate strong protective effects:

• 70-90% protective efficacy for seasonal prophylaxis in unvaccinated healthy adults (oseltamivir 75 mg once daily for 6 weeks) 3, 2, 5
• 68-89% efficacy for post-exposure household prophylaxis when started within 48 hours of exposure 3, 1, 2
• 92% reduction in influenza illness in nursing home residents during a 6-week prophylaxis study 3
• Zanamivir shows similar efficacy: 84% for seasonal prophylaxis and 72-82% for household prophylaxis 3, 7

Important Distinction: Influenza A vs. B

Oseltamivir appears less effective against influenza B compared to influenza A:

• Japanese observational studies showed children with influenza A resolved fever and stopped viral shedding more quickly than those with influenza B when treated with oseltamivir 3, 2
• Zanamivir demonstrates equal effectiveness against both influenza A and B 2, 8
• Consider zanamivir preferentially during confirmed influenza B outbreaks 8

Who Benefits Most from Treatment

High-risk and severely ill patients derive the greatest benefit, even when treatment starts beyond 48 hours:

• Hospitalized patients with severe influenza 3, 1
• Immunocompromised individuals (including those on long-term corticosteroids) 1
• Elderly patients (≥65 years) 1
• Pregnant women 1
• Children under 2 years of age 1
• Patients with chronic cardiac, pulmonary, or other chronic diseases 3, 1

For these populations, treatment should be initiated immediately based on clinical suspicion during flu season without waiting for laboratory confirmation, as delays reduce effectiveness. 1, 2

Adverse Effects

Common side effects are generally mild and transient:

• Oseltamivir: Nausea (3.66% increased risk) and vomiting (4.56% increased risk), reduced when taken with food 1, 2, 5
• Zanamivir: Upper respiratory symptoms, risk of bronchospasm in patients with underlying airways disease (asthma, COPD) 7, 9
• Vomiting in children occurs in approximately 15% versus 9% on placebo, but rarely leads to discontinuation 1
• No established link between oseltamivir and neuropsychiatric events 1

Critical Limitations and Caveats

Zanamivir is contraindicated in patients with underlying airways disease (asthma, COPD) due to risk of serious bronchospasm and lack of proven efficacy in this population. 7

Antivirals are not a substitute for annual influenza vaccination, which remains the primary prevention strategy. 3, 2, 7

Resistance considerations: Oseltamivir resistance remains low (<5% in the United States for current strains), but resistance can develop during treatment, particularly with influenza A (H1N1) at 27% versus 3% for H3N2 and 0% for influenza B. 2

Rapid influenza tests have poor sensitivity—negative results should not exclude treatment in high-risk patients during influenza season. 1, 2

Practical Dosing

Treatment dosing:

• Adults/adolescents ≥13 years: 75 mg twice daily for 5 days 1, 2
• Children (weight-based): ≤15 kg: 30 mg; >15-23 kg: 45 mg; >23-40 kg: 60 mg; >40 kg: 75 mg, all twice daily for 5 days 1, 2
• Zanamivir: 10 mg (two 5-mg inhalations) twice daily for 5 days 7

Prophylaxis dosing:

• Same doses as treatment but once daily instead of twice daily 1, 2
• Duration: 10 days for household prophylaxis, up to 28 days for seasonal prophylaxis 3, 7

Bottom Line for Clinical Practice

For otherwise healthy individuals with uncomplicated influenza, the benefit is modest (approximately 1 day symptom reduction) and general use is not strongly recommended. 3, 6

For high-risk, severely ill, or hospitalized patients, antivirals provide substantial benefit through reduced complications and mortality, and should be initiated immediately regardless of time since symptom onset. 1, 2 This mortality benefit persists even when treatment begins 48-96 hours after illness onset. 1

For prophylaxis, antivirals are highly effective (70-90% protection) but should be used as adjuncts to vaccination, not replacements, particularly for post-exposure household contacts of high-risk individuals and during institutional outbreaks. 3, 2, 5