What is the recommended antiviral treatment for patients presenting with influenza, particularly those at high risk of complications such as the elderly, young children, or individuals with chronic medical conditions?

Influenza Antiviral Treatment

Start oseltamivir 75 mg orally twice daily for 5 days immediately for any patient with confirmed or suspected influenza who is hospitalized, severely ill, or at high risk for complications—treatment should begin as soon as possible and should not be delayed while awaiting laboratory confirmation. 1, 2, 3

Who Requires Immediate Antiviral Treatment

Mandatory treatment groups where antivirals must be initiated regardless of time since symptom onset:

• Any hospitalized child or adult with suspected or confirmed influenza 1, 2
• Any patient with severe, complicated, or progressive illness attributable to influenza 1, 4
• Children younger than 2 years of age 1, 3, 4
• Adults 65 years and older 3, 4
• Pregnant women and women up to 2 weeks postpartum 1, 3, 4
• Immunocompromised patients (including those on chronic corticosteroids, chemotherapy, or with HIV) 1, 3, 4
• Patients with chronic medical conditions including asthma, diabetes mellitus, cardiac disease, chronic pulmonary disease, renal dysfunction, neurologic disorders, or hemoglobinopathies 1, 3

Treatment should be considered for otherwise healthy patients when symptom reduction is desired, particularly if treatment can be initiated within 48 hours of illness onset. 1

Timing of Treatment Initiation

Treatment provides maximum benefit when started within 48 hours of symptom onset, reducing illness duration by 17.6-29.9 hours and decreasing pneumonia risk by 50%. 2, 3, 5 However, do not withhold treatment in severely ill, hospitalized, or high-risk patients even if presenting beyond 48 hours, as clinical benefit persists in moderate-to-severe or progressive disease. 1, 4

Start treatment immediately based on clinical suspicion—do not delay while awaiting laboratory confirmation. 1, 2 Rapid antigen tests have poor sensitivity (particularly for H1N1) and negative results should never be used to rule out influenza or guide treatment decisions. 1

Recommended Antiviral Agents and Dosing

First-Line: Oseltamivir (Oral)

Adults and adolescents ≥13 years: 75 mg orally twice daily for 5 days 1, 2, 3, 6

Children 1-12 years (weight-based dosing): 1

• ≤15 kg: 30 mg twice daily

• 15-23 kg: 45 mg twice daily

• 23-40 kg: 60 mg twice daily

• 40 kg: 75 mg twice daily

Infants 3-11 months: 3 mg/kg/dose twice daily 1

Infants 0-3 months: 3 mg/kg/dose twice daily (limited data, but recommended based on high complication risk) 1

Oseltamivir can be taken with or without food, though administration with meals improves gastrointestinal tolerability. 2, 6 The oral suspension has a concentration of 6 mg/mL; if unavailable, capsules can be opened and mixed with sweetened liquid to 15 mg/mL concentration. 1

Alternative Options

Zanamivir (inhaled): 10 mg (two 5-mg inhalations) twice daily for 5 days, approved for treatment in patients ≥7 years and prophylaxis in patients ≥5 years. 1, 2 Avoid in patients with underlying reactive airway disease. 1

Peramivir (IV): Single 600 mg IV infusion over 15-30 minutes for ages 13-17 years; useful when oral or inhaled routes are not feasible. 2

Baloxavir (oral): Single dose based on weight (40 mg for 40-80 kg, 80 mg for ≥80 kg) for patients ≥12 years; offers convenience of single-dose therapy but has higher resistance emergence rates, particularly in Japan where usage is highest. 1, 2, 7

Expected Clinical Benefits

When initiated within 48 hours of symptom onset in otherwise healthy patients, oseltamivir provides: 2, 3, 5

• Reduction in illness duration by 17.6-29.9 hours
• 50% decrease in pneumonia risk
• 34% reduction in otitis media risk (in younger patients)
• Significant mortality benefit in hospitalized patients (OR 0.21 for death within 15 days)

Chemoprophylaxis Indications

Antiviral chemoprophylaxis (oseltamivir 75 mg once daily for 10 days, or zanamivir 10 mg once daily for 10 days) is recommended after known or suspected influenza exposure in: 1

• Children at high risk of complications for whom influenza vaccine is contraindicated
• Children at high risk during the 2 weeks after influenza vaccination (before optimal immunity develops)
• Unvaccinated family members or healthcare personnel with ongoing close exposure to unvaccinated high-risk children or infants <24 months
• Control of influenza outbreaks in closed institutional settings with high-risk populations
• As adjunctive protection for immunocompromised patients who may not respond adequately to vaccine

Chemoprophylaxis should ideally be started within 48 hours of exposure. 1 Chemoprophylaxis is not a substitute for vaccination, and susceptibility to influenza returns when medication is discontinued. 1

Critical Pitfalls to Avoid

Do not delay treatment while awaiting laboratory confirmation in high-risk or severely ill patients—clinical diagnosis during influenza season is sufficient. 1, 2

Do not withhold treatment based solely on time since symptom onset if the patient has moderate-to-severe illness, progressive disease, or high-risk features. 1, 4

Do not use amantadine or rimantadine due to high resistance rates (>99%) among currently circulating influenza A viruses. 4, 8

Do not use corticosteroids as adjunctive therapy for influenza treatment unless clinically indicated for other reasons, as they increase mortality risk and bacterial superinfection. 3, 4

Avoid aspirin in patients <19 years due to Reye's syndrome risk; use acetaminophen or ibuprofen for fever and myalgias instead. 2

Do not routinely prescribe antibiotics for previously healthy patients with acute bronchitis complicating influenza. 3 Consider antibiotics only for patients with worsening symptoms after initial improvement, high-risk patients with lower respiratory tract features, or patients not improving after 3-5 days of antiviral treatment. 3, 4

Monitoring and Follow-Up

Patients should show clinical improvement within 48 hours of starting antivirals. 3 Reassess if: 3

• Fever persists beyond 4-5 days
• Clinical deterioration occurs
• No improvement after 3-5 days of treatment

These scenarios suggest possible bacterial superinfection requiring empiric antibiotic therapy in addition to continued antiviral treatment. 4

Adverse Effects

Nausea and vomiting are the most common adverse effects, occurring in approximately 15% of oseltamivir-treated patients versus 9% on placebo. 2, 5 These effects are mild, transient, rarely lead to discontinuation, and are reduced when oseltamivir is taken with food. 2, 6, 5

Resistance Considerations

Antiviral resistance remains rare. During the 2023-2024 season, only 0.05-0.27% of tested influenza viruses showed reduced susceptibility to neuraminidase inhibitors. 1 Baloxavir resistance is slightly higher (0.5% globally, 4.5% in Japan where usage is highest). 1 Continuous monitoring by the CDC ensures treatment recommendations remain appropriate. 1