What are the treatment recommendations for influenza?

Treatment Recommendations for Influenza

Primary Treatment Recommendation

Oseltamivir (Tamiflu) is the antiviral drug of choice for treating influenza in all age groups, and should be initiated as soon as possible—ideally within 48 hours of symptom onset—for all hospitalized patients, those with severe or progressive illness, and high-risk individuals regardless of vaccination status. 1, 2

Who Should Receive Antiviral Treatment

Mandatory Treatment Groups (Start Immediately)

• All hospitalized patients with confirmed or suspected influenza, regardless of symptom duration 1, 2
• Patients with severe, complicated, or progressive illness (pneumonia, respiratory failure, neurologic complications) 1
• High-risk patients including:
  • Children younger than 2 years of age 1, 2
  • Adults 65 years and older 1, 3
  • Pregnant and postpartum women (within 2 weeks of delivery) 1, 3
  • Immunocompromised patients 1, 3
  • Patients with chronic medical conditions (pulmonary, cardiovascular, renal, hepatic, hematologic, metabolic, or neurologic disorders) 1, 3

Discretionary Treatment (Consider Strongly)

• Any otherwise healthy outpatient with confirmed or suspected influenza if treatment can be initiated within 48 hours of illness onset 1, 2, 4
• Children whose household contacts are younger than 6 months or have high-risk conditions 2

Timing of Treatment Initiation

Treatment should be started as soon as possible and should NOT be delayed while waiting for laboratory confirmation. 1, 2, 3

Optimal Timing

• Greatest benefit occurs when treatment is initiated within 12-24 hours of symptom onset, reducing illness duration by up to 3.1 days (74.6 hours) 5
• Treatment within 48 hours reduces illness duration by approximately 24-29 hours in otherwise healthy patients 1, 5, 4

Late Treatment (>48 Hours)

• Still recommended for hospitalized patients, severely ill patients, and high-risk groups even if more than 48 hours have passed since symptom onset 1
• Treatment initiated within 5 days of symptom onset in hospitalized adults was associated with reduced mortality (adjusted odds ratio 0.50) 1
• Treatment beyond 48 hours in ICU patients with H1N1 infection may still provide survival benefit 6
• Do NOT withhold treatment from high-risk or severely ill patients based solely on time since symptom onset 1

Recommended Medications and Dosing

Oseltamivir (First-Line Agent)

Adults and Adolescents (≥13 years):

• 75 mg orally twice daily for 5 days 1, 3, 7

Pediatric Patients (≥12 months)—Weight-Based Dosing:

• ≤15 kg: 30 mg twice daily 1, 7
• 15.1-23 kg: 45 mg twice daily 1, 7
• 23.1-40 kg: 60 mg twice daily 1, 7

• 40 kg: 75 mg twice daily 1, 7

Infants (Birth to <12 months):

• 9-11 months: 3.5 mg/kg per dose twice daily 1, 7
• 0-8 months (term infants): 3 mg/kg per dose twice daily 1, 7
• Preterm infants: Dosing varies by postmenstrual age (1.0-3.0 mg/kg twice daily) 3

The FDA has approved oseltamivir for treatment in children as young as 2 weeks of age, and both the CDC and AAP support its use in term and preterm infants from birth for severe influenza 1

Alternative Antiviral Agents

Zanamivir (Inhaled):

• 10 mg (two 5-mg inhalations) twice daily for 5 days 1
• Approved for patients ≥7 years for treatment 1
• Acceptable alternative but more difficult to administer 1, 2
• Contraindicated in patients with chronic respiratory disease (asthma, COPD) due to risk of bronchospasm 2

Peramivir (Intravenous):

• Approved for acute uncomplicated influenza in patients ≥2 years who have been symptomatic for no more than 2 days 2
• Recommended for severely ill patients with concerns about oral absorption 3

Amantadine and Rimantadine:

• Should NOT be used due to high levels of resistance among circulating influenza strains 1, 2

Formulation and Administration

• Oseltamivir is available as capsules (30,45,75 mg) and oral suspension (6 mg/mL) 1, 7
• May be taken with or without food, but administration with food may enhance tolerability and reduce gastrointestinal side effects 3, 7, 5
• If commercial oral suspension is unavailable, capsules may be opened and contents mixed with simple syrup or Ora-Sweet SF to achieve 6 mg/mL concentration 1

Treatment Duration

• Standard duration is 5 days for uncomplicated influenza 1, 3, 7
• Longer duration may be considered for immunocompromised patients, critically ill patients, or those with persistent fever after 6 days of treatment 3, 6
• No benefit exists for double-dose therapy compared to standard dosing based on randomized controlled trials 1, 6

Clinical Benefits of Treatment

Symptom Reduction

• Reduces illness duration by 17.6-29 hours in children with laboratory-confirmed influenza 1
• Reduces illness duration by approximately 24 hours in otherwise healthy adults 3, 4
• Earlier treatment (within 12 hours) provides greater benefit than later treatment 5

Complication Reduction

• Reduces risk of acute otitis media by 34% in children 1-5 years of age 1, 2
• May decrease hospitalization rates and need for subsequent antibiotics 3, 4
• Reduces influenza-associated mortality in hospitalized patients when started early 1
• In critically ill pediatric ICU patients, treatment was associated with reduced mortality (odds ratio 0.36) 1

Viral Shedding

• Significantly reduces virus isolation on days 2,4, and 7 after treatment initiation 8
• Reduction in viral shedding occurs even when treatment is started ≥48 hours after symptom onset 8

Adverse Effects and Safety

Common Side Effects

• Vomiting occurs in approximately 5-15% of treated patients, most commonly with the first dose 1, 3
• Nausea occurs in approximately 10-15% of patients 3, 5
• Diarrhea may occur in infants <1 year of age 2, 3
• Taking oseltamivir with food reduces gastrointestinal side effects 3, 5

Neuropsychiatric Concerns

• Despite reports from Japan of neuropsychiatric adverse effects, reviews of controlled clinical trial data and ongoing surveillance have failed to establish a link between oseltamivir and neurologic or psychiatric events 1, 2

Overall Tolerability

• Overall discontinuation rate is low (1.8%) 5
• Adverse events are generally transient and occur primarily with first dosing 5

Special Considerations

Renal Impairment

• Dose adjustment required for creatinine clearance <30 mL/min: reduce to 75 mg once daily in adults 3

Influenza B Considerations

• Oseltamivir has demonstrated activity against influenza B viruses, though may be less effective than against influenza A 1, 2
• In Japanese children, oseltamivir reduced influenza B illness duration from 173.9 to 110.0 hours (p=0.03), though the effect was less pronounced than with influenza A 2
• Treatment is still recommended for children with influenza B, particularly those under 2 years or with high-risk conditions 2

Antiviral Resistance

• Resistance to oseltamivir and zanamivir remains low (<1-4% depending on strain and season) 1, 2
• Continuous monitoring of resistance patterns is conducted by the CDC 1, 2
• High resistance to amantadine and rimantadine persists, making these agents unsuitable for current use 1, 2

Critical Pitfalls to Avoid

1. Do NOT delay treatment while waiting for laboratory confirmation in high-risk or severely ill patients 1, 2, 3
2. Do NOT withhold treatment from hospitalized or high-risk patients based solely on time since symptom onset (>48 hours) 1
3. Do NOT use rapid antigen tests alone to rule out influenza due to low sensitivity; negative results should not prevent treatment in high-risk patients 2
4. Do NOT use double-dose oseltamivir therapy—no additional benefit has been demonstrated 1, 6
5. Do NOT use amantadine or rimantadine due to widespread resistance 1, 2
6. Do NOT prescribe zanamivir to patients with asthma or chronic pulmonary disease due to bronchospasm risk 2

Prophylaxis Considerations

Post-exposure prophylaxis with oseltamivir (75 mg once daily for 10 days in adults) should be considered for:

• Asymptomatic individuals at very high risk of complications (severely immunocompromised) 9
• Unvaccinated household contacts of very high-risk individuals 9
• Must be initiated within 48 hours of exposure 9

Seasonal prophylaxis (75 mg once daily for up to 6 weeks) may be considered during community outbreaks, with extended duration (up to 12 weeks) for immunocompromised patients 7