Influenza Antiviral Therapy

Antiviral agents may be prescribed as treatment to potentially shorten the duration and decrease the severity of influenza infection. Antivirals may also be prescribed for chemoprophylaxis to prevent/attenuate a potential influenza infection following contact with an infected individual or in vulnerable individuals during a community outbreak (eg, nursing homes).

Amantadine and rimantadine are antiviral drugs in a class of medications known as adamantanes that were once prescribed for influenza treatment or prophylaxis. These medications are active against influenza A viruses, but not influenza B viruses. In recent past seasons, there has been a high prevalence (>99%) of influenza A(H3N2) and influenza A(H1N1)pdm09 (2009 H1N1) viruses resistant to adamantanes. Therefore, amantadine and rimantadine are not recommended for antiviral treatment or chemoprophylaxis of currently circulating influenza A viruses. ^[1]

Treatment of patients with influenza A and B

When used as treatment, initiation of antiviral agents should not be delayed and ideally should be started within 48 hours of the onset of symptoms.

Infectious Disease Society of America guidelines for antiviral therapy for influenza

The Infectious Disease Society of America (IDSA) guidelines for influenza antiviral therapy are as follows ^[2] :

High-risk individuals

Clinicians should initiate antivirals as soon as possible for adults and children with documented or suspected influenza, irrespective of influenza vaccination history, in the following cases:

• Hospitalized with influenza, regardless of illness duration before hospitalization
• Outpatients with severe or progressive illness, regardless of illness duration
• Children younger than 2 years and adults aged 65 years or older
• Women who are pregnant or within 2 weeks postpartum

Individuals not at high risk

Clinicians may consider antivirals for individuals with documented or suspected influenza, irrespective of influenza vaccination history, in the following cases:

• Outpatients with illness onset 2 days or less
• Symptomatic outpatients with household contacts at high risk
• Symptomatic healthcare providers who care for patients at high risk, particularly those who are severely immunocompromised

Treatment regimens

Treatment regimens for patients with influenza A and influenza B are outlined below. The regimens are based on patient age and weight. ^{[3, 4, 2, 5, 6, 7]}

Baloxavir marboxil (Xofluza)

Patients aged 5 years and older who are otherwise healthy, or those aged 12 years or older at high risk of developing influenza-related complications  ^[8]  

• < 20 kg: 2 mg/kg PO as a single dose (oral suspension)
• 20 to < 80 kg: 40 mg PO as a single dose (oral suspension or tablet)
• ≥ 80 kg: 80 mg PO as a single dose (oral suspension or tablet)

Oseltamivir (Tamiflu, generic)*

Adolescents and adults

• Aged ≥13 years: 75 mg PO q12h for 5 days

Children aged 1-12 years

• ≤15 kg: 30 mg PO q12h for 5 days
• >15 to 23 kg: 45 mg PO q12h for 5 days
• >23 to 40 kg: 60 mg PO q12h for 5 days
• >40 kg: 75 mg PO q12h for 5 days

Children aged 2 weeks to younger than 1 year

• 3 mg/kg/dose PO q12h for 5 days 

*See recommendations for decreasing dose with renal impairment 

Zanamivir (Relenza DIskhaler)

Adults and children aged ≥7 years

• 10 mg (two 5-mg inhalations) inhaled q12h for 5 days

Peramivir (Rapivab)

Infuse diluted IV over 15-30 minutes

Adolescents and adults

• Aged >13 years: 600 mg IV as a single dose
• CrCl 30-49 mL/min: 200 mg IV
• CrCl 10-29 mL/min: 100 mg IV

Children aged 6 months to 12 years

• 12 mg/kg IV as a single dose; not to exceed 600 mg/dose
• 6 months to 2 years - CrCl < 50 mL/min: Data are not available
• 2-12 years - CrCl 30-49 mL/min: 4 mg/kg IV
• 2-12 years - CrCl 10-29 mL/min: 2 mg/kg IV

Prophylaxis

Antivirals should not be used for routine or widespread chemoprophylaxis outside of institutional outbreaks; antiviral chemoprophylaxis can be considered in the following cases ^[2] :

• The duration of influenza season in adults and children aged 3 months or older who are at very high risk of complications and for whom influenza vaccination is contraindicated, unavailable, or expected to have low effectiveness
• The duration of influenza season in adults and children aged 3 months or older who have the highest risk of influenza-associated complications (eg, HSCT recipients)
• Short-term prophylaxis in addition to prompt flu vaccination in unvaccinated individuals at high risk as previously described or who are in contact with high-risk individuals

Baloxavir marboxil (Xofluza) 

Post-exposure prophylaxis for patients aged 5 years and older  ^[9]

• < 20 kg: 2 mg/kg PO as a single dose (oral suspension) 
• 20 kg to < 80 kg: 40 mg (20 mL) PO as a single dose (tablet or oral suspension) 
• ≥80 kg: 80 mg (40 mL) PO as a single dose (tablet or oral suspension) 

Oseltamivir (Tamiflu)*

Aged 1-12 years 

• < 15 kg: 30 mg PO once daily
• >15 to 23 kg: 45 mg PO once daily
• >23-40 kg: 60 mg PO once daily
• >40 kg: 75 mg PO once daily

Adults and adolescents: 75 mg PO once daily

Pre-exposure prophylaxis duration: Up to 6 weeks (or up to 12 weeks in immunocompromised patient)

Post-exposure prophylaxis duration: 10 days 

*See recommendations for decreasing dose with renal impairment

Zanamivir (Relenza)

Patients aged 7 years and older 

• 10 mg (two 5-mg oral inhalations) once daily
• Pre-exposure prophylaxis duration: 28 days
• Post-exposure prophylaxis duration: 10 days

Special populations

Inpatient

Antiviral therapy should be initiated as early as possible in hospitalized patients with suspected or confirmed influenza, preferably within the first 48 hours of illness. However, antiviral therapy may still improve outcomes in hospitalized patients or outpatient high-risk individuals if started after the initial 48 hours of illness. Zanamivir disc inhaler administration is not possible for intubated patients or very young children, and is not appropriate in patients with underlying airway disease (eg, asthma, COPD). Depending on the severity of illness, hospitalized patients may require more than 5 days of antiviral therapy.

Outpatient

Certain populations are at higher risk for complications from influenza, as a result, initiation of antiviral treatment is recommended as early as possible for suspected or confirmed influenza in the following patient populations:

• Patients with severe, complicated, or progressive illness
• Children < 2 years
• Adults ≥65 years
• Immunosuppressed patients
• Pregnant women or women who are 2 weeks postpartum
• Individuals < 19 years on long-term aspirin therapy
• American Indians/Alaska Natives
• Morbidly obese individuals (BMI of ≥40)
• Residents of nursing homes or other long-term care facilities
• Patients with certain chronic diseases such as chronic pulmonary (eg, asthma), cardiovascular (excluding hypertension), renal, hepatic, hematological (eg, sickle cell disease), or metabolic disorders (eg, diabetes mellitus), neurological disorders of the brain (eg, stroke), spinal cord, or peripheral nerves, muscular disorders (eg, cerebral palsy, muscular dystrophy), seizure disorders (eg, epilepsy), and patients with intellectual disability or moderate to severe developmental delay