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Influenza Antiviral Therapy

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.

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:

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.

Baloxavir marboxil (Xofluza)

Adolescents and adults aged 12 years or older

Dose based on body weight, as follows:

40 to < 80 kg: 40 mg PO as a single dose

≥ 80 kg: 80 mg PO as a single dose

Oseltamivir (Tamiflu, generic)

Adolescents and adults

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

Children aged 1-12 years

Oseltamivir treatment varies by weight, as follows:

≤15 kg: Oseltamivir 30 mg PO q12h for 5 days

>15 to 23 kg: Oseltamivir 45 mg PO q12h for 5 days

>23 to 40 kg: Oseltamivir 60 mg PO q12h for 5 days

>40 kg: Oseltamivir 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

Zanamivir (Relenza DIskhaler)

Adults and children aged ≥7 years

10 mg (2 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

Chemoprophylaxis of patients with suspected influenza

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

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

Adolescents and adults

Oseltamivir 75 mg PO once daily
or

Zanamivir (Relenza Diskhaler) 10 mg (two 5-mg inhalations) inhaled once daily

Children aged 1-12 years

Oseltamivir treatment varies by weight, as follows:

≤15 kg: oseltamivir 30 mg PO once daily for 7 days

>15 to 23 kg: oseltamivir 45 mg PO once daily for 7 days

>23 to 40 kg: oseltamivir 60 mg PO once daily for 7 days

>40 kg: oseltamivir 75 mg PO once daily for 7 days

Zanamivir prophylaxis (aged ≥5 y) consists of 10 mg (two 5-mg inhalations) inhaled PO once daily for 7 days.

Children younger than 1 year

Oseltamivir prophylaxis (aged 3 months to 1 year) consists of 3 mg/kg/dose PO once daily for 5 days.

In children younger than 3 months, oseltamivir prophylaxis is not recommended unless the situation is judged critical, owing to limited data in this age group.

Duration of chemoprophylaxis

Postexposure prophylaxis: 10 days when administered after a household exposure, or for high-risk patients, 7 days after the most recent known exposure when prophylaxis can be initiated within 48 hours of exposure

Pre-exposure prophylaxis: Dependent on duration of community outbreak as the antiviral needs to be taken every day during the outbreak to be maximally effective

Outbreaks in long-term care facilities and hospitals: Prophylaxis for ≥14 days and up to 7 days after the most recent known case was identified (CDC recommendation)

Oseltamivir: Up to 6 weeks

Zanamivir: Up to 4 weeks

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

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