Influenza Antivirals

Influenza antivirals shorten illness by about 1 day and reduce complications when given early, and in severe disease they lower mortality even when started later. Neuraminidase inhibitors (oseltamivir, zanamivir, peramivir) are the main class. Baloxavir acts by a different mechanism. The older adamantanes (amantadine, rimantadine) are no longer used because circulating strains are resistant.

Mechanism.

• Neuraminidase inhibitors block release of new virions from infected cells.
• Baloxavir inhibits the cap-dependent endonuclease of the viral polymerase, stopping transcription.

Pharmacokinetics. Oseltamivir is an oral prodrug converted to oseltamivir carboxylate and cleared by the kidney. Zanamivir is inhaled, with low systemic exposure. Baloxavir has a long half-life, so a single dose is enough.

• Oseltamivir: first choice for almost all patients, including pregnancy, young children and critical illness.
• Zanamivir: inhaled 10 mg (two inhalations) twice daily for 5 days. Not for asthma or chronic obstructive pulmonary disease because of bronchospasm; not for ventilated patients.
• Peramivir: single intravenous dose of 600 mg where available; useful when oral absorption is unreliable.
• Baloxavir: single oral dose, 40 mg for 40 to under 80 kg and 80 mg for 80 kg and over, in patients aged 5 years and over. Resistance mutation (I38T) can emerge during treatment. Not used alone in severely immunocompromised patients.

Who to treat. Start oseltamivir as early as possible, ideally within 48 hours of symptom onset, in:

• All hospitalised patients and any patient with severe, complicated or progressive illness, even after 48 hours.
• Outpatients at high risk: pregnancy and up to 2 weeks after delivery, age 65 years and over, age under 2 years, chronic heart, lung, kidney or liver disease, diabetes, obesity, immunosuppression, sickle cell disease.
• Suspected avian influenza.

Oseltamivir dosing (treatment, 5 days).

• Adults: 75 mg twice daily. Higher doses have not shown extra benefit in severe disease.
• Children over 1 year: 15 kg or less 30 mg; over 15 to 23 kg 45 mg; over 23 to 40 kg 60 mg; over 40 kg 75 mg, each twice daily.
• Infants under 1 year: 3 mg/kg twice daily (3.5 mg/kg from 9 to 11 months); preterm infants need specialist dosing.
• Prophylaxis after close contact in high-risk people: the same dose once daily for 7 to 10 days.

Renal adjustment. Creatinine clearance 30 to 60 mL/min: 30 mg twice daily. 10 to 30 mL/min: 30 mg once daily. Haemodialysis: 30 mg after each session.

Region. In East Africa, seasonality varies by location and oseltamivir supply is limited. Early empirical treatment is justified for severe acute respiratory illness during local influenza activity while tests are pending.

Adverse effects. Oseltamivir: nausea and vomiting (reduced by taking with food), rarely neuropsychiatric events, mostly in children, and serious skin reactions. Zanamivir: bronchospasm. Baloxavir: diarrhoea, bronchitis.

Interactions. Few. Live attenuated influenza vaccine is made less effective if given from 48 hours before to 2 weeks after antivirals. Baloxavir absorption is reduced by polyvalent cations (calcium, iron, magnesium, aluminium).

Monitoring. Renal function for dose adjustment, hydration, and clinical response at 48 to 72 hours. Persisting fever at 5 days or worsening signs need review for bacterial pneumonia.

Special groups.

• Pregnancy: oseltamivir is preferred; baloxavir data are limited.
• Breastfeeding: oseltamivir is acceptable.
• Older adults: reduce for renal function.
• Immunocompromised: prolonged courses may be needed under specialist direction because viral shedding continues.

Referral and escalation. Refer for respiratory failure, immunosuppression with persistent shedding, or suspected resistant virus.