Baloxavir Marboxil

Baloxavir marboxil is an oral prodrug of an influenza cap-dependent endonuclease inhibitor, given as a single dose for uncomplicated influenza A and B and for post-exposure prophylaxis. It shortens illness similarly to oseltamivir and lowers viral load more quickly. Resistance (PA I38T) can emerge during treatment, particularly in children. It has not been shown to improve outcomes in severe influenza.

Class. Cap-dependent endonuclease inhibitor antiviral.

Mechanism. The active baloxavir acid inhibits the polymerase acidic (PA) protein endonuclease, blocking viral mRNA initiation and replication.

Pharmacokinetics. Oral prodrug rapidly hydrolysed in the gut and liver. Half life about 79 hours, allowing single-dose use. Highly protein bound; faecal elimination. Absorption is reduced by polyvalent cations.

Uncomplicated influenza treatment (age 5 years and over, or 1 year and over in some regions).

• Single oral dose: 40 mg for 40 kg to under 80 kg; 80 mg for 80 kg or more; started within 48 hours of onset.
• Children under 40 kg (where licensed): 2 mg/kg single dose (granules), maximum 40 mg.

Post-exposure prophylaxis. The same single dose, within 48 hours of contact.

Severe or hospitalised influenza. Not advised as monotherapy; evidence of added benefit with oseltamivir is not established.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 80 mg once.

Main alternatives. Oseltamivir or zanamivir.

Contraindications. Hypersensitivity to baloxavir or any component.

Serious adverse effects. Anaphylaxis, angioedema and severe skin reactions (rare); bleeding events were reported.

Common adverse effects. Diarrhoea, nausea, bronchitis, headache.

Interactions. Do not take with dairy products, calcium-fortified drinks, antacids, laxatives or supplements containing calcium, iron, magnesium, aluminium or zinc (chelation lowers levels). Live attenuated influenza vaccine should be avoided for 2 weeks after.

Common prescribing errors. Giving with dairy or antacids, using as monotherapy in severe disease, and repeating the dose.

Special groups.

• Pregnancy: limited data; oseltamivir preferred.
• Breastfeeding: no data; avoid or use oseltamivir.
• Children: age and weight limits by region; resistance emerges more often.
• Older adults: no adjustment.
• Kidney impairment: mild to moderate: no adjustment; severe: limited data.
• Liver impairment: mild to moderate: no adjustment; severe: not studied.

Formulations. Tablets 20 mg and 40 mg; granules for suspension (where licensed).

Administration. With or without food, taken with water; separate from cation-containing products by at least 2 hours.

Baseline. Weight and confirmation of influenza by test where available.

Monitoring. Clinical response at 48 hours; reassess for persistent fever or worsening symptoms.

Stopping thresholds. Not applicable for a single dose; treat hypersensitivity.

Referral and escalation. Admission for severe illness; specialist review for immunocompromised patients (prolonged shedding and resistance risk).