Baloxavir Marboxil

• Treatment of acute uncomplicated influenza in patients aged 12 years and older who have been symptomatic for no more than 48 hours.
• Post-exposure prophylaxis of influenza in individuals aged 12 years and older who have been exposed to the influenza virus but are not yet symptomatic.

Off-label or investigational uses:

• Treatment of influenza in pediatric patients aged 5 to 11 years (approved in some regions).
• Use in outbreaks in institutional settings to limit influenza spread.

• Route: Oral administration.
• Adult and adolescents (≥12 years):
• Body weight 40 kg to <80 kg: 40 mg once.
• Body weight ≥80 kg: 80 mg once.
• Pediatrics (5 to <12 years):
• 10 to <20 kg: 20 mg once.
• 20 to <40 kg: 40 mg once.
• Elderly: No dosage adjustment required.
• Renal and hepatic impairment: No dosage adjustments necessary for mild to moderate impairment; insufficient data for severe impairment — use with caution.
• Administration notes:
• May be taken with or without food.
• Avoid concomitant use or administration close to products containing polyvalent cations (calcium, magnesium, iron, zinc, selenium) as they reduce absorption. Separate administration by at least 4 hours.

Baloxavir marboxil is a prodrug that is rapidly converted to the active metabolite baloxavir acid. It inhibits the cap-dependent endonuclease activity of the viral polymerase acidic (PA) protein, a critical enzyme required for viral mRNA synthesis. By blocking this enzyme, it prevents viral replication by stopping the "cap-snatching" process essential for transcription of viral mRNA, leading to reduced viral load and shortened duration of symptoms.

• Absorption: Rapid; peak plasma levels reached approximately 4 hours after oral dosing.
• Bioavailability: Approximately 50%.
• Distribution: Extensive plasma protein binding (~93%).
• Metabolism: Metabolized primarily by uridine diphosphate-glucuronosyltransferase (UGT1A3) and cytochrome P450 enzyme CYP3A4.
• Elimination half-life: Approximately 79 hours.
• Excretion: Primarily eliminated in feces (~80%); minimal renal excretion.

• Pregnancy: No well-controlled studies in pregnant women. Animal studies show no evidence of harm; use only if clearly needed.
• Lactation: Unknown if excreted in human milk; exercise caution when administered to breastfeeding women.

• Primary class: Antiviral agent.
• Subclass: Influenza polymerase acidic (PA) endonuclease inhibitor.
• Generation: First-in-class cap-dependent endonuclease inhibitor.

• Hypersensitivity to baloxavir marboxil or any component of the formulation.
• Known severe allergic reaction to similar antiviral agents.

• Risk of hypersensitivity reactions including anaphylaxis.
• Potential for emergence of viral resistance, especially with PA/I38T mutation.
• Avoid use as a substitute for influenza vaccination.
• Avoid coadministration with cation-containing products which reduce absorption.
• Use with caution in immunocompromised patients due to possible treatment failure or resistance.

• Common: Diarrhea, bronchitis, nausea, headache.
• Serious but rare: Hypersensitivity reactions such as rash, urticaria, and anaphylaxis.
• Side effects typically occur within the first day post-administration and are mild to moderate in severity.

• Caution with polyvalent cations (e.g., calcium, magnesium, iron, zinc) due to decreased absorption if co-administered; separate dosing by at least 4 hours.
• Avoid live attenuated influenza vaccine (LAIV) within 2 weeks after or 48 hours before baloxavir administration.
• Minimal involvement of CYP450 enzymes reduces potential for significant drug-drug interactions.

• Recognized by WHO and CDC as an effective single-dose treatment for uncomplicated influenza.
• EMA extended approval for treatment and prophylaxis in children aged 5 years and older.
• Ongoing surveillance for resistance patterns, especially mutations affecting endonuclease activity.
• No recent major changes in dosing recommendations or safety warnings.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).
• Protect from moisture and light by keeping in original packaging until use.
• Do not freeze.
• Tablets are for oral use and require no reconstitution.