What is the recommended dose of Xofluza (baloxavir marboxil) for adults, adolescents, and children based on weight, and are dose adjustments required for hepatic or renal impairment?

Xofluza Dosing Recommendations

Xofluza (baloxavir marboxil) is administered as a single oral dose based on body weight: 40 mg for patients weighing less than 80 kg and 80 mg for patients weighing 80 kg or more, with no dose adjustments required for hepatic or renal impairment. 1, 2

Weight-Based Dosing for Adults and Adolescents ≥12 Years

The dosing is straightforward and weight-dependent:

• Patients weighing <80 kg: 40 mg as a single oral dose 1, 2
• Patients weighing ≥80 kg: 80 mg as a single oral dose 1, 2

This single-dose regimen is FDA-approved for treatment of acute uncomplicated influenza within 48 hours of symptom onset in patients ≥12 years of age. 3, 4

Pediatric Dosing (Ages 5-11 Years)

For children 5 years and older weighing less than 20 kg, the recommended dose is 2 mg/kg as a single dose. 5 However, a critical limitation exists: the oral suspension formulation of baloxavir was not available in the United States for the 2023-2024 influenza season, restricting use in children who weigh less than 20 kg. 3 Availability for the 2024-2025 season remains uncertain. 3

For children weighing ≥20 kg, the adult weight-based dosing applies (40 mg for <80 kg). 1

Timing of Administration

Treatment must be initiated within 48 hours of symptom onset for optimal efficacy. 3, 4, 2 The single-dose nature of Xofluza offers a significant compliance advantage over oseltamivir's twice-daily, 5-day regimen, particularly when adherence is a concern. 3

Hepatic and Renal Impairment

No dosage adjustment is needed in patients with mild-to-moderate hepatic or renal impairment. 2 This represents a practical advantage over some other antivirals that require complex renal dose adjustments.

Administration Instructions and Drug Interactions

Critical administration caveat: Baloxavir should not be administered with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements containing calcium, iron, magnesium, selenium, or zinc. 3 These products can significantly reduce baloxavir absorption and efficacy.

The medication can be administered orally or via feeding tube. 3

Special Populations and Contraindications

Baloxavir is not recommended for:

• Severely immunocompromised patients as monotherapy (due to concerns about resistance emergence) 3
• Pregnant or breastfeeding women 3
• Children younger than 5 years (not FDA-approved for this age group) 3

Clinical Efficacy and Resistance Considerations

Baloxavir demonstrates similar efficacy to oseltamivir in reducing time to symptom alleviation, with the added benefit of more rapid viral load reduction. 3, 4, 1 In one randomized controlled trial, baloxavir showed superior efficacy to oseltamivir specifically for influenza B. 3

Important caveat: Post-hoc analyses in Japanese children <12 years revealed symptom recurrence after day 4 in 54.5% of treated children <6 years, with fever recurrence in 50%. 3 This finding warrants careful monitoring in younger pediatric patients.

Polymerase acidic protein variants with reduced baloxavir susceptibility emerged in approximately 5% of treated patients in clinical trials. 6 This highlights the importance of reserving baloxavir for appropriate clinical scenarios and avoiding use as monotherapy in severely immunocompromised individuals. 3

Safety Profile

Baloxavir is well tolerated with mild adverse events including diarrhea, bronchitis, nausea, nasopharyngitis, and headache. 4, 1, 2 The safety profile is comparable to placebo and similar to oseltamivir. 7, 6 In pediatric trials, gastrointestinal adverse events (vomiting/diarrhea) occurred in 10.4% of baloxavir-treated children versus 17.2% with oseltamivir. 7

Practical Clinical Algorithm

1. Confirm patient eligibility: Age ≥5 years (or ≥12 years for full FDA approval), symptom duration <48 hours, acute uncomplicated influenza
2. Assess contraindications: Pregnancy, breastfeeding, severe immunocompromise
3. Weigh the patient to determine correct dose
4. Instruct patient to avoid dairy, calcium-fortified beverages, antacids, and polyvalent cation supplements for several hours before and after administration
5. Administer single dose: 40 mg (<80 kg) or 80 mg (≥80 kg)
6. No dose adjustment needed for renal or hepatic impairment