What is the recommended treatment and dosage for Xofluza (baloxavir marboxil) in patients with acute uncomplicated influenza?

Xofluza (Baloxavir Marboxil) Treatment and Dosing

Xofluza is administered as a single weight-based oral dose for treatment of acute uncomplicated influenza in patients ≥12 years of age within 48 hours of symptom onset, or for post-exposure prophylaxis within 48 hours of contact with an influenza-infected individual. 1

FDA-Approved Indications

Treatment of Acute Uncomplicated Influenza:

• Approved for patients ≥12 years of age who have been symptomatic for no more than 48 hours 1
• Includes both otherwise healthy patients and those at high risk of developing influenza-related complications 1

Post-Exposure Prophylaxis:

• Approved for persons ≥12 years of age following contact with an individual who has influenza 1
• Must be administered within 48 hours of exposure 2

Dosing Regimen

Weight-Based Single Dose (Tablets): 1

• <80 kg body weight: One 40 mg tablet as a single dose
• ≥80 kg body weight: One 80 mg tablet as a single dose

Oral Suspension (for patients unable to swallow tablets): 1

• <80 kg: 40 mg/20 mL (1 bottle) as a single dose
• ≥80 kg: 80 mg/40 mL (2 bottles) as a single dose
• Must be used within 10 hours after constitution 1

Administration Guidelines

Critical Drug Interactions to Avoid:

• Do NOT administer with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (calcium, iron, magnesium, selenium, or zinc) 1, 3
• These products significantly reduce baloxavir absorption 1

Timing:

• May be taken with or without food 1
• Can be administered orally or via feeding tube (suspension formulation) 1

Clinical Efficacy

Symptom Resolution:

• Baloxavir demonstrates similar efficacy to oseltamivir in reducing time to symptom improvement 3
• In high-risk patients, median time to improvement was 73.2 hours with baloxavir versus 102.3 hours with placebo (p<0.0001) 4
• Superior efficacy compared to oseltamivir specifically for influenza B infections 3

Viral Load Reduction:

• Baloxavir reduces viral shedding duration more rapidly than oseltamivir 3
• Significantly reduces viral load within 1 day of treatment compared to both placebo and oseltamivir 5

Special Populations and Considerations

Pediatric Patients:

• Currently approved only for ages ≥12 years 1
• Studies in children 1-<12 years show similar safety and efficacy profiles 6
• Oral suspension formulation availability in the United States has been limited 3
• Important caveat: In children <6 years of age, symptom recurrence after day 4 occurred in 54.5% and fever recurrence in 50% 3

Severely Immunocompromised Patients:

• NOT recommended as monotherapy due to risk of resistance emergence 3
• Consider combination therapy or alternative agents 3

Pregnancy and Breastfeeding:

• NOT recommended for pregnant or breastfeeding women 3

Resistance Concerns

Polymerase Acidic Protein (PA) Variants:

• Amino acid substitutions (Ile38Thr, Ile38Met, Ile38Asn) conferring reduced susceptibility emerged in approximately 5% of treated patients 4
• Evidence of human-to-human transmission of resistant variants exists 7
• Ongoing surveillance is critical 7

When to Choose Baloxavir Over Oseltamivir

Baloxavir is particularly advantageous when: 3

• Compliance is a concern (single dose vs. 5-day course)
• Poor tolerance of multiple-dose regimens
• Influenza B infection is suspected or confirmed 3
• During oseltamivir shortages (as occurred in 2022-2023) 3

Safety Profile

Common Adverse Events: 4, 6

• Diarrhea, bronchitis, nausea, nasopharyngitis, headache
• Overall incidence similar to placebo (25% vs. 30%) 4
• Well tolerated in pediatric populations 6

Serious Reactions:

• Anaphylaxis, angioedema, urticaria, and erythema multiforme reported in post-marketing surveillance 1
• Contraindicated in patients with known hypersensitivity 1

Post-Exposure Prophylaxis Specifics

Eligible Populations: 2

• Asymptomatic individuals at very high risk of complications (e.g., severely immunocompromised)
• Unvaccinated household contacts of very high-risk individuals

Dosing for Prophylaxis:

• Same weight-based single dose as treatment 1
• Must be initiated within 48 hours of exposure 2

Critical Monitoring:

• If symptoms develop during prophylaxis, immediately switch to full treatment dosing with a different antiviral class if possible 2

Common Pitfalls to Avoid

• Do not delay treatment beyond 48 hours of symptom onset for optimal efficacy 1
• Do not use as monotherapy in severely immunocompromised patients 3
• Do not administer with polyvalent cations (dairy, supplements, antacids) 1, 3
• Do not use as substitute for vaccination - always offer influenza vaccine when not contraindicated 2
• Do not routinely use for prophylaxis in all exposed individuals - reserve for very high-risk groups 2