What is the role of Xofluza (baloxavir marboxil) in treating influenza in patients 12 years and older with underlying health conditions or at high risk for complications?

Xofluza (Baloxavir Marboxil) for Influenza Treatment in High-Risk Patients

Xofluza is an acceptable alternative to oseltamivir for treating influenza in patients 12 years and older with high-risk conditions, particularly when medication compliance is a concern, though oseltamivir remains the preferred first-line agent. 1

Primary Recommendation

Oseltamivir remains the drug of choice for managing influenza in high-risk patients, including those with underlying health conditions, due to cumulative clinical experience, relative cost, and ease of administration. 1 However, Xofluza offers a valuable alternative option in specific clinical scenarios.

When to Consider Xofluza Over Oseltamivir

Xofluza should be considered as an alternative when:

• Compliance is a concern - The single-dose regimen eliminates the need for multiple doses over 5 days 1
• Poor tolerance of multi-dose regimens - Patients who cannot tolerate or have difficulty with twice-daily dosing for 5 days 1
• Influenza B infection - Baloxavir demonstrated superior efficacy compared to oseltamivir specifically for influenza B in randomized controlled trials 1

FDA-Approved Indications

Xofluza is approved for:

• Treatment: Acute uncomplicated influenza in patients ≥12 years (including high-risk patients) who have been symptomatic for ≤48 hours 2
• Post-exposure prophylaxis: Patients ≥12 years following contact with an influenza-infected individual 2

Dosing for High-Risk Patients

Single oral dose based on body weight: 2

• <80 kg: 40 mg as a single dose
• ≥80 kg: 80 mg as a single dose

Critical timing: Administer within 48 hours of symptom onset for treatment or within 48 hours of exposure for prophylaxis 2

Comparative Efficacy in High-Risk Populations

Clinical outcomes with baloxavir are generally similar to neuraminidase inhibitors (oseltamivir) in high-risk patients: 1

• In the CAPSTONE-2 trial of high-risk outpatients, median time to symptom improvement was 73.2 hours with baloxavir versus 102.3 hours with placebo (p<0.0001) 3
• Time to symptom improvement was comparable between baloxavir (73.2 hours) and oseltamivir (81.0 hours) 3
• Baloxavir reduces viral shedding duration more rapidly than oseltamivir, which may have implications for transmission reduction 1, 4

Important Limitations and Caveats

Resistance Concerns

Polymerase acidic protein variants with reduced baloxavir susceptibility emerged in approximately 9.7% of treated patients in phase 3 trials 4, though all tested influenza viruses during 2019-2020 remained susceptible 1. This is higher than resistance rates seen with oseltamivir and requires ongoing surveillance.

Not Recommended For:

• Severely immunocompromised patients as monotherapy - Risk of resistance emergence 1
• Pregnant or breastfeeding women 1
• Hospitalized patients with serious/complicated influenza - Oseltamivir is the only AAP-recommended drug for hospitalized children and should be extrapolated to adults 1

Drug Interactions

Avoid coadministration with: 2

• Dairy products
• Calcium-fortified beverages
• Polyvalent cation-containing laxatives or antacids
• Oral supplements (calcium, iron, magnesium, selenium, zinc)

These interactions can significantly reduce baloxavir absorption and efficacy.

Safety Profile

Baloxavir is well tolerated with a safety profile comparable to placebo: 3

• Adverse events in 25% of baloxavir recipients versus 30% with placebo 3
• Most common: diarrhea (3%), bronchitis (3%), nausea (2%), sinusitis (2%), headache (1%) 2
• Serious adverse events were rare and similar across treatment groups 3

Post-Exposure Prophylaxis

For prophylaxis in high-risk patients ≥12 years: 5

• Single dose within 48 hours of exposure to an influenza-infected individual 2
• Particularly useful for severely immunocompromised patients or unvaccinated household contacts of high-risk individuals 5
• If symptoms develop while on prophylaxis, immediately switch to full treatment dosing 5

Practical Algorithm for High-Risk Patients ≥12 Years

1. First-line: Oseltamivir 75 mg twice daily for 5 days 1

2. Switch to Xofluza if:

   • Compliance concerns with 5-day regimen
   • Intolerance to oseltamivir
   • Influenza B confirmed
   • Patient preference for single-dose therapy

3. Avoid Xofluza if:

   • Severely immunocompromised (use oseltamivir)
   • Pregnant or breastfeeding
   • Hospitalized with severe/complicated influenza
   • Recent intake of calcium/iron/magnesium supplements or dairy products

4. Timing is critical: Initiate within 48 hours of symptom onset regardless of which agent is chosen 1

Common Pitfalls to Avoid

• Do not delay treatment beyond 48 hours - Both agents work best when started early, though some benefit exists even after 48 hours in high-risk patients 1
• Do not use Xofluza with dairy or supplements - This significantly reduces drug absorption 2
• Do not use as monotherapy in severely immunocompromised patients - Higher resistance risk 1
• Do not substitute chemoprophylaxis for vaccination - Vaccination remains the primary prevention strategy 1