What is the recommended treatment with Xofluza (baloxavir marboxil) for patients diagnosed with acute uncomplicated influenza, particularly for high-risk patients such as the elderly, young children, and those with chronic health conditions like heart disease, lung disease, or diabetes?

Xofluza (Baloxavir Marboxil) Treatment Recommendations for Acute Uncomplicated Influenza

Xofluza is FDA-approved for treatment of acute uncomplicated influenza in patients ≥12 years of age who have been symptomatic for no more than 48 hours, administered as a single weight-based oral dose (40 mg for <80 kg, 80 mg for ≥80 kg). 1

FDA-Approved Indications and Dosing

Treatment Indication:

• Approved for acute uncomplicated influenza in patients ≥12 years who are otherwise healthy OR at high risk of developing influenza-related complications 1
• Must be initiated within 48 hours of symptom onset 1

Dosing:

• <80 kg body weight: Single 40 mg oral dose 1
• ≥80 kg body weight: Single 80 mg oral dose 1
• Available as tablets or oral suspension (2 mg/mL when constituted) 1

Administration Requirements and Drug Interactions

Critical administration instructions:

• Avoid coadministration with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (calcium, iron, magnesium, selenium, zinc) as these significantly reduce absorption 2, 1
• May be taken with or without food 1
• Can be administered orally or via feeding tube 2

Contraindications and Precautions

Absolute contraindications:

• Pregnancy 2
• Breastfeeding 2
• Severely immunocompromised patients as monotherapy (due to resistance concerns) 2
• History of hypersensitivity to baloxavir marboxil 1

Comparative Efficacy with Oseltamivir

Clinical outcomes:

• Time to symptom alleviation is similar between baloxavir and oseltamivir in otherwise healthy patients 2, 3
• Baloxavir demonstrates superior efficacy against influenza B compared to oseltamivir in adolescents and adults 2
• Baloxavir reduces viral shedding more rapidly than oseltamivir (within 1 day of treatment) 2, 3

Pediatric considerations:

• In children 5-11 years, fever duration was similar between baloxavir and oseltamivir 2
• In children <6 years, symptom recurrence after day 4 occurred in 54.5% and fever recurrence in 50% with baloxavir 2

Current Guideline Recommendations

The American Academy of Pediatrics (AAP) recommends oseltamivir as the antiviral drug of choice for influenza management in children, particularly for hospitalized patients. 2

Baloxavir positioning:

• Considered an alternative to oseltamivir when compliance is a concern or poor tolerance of multiple-dose regimens 2
• The single-dose regimen offers convenience advantages 2, 4, 5
• Not recommended as first-line for hospitalized or severely ill patients due to limited data in this population 2

High-Risk Patient Populations

Patients at high risk for influenza complications who may receive baloxavir include: 1, 6

• Adults ≥65 years of age
• Patients with chronic cardiac disease
• Patients with chronic pulmonary disease (including asthma)
• Patients with diabetes mellitus
• Patients with chronic renal disease
• Patients with chronic liver disease

Important caveat: While FDA-approved for high-risk patients, oseltamivir remains the preferred agent for hospitalized or severely ill high-risk patients based on more extensive clinical experience 2, 7

Resistance Concerns

Emergence of resistance variants:

• Polymerase acidic protein variants with reduced baloxavir susceptibility (I38T/M/F substitutions) emerged in 9.7% of treated patients in phase 3 trials 2, 3
• Decreased susceptibility has been reported more commonly in Japan where baloxavir use is more prevalent 2
• Ongoing surveillance is critical to monitor resistance patterns 2, 5

Post-Exposure Prophylaxis

FDA approval for prophylaxis:

• Approved for post-exposure prophylaxis in persons ≥12 years following contact with an influenza-infected individual 1
• Single dose administered within 48 hours of exposure 2
• Efficacy: 1% developed influenza with baloxavir vs 13% with placebo in household contacts 2

Guideline recommendations for prophylaxis:

• Consider for severely immunocompromised persons after household exposure 8
• Consider for unvaccinated household contacts of very high-risk individuals 8
• Neuraminidase inhibitors (oseltamivir, zanamivir) remain the primary recommended agents for post-exposure prophylaxis in most guidelines 8

Practical Clinical Algorithm

For otherwise healthy outpatients ≥12 years with acute uncomplicated influenza:

1. Confirm symptom duration <48 hours 1
2. Verify no contraindications (pregnancy, breastfeeding, severe immunocompromise) 2, 1
3. Counsel patient to avoid dairy products and supplements for several hours around dosing 2, 1
4. Prescribe single weight-based dose 1
5. Consider baloxavir particularly when compliance with 5-day oseltamivir regimen is a concern 2

For high-risk or hospitalized patients:

1. Prioritize oseltamivir as first-line therapy 2, 7
2. Consider baloxavir only if oseltamivir is contraindicated or not tolerated 2
3. Do not delay treatment waiting for laboratory confirmation 7, 9

Common Pitfalls to Avoid

• Do not use baloxavir in pregnant or breastfeeding women 2
• Do not use as monotherapy in severely immunocompromised patients due to resistance emergence risk 2
• Do not administer with dairy products or supplements containing polyvalent cations 2, 1
• Do not assume baloxavir is superior to oseltamivir for symptom reduction—efficacy is similar 2
• Do not use baloxavir as first-line in hospitalized patients—oseltamivir has more robust evidence in severe disease 2, 9

Adverse Effects

Common adverse events (≥1%): 1

• Diarrhea (3%)
• Bronchitis (3%)
• Nausea (2%)
• Sinusitis (2%)
• Headache (1%)

Overall tolerability:

• Adverse events reported in 20.7% of baloxavir recipients vs 24.6% with placebo and 24.8% with oseltamivir 3
• Generally well tolerated with only mild adverse events 4, 5, 10

Availability Considerations

Important supply issue:

• The oral suspension formulation was not available in the United States for the 2023-2024 influenza season, limiting use in patients <80 kg who cannot swallow tablets 2
• Availability for 2024-2025 season is uncertain at this time 2