Is baloxivir (Xofluza) effective against influenza B in patients with a history of respiratory or cardiac disease, and are there any contraindications to its use?

Baloxavir Efficacy Against Influenza B and Contraindications

Baloxavir is effective against influenza B and has better efficacy than oseltamivir specifically for influenza B treatment, with no absolute contraindications to its use, though treatment-emergent resistance is a concern particularly in young children. 1

Efficacy Against Influenza B

Baloxavir demonstrates superior efficacy compared to oseltamivir for influenza B infections. In a randomized controlled trial enrolling adolescents and adults, baloxavir showed better efficacy than oseltamivir specifically in the treatment of influenza B. 1 This is particularly noteworthy given that neuraminidase inhibitors have historically shown less consistent efficacy against influenza B compared to influenza A. 2

Mechanism and Activity

• Baloxavir works through a novel mechanism by inhibiting the cap-dependent endonuclease activity of the viral PA polymerase subunit, blocking viral mRNA transcription. 3, 4
• It has demonstrated activity against both influenza A and B viruses, including strains resistant to neuraminidase inhibitors. 5
• The drug significantly reduces viral load within 1 day after treatment compared to both placebo and oseltamivir. 3

Clinical Outcomes

• Baloxavir provides similar overall clinical outcomes to neuraminidase inhibitors in terms of symptom duration. 1
• Some observational studies suggest more rapid resolution of fever in children treated with baloxavir compared with oseltamivir, though a post hoc analysis of children 5-11 years showed similar fever durations. 1
• Baloxavir reduces the duration of viral shedding compared to oseltamivir in patients infected with influenza. 1

Contraindications and Safety Profile

There are no absolute contraindications to baloxavir use. 6 The drug is well tolerated with only mild adverse events reported, including nausea, headache, diarrhea, bronchitis, and nasopharyngitis. 3, 5

Important Safety Considerations

• Hypersensitivity reactions: While no formal contraindication exists, hypersensitivity reactions including anaphylaxis have been reported postmarketing for similar antivirals. 6
• Renal impairment: Unlike oseltamivir, baloxavir does not require dose adjustment for renal insufficiency, as it is not primarily renally cleared. 6

Critical Resistance Concerns

The most significant limitation of baloxavir is treatment-emergent resistance, particularly in young children and those infected with influenza A(H3N2). 1

Resistance Patterns

• In an analysis of four pediatric trials, treatment-emergent resistance substitutions after baloxavir use were highest in subjects <5 years of age, with a clear peak in children 2-4 years of age. 1
• Resistance was substantially higher in subjects infected with influenza A(H3N2) compared to other strains. 1
• Globally, reduced susceptibility to baloxavir was observed in 0.5% during the 2018-2019 season and 0.1% during the 2019-2020 season, though rates were higher in Japan (4.5%) where baloxavir use is highest. 1
• During the 2023-2024 season, one influenza A H3N2 virus exhibited decreased susceptibility to baloxavir. 1

Clinical Implications of Resistance

Knowledge of the circulating influenza strain may influence the decision to use baloxavir. 1 Given the higher resistance rates with H3N2 strains and in young children, clinicians should consider these factors when choosing between baloxavir and neuraminidase inhibitors.

Approved Indications and Dosing

• Baloxavir is approved for treatment of acute uncomplicated influenza in otherwise healthy patients ≥12 years of age and those at high risk of developing influenza-related complications. 1
• It is also FDA-approved for postexposure prophylaxis in persons ≥5 years of age within 48 hours of contact with an individual with influenza. 1
• Single-dose administration: 40 mg orally once for patients <80 kg; 80 mg orally once for patients ≥80 kg, given within 48 hours of symptom onset. 3

Formulation Availability Issue

A critical caveat: The oral suspension formulation of baloxavir was not available in the United States for the 2023-2024 influenza season, limiting use in children who weigh less than 20 kg. 1 Availability for the 2024-2025 season remains uncertain. 1

Special Populations

Patients with Respiratory or Cardiac Disease

For patients with a history of respiratory or cardiac disease, baloxavir can be used safely as there are no specific contraindications for these populations. 1 However, the American Academy of Pediatrics still recommends oseltamivir as the drug of choice due to:

• More extensive cumulative experience in diverse patient populations 1
• Lower cost 1
• Established efficacy data in high-risk patients 1

Immunocompromised Patients

Baloxavir is not routinely recommended for immunocompromised patients. 1 The CDC notes limited efficacy data in immunocompromised patients with oseltamivir- or peramivir-resistant influenza, and due to limited data and emergence of resistant strains, baloxavir is not routinely recommended in this population. 1

Clinical Decision-Making Algorithm

When to choose baloxavir over oseltamivir:

1. Influenza B infection confirmed or suspected - baloxavir shows superior efficacy 1
2. Compliance concerns - single-dose administration improves adherence 1
3. Patient age ≥12 years and weight ≥20 kg - within approved indications 1
4. Influenza A(H1N1) or unknown strain - lower resistance risk 1

When to avoid baloxavir:

1. Children <5 years of age - high resistance emergence rates 1
2. Known H3N2 circulation - higher resistance rates 1
3. Immunocompromised patients - limited efficacy data and resistance concerns 1
4. Hospitalized or severely ill patients - oseltamivir remains preferred with more extensive safety data 1
5. Weight <20 kg - oral suspension unavailable 1