What are the risks and considerations for using Xofluza (baloxavir marboxil) in pediatric patients with regards to rhabdomyolysis?

Xofluza (Baloxavir Marboxil) and Rhabdomyolysis Risk in Pediatric Patients

Xofluza (baloxavir marboxil) has no documented association with rhabdomyolysis in pediatric patients, and can be safely used in children ≥5 years of age for influenza treatment.

Safety Profile of Xofluza in Pediatric Patients

Baloxavir marboxil (Xofluza) is FDA-approved for treatment of acute uncomplicated influenza in children 5 years and older. According to the most recent American Academy of Pediatrics (AAP) guidelines for influenza prevention and control (2024), the safety profile of baloxavir in pediatric patients is well established 1.

The most common adverse events reported with baloxavir use in children include:

• Nausea
• Vomiting
• Diarrhea
• Headache
• Bronchitis
• Nasopharyngitis

Clinical Trial Evidence

In the miniSTONE-2 trial, a randomized, double-blind, active-controlled phase 3 study that evaluated baloxavir in children 1-<12 years old:

• No serious adverse events were reported
• No hospitalizations occurred
• Gastrointestinal symptoms were the most common side effects 2

A post-hoc analysis of this trial specifically examining children 5-11 years old confirmed:

• Low incidence of adverse events
• No serious adverse events
• No deaths
• Most common adverse events were vomiting (5% baloxavir vs 18% oseltamivir), diarrhea (5% vs 0%), and otitis media (0% vs 5%) 3

Rhabdomyolysis and Influenza

While rhabdomyolysis has been reported as a rare complication of influenza A infection itself 4, there is no evidence in the current guidelines or clinical trials linking baloxavir treatment with rhabdomyolysis in pediatric patients.

The 2024 AAP guidelines for influenza prevention and control do not mention rhabdomyolysis as a potential adverse effect of baloxavir 1. This is significant because these guidelines represent the most up-to-date recommendations for influenza management in children.

Considerations for Baloxavir Use in Pediatric Patients

When prescribing baloxavir for pediatric patients, consider the following:

1. Age and weight requirements:

   • Approved for children ≥5 years of age
   • Dosing is weight-based: 40 mg for patients weighing <80 kg, 80 mg for those ≥80 kg 1

2. Administration considerations:

   • Single-dose regimen (advantage for compliance)
   • Should not be administered with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (calcium, iron, magnesium, selenium, zinc) 1
   • Can be administered orally or by feeding tube 1

3. Timing of treatment:

   • Must be given within 48 hours of symptom onset for optimal efficacy 1

4. Special populations:

   • Not recommended as monotherapy for severely immunocompromised individuals
   • Not recommended for pregnant or breastfeeding individuals 1

5. Resistance concerns:

   • Higher incidence of treatment-emergent resistance in children <5 years, with peak in ages 2-4 years
   • Resistance is substantially higher in patients infected with influenza A(H3N2) 1

Comparative Efficacy

Baloxavir has demonstrated efficacy similar to oseltamivir in pediatric patients:

• Median time to alleviation of symptoms: 138.1 hours with baloxavir versus 150.0 hours with oseltamivir 2
• More rapid reduction in viral load compared to oseltamivir 1, 3
• Shorter median time to cessation of viral shedding (1 day vs approximately 3 days) 3

Clinical Algorithm for Baloxavir Use in Pediatric Patients

1. Confirm influenza diagnosis (clinical or laboratory)
2. Verify eligibility:
   • Age ≥5 years
   • Within 48 hours of symptom onset
   • No contraindications (severe immunocompromise, pregnancy, breastfeeding)
3. Determine appropriate dose based on weight
4. Administer as single dose away from products containing polyvalent cations
5. Monitor for common adverse effects (primarily gastrointestinal)

Conclusion

Based on the most recent guidelines and clinical trial data, baloxavir marboxil (Xofluza) has not been associated with rhabdomyolysis in pediatric patients and has a favorable safety profile. The most common adverse events are mild gastrointestinal symptoms. While influenza infection itself can rarely cause rhabdomyolysis, there is no evidence suggesting that baloxavir treatment increases this risk.