baloxavir marboxil
Brand: Xofluza
Prototype Drug
Drug Class: cap-dependent endonuclease inhibitor antiviral
Drug Family: antiviral
Subclass: influenza PA endonuclease inhibitor (first-in-class)
Organ Systems: infectious-disease
Mechanism of Action
Prodrug converted to baloxavir; inhibits the PA subunit of influenza RNA polymerase, specifically its cap-dependent endonuclease activity — preventing 'cap snatching' required for viral mRNA transcription; first novel influenza mechanism in 20 years.
influenza PA subunit cap-dependent endonuclease
Indications
- acute uncomplicated influenza in adults and pediatric patients (≥5 years or ≥20 kg, or high-risk)
- influenza prophylaxis (post-exposure)
Contraindications
- baloxavir hypersensitivity
Adverse Effects
Common
- diarrhea
- bronchitis
- nasopharyngitis
Serious
- anaphylaxis/hypersensitivity
- resistance emergence (PA I38X mutations)
Pharmacokinetics (ADME)
| Absorption | prodrug; 80% bioavailability; take with food but NOT high-fat meal (reduces Cmax); NOT taken with calcium-fortified foods |
| Distribution | widely distributed; moderate protein binding |
| Metabolism | prodrug hydrolyzed to active baloxavir by arylacetamide deacetylase (AADAC) enzymes |
| Excretion | primarily fecal (80%); renal minimal |
| Half-life | 79 hours (active metabolite baloxavir) |
| Onset | 4 hours |
| Peak | 4 hours |
| Duration | single dose is complete treatment for uncomplicated influenza |
| Protein Binding | >92% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| polyvalent cations (antacids, laxatives, calcium-fortified foods) | chelation reduces baloxavir absorption; take separately | major |
| live attenuated influenza vaccine | may reduce efficacy; avoid concurrent administration | moderate |
Nursing Considerations
- Administer as a single dose weight-based oral regimen; must NOT be taken with calcium-enriched foods, antacids, or laxatives containing polyvalent cations.
- Initiate within 48 hours of symptom onset for efficacy; single dose is the complete treatment for uncomplicated influenza.
- Baloxavir reduces influenza viral shedding more rapidly than neuraminidase inhibitors — potentially relevant for infection control in household transmission.
- Monitor for resistance emergence in severely immunocompromised patients who receive baloxavir, as these patients may need re-treatment.
Clinical Pearls
- Baloxavir's novel mechanism (cap-dependent endonuclease inhibition) provides no cross-resistance with neuraminidase inhibitors, making it valuable for oseltamivir-resistant influenza.
- The single-dose, weight-based oral regimen offers an adherence advantage over 5-day twice-daily oseltamivir, and baloxavir achieves faster viral clearance in clinical trials, though clinical outcomes differences are modest.
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.