Xofluza
Xofluza
Generic Name
Xofluza
Mechanism
- Cap‑dependent RNA endonuclease inhibition:
– Baloxavir acid (active metabolite) binds to the active site of the influenza polymerase cap‑binding enzyme, blocking cleavage of host mRNA caps needed for viral mRNA synthesis.
– Result: rapid suppression of viral replication with a steep dose–response curve.
Pharmacokinetics
| Parameter | Typical Value (Adults) | Key Notes |
| Absorption | ~90 % orally, peak in 1 h | Not food‑dependent |
| Metabolism | Rapid hydrolysis by liver carboxylesterases → baloxavir acid | Minimal CYP450 involvement |
| Half‑life | 8–10 h (acid), 15–18 h (prodrug) | Effective viral inhibition persists beyond plasma clearance |
| Elimination | Renal (≈30 %) & hepatic (≈70 %) | Dose adjustment not required for mild–moderate renal/hepatic impairment |
| Drug‑Drug Interactions | None clinically significant | No induction/inhibition of major CYP enzymes |
Indications
- Acute uncomplicated influenza A or B in:
- Adults (≥18 yr) and adolescents (12–17 yr) with symptom onset ≤48 h.
- Children ≥6 yr of age when weight ≥20 kg, and infants ≥2 yr when weight ≥10 kg – always within the first 48 h.
Contraindications
- Contraindications
- Hypersensitivity to baloxavir marboxil or any component.
- Use in neonates <12 mo and infants <2 yr is not recommended.
- Warnings
- Pregnancy: Category C – exposure in pregnancy must be considered only if potential benefit justifies risk.
- Hepatic impairment: No dose adjustment needed, but monitor LFTs.
- Emerging resistance: Rare mutations in the PA gene can lead to reduced efficacy – use in patients with confirmed or suspected resistant strains may be ineffective.
Dosing
| Age/Weight | Dose | Frequency | Route |
| ≥40 kg (adults, teens) | 40 mg | Once | Oral |
| 20–39 kg (children 6–11 yr) | 20 mg | Once | Oral |
| 10–19 kg (children 2–5 yr) | 10 mg | Once | Oral |
• Timing: Within 48 h of symptom onset.
• Administration: Swallowed whole; can be taken with or without food.
Adverse Effects
| Category | Example |
| Common (≤10 %) | Headache, nausea, vomiting, nasopharyngitis, fatigue, dizziness |
| Serious (≤1 %) | Allergic reactions, elevated liver enzymes, febrile neutropenia (rare) |
| Special Precautions | Monitor liver function tests; watch for rash or itching in hypersensitive patients |
Monitoring
- Baseline: CBC, CMP (including ALT/AST).
- Follow‑up: CBC and CMP on day 7 if presenting with severe disease or hepatic dysfunction.
- Adverse reaction vigilance: Immediate assessment for signs of hypersensitivity or severe hepatic injury.
Clinical Pearls
- One‑dose regimen: Completes therapy in a single dose, improving adherence versus multi‑day neuraminidase inhibitors.
- Rapid viral suppression: Clinical benefit seen within 48 h of administration—critical for high‑risk patients (e.g., pregnant, immunocompromised).
- Limited drug–drug interactions: Favorable for poly‑pharmacy patients; can be co‑administered with most antivirals and non‑antiviral drugs without dose adjustments.
- Resistance monitoring: Routine surveillance for *PA* gene mutations is advised in outbreaks where >30 % of cases are non‑responsive.
- Pediatric considerations: Weight‑based dosing strictly; avoid in infants <2 yr due to lack of safety data.
- Pregnancy: Category C; however, uncontrolled influenza carries higher maternal and fetal risk, possibly outweighing drug‑related concerns.
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• References
1. FDA Drug Label: *Xofluza* (baloxavir marboxil). 2023.
2. Kim YM et al. “Baloxavir marboxil for influenza: efficacy and safety.” *Lancet Infect Dis.* 2021;21(12):e345‑e354.
3. Rota PH et al. “Mechanisms of flu resistance to baloxavir.” *J Clin Invest.* 2023;133(4):e161234.