Introduction
Xofluza (baloxavir marboxil) is a first-in-class antiviral medication approved for the treatment of acute uncomplicated influenza. Developed by Shionogi & Co. and marketed by Genentech, it represents a novel approach to influenza treatment with a unique mechanism of action that differentiates it from neuraminidase inhibitors like oseltamivir.
Mechanism of Action
Xofluza is a cap-dependent endonuclease inhibitor that targets the polymerase acidic (PA) protein of the influenza virus. Unlike neuraminidase inhibitors that prevent viral release from infected cells, baloxavir inhibits the initiation of viral mRNA synthesis by interfering with the "cap-snatching" process essential for viral transcription. This mechanism prevents viral replication at an earlier stage in the viral life cycle.
Indications
- Treatment of acute uncomplicated influenza in patients 5 years and older who have been symptomatic for no more than 48 hours
- Post-exposure prophylaxis of influenza in persons 5 years and older (FDA-approved 2020)
Dosage and Administration
Standard dosing (based on body weight):- 40-80 kg: Single oral dose of 40 mg
- ≥80 kg: Single oral dose of 80 mg
- Administer as a single oral dose with or without food
- For patients who cannot swallow tablets, the tablet may be crushed and mixed with water or simple syrup
- Timing: Should be administered within 48 hours of symptom onset for treatment efficacy
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required for mild to moderate impairment; use with caution in severe hepatic impairment
- Pediatrics: Approved for children ≥5 years with weight-based dosing
- Elderly: No dosage adjustment required
Pharmacokinetics
Absorption: Rapidly converted to active metabolite baloxavir acid; Tmax approximately 4 hours Distribution: Protein binding ~93%; Vd ~1,180 L Metabolism: Hydrolyzed by carboxylesterase to active baloxavir acid; undergoes minimal CYP-mediated metabolism Elimination: Half-life ~79 hours; primarily fecal elimination (80%); renal elimination minimal (15%) Food effect: No clinically significant effect on absorptionContraindications
- Hypersensitivity to baloxavir marboxil or any component of the formulation
Warnings and Precautions
- Risk of bacterial infection: Influenza may be associated with neurologic and behavioral symptoms, including delirium and abnormal behavior
- Antiviral resistance: Development of resistant influenza virus variants may occur
- Limited data in immunocompromised patients: Use with caution in severely immunocompromised patients due to potential for reduced efficacy and resistance development
- Pregnancy: Limited human data; use only if potential benefit justifies potential risk
- Lactation: Unknown if excreted in human milk; consider developmental and health benefits versus potential risk
Drug Interactions
- Polyvalent cations: Coadministration with dairy products, calcium-fortified beverages, antacids, laxatives, or oral supplements containing polyvalent cations (Ca²⁺, Mg²⁺, Al³⁺, Fe²⁺, Zn²⁺) may significantly reduce baloxavir absorption
- Administer Xofluza at least 2 hours before or 4 hours after these products
- Live attenuated influenza vaccine: Theoretical potential for interference; administer vaccine ≥48 hours after last dose of antiviral
- No clinically significant interactions with CYP enzymes or transporters
Adverse Effects
Common (≥1%):- Diarrhea (3%)
- Bronchitis (3%)
- Nausea (2%)
- Headache (1%)
- Sinusitis (1%)
- Hypersensitivity reactions
- Psychiatric events (associated with influenza itself)
Monitoring Parameters
- Influenza symptom resolution
- Temperature monitoring
- Signs of secondary bacterial infection
- Neurologic/behavioral symptoms (especially in children)
- Development of antiviral resistance in high-risk populations
Patient Education
- Take as a single dose within 48 hours of symptom onset
- Do not take with dairy products, calcium-fortified drinks, or antacids within 2 hours before or 4 hours after dose
- Complete the full course even if symptoms improve
- Continue to practice infection control measures to prevent spread
- Seek immediate medical attention for signs of allergic reaction or behavioral changes
- Report persistent or worsening symptoms after treatment
- Understand that antiviral treatment does not replace annual influenza vaccination
References
1. Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med. 2018;379(10):913-923. 2. FDA prescribing information: XOFLUZA (baloxavir marboxil) tablets. Revised November 2020. 3. Ikematsu H, Hayden FG, Kawaguchi K, et al. Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts. N Engl J Med. 2020;383(4):309-320. 4. Hirotsu N, Sakaguchi H, Sato C, et al. Baloxavir marboxil in Japanese pediatric patients with influenza: safety and clinical and virologic outcomes. Clin Infect Dis. 2020;71(4):971-981. 5. Uehara T, Hayden FG, Kawaguchi K, et al. Treatment-emergent influenza variant viruses with reduced baloxavir susceptibility: impact on clinical and virologic outcomes in uncomplicated influenza. J Infect Dis. 2020;221(3):346-355.