XOFLUZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XOFLUZA (XOFLUZA).
Baloxavir marboxil is a prodrug that is converted to baloxavir acid, which inhibits the cap-dependent endonuclease activity of the influenza virus polymerase acidic protein, thereby preventing viral mRNA transcription and replication.
| Metabolism | Baloxavir marboxil is primarily hydrolyzed to active baloxavir acid by CES1, CES2, and cathepsin A. Baloxavir acid is further metabolized via UGT1A3 to an inactive glucuronide, with minor metabolism by CYP3A4. |
| Excretion | Baloxavir marboxil is primarily excreted via feces (80.1%) and urine (14.7%) after oral administration, with <1% as unchanged drug in urine. |
| Half-life | The terminal elimination half-life of baloxavir marboxil is approximately 79.1 hours (range 53–107 hours), supporting single-dose therapy for influenza. |
| Protein binding | Baloxavir marboxil is 92.9–93.9% bound to human plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 1180 L (about 16.9 L/kg for a 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is not precisely determined due to rapid conversion; however, baloxavir marboxil is well absorbed with peak plasma concentrations reached within 4 hours. |
| Onset of Action | Onset of antiviral effect is within 24 hours of oral administration, with maximal viral load reduction observed by day 2. |
| Duration of Action | Single oral dose provides antiviral activity lasting the duration of the influenza episode, with clinical trials showing reduced time to symptom alleviation by about 1 day vs placebo. |
40 mg orally once as a single dose; for patients weighing ≥80 kg, 80 mg orally once as a single dose.
| Dosage form | FOR SUSPENSION |
| Renal impairment | No dosage adjustment required for mild to severe renal impairment (CrCl ≥15 mL/min). Not studied in end-stage renal disease (CrCl <15 mL/min) or dialysis; use with caution. |
| Liver impairment | No dosage adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | For patients ≥5 years and ≥20 kg: weight-based single dose according to body weight: 20–<40 kg: 40 mg; 40–<80 kg: 40 mg; ≥80 kg: 80 mg. |
| Geriatric use | No specific dose adjustment required; pharmacokinetics similar to younger adults. No dose adjustment based on age alone. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XOFLUZA (XOFLUZA).
| Breastfeeding | It is not known whether baloxavir marboxil or its metabolites are excreted in human milk. Baloxavir marboxil and its metabolites are excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. The M/P ratio is unknown. |
| Teratogenic Risk | There are no adequate and well-controlled studies in pregnant women. Animal studies have shown no evidence of teratogenicity or fetotoxicity at systemic exposures up to 9 times the human exposure at the recommended dose. However, because animal reproduction studies are not always predictive of human response, Xofluza should be used during pregnancy only if clearly needed. No trimester-specific risks have been identified. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of hypersensitivity to baloxavir marboxil or any component of the formulation"]
| Precautions | ["Efficacy has not been established in patients with severe influenza requiring hospitalization","Bacterial infections may occur concurrently or as complications of influenza; baloxavir is not effective against bacterial infections","Hypersensitivity reactions including anaphylaxis, urticaria, and angioedema have been reported","Increased risk of egg-related hypersensitivity in patients with egg allergy (note: limited data)"] |
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| Fetal Monitoring | No specific maternal or fetal monitoring is required beyond standard prenatal care. However, pregnancy status should be confirmed before administration in women of childbearing potential. If used during pregnancy, monitor for adverse effects such as nausea, diarrhea, or headache. |
| Fertility Effects | There are no human data on the effect of baloxavir marboxil on fertility. In animal studies, there were no effects on mating or fertility in male or female rats at exposures up to 9 times the human exposure at the recommended dose. |