Single-Dose XOFLUZA Was as Safe and Well Tolerated as Placebo in Clinical Trials

Single-dose XOFLUZA had a similar adverse event (AE) rate as placebo—including in patients aged ≥12 years at high risk of developing complications from the flu.1

The below table shows AEs that occurred in at least 1% of patients (aged ≥12 years) receiving either XOFLUZA or placebo in acute uncomplicated influenza in Trials T0821, T0831, and T0832.1*

Adverse Event XOFLUZA (n=1440) Placebo (n=1136)
Diarrhea 3% 4%
Bronchitis 3% 4%
Nausea 2% 3%
Sinusitis 2% 3%
Headache 1% 1%

*Based on combined data from 3 trials, a total of 1640 subjects received XOFLUZA: 1334 (81%) were adults (18-64 years of age), 209 (13%) were adults 65 years of age or older, and 97 (6%) were adolescents (12-17 years of age). Of these, 1440 subjects received XOFLUZA at the recommended dose.1

The below table shows the most frequently reported AEs that occurred in ≥5% of otherwise healthy patients (aged 5 to <12 years) in the XOFLUZA arm in acute uncomplicated influenza in Trial CP40563.1

Adverse Event XOFLUZA (n=79)
Vomiting 5%
Diarrhea 5%

Trial CP40563 was a randomized, double-blind, multicenter, active-controlled study designed to evaluate the safety, efficacy, and pharmacokinetics of a single oral dose of XOFLUZA compared with oseltamivir in otherwise healthy pediatric subjects (including subjects aged 5 to <12 years) with influenza-like symptoms. A total of 118 subjects aged 5 to <12 years were randomized and received a single one-time oral dose of XOFLUZA (n=79) based on body weight (2 mg/kg for subjects weighing <20 kg or 40 mg for subjects weighing ≥20 kg) or oseltamivir (n=39) for 5 days (dose based on body weight). The primary objective was to compare the safety of a single one-time dose of XOFLUZA with 5 days of oseltamivir administered twice daily. Of the 118 randomized subjects aged 5 to <12 years in Trial CP40563, 94 subjects had influenza confirmed by RT-PCR at baseline or during the trial. The median time to alleviation of influenza signs and symptoms was 138 hours in the XOFLUZA arm (95% CI: 117, 163) and 126 hours in the oseltamivir arm (95% CI: 96, 166).1

A Safe Antiviral Flu Rx for Post-Exposure Prophylaxis1

The safety profile of XOFLUZA was similar in patients aged 5 to <12 years and in patients aged 12 years and older.1

No serious treatment-related adverse events were reported.14

XOFLUZA® (baloxavir marboxil) Household Members

Single-dose XOFLUZA helps protect people who’ve been exposed to the flu by reducing their risk of infection.1

Trial T0834 was a phase 3, randomized, double-blind, multicenter, placebo-controlled study designed to evaluate the efficacy of a single oral dose of XOFLUZA compared with placebo in the prevention of influenza in subjects who were household contacts of influenza-infected patients in Japan. Influenza-infected index patients were required to have onset of symptoms for ≤48 hours, and subjects (household contacts) were required to have lived with the influenza-infected index patient for ≥48 hours. A total of 715 subjects (XOFLUZA n=360, placebo n=355) aged 5 years and older were randomized and received a single oral dose of XOFLUZA according to body weight and age, or placebo, on Day 1. Subjects received a single dose of 40 mg or 80 mg of XOFLUZA according to body weight (20 kg to <80 kg or ≥80 kg, respectively). The primary efficacy endpoint was the proportion of household subjects who were infected with influenza virus and presented with fever and at least one respiratory symptom from Day 1 to Day 10. Influenza infection was confirmed by RT-PCR, fever was defined as a body temperature (axillary) ≥37.5°C, and respiratory symptoms were defined as having a symptom of “cough” or “nasal discharge/nasal congestion” with a severity of moderate or severe as assessed by the subject. In subjects that were 5 years of age and older, there was a statistically significant reduction in the proportion of household contacts (subjects) with laboratory-confirmed clinical influenza from 13% in the placebo group to 2% in the XOFLUZA group.1

Indication

XOFLUZA is an influenza virus polymerase acidic (PA) endonuclease inhibitor indicated for:

  • Treatment of acute uncomplicated influenza in patients who have been symptomatic for no more than 48 hours and who are:
    • otherwise healthy adults and pediatric patients 5 years of age and older, OR
    • adults and pediatric patients 12 years of age and older who are at high risk of developing influenza-related complications
  • Post-exposure prophylaxis (PEP) of influenza in patients 5 years of age and older following contact with an individual who has influenza.

 

Limitations of Use
Influenza viruses change over time, and factors such as the virus type or subtype, emergence of resistance, or changes in viral virulence could diminish the clinical benefit of antiviral drugs. Consider available information on drug susceptibility patterns for circulating influenza virus strains when deciding whether to use XOFLUZA.

Important Safety Information

Contraindications
XOFLUZA is contraindicated in patients with a history of hypersensitivity to baloxavir marboxil or any of its ingredients. Serious allergic reactions have included anaphylaxis, angioedema, urticaria, and erythema multiforme.

 

Warnings and Precautions

Hypersensitivity:
 Cases of anaphylaxis, urticaria, angioedema, and erythema multiforme have been reported in postmarketing experience with XOFLUZA.  Appropriate treatment should be instituted if an allergic-like reaction occurs or is suspected.
 

Increased Incidence of Treatment-Emergent Resistance in Patients Less Than 5 Years of Age: XOFLUZA is not indicated in patients less than 5 years of age due to increased incidence of treatment-emergent resistance in this age group. In clinical trials, the incidence of virus with treatment-emergent substitutions associated with reduced susceptibility to baloxavir (resistance) was higher in pediatric subjects younger than 5 years of age (43%, 36/83) than in pediatric subjects ≥5 years to <12 years of age (16%, 19/117) or subjects ≥12 years of age (7%, 60/842). The potential for transmission of resistant strains in the community has not been determined.
 

Risk of bacterial Infections: There is no evidence of the efficacy of XOFLUZA in any illness caused by pathogens other than influenza viruses. Serious bacterial infections may begin with influenza-like symptoms or may coexist with, or occur as, a complication of influenza. XOFLUZA has not been shown to prevent such complications. Prescribers should be alert to potential secondary bacterial infections and treat them as appropriate.

Adverse Reactions

  • The most common adverse reactions (≥1%) in adult and adolescent patients (≥12 years of age) in clinical studies for acute uncomplicated influenza were diarrhea (3%), bronchitis (3%), nausea (2%), sinusitis (2%), and headache (1%).
  • The most frequently reported adverse reactions (≥5%) in pediatric patients (5 to <12 years of age) in clinical studies for acute uncomplicated influenza were vomiting (5%) and diarrhea (5%).
  • The safety profile reported in a clinical study for post-exposure prophylaxis was similar in pediatric patients ages 5 to <12 years old as that reported in adults and adolescents 12 years of age and older.

Drug Interactions

Polyvalent cations:
 Coadministration with polyvalent cation-containing products may decrease plasma concentrations of baloxavir, which may reduce XOFLUZA efficacy. Avoid coadministration of XOFLUZA with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc).

 

Vaccines: The concurrent use of XOFLUZA with intranasal live attenuated influenza vaccine (LAIV) has not been evaluated. Concurrent administration of antiviral drugs may inhibit viral replication of LAIV and, thereby, decrease the effectiveness of LAIV vaccination. Interactions between inactivated influenza vaccines and XOFLUZA have not been evaluated.


For additional Important Safety Information, please see the XOFLUZA full Prescribing Information.

You are encouraged to report side effects to Genentech by calling 1-888-835-2555 or to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.