General dosing information:

• Because antiviral resistance patterns can change over time, monitor local antiviral resistance surveillance data. If patients become symptomatic or have worsening symptoms after or during the use of an antiviral agent, a resistant organism is possible.[62315][63866]

Seasonal influenza virus:

• Antiviral treatment with baloxavir is recommended for outpatients with acute uncomplicated influenza infection who are at higher risk for influenza complications (i.e., adults 65 years and older; patients with chronic conditions; immunosuppressed patients; females who are pregnant or postpartum [less than 2 weeks since delivery]; children on long-term aspirin therapy; American Indians/Alaska Natives; morbidly obese patients; and residents of long-term care facilities). Treatment may also be considered for previously healthy, symptomatic patients that are not considered high risk based on clinical judgment if treatment can be initiated within 48 hours of symptom onset.
• When indicated, antiviral therapy should be started as soon as possible after illness onset, ideally within 48 hours of symptom onset.
• In general, post-exposure chemoprophylaxis is only recommended when antivirals can be initiated within 48 hours of exposure. The decision regarding who should receive post-exposure prophylaxis is dependent on patient risk factors, type and duration of exposure, clinical judgment, and product availability. Chemoprophylaxis lowers but does not eliminate the risk for influenza infection.
• The 2009 H1N1 influenza virus (swine influenza) is included in seasonal influenza A viruses.[62315][63866]

Novel influenza A viruses associated with severe human disease, including avian influenza virus:

• Antiviral therapy is recommended as early as possible for patients with suspected or confirmed cases, even if more than 48 hours have elapsed since illness onset. Treatment is also recommended for any patient with recent or close contact with a confirmed or probable case.[62336][62338]

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.[63687]

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.[63687]

Baloxavir marboxil is an oral antiviral drug given as a single weight-based dose. It is approved to treat uncomplicated influenza infections in patients who have been symptomatic for no more than 48 hours and who are: otherwise healthy adults and pediatric patients 5 years and older or adults and pediatric patients 12 years and older who are at high risk of developing influenza-related complications. Baloxavir is also approved for postexposure influenza prophylaxis in adults and pediatric patients 5 years and older. Baloxavir is active against both influenza A and B viruses. It is the first drug approved that targets the influenza virus-specific enzyme polymerase acidic (PA) protein, which is located within the viral RNA polymerase complex. By inhibiting the endonuclease activity of the PA protein, the drug prevents viral gene transcription and ultimately viral replication. Baloxavir is not a substitute for an annual influenza virus vaccination. Instead, antiviral drugs are considered adjuncts to the prevention and control of influenza; annual influenza vaccination remains the main option for reducing the impact of influenza.[62315][63687]

For storage information, see the specific product information within the How Supplied section.

Baloxavir marboxil is contraindicated for use in patients with a known allergic reaction to the drug or any of its components. Cases of anaphylaxis, angioedema, urticaria, and erythema multiforme have been reported during postmarketing use of the drug. If anaphylaxis or a serious allergic reaction develops during treatment, institute appropriate therapy.[63687]

Baloxavir, the active metabolite of baloxavir marboxil, is responsible for the drugs antiviral activity. Baloxavir inhibits the endonuclease activity of polymerase acidic (PA) protein, an influenza virus-specific enzyme in the viral RNA polymerase complex. By blocking the PA protein, baloxavir prevents viral gene transcription and ultimately influenza virus replication.[63687]

Influenza viruses are classified into 3 distinct types, influenza A, B, and C; with influenza infections being attributed to either the influenza A virus or influenza B virus. Influenza A is further divided into subtypes based on their hemagglutinin (H or HA) and neuraminidase (N or NA) activity. At least 16 distinct HAs (H1 to H16) and 9 NAs (N1 to N9) have been described. In 2009, a novel influenza A H1N1 virus (previously referred to as swine influenza) was identified; this virus is included in season influenza A viruses. Human cases of influenza illness from the avian H5N1 virus (commonly known as avian flu) have been reported since 1997. Human infections with avian H7N9, H5N2, H5N8, H9N2, H7N7, and H7N3 viruses have also been described.[36906] [62337]

Based on data from an MDCK-cell-based plaque reduction assay, the median 50% effective concentrations (EC₅₀) of baloxavir are 0.73 nM (n = 31; range 0.2 to 1.85 nM) for subtype A/H1N1 strains, 0.83 nM (n = 33; range 0.35 to 2.63 nM) for subtype A/H3N2 strains, and 5.97 nM (n = 30; range 2.67 to 14.23 nM) for type B strains. A virus titer reduction assay found the 90% effective concentration (EC₉₀) values against avian subtypes A/H5N1 and A/H7N9 to be in the range of 0.8 to 3.16 nM. A relationship between antiviral activity in cell culture and clinical efficacy (i.e., inhibition of influenza virus replication) in humans has not been established. In clinical studies in patients with confirmed influenza virus infection, the incidence of treatment-emergent amino acid substitutions associated with reduced susceptibility to baloxavir was 4.5% (n = 6 of 134) in influenza A/H1N1 virus, 10.9% (n = 53 of 485) in influenza A/H3N2 virus, and 0.9% (n = 2 of 224) in influenza B virus. In a post-exposure prophylaxis trial, 31 patients were evaluated for resistance. Of these, influenza virus with substitutions associated with reduced susceptibility to baloxavir was identified in 7 of 7 patients who developed clinical influenza and 8 of 24 patients who did not meet the primary endpoint definition for clinical influenza. Selection of influenza viruses with reduced susceptibility to baloxavir has occurred in higher frequencies in pediatric patients with overall frequencies of 20% (n = 4 of 20) in influenza A/H1N1 virus, 27.9% (n = 34 of 122) in influenza A/H3N2 virus, and 0% (n = 0 of 21) in influenza B virus in pooled data from 3 pediatric treatment trials in patients younger than 12 years. Specific amino acid substitutions were E23K/R, I38F/N/S/T for influenza A/H1N1 virus; E23G/K, A37T, I38M/T, E199G for influenza A/H3N2 virus; and I38T for influenza B virus. Cross-resistance between baloxavir and neuraminidase inhibitors (i.e., oseltamivir, peramivir, zanamivir) or M2 proton channel inhibitors (i.e., amantadine, rimantadine) is not expected. Baloxavir is active against neuraminidase inhibitor-resistant strains. Similarly, oseltamivir is active against viruses with reduced susceptibility to baloxavir. Consider concurrently available surveillance information on influenza drug susceptibility patterns and treatment effects when deciding on it and which anti-influenza medication to use.[63687]

Baloxavir marboxil is administered orally. Once in systemic circulation, the drug is hydrolyzed to form baloxavir (the active metabolite). Baloxavir is 92.9% to 93.9% bound to human plasma proteins and has a volume of distribution of 1,180 L and a blood cell to blood ratio of 48.5% to 54.4%. The primary metabolic pathway is via uridine diphosphate glucuronosyl transferase (UGT1A3) with secondary contributions from CYP3A4. The terminal elimination half-life is 79.1 hours.[63687]

Affected cytochrome P450 isoenzymes and drug transporters: P-glycoprotein (P-gp)

Both baloxavir marboxil and baloxavir are substrates of the drug transporter P-gp.[63687]