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Mechanism of Action
US Drug Names
80 mg PO as a single dose within 48 hours of symptom onset.
40 mg PO as a single dose within 48 hours of symptom onset.
80 mg PO as a single dose administered as soon as possible after contact with an individual who has influenza.
40 mg PO as a single dose administered as soon as possible after contact with an individual who has influenza.
weight 80 kg or more: 80 mg PO.
weight less than 80 kg: 40 mg PO.
12 years and weight 80 kg or more: 80 mg PO.
12 years and weight less than 80 kg: 40 mg PO.
1 to 11 years: Safety and efficacy have not been established.
Safety and efficacy have not been established.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Baloxavir marboxil is an oral antiviral drug; it is given as a single weight-based dose in patients 12 years and older. It is approved to treat uncomplicated influenza infections in patients who have had symptoms for less than 48 hours and who are otherwise healthy or at high risk of developing influenza-related complications as well as for post-exposure influenza prophylaxis. 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.
For storage information, see the specific product information within the How Supplied section.
Gastrointestinal adverse reactions reported during clinical trials with baloxavir marboxil include diarrhea (3%) and nausea (2%). Other adverse reactions reported during postmarketing use include vomiting, hematochezia, melena, vomiting, and colitis.
Dermatologic and immune system adverse reactions reported during postmarketing use of baloxavir marboxil include cases of anaphylactic shock, anaphylactic and anaphylactoid reactions, hypersensitivity reactions, angioedema (swelling of face, eyelids, and tongue), rash, urticaria, and erythema multiforme.
Headache was reported in 1% of patients during clinical trials with baloxavir marboxil. Other adverse reactions reported during postmarketing use include delirium, abnormal behavior, and hallucinations.
Respiratory adverse events reported during clinical trials with baloxavir marboxil include bronchitis (3%), sinusitis (2%), and naso-pharyngitis (6%).
Antiviral medications with activity against influenza, such as baloxavir marboxil, are not substitutes for receipt of an annual influenza vaccination; these medications should be used as an adjunct to the vaccine in the control of influenza. Interaction studies with baloxavir marboxil and influenza vaccines have not been conducted. Concurrent administration may interfere with the viral replication necessary after administration of the live attenuated influenza vaccine for the proper development of immunity.
Serious bacterial infections may begin with influenza-type symptoms or may coexist with or occur as complications of influenza. There are no data to suggest baloxavir marboxil is effective in preventing such complications or treating a viral infection other than influenza virus A and B. Baloxavir marboxil is most effective when initiated within 48 hours of symptom onset.
No data are available regarding the use of baloxavir marboxil during human pregnancy. In animal studies, adverse developmental effects were not observed in rats or rabbits with systemic drug exposures of approximately 5- and 7-times, respectively, the exposure at the maximum recommended human dose. When deciding on treatment, health care providers are advised to consider that pregnant women are at higher risk of severe complications from influenza, which may result in adverse pregnancy or fetal outcomes (i.e., maternal death, stillbirth, birth defects, preterm delivery, low birth weight, small gestational age). The CDC does not recommend baloxavir during pregnancy due to the lack of safety data; oseltamivir is the preferred treatment in pregnant women.
It is not known if baloxavir marboxil is excreted in human milk, or if the drug has an adverse effect on milk production or a breastfed infant. Due to the lack of safety data, the CDC does not recommend baloxavir in breast-feeding mothers. Zanamivir and oseltamivir may be potential alternatives to consider during breast-feeding. However, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.  
Due to the risk of serious hypersensitivity reactions or anaphylaxis, 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.
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.
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. 
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.
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.
Affected cytochrome P450 isoenzymes and drug transporters: P-glycoprotein (P-gp)
Both baloxavir marboxil and baloxavir are substrates of the drug transporter P-gp.
Peak baloxavir concentrations are achieved 4 hours after oral administration. The systemic drug exposure (AUC) for the 40 mg dose is 5520 ng x hour/mL and the AUC for the 80 mg dose is 6930 ng x hour/mL. The maximum plasma concentration (Cmax) for the 40 mg dose is 68.9 ng/mL and the Cmax for the 80 mg dose is 82.5 ng/mL. When administered with food, the AUC is decreased by 36% and the Cmax is decreased by 48%.
In animal studies, a 48% to 63% decrease in baloxavir exposure was observed when coadministered with calcium, aluminum, magnesium, or iron. No studies have been conducted in humans.
The effects of severe hepatic impairment on the pharmacokinetics of baloxavir marboxil or its active metabolite have not been evaluated. No clinically meaningful differences were identified when comparing baloxavir pharmacokinetics in patients with normal and moderate hepatic impairment (Child-Pugh B).
The effects of severe renal impairment on the pharmacokinetics of baloxavir marboxil or its active metabolite have not been evaluated. No clinically meaningful differences were observed when baloxavir marboxil was administered to patients with creatinine clearance 50 mL/minute or higher.
No clinically significant differences in the pharmacokinetics of baloxavir were observed based on age (i.e., adolescents vs. adults).
No clinically significant differences in the pharmacokinetics of baloxavir were observed based on sex.
Systemic exposure (AUC) of baloxavir is approximately 35% lower in non-Asian as compared with Asians; however, this difference is not considered clinically significant.
As body weight increases, systemic exposure (AUC) of baloxavir decreases; however, when dosed with the recommended weight-based dosing, no clinically significant difference in AUC was observed between body weight groups (i.e., less than 80 kg vs. 80 kg or more).
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