Xofluza

Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 ) 05/2025

1 INDICATIONS AND USAGE XOFLUZA is an influenza virus polymerase acidic (PA) endonuclease inhibitor indicated for: Treatment of acute uncomplicated influenza in patients 5 years of age and older who have been symptomatic for no more than 48 hours and who are otherwise healthy or at high risk of developing influenza-related complications . ( 1.1 ) Post-exposure prophylaxis of influenza in patients 5 years of age and older following contact with an individual who has influenza. ( 1.2 ) 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. ( 1.3 ) 1.1 Treatment of Influenza XOFLUZA is indicated for treatment of acute uncomplicated influenza in patients 5 years of age and older who have been symptomatic for no more than 48 hours and who are otherwise healthy or at high risk of developing influenza-related complications 1 [see Clinical Studies (14.1 , 14.2 , and 14.3 ]. 1.2 Post-Exposure Prophylaxis of Influenza XOFLUZA is indicated for post-exposure prophylaxis of influenza in persons 5 years of age and older following contact with an individual who has influenza [see Clinical Studies (14.4) ]. 1.3 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 [see Warnings and Precautions (5.2) , Microbiology (12.4) and Clinical Studies (14) ] .

2 DOSAGE AND ADMINISTRATION Treatment and Post-Exposure Prophylaxis of Influenza Take XOFLUZA as a single dose as soon as possible and within 48 hours of influenza symptom onset for treatment of acute uncomplicated influenza or following contact with an individual who has influenza. XOFLUZA may be taken with or without food. ( 2.1 , 2.2 ) Patient Body Weight Recommended Single Oral Dose in Patients 5 Years of Age and Older (Tablets) 20 kg to less than 80 kg One 40 mg tablet (blister card contains one 40 mg tablet) At least 80 kg One 80 mg tablet (blister card contains one 80 mg tablet) Patient Body Weight Recommended Single Oral Dose in Patients 5 Years of Age and Older For Oral Suspension (Packets) 15 kg to less than 20 kg One 30 mg packet 20 kg to less than 80 kg One 40 mg packet At least 80 kg 80 mg (two 40 mg packets) Patient Body Weight Recommended Single Oral Dose in Patients 5 Years of Age and Older For Oral Suspension (Bottles) Less than 20 kg 2 mg/kg 20 kg to less than 80 kg 40 mg (20 mL) At least 80 kg 80 mg (40 mL) Refer to the Full Prescribing Information for additional information on the recommended dosage and preparation of XOFLUZA for oral suspension (bottles) or for oral suspension (packets) for both for oral or enteral use in patients 5 years of age and older. ( 2.2 , 2.3 ) 2.1 Dosage and Administration Overview XOFLUZA is available in two dosage forms: XOFLUZA tablets (40 mg and 80 mg). XOFLUZA for oral suspension is available in two different presentations: packets (30 mg and 40 mg) and bottles (2 mg/mL). If the patient weighs less than 15 kg, XOFLUZA for oral suspension in bottle is the recommended presentation. Both presentations of the for oral suspension are intended for patients who are unable to or have difficulty swallowing tablets, or those who require enteral administration [see Dosage and Administration (2.2 , 2.3 , 2.4) ] . Take XOFLUZA as soon as possible after influenza symptom onset or exposure to influenza [see Dosage and Administration (2.2) ] . XOFLUZA may be taken with or without food. However, concomitant use of XOFLUZA with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc) should be avoided [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ]. 2.2 Recommended Dosage Treatment of Acute Uncomplicated Influenza or Post-Exposure Prophylaxis in Adults, and Pediatric Patients (5 Years of Age and Older) Take XOFLUZA as a single dose as soon as possible and within 48 hours of influenza symptom onset for treatment of acute uncomplicated influenza or following contact with an individual who has influenza. The recommended dosage of XOFLUZA in patients 5 years of age or older is a single weight-based dose displayed in Tables 1 , 2 and 3 . Table 1 XOFLUZA Tablets: Recommended Dosage in Adults and Pediatric Patients 5 Years of Age and Older Patient Body Weight Recommended Single Oral Dose (Tablets) Recommended XOFLUZA dosage is based on the patient's weight. 20 kg to less than 80 kg One 40 mg tablet (blister card contains one 40 mg tablet) At least 80 kg One 80 mg tablet (blister card contains one 80 mg tablet) Table 2 XOFLUZA for Oral Suspension (Packets): Recommended Dosage in Adults and Pediatric Patients 5 Years of Age and Older Patient Body Weight Recommended Single Oral Dose (Packets) Recommended XOFLUZA dosage is based on the patient's weight. 15 kg Patients who weigh less than 15 kg should receive XOFLUZA for oral suspension (bottles). to less than 20 kg One 30 mg packet 20 kg to less than 80 kg One 40 mg packet At least 80 kg 80 mg (two 40 mg packets) Table 3 XOFLUZA for Oral Suspension (Bottles): Recommended Dosage in Adults and Pediatric Patients 5 Years of Age and Older Patient Body Weight Recommended Single Oral Dose Recommended XOFLUZA dosage is based on the patient's weight. , Use a measuring device (oral syringe) to measure the prescribed dose for use. (For Ora …

3 DOSAGE FORMS AND STRENGTHS Tablets: 40 mg and 80 mg. ( 3 ) For oral suspension (packets): 30 mg and 40 mg per packet in about 15-20 mL of drinking water. ( 3 ) For oral suspension (bottles): 40 mg/20 mL (2 mg/mL) after reconstitution. ( 3 ). XOFLUZA Tablets: 40 mg: white to light yellow, oblong-shaped, film-coated, debossed with "BXM40" on one side. 80 mg: white to light yellow, oblong shaped, film-coated, debossed with "BXM80" on one side. XOFLUZA for Oral Suspension (Packets): 30 mg: white to light yellow granules with strawberry flavor (each packet contains 30 mg baloxavir marboxil). 40 mg: white to light yellow granules with strawberry flavor (each packet contains 40 mg baloxavir marboxil). XOFLUZA for Oral Suspension (Bottles): 40 mg/20 mL (2 mg/mL) of baloxavir marboxil after reconstitution with 20 mL of drinking water or sterile water. The granules are white to light yellow. The reconstituted product is a greyish white, white to light yellow opaque suspension with strawberry flavor.

4 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 [see Warnings and Precautions (5.1) ]. XOFLUZA is contraindicated in patients with a history of hypersensitivity to baloxavir marboxil or any of its ingredients. ( 4 )

6 ADVERSE REACTIONS Adverse events reported in at least 1% of adult and adolescent influenza subjects treated with XOFLUZA included diarrhea (3%), bronchitis (3%), nausea (2%), sinusitis (2%), and headache (1%). ( 6.1 ) Adverse events reported in at least 5% of pediatric subjects (5 to < 12 years) treated with XOFLUZA included vomiting (5%) and diarrhea (5%). To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The overall safety profile of XOFLUZA is based on data from 2,079 subjects, 5 years of age and older in 5 controlled clinical trials who received XOFLUZA. Of these subjects, 1,943 were adults and adolescents (≥ 12 years of age) and 136 were in the pediatric age group (5 to < 12 years of age) [see Clinical Studies (14) ] . Treatment of Acute Uncomplicated Influenza Adult and Adolescent Subjects (≥ 12 Years of Age): The safety of XOFLUZA in adult and adolescent subjects is based on data from 3 placebo-controlled trials in which a total of 1,640 subjects received XOFLUZA: 1,334 (81%) subjects were 18 to 64 years of age, 209 (13%) subjects were adults 65 years of age or older, and 97 (6%) subjects were adolescents 12 to 17 years of age. These trials included otherwise healthy adults and adolescents (N=910) and subjects at high risk of developing complications associated with influenza (N=730). Of these, 1,440 subjects received XOFLUZA at the recommended dose [see Clinical Studies (14.1 , 14.2) ]. Trial T0821 was a phase 2 dose-finding placebo-controlled trial where otherwise healthy adult subjects 20 to 64 years of age received single oral dose of XOFLUZA or placebo. Trial T0831 was a placebo- and active-controlled trial in otherwise healthy adults and adolescents 12 to 64 years of age; subjects received weight-based XOFLUZA or placebo as a single oral dose on Day 1 or oseltamivir twice a day for 5 days. Trial T0832 was a randomized, double-blind, placebo- and active-controlled trial where adults and adolescents at high risk of influenza complications 12 years of age and older received either XOFLUZA, placebo or oseltamivir. Table 4 displays the most common adverse events (regardless of causality assessment) reported in at least 1% of adult and adolescent subjects who received XOFLUZA at the recommended dose in Trials T0821, T0831, and T0832. Table 4 Incidence of Adverse Events Occurring in at Least 1% of Adult and Adolescent Subjects Receiving XOFLUZA in the Acute Uncomplicated Influenza Trials T0821, T0831, and T0832 Adverse Event XOFLUZA (N=1,440) Placebo (N=1,136) Diarrhea 3% 4% Bronchitis 3% 4% Nausea 2% 3% Sinusitis 2% 3% Headache 1% 1% Pediatric Subjects (5 to < 12 Years of Age): In an active-controlled, double-blind trial Trial CP40563 in pediatric subjects, a total of 79 subjects 5 to less than 12 years of age, received the recommended weight-based dosage of XOFLUZA, and 39 subjects received oseltamivir. Of the 118 subjects 5 to less than 12 years of age in Trial CP40563, 15 subjects in the XOFLUZA arm and 4 subjects in the oseltamivir arm were at high risk of developing influenza complications. The most frequently reported AEs (≥ 5%) in all subjects in the XOFLUZA treatment arm were vomiting (5%) and diarrhea (5%). Vomiting was reported in 18% of subjects in the oseltamivir arm [see Clinical Studies (14.3 ]. There are limited safety data in patients 5 to <12 years at high risk of developing influenza complications. Post-Exposure Prophylaxis of Influenza In a placebo-controlled clinical trial, Trial T0834, conducted in adults, and pediatric subjects ≥ 5 years of age, a total of 360 subjects received XOFLUZA, of which 291 (81%) were adults ≥ 18 years; 12 …

7 DRUG INTERACTIONS 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). ( 2.1 , 7.1 ) Live attenuated influenza vaccines may be affected by antivirals. ( 7.2 ) 7.1 Effect of Other Drugs on XOFLUZA Baloxavir may form a chelate with polyvalent cations such as calcium, aluminum, or magnesium. Coadministration with polyvalent cation-containing products may decrease plasma concentrations of baloxavir [see Clinical Pharmacology (12.3) ], 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). 7.2 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.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with XOFLUZA in pregnant women to inform a drug-associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with influenza virus infection in pregnancy (see Clinical Considerations ). In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits with oral administration of baloxavir marboxil at exposures approximately 5 (rats) and 7 (rabbits) times the systemic baloxavir exposure at the maximum recommended human dose (MRHD) (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes, including maternal death, stillbirth, birth defects, preterm delivery, low birth weight, and small for gestational age. Data Animal Data Baloxavir marboxil was administered orally to pregnant rats (20, 200, or 1,000 mg/kg/day from gestation day 6 to 17) and rabbits (30, 100, or 1,000 mg/kg/day from gestation day 7 to 19). No adverse embryo-fetal effects were observed in rats up to the highest dose of baloxavir marboxil (1,000 mg/kg/day), resulting in systemic baloxavir exposure (AUC) of approximately 5 times the exposure at the MRHD. In rabbits, fetal skeletal variations occurred at a maternally toxic dose (1,000 mg/kg/day) resulting in 2 abortions out of 19 pregnancies. No adverse maternal or embryo-fetal effects were observed in rabbits at the middle dose (100 mg/kg/day) resulting in systemic baloxavir exposure (AUC) approximately 7 times the exposure at the MRHD. In the prenatal and postnatal development study in rats, baloxavir marboxil was administered orally at 20, 200, or 1,000 mg/kg/day from gestation day 6 to postpartum/lactation day 20. No significant effects were observed in the offspring at maternal systemic baloxavir exposure (AUC) approximately 5 times the exposure at the MRHD. 8.2 Lactation Risk Summary There are no data on the presence of baloxavir marboxil in human milk, the effects on the breastfed infant, or the effects on milk production. Baloxavir and its related metabolites were present in the milk of lactating rats (see Data ) . The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for XOFLUZA and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. Data In a lactation study, baloxavir and its related metabolites were excreted in the milk of lactating rats administered baloxavir marboxil (1 mg/kg) on postpartum/lactation day 11, with peak milk concentration approximately 5 times that of maternal plasma concentrations occurring 2 hours post-dose. No effects of baloxavir marboxil on growth and postnatal development were observed in nursing pups at the highest oral dose tested in rats. Maternal systemic exposure was approximately 5 times the baloxavir exposure in humans at the MRHD. 8.4 Pediatric Use Treatment of Acute Uncomplicated Influenza in Adolescent Subjects (≥ 12 Years of Age) The safety and effectiveness of XOFLUZA for the treatment of acute uncomplicated influenza in adolescent subjects 12 years of age and older weighing at least 40 kg is supported by one randomized, double-blind, controlled trial in otherwise healthy subjects Trial T0831 and one trial in subjects at high risk of developing influenza-related complications Trial T0832 [see Clinical Studies (14.1) ]. A total of 117 otherwise healt …

12.1 Mechanism of Action Baloxavir marboxil is an antiviral drug with activity against influenza virus [see Microbiology (12.4) ].

11 DESCRIPTION Baloxavir marboxil is an influenza virus PA endonuclease inhibitor. The active component of XOFLUZA is baloxavir marboxil. The chemical name of baloxavir marboxil is ({(12aR)-12-[(11S)-7,8-Difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-6,8-dioxo-3,4,6,8,12,12a-hexahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazin-7-yl}oxy)methyl methyl carbonate. The empirical formula of baloxavir marboxil is C 27 H 23 F 2 N 3 O 7 S, and the chemical structure is shown below. Baloxavir marboxil has a molecular mass of 571.55 grams per mole and a partition coefficient (log P) of 2.26. It is freely soluble in dimethylsulfoxide, soluble in acetonitrile, slightly soluble in methanol and ethanol, and practically insoluble in water. XOFLUZA is supplied as tablets and for oral suspension (in packets and in bottles). XOFLUZA tablets are white to light yellow, film-coated for oral administration . The 40 mg film-coated tablet contains 40 mg of baloxavir marboxil, and the 80 mg film-coated tablet contains 80 mg of baloxavir marboxil. The inactive ingredients of XOFLUZA tablets are: croscarmellose sodium, hypromellose, lactose monohydrate, microcrystalline cellulose, povidone K25, sodium stearyl fumarate, talc, and titanium dioxide. XOFLUZA for oral suspension (packets) is supplied as white to light yellow granules in a packet. Each packet contains either 30 mg or 40 mg of baloxavir marboxil. The granules must be reconstituted in about 15 to 20 mL of room temperature drinking water. The inactive ingredients are: hypromellose, maltitol, mannitol, povidone K25, silicon dioxide, sodium chloride, strawberry flavor, sucralose, and talc. XOFLUZA for oral suspension (bottles) is supplied as white to light yellow granules in an amber glass bottle. Each bottle contains 40 mg (nominal) of baloxavir marboxil. The granules must be reconstituted with 20 mL of drinking water or sterile water to yield a 2 mg/mL greyish white, white to light yellow opaque suspension with strawberry flavor. The inactive ingredients are: hypromellose, maltitol, mannitol, povidone K25, silicon dioxide, sodium chloride, strawberry flavor, sucralose, and talc. Chemical Structure

10 OVERDOSAGE Treatment of an overdose of XOFLUZA should consist of general supportive measures, including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with XOFLUZA. Baloxavir is unlikely to be significantly removed by dialysis due to high serum protein binding [see Clinical Pharmacology (12.3) ].

16 HOW SUPPLIED/STORAGE AND HANDLING XOFLUZA is supplied as tablets (40 mg and 80 mg), granules (30 mg and 40 mg) that are reconstituted into a for oral suspension (packets) and as granules that are reconstituted into a for oral suspension (bottles) [40 mg/20 mL (2 mg/mL)] . The single oral dose to be administered depends on body weight [see Dosage and Administration (2.2) ]. XOFLUZA Tablets How Supplied 40 mg white to light yellow, oblong-shaped, film-coated tablets debossed with "BXM40" on one side available as: 1 × 40 mg tablet per blister card in secondary packaging: NDC 50242-860-01 80 mg white to light yellow, oblong shaped, film-coated tablets debossed with "BXM80" on one side available as: 1 × 80 mg tablet per blister card in secondary packaging: NDC 50242-877-01 Storage: Store tablets in their blister package at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. XOFLUZA for Oral Suspension (Packets) How Supplied: XOFLUZA for oral suspension (packets) are supplied as granules that are white to light yellow in packets. The granules are reconstituted in about 15 to 20 mL of room temperature drinking water to form an oral suspension. Each carton contains 1 packet available as: 1 × 30 mg packet: NDC 50242-599-01 1 × 40 mg packet: NDC 50242-617-01 There is no preservative. Storage: Store granules (packets) at 20°C to 25°C (68°F to 77°F) and keep in the original package; excursions are permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. XOFLUZA for Oral Suspension (Bottles) How Supplied: XOFLUZA for oral suspension, 40 mg/20 mL (2 mg/mL) are supplied as white to light yellow granules in an amber glass bottle with a child-resistant cap. When reconstituted with drinking water or sterile water, the usable volume of the for oral suspension is 20 mL, equivalent to 40 mg of baloxavir marboxil. XOFLUZA for oral suspension is available as: 40 mg/20 mL (2 mg/mL) for oral suspension: NDC 50242-583-01 There is no preservative. Must administer within 10 hours after reconstitution. Storage: Store granules (bottles) at 20°C to 25°C (68°F to 77°F) and keep in the original bottle; excursions are permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature] . Store reconstituted suspension no longer than 10 hours at 20°C to 25°C (68°F to 77°F) when reconstituted with drinking water or sterile water. The suspension must be discarded if not used within 10 hours of preparation or if suspension has been stored above 25°C (77°F).