Baloflu

1 INDICATIONS AND USAGE XOFLUZA is an influenza virus polymerase acidic (PA) endonuclease inhibitor indicated for: Treatment of acute uncomplicated influenza in patients 12 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 12 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 the treatment of acute uncomplicated influenza in patients 12 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 (14.2) ]. 1.2 Post-Exposure Prophylaxis of Influenza XOFLUZA is indicated for post-exposure prophylaxis of influenza in persons 12 years of age and older following contact with an individual who has influenza [see Clinical Studies (14.3) ]. 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 Microbiology (12.4) and Clinical Studies (14) ] .

2 DOSAGE AND ADMINISTRATION Treatment and Post-Exposure Prophylaxis of Influenza XOFLUZA should be taken 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 should be taken with or without food. ( 2.1 , 2.2 ) Patient Body Weight (kg) Recommended Single Oral Dose in Patients 12 Years of Age and Older 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) Refer to the Full Prescribing Information for information on recommended dosage of XOFLUZA oral suspension in adults and adolescents (12 years of age and older). ( 2.2 ) Refer to the Full Prescribing Information for additional information on preparation of XOFLUZA for oral suspension for oral or enteral use. ( 2.3 ) 2.1 Dosage and Administration Overview XOFLUZA is available in two dosage forms: XOFLUZA tablets XOFLUZA for oral suspension. This granule formulation is intended for patients who are unable to or have difficulty swallowing tablets, or those who require enteral administration [see Dosage and Administration (2.3) ] . XOFLUZA should be taken as soon as possible after influenza symptom onset or exposure to influenza and may be taken with or without food. However, 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) 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 Adolescents (12 Years of Age and Older) XOFLUZA should be taken 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…

12.2 Pharmacodynamics Cardiac Electrophysiology At twice the expected exposure from recommended dosing, XOFLUZA did not prolong the QTc interval. Exposure-Response Relationships When XOFLUZA is dosed by weight, as recommended (40 mg in patients weighing 40–80 kg; 80 mg in patients weighing at least 80 kg), no difference in baloxavir exposure-response (time to alleviation of influenza symptoms in the otherwise healthy population or time to improvement of influenza symptoms in the high risk population) relationship has been observed.

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 ) 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 1,943 subjects 12 years of age and older in 4 controlled clinical trials who received XOFLUZA [see Clinical Studies (14) ] . Treatment of Acute Uncomplicated Influenza Adult and Adolescent Subjects: 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 1 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 2 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 3 was a randomized, double-blind, placebo- and active-controlled trial where adults and…

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 )

5 WARNINGS AND PRECAUTIONS Hypersensitivity such as anaphylaxis, angioedema, urticaria, and erythema multiforme: Initiate appropriate treatment if an allergic-like reaction occurs or is suspected. ( 5.1 ) Risk of bacterial infection: 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. ( 5.2 ) 5.1 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. The use of XOFLUZA is contraindicated in patients with known hypersensitivity to XOFLUZA [see Contraindications (4) and Adverse Reactions (6.2) ]. 5.2 Risk of Bacterial Infections There is no evidence of 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.

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.