HIGHLIGHTS OF PRESCRIBING INFORMATION …

1 HIGHLIGHTS OF PRESCRIBING INFORMATION - Community outbreak: Based on weight once daily for up to 6 weeks These HIGHLIGHTS do not include all the INFORMATION needed to use Renally impaired adult patients (creatinine clearance >30-60 mL/min): TAMIFLU safely and effectively. See full PRESCRIBING INFORMATION for Reduce to 30 mg once daily ( ). TAMIFLU. Renally impaired adult patients (creatinine clearance >10-30 mL/min): Reduce to 30 mg once every other day ( ).. TAMIFLU (oseltamivir phosphate) capsules, for oral use ESRD patients on hemodialysis: Reduce to 30 mg immediately and then . TAMIFLU (oseltamivir phosphate) for oral suspension 30 mg after alternate hemodialysis cycles for the recommended duration of Initial Approval: 1999 prophylaxis ( ).

2 ESRD patients on CAPD: Reduce to 30 mg immediately and then 30 mg -------------------------- RECENT MAJOR CHANGES -------------------------- once weekly for the recommended duration of prophylaxis ( ). Warnings and Precautions ( ) 06/2016. --------------------- DOSAGE FORMS AND STRENGTHS --------------------- -------------------------- INDICATIONS AND USAGE --------------------------- Capsules: 30 mg, 45 mg, 75 mg (3). TAMIFLU is an influenza neuraminidase inhibitor (NAI) indicated for: For oral suspension: 360 mg oseltamivir base supplied as powder treatment of acute, uncomplicated influenza A and B in patients 2 weeks (constituted to a final concentration of 6 mg/mL) (3). of age and older who have been symptomatic for no more than 48 hours.

3 ( ) ----------------------------- CONTRAINDICATIONS ----------------------------- prophylaxis of influenza A and B in patients 1 year and older. ( ) Patients with known serious hypersensitivity to oseltamivir or any of the Limitations of Use: components of TAMIFLU (4). Not a substitute for annual influenza vaccination. ( ). Consider available INFORMATION on influenza drug susceptibility patterns -----------------------WARNINGS AND PRECAUTIONS ----------------------- and treatment effects when deciding whether to use. ( ) Serious skin/hypersensitivity reactions such as Stevens-Johnson Not recommended for patients with end-stage renal disease not undergoing Syndrome, toxic epidermal necrolysis and erythema multiforme: dialysis.

4 ( ) Discontinue TAMIFLU and initiate appropriate treatment if allergic-like reactions occur or are suspected. ( ). ---------------------- DOSAGE AND ADMINISTRATION ---------------------- Neuropsychiatric events: Patients with influenza , including those receiving treatment of influenza ( ) TAMIFLU, particularly pediatric patients, may be at an increased risk of Adults and adolescents (13 years and older): 75 mg twice daily for 5 days confusion or abnormal behavior early in their illness. Monitor for signs of Pediatric patients 1 to 12 years of age: Based on weight twice daily for abnormal behavior. ( ). 5 days Pediatric patients 2 weeks to less than 1 year of age: 3mg/kg twice daily ----------------------------- ADVERSE REACTIONS ------------------------------ for 5 days Most common adverse reactions (>1% and more common than with placebo): Renally impaired adult patients (creatinine clearance >30-60 mL/min): treatment studies Nausea, vomiting, headache.

5 ( ). Reduce to 30 mg twice daily for 5 days ( ) prophylaxis studies Nausea, vomiting, headache, pain. ( ). Renally impaired adult patients (creatinine clearance >10-30 mL/min): Reduce to 30 mg once daily for 5 days ( ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at ESRD patients on hemodialysis: Reduce to 30 mg immediately and then 1-888-835-2555 or FDA at 1-800-FDA-1088 or 30 mg after every hemodialysis cycle. treatment duration not to exceed 5. days ( ) ------------------------------DRUG INTERACTIONS ------------------------------ ESRD patients on CAPD: Reduce to a single 30 mg dose immediately Live attenuated influenza vaccine (LAIV), intranasal: ( ) Avoid administration of LAIV within 2 weeks before or 48 hours after prophylaxis of influenza ( ) TAMIFLU use, unless medically indicated.

6 (7). Adults and adolescents (13 years and older): 75 mg once daily for at least 10 days See 17 for PATIENT COUNSELING INFORMATION and FDA- - Community outbreak: 75 mg once daily for up to 6 weeks approved patient labeling Pediatric patients 1 to 12 years of age: Based on weight once daily for Revised: 06/2016. 10 days 1. _____. FULL PRESCRIBING INFORMATION : CONTENTS* Drugs Without Clinically Significant Drug Interaction with 1 INDICATIONS AND USAGE TAMIFLU. treatment of influenza 8 USE IN SPECIFIC POPULATIONS prophylaxis of influenza Pregnancy Limitations of Use Nursing Mothers 2 DOSAGE AND ADMINISTRATION Pediatric Use Dosage and Administration Overview Geriatric Use Recommended Dosage for treatment of influenza Renal Impairment Recommended Dosage for prophylaxis of influenza Hepatic Impairment Dosage in Patients with Renal Impairment Use in Patients with Chronic Conditions Preparation and Storage of Constituted TAMIFLU Oral Immunocompromised Patients Suspension 10 OVERDOSAGE Emergency Preparation of Oral Suspension from 75 mg TAMIFLU 11 DESCRIPTION Capsules 12 CLINICAL PHARMACOLOGY 3 DOSAGE FORMS AND STRENGTHS Mechanism of Action 4

7 CONTRAINDICATIONS Pharmacokinetics 5 WARNINGS AND PRECAUTIONS Microbiology Serious Skin/Hypersensitivity Reactions 13 NONCLINICAL TOXICOLOGY Neuropsychiatric Events Carcinogenesis, Mutagenesis, Impairment of Fertility Risk of Bacterial Infections 14 CLINICAL STUDIES Fructose Intolerance in Patients with Hereditary Fructose treatment of influenza Intolerance prophylaxis of influenza 6 ADVERSE REACTIONS 16 HOW SUPPLIED/STORAGE AND HANDLING Clinical Trials Experience 17 PATIENT COUNSELING INFORMATION Postmarketing Experience 7 DRUG INTERACTIONS. *Sections or subsections omitted from the full PRESCRIBING INFORMATION are not influenza Vaccines listed. _____. 2. FULL PRESCRIBING INFORMATION .

8 1 INDICATIONS AND USAGE. treatment of influenza TAMIFLU is indicated for the treatment of acute, uncomplicated illness due to influenza A and B infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. prophylaxis of influenza TAMIFLU is indicated for the prophylaxis of influenza A and B in patients 1 year and older. Limitations of Use TAMIFLU is not a substitute for early influenza vaccination on an annual basis as recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. influenza viruses change over time. Emergence of resistance substitutions could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs.

9 Prescribers should consider available INFORMATION on influenza drug susceptibility patterns and treatment effects when deciding whether to use TAMIFLU [see Microbiology ( )]. TAMIFLU is not recommended for patients with end-stage renal disease not undergoing dialysis [see Dosage and Administration ( ) and Use in Specific Populations ( )]. 2 DOSAGE AND ADMINISTRATION. Dosage and Administration Overview Administer TAMIFLU for the treatment of influenza in patients 2 weeks of age or older [see Dosage and Administration ( )] or for prophylaxis of influenza in patients 1 year and older [see Dosage and Administration ( )] using: TAMIFLU capsules or TAMIFLU for oral suspension (supplied as a powder).

10 This is the preferred formulation (6 mg per mL). for patients who cannot swallow capsules. Prior to use, the supplied TAMIFLU powder must be constituted with water by the pharmacist to produce the oral suspension [see Dosage and Administration ( )]. The capsules and oral suspension may be taken with or without food; however, tolerability may be enhanced if TAMIFLU is taken with food. Adjust the TAMIFLU dosage in patients with moderate or severe renal impairment [see Dosage and Administration ( )]. For patients who cannot swallow capsules, TAMIFLU for oral suspension is the preferred formulation. When TAMIFLU for oral suspension is not available from wholesaler or the manufacturer, TAMIFLU capsules may be opened and mixed with sweetened liquids such as regular or sugar-free chocolate syrup, corn syrup, caramel topping, or light brown sugar (dissolved in water).