HIGHLIGHTS OF PRESCRIBING INFORMATION No recommendation for dosage adjustment can be made for pediatric These highlights do not include all the information needed to use patients 6 months to less than 2 years of age with creatinine clearance RAPIVAB safely and effectively. See full prescribing information for less than 50 mL/min (2.2) RAPIVAB. Hemodialysis: Administer after dialysis (2.2) RAPIVAB must be diluted prior to administration (2.3) ® RAPIVAB (peramivir) injection, for intravenous use See the Full Prescribing Information for drug compatibility information Initial U.S. Approval: 2014 (2.4) --------------------------RECENT MAJOR CHANGES-------------------------- ------------------------DOSAGE FORMS AND STRENGTHS------------------- Indications and Usage (1) 01/2021 Injection: 200 mg in 20 mL (10 mg/mL) in a single-use vial (3) Dosage and Administration Dosage in Acute Uncomplicated Influenza (2.1) 01/2021 --------------------------------CONTRAINDICATIONS------------------------------ Dosing in Patients with Renal Impairment (2.2) 01/2021 Patients with known serious hypersensitivity or anaphylaxis to peramivir or Preparation of RAPIVAB for Intravenous Infusion (2.3) 01/2021 any component of RAPIVAB (4) ---------------------------INDICATIONS AND USAGE--------------------------- --------------------------WARNINGS AND PRECAUTIONS---------------------- RAPIVAB is an influenza virus neuraminidase inhibitor indicated for the Cases of anaphylaxis and serious skin/hypersensitivity reactions such treatment of acute uncomplicated influenza in patients 6 months and older as Stevens-Johnson syndrome and erythema multiforme have occurred who have been symptomatic for no more than two days. (1) with RAPIVAB. Discontinue RAPIVAB and initiate appropriate treatment if anaphylaxis or serious skin reaction occurs or is suspected. (5.1) Limitations of Use: Neuropsychiatric events: Patients with influenza may be at an Efficacy based on clinical trials in which the predominant influenza virus increased risk of hallucinations, delirium and abnormal behavior early in type was influenza A; a limited number of subjects infected with their illness. Monitor for signs of abnormal behavior. (5.2) influenza B virus were enrolled. (1) Consider available information on influenza drug susceptibility patterns -----------------------------ADVERSE REACTIONS-------------------------------- and treatment effects when deciding whether to use. (1) Most common adverse reaction (incidence >2%) is diarrhea. (6) Efficacy could not be established in patients with serious influenza requiring hospitalization. (1) To report SUSPECTED ADVERSE REACTIONS, contact BioCryst Pharmaceuticals, Inc. at 1-833-633-2279 or FDA at 1-800-FDA-1088 or -------------------------DOSAGE AND ADMINISTRATION--------------------- www.fda.gov/medwatch Administer RAPIVAB as a single dose within 2 days of onset of influenza symptoms (2.1) ---------------------------------DRUG INTERACTIONS----------------------------- Administer RAPIVAB by intravenous infusion for a minimum of 15 Live attenuated influenza vaccine (LAIV), intranasal: Avoid use of LAIV minutes (2.1) within 2 weeks before or 48 hours after administration of RAPIVAB, unless medically indicated (7.1) Recommended Dosage Single Dose See 17 for PATIENT COUNSELING INFORMATION. Adults and adolescents (13 years and older) 600 mg 12 mg/kg Revised: 01/2021 Pediatric patients (6 months to 12 years of age) (up to 600 mg) Recommended Dosage Creatinine Clearance (mL/min) Adjustments in Patients with Altered Creatinine ≥ 50 30-49 10-29 Clearance Adults and adolescents 600 mg 200 mg 100 mg (13 years and older) Pediatric patients * 12 mg/kg 4 mg/kg 2 mg/kg (2 to 12 years of age) * Up to maximum dose of 600 mg 1 Reference ID: 4738205 FULL PRESCRIBING INFORMATION: CONTENTS* 8.5 Geriatric Use 8.6 Patients with Impaired Renal Function 1 INDICATIONS AND USAGE 8.7 Patients with Serious Influenza Requiring Hospitalization 2 DOSAGE AND ADMINISTRATION 10 OVERDOSAGE 2.1 Dosage in Acute Uncomplicated Influenza 11 DESCRIPTION 2.2 Dosing in Patients with Renal Impairment 12 CLINICAL PHARMACOLOGY 2.3 Preparation of RAPIVAB for Intravenous Infusion 12.1 Mechanism of Action 2.4 Drug Compatibility 12.2 Cardiac Electrophysiology 3 DOSAGE FORMS AND STRENGTHS 12.3 Pharmacokinetics 4 CONTRAINDICATIONS 12.4 Microbiology 5 WARNINGS AND PRECAUTIONS 13 NONCLINICAL TOXICOLOGY 5.1 Serious Skin/Hypersensitivity Reactions 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.2 Neuropsychiatric Events 13.2 Animal Toxicology and/or Pharmacology 5.3 Risk of Bacterial Infections 14 CLINICAL STUDIES 6 ADVERSE REACTIONS 14.1 Acute Uncomplicated Influenza in Adults 6.1 Clinical Trials Experience 14.2 Acute Uncomplicated Influenza in Pediatric Subjects 6.2 Postmarketing Experience 14.3 Serious Influenza Requiring Hospitalization 7 DRUG INTERACTIONS 16 HOW SUPPLIED/STORAGE AND HANDLING 7.1 Influenza Vaccines 17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing information are 8 USE IN SPECIFIC POPULATIONS not listed 8.1 Pregnancy 8.2 Lactation 8.4 Pediatric Use 2 Reference ID: 4738205 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE RAPIVAB is indicated for the treatment of acute uncomplicated influenza in patients 6 months and older who have been symptomatic for no more than 2 days. Limitations of Use: Efficacy of RAPIVAB is based on clinical trials of naturally occurring influenza in which the predominant influenza infections were influenza A virus; a limited number of subjects infected with influenza B virus were enrolled. 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. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use RAPIVAB [see Microbiology (12.4)]. The efficacy of RAPIVAB could not be established in patients with serious influenza requiring hospitalization [see Clinical Studies (14.3)]. 2 DOSAGE AND ADMINISTRATION 2.1 Dosage in Acute Uncomplicated Influenza Administer RAPIVAB within 2 days of onset of symptoms of influenza. Adults and Adolescents (13 years of age and older) The recommended dosage of RAPIVAB in adult and adolescent patients 13 years of age or older with acute uncomplicated influenza is a single 600 mg dose, administered via intravenous infusion for 15 to 30 minutes. Pediatric Patients (6 months to 12 years of age) The recommended dosage of RAPIVAB in pediatric patients 6 months to 12 years of age with acute uncomplicated influenza is a single 12 mg/kg dose (up to a maximum dose of 600 mg), administered via intravenous infusion for 15 to 30 minutes. 2.2 Dosing in Patients with Renal Impairment Significantly increased drug exposures were observed when RAPIVAB was administered to adult subjects with renal dysfunction [see Clinical Pharmacology (12.3)]. Therefore, the RAPIVAB dosage should be reduced for patients with baseline creatinine clearance below 50 mL/min using the recommendations in Table 1 and Table 2. No dosage adjustment is required for single administration of RAPIVAB in patients with creatinine clearance of 50 mL/min or higher [see Clinical Pharmacology (12.3)]. In patients with chronic renal impairment maintained on hemodialysis, RAPIVAB should be administered after dialysis at a dose adjusted based on renal function (Table 1 and Table 2) [see Clinical Pharmacology (12.3)]. Table 1. Dosage Adjustment for Adults and Adolescents (13 years and older) with Altered Creatinine Clearance * Creatinine Clearance (mL/min) ≥50 30-49 10-29 Recommended Dose (mg) 600 mg 200 mg 100 mg * Calculated using the Cockcroft and Gault equation. 3 Reference ID: 4738205 Table 2. Dosage Adjustment for Pediatric Patients (2 to 12 years of age) with Altered Creatinine Clearance Creatinine Clearance* (mL/min) ≥50 30-49 10-29 Recommended Dose (mg/kg)** 12 mg/kg 4 mg/kg 2 mg/kg * Calculated using the Cockcroft and Gault equation. ** Up to maximum dose of 600 mg No data are available to inform a recommendation for dosage adjustment with RAPIVAB in pediatric patients 6 months to less than 2 years of age with creatinine clearance less than 50 mL/min [see Use in Specific Populations (8.4, 8.6), Clinical Pharmacology (12.3)]. 2.3 Preparation of RAPIVAB for Intravenous Infusion Use aseptic technique during the preparation of RAPIVAB to prevent inadvertent microbial contamination. There is no preservative or bacteriostatic agent present in the solution. Follow the steps below to prepare a diluted solution of RAPIVAB: (a) Do not use if seal over bottle opening is broken or missing. (b) Visually inspect RAPIVAB for particulate matter and discoloration prior to administration. (c) Dilute an appropriate dose of RAPIVAB 10 mg/mL solution [see Dosage and Administration (2.1, 2.2)] in 0.9% or 0.45% sodium chloride, 5% dextrose, or lactated Ringer’s. The maximum infusion volume is provided in Table 3. The final concentration of diluted RAPIVAB for administration should be between 1 mg/mL and 6 mg/mL. Table 3. Maximum Infusion Volume by Age and Weight Maximum Infusion Age Weight (kg) Volume* (mL) Infants 6 months to 1 year of age Any 25 mL 5 kg to less than 10 kg 25 mL 10 kg to less than 15 kg 50 mL Adults and pediatric patients 1 year and older 15 kg to less than 20 kg 75 mL At least 20 kg 100 mL *Infusion volume is the total volume of RAPIVAB 10 mg/mL solution and