US-10672 HIGHLIGHTS OF PRESCRIBING …

1 US-10672 . HIGHLIGHTS OF PRESCRIBING information -----------------------------DOSAGE FORMS AND STRENGTHS---------------------------- These HIGHLIGHTS do not include all the information needed to use SYNAGIS safely Single-dose liquid solution vials: 50 mg per mL and 100 mg per 1 mL. (3). and effectively. See full PRESCRIBING information for SYNAGIS. ------------------------------------CONT RAINDICATIONS--------------------------- --------- Previous significant hypersensitivity reaction to Synagis. (4). SYNAGIS (palivizumab) injection, for intramuscular use -------------------------------WARNINGS AND PRECAUTIONS----------------------------- Initial Approval: 1998 Anaphylaxis and anaphylactic shock (including fatal cases), and other severe acute hypersensitivity reactions have been reported.

2 Permanently discontinue ----------------------------------INDICA TIONS AND USAGE--------------------------------- Synagis and administer appropriate medications if such reactions occur. ( ). Synagis is a respiratory syncytial virus (RSV) F protein inhibitor monoclonal antibody indicated for the prevention of serious lower respiratory tract disease caused by As with any intramuscular injection, Synagis should be given with caution to respiratory syncytial virus (RSV) in pediatric patients: children with thrombocytopenia or any coagulation disorder. ( ). with a history of premature birth (less than or equal to 35 weeks gestational age) Palivizumab may interfere with immunological-based RSV diagnostic tests such and who are 6 months of age or younger at the beginning of RSV season, as some antigen detection-based assays.

3 ( , ). with bronchopulmonary dysplasia (BPD) that required medical treatment within ------------------------------------ADVE RSE REACTIONS------------------------------- ----- the previous 6 months and who are 24 months of age or younger at the beginning Adverse reactions occurring greater than or equal to 10% and at least 1% more of RSV season, frequently than placebo are fever and rash. ( ). with hemodynamically significant congenital heart disease (CHD) and who are To report SUSPECTED ADVERSE REACTIONS, contact MedImmune at 24 months of age or younger at the beginning of RSV season. 1-877-633-4411 or FDA at 1-800-FDA-1088 or Limitations of Use: The safety and efficacy of Synagis have not been established for ------------------------------USE IN SPECIFIC POPULATIONS----------------------------- - treatment of RSV disease.

4 (1) Safety and effectiveness in children older than 24 months of age at the start of dosing ------------------------------DOSAGE AND ADMINISTRATION-------------------------- ---- have not been established. ( ). 15 mg per kg of body weight, administered intramuscularly prior to commencement See 17 for PATIENT COUNSELING information and FDA-approved patient of the RSV season and remaining doses administered monthly throughout the RSV labeling. season. ( ). Children undergoing cardio-pulmonary bypass should receive an additional dose of Revised: 05/2017. Synagis as soon as possible after the cardio-pulmonary bypass procedure (even if sooner than a month from the previous dose). Thereafter, doses should be administered monthly as scheduled.

5 ( , ). FULL PRESCRIBING information : CONTENTS* 7 DRUG INTERACTIONS. 1 INDICATIONS AND USAGE 8 USE IN SPECIFIC POPULATIONS. 2 DOSAGE AND ADMINISTRATION Pregnancy Dosing information Lactation Administration Instructions Pediatric Use 3 DOSAGE FORMS AND STRENGTHS 10 OVERDOSAGE. 4 CONTRAINDICATIONS 11 DESCRIPTION. 5 WARNINGS AND PRECAUTIONS 12 CLINICAL PHARMACOLOGY. Hypersensitivity Reactions Mechanism of Action Coagulation Disorders Pharmacokinetics RSV Diagnostic Test Interference Microbiology Treatment of RSV Disease 13 NONCLINICAL TOXICOLOGY. Proper Administration Carcinogenesis, Mutagenesis, Impairment of Fertility 6 ADVERSE REACTIONS 14 CLINICAL STUDIES. Clinical Studies Experience 16 HOW SUPPLIED/STORAGE AND HANDLING.

6 Postmarketing Experience 17 PATIENT COUNSELING information . *Sections or subsections omitted from the full PRESCRIBING information are not listed. FULL PRESCRIBING information continue to receive monthly doses throughout the RSV season. In the northern hemisphere, the RSV season typically commences in November and lasts through 1 INDICATIONS AND USAGE. April, but it may begin earlier or persist later in certain communities. Synagis is indicated for the prevention of serious lower respiratory tract disease Synagis serum levels are decreased after cardio-pulmonary bypass [see Clinical caused by respiratory syncytial virus (RSV) in pediatric patients: Pharmacology ( )]. Children undergoing cardio-pulmonary bypass should with a history of premature birth (less than or equal to 35 weeks gestational receive an additional dose of Synagis as soon as possible after the cardio-pulmonary age) and who are 6 months of age or younger at the beginning of RSV season, bypass procedure (even if sooner than a month from the previous dose).

7 Thereafter, with bronchopulmonary dysplasia (BPD) that required medical treatment doses should be administered monthly as scheduled. within the previous 6 months and who are 24 months of age or younger at the The efficacy of Synagis at doses less than 15 mg per kg, or of dosing less frequently beginning of RSV season, than monthly throughout the RSV season, has not been established. with hemodynamically significant congenital heart disease (CHD) and who Administration Instructions are 24 months of age or younger at the beginning of RSV season [see Clinical Studies (14)]. DO NOT DILUTE THE PRODUCT. DO NOT SHAKE OR VIGOROUSLY AGITATE THE VIAL. Limitations of Use: Parenteral drug products should be inspected visually for particulate matter The safety and efficacy of Synagis have not been established for treatment of RSV.

8 And discoloration prior to administration. Do not use any vials exhibiting disease [see Warnings and Precautions ( )]. particulate matter or discoloration. 2 DOSAGE AND ADMINISTRATION Using aseptic techniques, attach a sterile needle to a sterile syringe. Dosing information Remove the flip top from the Synagis vial and wipe the rubber stopper with The recommended dose of Synagis is 15 mg per kg of body weight given monthly a disinfectant ( , 70% isopropyl alcohol). Insert the needle into the vial by intramuscular injection. The first dose of Synagis should be administered prior to and withdraw into the syringe an appropriate volume of solution. Administer commencement of the RSV season and the remaining doses should be administered immediately after drawing the dose into the syringe.

9 Monthly throughout the RSV season. Children who develop an RSV infection should SYNAGIS (palivizumab) injection, for intramuscular use 2. Synagis should be administered in a dose of 15 mg per kg intramuscularly comparing the liquid and lyophilized formulations were comparable for the two using aseptic technique, preferably in the anterolateral aspect of the thigh. formulations, and were similar to those observed with Synagis in Trials 1 and 2. The gluteal muscle should not be used routinely as an injection site because Immunogenicity of the risk of damage to the sciatic nerve. The dose (volume of injection in mL). per month = patient weight (kg) x 15 mg per kg 100 mg per mL of Synagis.

10 In Trial 1, the incidence of anti-palivizumab antibody following the fourth injection Injection volumes over 1 mL should be given as a divided dose. was in the placebo group and in the Synagis group. In children receiving Synagis for a second season, one of the fifty-six children had transient, low titer Synagis is supplied as a single-dose vial and does not contain preservatives. reactivity. This reactivity was not associated with adverse events or alteration in Do not re-enter the vial after withdrawal of drug; discard unused portion. Only serum concentrations. Immunogenicity was not assessed in Trial 2. administer one dose per vial. A trial of high-risk preterm children less than or equal to 24 months of age was Use sterile disposable syringes and needles.