These Highlights Do Not Include All The Information Needed To Use Synagis Safely And Effectively. See Full Prescribing Information For Synagis.

Limitations of Use:

The safety and efficacy of Synagis have not been established for treatment of RSV disease [see Warnings and Precautions ( 5.4)] .

Storage

Upon receipt and until use, Synagis should be stored between 2°C and 8°C (36°F and 46°F) in its original container. DO NOT freeze. DO NOT use beyond the expiration date.

Overdoses with doses up to 85 mg per kg have been reported in clinical studies and post-marketing experience with Synagis, and in some cases, adverse reactions were reported. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.

Palivizumab is a humanized monoclonal antibody (IgG1κ) produced by recombinant DNA technology, directed to an epitope in the A antigenic site of the F protein of RSV. Palivizumab is a composite of human (95%) and murine (5%) antibody sequences. The human heavy chain sequence was derived from the constant domains of human IgG1 and the variable framework regions of the V _Hgenes Cor and Cess. The human light chain sequence was derived from the constant domain of Cκ and the variable framework regions of the V _Lgene K104 with Jκ -4. The murine sequences were derived from a murine monoclonal antibody, Mab 1129, in a process that involved the grafting of the murine complementarity determining regions into the human antibody frameworks. Palivizumab is composed of two heavy chains and two light chains and has a molecular weight of approximately 148,000 Daltons.

Synagis is supplied as a sterile, preservative-free liquid solution at 100 mg per mL to be administered by intramuscular injection. Thimerosal or other mercury-containing salts are not used in the production of Synagis. The solution has a pH of 6.0 and should appear clear or slightly opalescent.

Each 100 mg single-dose vial of Synagis liquid solution contains 100 mg of palivizumab and also contains chloride (0.5 mg), glycine (0.1 mg), and histidine (3.9 mg), in a volume of 1 mL.

Each 50 mg single-dose vial of Synagis liquid solution contains 50 mg of palivizumab and also contains chloride (0.2 mg), glycine (0.06 mg), and histidine (1.9 mg), in a volume of 0.5 mL.

The safety and effectiveness of Synagis in children older than 24 months of age at the start of dosing have not been established [see Clinical Studies ( 14) ].

The safety and efficacy of Synagis were assessed in two randomized, double-blind, placebo-controlled trials of prophylaxis against RSV infection in children at high risk of an RSV-related hospitalization. Trial 1 was conducted during a single RSV season and studied a total of 1502 children less than or equal to 24 months of age with BPD or infants with premature birth (less than or equal to 35 weeks gestation) who were less than or equal to 6 months of age at study entry. Trial 2 was conducted over four consecutive seasons among a total of 1287 children less than or equal to 24 months of age with hemodynamically significant congenital heart disease. In both trials participants received 15 mg per kg Synagis or an equivalent volume of placebo via intramuscular injection monthly for five injections and were followed for 150 days from randomization. In Trial 1, 99% of all subjects completed the study and 93% completed all five injections. In Trial 2, 96% of all subjects completed the study and 92% completed all five injections. The incidence of RSV hospitalization is shown in Table 1. The results were shown to be statistically significant using Fisher's exact test.

In Trial 1, the reduction of RSV hospitalization was observed both in children with BPD (34/266 [12.8%] placebo versus 39/496 [7.9%] Synagis) and in premature infants without BPD (19/234 [8.1%] placebo versus 9/506 [1.8%] Synagis). In Trial 2, reductions were observed in acyanotic (36/305 [11.8%] placebo versus 15/300 [5.0%] Synagis) and cyanotic children (27/343 [7.9%] placebo versus 19/339 [5.6%] Synagis).

The clinical studies do not suggest that RSV infection was less severe among children hospitalized with RSV infection who received Synagis for RSV prophylaxis compared to those who received placebo.

Synagis is contraindicated in children who have had a previous significant hypersensitivity reaction to Synagis [see Warnings and Precautions ( 5.1) ].

The most serious adverse reactions occurring with Synagis are anaphylaxis and other acute hypersensitivity reactions [see Warnings and Precautions ( 5.1) ].

No formal drug-drug interaction studies were conducted. In Trial 1, the proportions of children in the placebo and Synagis groups who received routine childhood vaccines, influenza vaccine, bronchodilators, or corticosteroids were similar and no incremental increase in adverse reactions was observed among children receiving these agents.

In children less than or equal to 24 months of age without congenital heart disease (CHD), the mean half-life of palivizumab was 20 days and monthly intramuscular doses of 15 mg per kg achieved mean ± SD 30 day trough serum drug concentrations of 37 ± 21 mcg per mL after the first injection, 57 ± 41 mcg per mL after the second injection, 68 ± 51 mcg per mL after the third injection, and 72 ± 50 mcg per mL after the fourth injection. Trough concentrations following the first and fourth Synagis dose were similar in children with CHD and in non-cardiac patients. In children given Synagis for a second season, the mean ± SD serum concentrations following the first and fourth injections were 61 ± 17 mcg per mL and 86 ± 31 mcg per mL, respectively.

In 139 children less than or equal to 24 months of age with hemodynamically significant CHD who received Synagis and underwent cardio-pulmonary bypass for open-heart surgery, the mean ± SD serum palivizumab concentration was 98 ± 52 mcg per mL before bypass and declined to 41 ± 33 mcg per mL after bypass, a reduction of 58% [see Dosage and Administration ( 2.1) ].The clinical significance of this reduction is unknown.

Specific studies were not conducted to evaluate the effects of demographic parameters on palivizumab systemic exposure. However, no effects of gender, age, body weight, or race on palivizumab serum trough concentrations were observed in a clinical study with 639 children with CHD (less than or equal to 24 months of age) receiving five monthly intramuscular injections of 15 mg per kg of Synagis.

The pharmacokinetics and safety of Synagis liquid solution and Synagis lyophilized formulation administered via intramuscular injection at 15 mg per kg were studied in a cross-over trial of 153 infants less than or equal to 6 months of age with a history of prematurity. The results of this trial indicated that the trough serum concentrations of palivizumab were comparable between the liquid solution and the lyophilized formulation, which was the formulation used in the clinical studies.

A population pharmacokinetic analysis was performed across 22 studies in 1800 patients (1684 pediatric and 116 adult patients) to characterize palivizumab pharmacokinetics and inter-subject variability in serum concentrations. Palivizumab pharmacokinetics was described by a two-compartment linear model with an elimination half-life of 24.5 days in pediatric patients. Clearance of palivizumab in a typical pediatric patient (body weight 4.5 kg) less than or equal to 24 months of age without CHD was estimated to be 11 mL per day with a bioavailability of 70% following intramuscular administration. The inter-patient variability in drug clearance was 48.7% (CV%). Covariate analysis did not identify any factors that could account for the inter-patient variability in order to predict serum concentrations a priori in an individual patient.

The recommended dose of Synagis is 15 mg per kg of body weight given monthly by intramuscular injection. The first dose of Synagis should be administered prior to commencement of the RSV season and the remaining doses should be administered monthly throughout the RSV season. Children who develop an RSV infection should continue to receive monthly doses throughout the RSV season. In the northern hemisphere, the RSV season typically commences in November and lasts through April, but it may begin earlier or persist later in certain communities.

Synagis serum levels are decreased after cardio-pulmonary bypass [see Clinical Pharmacology ( 12.3) ].Children undergoing cardio-pulmonary bypass should receive an additional dose of 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.

The efficacy of Synagis at doses less than 15 mg per kg, or of dosing less frequently than monthly throughout the RSV season, has not been established.

Synagis is indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients:

• with a history of premature birth (less than or equal to 35 weeks gestational age) and who are 6 months of age or younger at the beginning of RSV season,
• with bronchopulmonary dysplasia (BPD) that required medical treatment within the previous 6 months and who are 24 months of age or younger at the beginning of RSV season,
• with hemodynamically significant congenital heart disease (CHD) and who are 24 months of age or younger at the beginning of RSV season [see Clinical Studies ( 14) ].

Palivizumab is a recombinant humanized monoclonal antibody with anti-RSV activity [see Microbiology ( 12.4) ].

Synagis is for intramuscular use only. As with any intramuscular injection, Synagis should be given with caution to children with thrombocytopenia or any coagulation disorder.

The single-dose vial of Synagis does not contain a preservative. Administration of Synagis should occur immediately after dose withdrawal from the vial. The vial should not be re-entered. Discard any unused portion.

• Anaphylaxis and anaphylactic shock (including fatal cases), and other severe acute hypersensitivity reactions have been reported. Permanently discontinue Synagis and administer appropriate medications if such reactions occur. ( 5.1)
• As with any intramuscular injection, Synagis should be given with caution to children with thrombocytopenia or any coagulation disorder. ( 5.2)
• Palivizumab may interfere with immunological-based RSV diagnostic tests such as some antigen detection-based assays. ( 5.3, 12.4)

15 mg per kg of body weight, administered intramuscularly prior to commencement of the RSV season and remaining doses administered monthly throughout the RSV season. ( 2.1)

Children undergoing cardio-pulmonary bypass should receive an additional dose of 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. ( 2.1, 12.3)

Single-dose liquid solution vials: 50 mg per 0.5 mL and 100 mg per 1 mL.

The safety and efficacy of Synagis have not been established for treatment of RSV disease.

The following adverse reactions have been identified during post approval use of Synagis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Disorders: severe thrombocytopenia (platelet count less than 50,000 per microliter)

General Disorders and Administration Site Conditions: injection site reactions

Limited information from post-marketing reports suggests that, within a single RSV season, adverse events after a sixth or greater dose of Synagis are similar in character and frequency to those after the initial five doses.

Safety and effectiveness in children older than 24 months of age at the start of dosing have not been established. ( 8.4)

Cases of anaphylaxis and anaphylactic shock, including fatal cases, have been reported following initial exposure or re-exposure to Synagis. Other acute hypersensitivity reactions, which may be severe, have also been reported on initial exposure or re-exposure to Synagis. Signs and symptoms may include urticaria, pruritus, angioedema, dyspnea, respiratory failure, cyanosis, hypotonia, hypotension, and unresponsiveness. The relationship between these reactions and the development of antibodies to Synagis is unknown. If a significant hypersensitivity reaction occurs with Synagis, its use should be permanently discontinued. If anaphylaxis or other significant hypersensitivity reaction occurs, administer appropriate medications (e.g., epinephrine) and provide supportive care as required. If a mild hypersensitivity reaction occurs, clinical judgment should be used regarding cautious readministration of Synagis.

• DO NOT DILUTE THE PRODUCT.
• DO NOT SHAKE OR VIGOROUSLY AGITATE THE VIAL.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any vials exhibiting particulate matter or discoloration.
• Using aseptic techniques, attach a sterile needle to a sterile syringe. Remove the flip top from the Synagis vial and wipe the rubber stopper with a disinfectant (e.g., 70% isopropyl alcohol). Insert the needle into the vial and withdraw into the syringe an appropriate volume of solution. Administer immediately after drawing the dose into the syringe.
• Synagis should be administered in a dose of 15 mg per kg intramuscularly using aseptic technique, preferably in the anterolateral aspect of the thigh. The gluteal muscle should not be used routinely as an injection site because 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. Injection volumes over 1 mL should be given as a divided dose.
• Synagis is supplied as a single-dose vial and does not contain preservatives. Do not re-enter the vial after withdrawal of drug; discard unused portion. Only administer one dose per vial.
• Use sterile disposable syringes and needles. To prevent the transmission of hepatitis viruses or other infectious agents from one person to another, DO NOT reuse syringes and needles.

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 data described below reflect exposure to Synagis (n=1639) compared with placebo (n=1143) in children 3 days to 24.1 months of age at high risk of RSV-related hospitalization in two clinical trials. Trial 1 was conducted during a single RSV season and studied a total of 1502 children less than or equal to 24 months of age with BPD or infants with premature birth (less than or equal to 35 weeks gestation) who were less than or equal to 6 months of age at study entry. Trial 2 was conducted over four consecutive seasons among a total of 1287 children less than or equal to 24 months of age with hemodynamically significant congenital heart disease.

In Trials 1 and 2 combined, fever and rash were each reported more frequently among Synagis than placebo recipients, 27% versus 25%, and 12% versus 10%, respectively. Adverse reactions observed in the 153-patient crossover study comparing the liquid and lyophilized formulations were comparable for the two formulations, and were similar to those observed with Synagis in Trials 1 and 2.

Advise the patient's caregiver to read the FDA-approved patient labeling ( Patient Information)

Synagis is supplied in single-dose vials as a preservative-free, sterile liquid solution at 100 mg per mL for intramuscular injection.

50 mg vial NDC 66658-230-01

The 50 mg vial contains 50 mg Synagis in 0.5 mL.

100 mg vial NDC 66658-231-01

The 100 mg vial contains 100 mg Synagis in 1 mL.

The rubber stopper used for sealing vials of Synagis is not made with natural rubber latex.

Palivizumab may interfere with immunological-based RSV diagnostic tests such as some antigen detection-based assays. In addition, palivizumab inhibits virus replication in cell culture, and therefore may also interfere with viral culture assays. Palivizumab does not interfere with reverse transcriptase-polymerase chain reaction based assays. Assay interference could lead to false-negative RSV diagnostic test results. Therefore, diagnostic test results, when obtained, should be used in conjunction with clinical findings to guide medical decisions [see Microbiology ( 12.4) ].

NDC 66658-231-01

100 mg/mL

SYNAGIS ^®

PALIVIZUMAB

For Intramuscular

Injection Only

US Lic. 1859

NDC 66658-231-01

SYNAGIS ^®

PALIVIZUMAB

100 mg/mL

For Intramuscular Injection Only

Store at 2 to 8°C (36 to 46°F).

Single-dose vial.

Discard unused portion.

NDC 66658-230-01

50 mg/0.5 mL

SYNAGIS ^®

PALIVIZUMAB

For Intramuscular

Injection Only

US Lic. 1859

NDC 66658-230-01

SYNAGIS ^®

PALIVIZUMAB

50 mg/0.5 mL

For Intramuscular Injection Only

Store at 2 to 8°C (36 to 46°F).

Single-dose vial.

Discard unused portion.

Carcinogenesis, mutagenesis, and reproductive toxicity studies have not been performed.

Limitations of Use:

The safety and efficacy of Synagis have not been established for treatment of RSV disease [see Warnings and Precautions ( 5.4)] .

Storage

Upon receipt and until use, Synagis should be stored between 2°C and 8°C (36°F and 46°F) in its original container. DO NOT freeze. DO NOT use beyond the expiration date.

Overdoses with doses up to 85 mg per kg have been reported in clinical studies and post-marketing experience with Synagis, and in some cases, adverse reactions were reported. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.

Palivizumab is a humanized monoclonal antibody (IgG1κ) produced by recombinant DNA technology, directed to an epitope in the A antigenic site of the F protein of RSV. Palivizumab is a composite of human (95%) and murine (5%) antibody sequences. The human heavy chain sequence was derived from the constant domains of human IgG1 and the variable framework regions of the V _Hgenes Cor and Cess. The human light chain sequence was derived from the constant domain of Cκ and the variable framework regions of the V _Lgene K104 with Jκ -4. The murine sequences were derived from a murine monoclonal antibody, Mab 1129, in a process that involved the grafting of the murine complementarity determining regions into the human antibody frameworks. Palivizumab is composed of two heavy chains and two light chains and has a molecular weight of approximately 148,000 Daltons.

Synagis is supplied as a sterile, preservative-free liquid solution at 100 mg per mL to be administered by intramuscular injection. Thimerosal or other mercury-containing salts are not used in the production of Synagis. The solution has a pH of 6.0 and should appear clear or slightly opalescent.

Each 100 mg single-dose vial of Synagis liquid solution contains 100 mg of palivizumab and also contains chloride (0.5 mg), glycine (0.1 mg), and histidine (3.9 mg), in a volume of 1 mL.

Each 50 mg single-dose vial of Synagis liquid solution contains 50 mg of palivizumab and also contains chloride (0.2 mg), glycine (0.06 mg), and histidine (1.9 mg), in a volume of 0.5 mL.

The safety and effectiveness of Synagis in children older than 24 months of age at the start of dosing have not been established [see Clinical Studies ( 14) ].

The safety and efficacy of Synagis were assessed in two randomized, double-blind, placebo-controlled trials of prophylaxis against RSV infection in children at high risk of an RSV-related hospitalization. Trial 1 was conducted during a single RSV season and studied a total of 1502 children less than or equal to 24 months of age with BPD or infants with premature birth (less than or equal to 35 weeks gestation) who were less than or equal to 6 months of age at study entry. Trial 2 was conducted over four consecutive seasons among a total of 1287 children less than or equal to 24 months of age with hemodynamically significant congenital heart disease. In both trials participants received 15 mg per kg Synagis or an equivalent volume of placebo via intramuscular injection monthly for five injections and were followed for 150 days from randomization. In Trial 1, 99% of all subjects completed the study and 93% completed all five injections. In Trial 2, 96% of all subjects completed the study and 92% completed all five injections. The incidence of RSV hospitalization is shown in Table 1. The results were shown to be statistically significant using Fisher's exact test.

In Trial 1, the reduction of RSV hospitalization was observed both in children with BPD (34/266 [12.8%] placebo versus 39/496 [7.9%] Synagis) and in premature infants without BPD (19/234 [8.1%] placebo versus 9/506 [1.8%] Synagis). In Trial 2, reductions were observed in acyanotic (36/305 [11.8%] placebo versus 15/300 [5.0%] Synagis) and cyanotic children (27/343 [7.9%] placebo versus 19/339 [5.6%] Synagis).

The clinical studies do not suggest that RSV infection was less severe among children hospitalized with RSV infection who received Synagis for RSV prophylaxis compared to those who received placebo.

Synagis is contraindicated in children who have had a previous significant hypersensitivity reaction to Synagis [see Warnings and Precautions ( 5.1) ].

The most serious adverse reactions occurring with Synagis are anaphylaxis and other acute hypersensitivity reactions [see Warnings and Precautions ( 5.1) ].

No formal drug-drug interaction studies were conducted. In Trial 1, the proportions of children in the placebo and Synagis groups who received routine childhood vaccines, influenza vaccine, bronchodilators, or corticosteroids were similar and no incremental increase in adverse reactions was observed among children receiving these agents.

In children less than or equal to 24 months of age without congenital heart disease (CHD), the mean half-life of palivizumab was 20 days and monthly intramuscular doses of 15 mg per kg achieved mean ± SD 30 day trough serum drug concentrations of 37 ± 21 mcg per mL after the first injection, 57 ± 41 mcg per mL after the second injection, 68 ± 51 mcg per mL after the third injection, and 72 ± 50 mcg per mL after the fourth injection. Trough concentrations following the first and fourth Synagis dose were similar in children with CHD and in non-cardiac patients. In children given Synagis for a second season, the mean ± SD serum concentrations following the first and fourth injections were 61 ± 17 mcg per mL and 86 ± 31 mcg per mL, respectively.

In 139 children less than or equal to 24 months of age with hemodynamically significant CHD who received Synagis and underwent cardio-pulmonary bypass for open-heart surgery, the mean ± SD serum palivizumab concentration was 98 ± 52 mcg per mL before bypass and declined to 41 ± 33 mcg per mL after bypass, a reduction of 58% [see Dosage and Administration ( 2.1) ].The clinical significance of this reduction is unknown.

Specific studies were not conducted to evaluate the effects of demographic parameters on palivizumab systemic exposure. However, no effects of gender, age, body weight, or race on palivizumab serum trough concentrations were observed in a clinical study with 639 children with CHD (less than or equal to 24 months of age) receiving five monthly intramuscular injections of 15 mg per kg of Synagis.

The pharmacokinetics and safety of Synagis liquid solution and Synagis lyophilized formulation administered via intramuscular injection at 15 mg per kg were studied in a cross-over trial of 153 infants less than or equal to 6 months of age with a history of prematurity. The results of this trial indicated that the trough serum concentrations of palivizumab were comparable between the liquid solution and the lyophilized formulation, which was the formulation used in the clinical studies.

A population pharmacokinetic analysis was performed across 22 studies in 1800 patients (1684 pediatric and 116 adult patients) to characterize palivizumab pharmacokinetics and inter-subject variability in serum concentrations. Palivizumab pharmacokinetics was described by a two-compartment linear model with an elimination half-life of 24.5 days in pediatric patients. Clearance of palivizumab in a typical pediatric patient (body weight 4.5 kg) less than or equal to 24 months of age without CHD was estimated to be 11 mL per day with a bioavailability of 70% following intramuscular administration. The inter-patient variability in drug clearance was 48.7% (CV%). Covariate analysis did not identify any factors that could account for the inter-patient variability in order to predict serum concentrations a priori in an individual patient.

The recommended dose of Synagis is 15 mg per kg of body weight given monthly by intramuscular injection. The first dose of Synagis should be administered prior to commencement of the RSV season and the remaining doses should be administered monthly throughout the RSV season. Children who develop an RSV infection should continue to receive monthly doses throughout the RSV season. In the northern hemisphere, the RSV season typically commences in November and lasts through April, but it may begin earlier or persist later in certain communities.

Synagis serum levels are decreased after cardio-pulmonary bypass [see Clinical Pharmacology ( 12.3) ].Children undergoing cardio-pulmonary bypass should receive an additional dose of 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.

The efficacy of Synagis at doses less than 15 mg per kg, or of dosing less frequently than monthly throughout the RSV season, has not been established.

Synagis is indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients:

• with a history of premature birth (less than or equal to 35 weeks gestational age) and who are 6 months of age or younger at the beginning of RSV season,
• with bronchopulmonary dysplasia (BPD) that required medical treatment within the previous 6 months and who are 24 months of age or younger at the beginning of RSV season,
• with hemodynamically significant congenital heart disease (CHD) and who are 24 months of age or younger at the beginning of RSV season [see Clinical Studies ( 14) ].

Palivizumab is a recombinant humanized monoclonal antibody with anti-RSV activity [see Microbiology ( 12.4) ].

Synagis is for intramuscular use only. As with any intramuscular injection, Synagis should be given with caution to children with thrombocytopenia or any coagulation disorder.

The single-dose vial of Synagis does not contain a preservative. Administration of Synagis should occur immediately after dose withdrawal from the vial. The vial should not be re-entered. Discard any unused portion.

• Anaphylaxis and anaphylactic shock (including fatal cases), and other severe acute hypersensitivity reactions have been reported. Permanently discontinue Synagis and administer appropriate medications if such reactions occur. ( 5.1)
• As with any intramuscular injection, Synagis should be given with caution to children with thrombocytopenia or any coagulation disorder. ( 5.2)
• Palivizumab may interfere with immunological-based RSV diagnostic tests such as some antigen detection-based assays. ( 5.3, 12.4)

15 mg per kg of body weight, administered intramuscularly prior to commencement of the RSV season and remaining doses administered monthly throughout the RSV season. ( 2.1)

Children undergoing cardio-pulmonary bypass should receive an additional dose of 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. ( 2.1, 12.3)

Single-dose liquid solution vials: 50 mg per 0.5 mL and 100 mg per 1 mL.

The safety and efficacy of Synagis have not been established for treatment of RSV disease.

The following adverse reactions have been identified during post approval use of Synagis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Disorders: severe thrombocytopenia (platelet count less than 50,000 per microliter)

General Disorders and Administration Site Conditions: injection site reactions

Limited information from post-marketing reports suggests that, within a single RSV season, adverse events after a sixth or greater dose of Synagis are similar in character and frequency to those after the initial five doses.

Safety and effectiveness in children older than 24 months of age at the start of dosing have not been established. ( 8.4)

Cases of anaphylaxis and anaphylactic shock, including fatal cases, have been reported following initial exposure or re-exposure to Synagis. Other acute hypersensitivity reactions, which may be severe, have also been reported on initial exposure or re-exposure to Synagis. Signs and symptoms may include urticaria, pruritus, angioedema, dyspnea, respiratory failure, cyanosis, hypotonia, hypotension, and unresponsiveness. The relationship between these reactions and the development of antibodies to Synagis is unknown. If a significant hypersensitivity reaction occurs with Synagis, its use should be permanently discontinued. If anaphylaxis or other significant hypersensitivity reaction occurs, administer appropriate medications (e.g., epinephrine) and provide supportive care as required. If a mild hypersensitivity reaction occurs, clinical judgment should be used regarding cautious readministration of Synagis.

• DO NOT DILUTE THE PRODUCT.
• DO NOT SHAKE OR VIGOROUSLY AGITATE THE VIAL.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any vials exhibiting particulate matter or discoloration.
• Using aseptic techniques, attach a sterile needle to a sterile syringe. Remove the flip top from the Synagis vial and wipe the rubber stopper with a disinfectant (e.g., 70% isopropyl alcohol). Insert the needle into the vial and withdraw into the syringe an appropriate volume of solution. Administer immediately after drawing the dose into the syringe.
• Synagis should be administered in a dose of 15 mg per kg intramuscularly using aseptic technique, preferably in the anterolateral aspect of the thigh. The gluteal muscle should not be used routinely as an injection site because 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. Injection volumes over 1 mL should be given as a divided dose.
• Synagis is supplied as a single-dose vial and does not contain preservatives. Do not re-enter the vial after withdrawal of drug; discard unused portion. Only administer one dose per vial.
• Use sterile disposable syringes and needles. To prevent the transmission of hepatitis viruses or other infectious agents from one person to another, DO NOT reuse syringes and needles.

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 data described below reflect exposure to Synagis (n=1639) compared with placebo (n=1143) in children 3 days to 24.1 months of age at high risk of RSV-related hospitalization in two clinical trials. Trial 1 was conducted during a single RSV season and studied a total of 1502 children less than or equal to 24 months of age with BPD or infants with premature birth (less than or equal to 35 weeks gestation) who were less than or equal to 6 months of age at study entry. Trial 2 was conducted over four consecutive seasons among a total of 1287 children less than or equal to 24 months of age with hemodynamically significant congenital heart disease.

In Trials 1 and 2 combined, fever and rash were each reported more frequently among Synagis than placebo recipients, 27% versus 25%, and 12% versus 10%, respectively. Adverse reactions observed in the 153-patient crossover study comparing the liquid and lyophilized formulations were comparable for the two formulations, and were similar to those observed with Synagis in Trials 1 and 2.

Advise the patient's caregiver to read the FDA-approved patient labeling ( Patient Information)

Synagis is supplied in single-dose vials as a preservative-free, sterile liquid solution at 100 mg per mL for intramuscular injection.

50 mg vial NDC 66658-230-01

The 50 mg vial contains 50 mg Synagis in 0.5 mL.

100 mg vial NDC 66658-231-01

The 100 mg vial contains 100 mg Synagis in 1 mL.

The rubber stopper used for sealing vials of Synagis is not made with natural rubber latex.

Palivizumab may interfere with immunological-based RSV diagnostic tests such as some antigen detection-based assays. In addition, palivizumab inhibits virus replication in cell culture, and therefore may also interfere with viral culture assays. Palivizumab does not interfere with reverse transcriptase-polymerase chain reaction based assays. Assay interference could lead to false-negative RSV diagnostic test results. Therefore, diagnostic test results, when obtained, should be used in conjunction with clinical findings to guide medical decisions [see Microbiology ( 12.4) ].

NDC 66658-231-01

100 mg/mL

SYNAGIS ^®

PALIVIZUMAB

For Intramuscular

Injection Only

US Lic. 1859

NDC 66658-231-01

SYNAGIS ^®

PALIVIZUMAB

100 mg/mL

For Intramuscular Injection Only

Store at 2 to 8°C (36 to 46°F).

Single-dose vial.

Discard unused portion.

NDC 66658-230-01

50 mg/0.5 mL

SYNAGIS ^®

PALIVIZUMAB

For Intramuscular

Injection Only

US Lic. 1859

NDC 66658-230-01

SYNAGIS ^®

PALIVIZUMAB

50 mg/0.5 mL

For Intramuscular Injection Only

Store at 2 to 8°C (36 to 46°F).

Single-dose vial.

Discard unused portion.

Carcinogenesis, mutagenesis, and reproductive toxicity studies have not been performed.