Synagis

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1.   NAME OF THE MEDICINAL PRODUCT 
 
Synagis 50 mg powder and solvent for solution for injection  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
Each vial contains 50 mg palivizumab*, providing 100 mg/ml of palivizumab when reconstituted as 
recommended. 
 
*Palivizumab is a recombinant humanised monoclonal antibody produced by DNA technology in 
mouse myeloma host cells. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection. 
 
The powder is a white to off-white cake. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Synagis is indicated for the prevention of serious lower respiratory tract disease requiring 
hospitalisation caused by respiratory syncytial virus (RSV) in children at high risk for RSV disease:  
 
• Children born at 35 weeks of gestation or less and less than 6 months of age at the onset of the 

RSV season. 
• Children less than 2 years of age and requiring treatment for bronchopulmonary dysplasia 

within the last 6 months. 
• Children less than 2 years of age and with haemodynamically significant congenital heart 

disease. 
 

4.2 Posology and method of administration 
 
Posology 
The recommended dose of palivizumab is 15 mg/kg of body weight, given once a month during 
anticipated periods of RSV risk in the community.  
 
The volume (expressed in ml) of // Palivizumab // to be administered at one-monthly intervals = 
[patient weight in kg] multiplied by 0.15. 
 
Where possible, the first dose should be administered prior to commencement of the RSV season.  
Subsequent doses should be administered monthly throughout the RSV season.  The efficacy of 
palivizumab at doses other than 15 mg per kg or of dosing differently from monthly throughout the 
RSV season, has not been established. 
 
The majority of experience including the pivotal phase III clinical trials with palivizumab has been 
gained with 5 injections during one season (see section 5.1).  Data, although limited, are available on 
greater than 5 doses (see sections 4.8 and 5.1), therefore the benefit in terms of protection beyond 5 
doses has not been established. 
 



3 

To reduce risk of rehospitalisation, it is recommended that children receiving palivizumab who are 
hospitalised with RSV continue to receive monthly doses of palivizumab for the duration of the RSV 
season.   
 
For children undergoing cardiac bypass, it is recommended that a 15 mg/kg of body weight injection 
of palivizumab be administered as soon as stable after surgery to ensure adequate palivizumab serum 
levels.  Subsequent doses should resume monthly through the remainder of the RSV season for 
children that continue to be at high risk of RSV disease (see section 5.2). 
 
Method of administration 
Palivizumab is administered intramuscularly, 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 injection should be given using standard aseptic technique.  
 
Injection volumes over 1 ml should be given as a divided dose. 
 
To ensure the correct volume is reconstituted for Synagis, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or to other 
humanised monoclonal antibodies. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Allergic reactions including very rare cases of anaphylaxis and anaphylactic shock have been reported 
following palivizumab administration.  In some cases, fatalities have been reported (see section 4.8).   
 
Medicinal products for the treatment of severe hypersensitivity reactions, including anaphylaxis and 
anaphylactic shock, should be available for immediate use following administration of palivizumab. 
 
A moderate to severe acute infection or febrile illness may warrant delaying the use of palivizumab, 
unless, in the opinion of the physician, withholding palivizumab entails a greater risk.  A mild febrile 
illness, such as mild upper respiratory infection, is not usually reason to defer administration of 
palivizumab. 
 
Palivizumab should be given with caution to patients with thrombocytopaenia or any coagulation 
disorder. 
 
The efficacy of palivizumab when administered to patients as a second course of treatment during an 
ensuing RSV season has not been formally investigated in a study performed with this objective.  The 
possible risk of enhanced RSV infection in the season following the season in which the patients were 
treated with palivizumab has not been conclusively ruled out by studies performed aiming at this 
particular point. 
 
4.5   Interaction with other medicinal products and other forms of interaction 
 
No formal interactions studies with other medicinal products were conducted.  In the phase III IMpact-
RSV study in the premature and bronchopulmonary dysplasia paediatric populations, the proportions 
of patients in the placebo and palivizumab groups who received routine childhood vaccines, influenza 
vaccine, bronchodilators or corticosteroids were similar and no incremental increase in adverse 
reactions was observed among patients receiving these agents. 
 



4 

Since the monoclonal antibody is specific for RSV, palivizumab is not expected to interfere with the 
immune response to vaccines. 
 
Palivizumab may interfere with immune-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. 
 
4.6 Fertility, pregnancy and lactation 
 
Not relevant.  Synagis is not indicated for use in adults.  Data on fertility, pregnancy and lactation are 
not available. 
 
4.7 Effects on ability to drive and use machines 
 
Not relevant. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most serious adverse reactions occurring with palivizumab are anaphylaxis and other acute 
hypersensitivity reactions.  Common adverse reactions occurring with palivizumab are fever, rash and 
injection site reaction. 
 
Tabulated list of adverse reactions 
Adverse reactions  both clinical and laboratory, are displayed by system organ class and frequency 
(very common  ≥ 1/10; common  ≥ 1/100 to < 1/10; uncommon  ≥ 1/1,000 to < 1/100 ; rare ≥ 1/10,000 
to < 1/1,000) in studies conducted in premature and bronchopulmonary dysplasia paediatric patients, 
and paediatric congenital heart disease patients. 
 
The adverse reactions identified via post-marketing surveillance 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 palivizumab exposure.  The frequency for these "ADRs" as presented in the 
table below was estimated using the safety data of the two registration clinical studies.  The incidences 
of these reactions in these studies showed no difference between the palivizumab and placebo groups 
and the reactions were not drug related. 



5 

 
Undesirable effects in clinical studies* and post-marketing reports in paediatric patients 
MedDRA system organ 
class 

Frequency  ADR  

Blood and lymphatic 
system disorders 

Uncommon Thrombocytopenia# 

Immune system disorders Not known Anaphylaxis, anaphylactic 
shock (in some cases, 
fatalities have been 
reported.)# 

Nervous system disorders Uncommon Convulsion# 
Respiratory, thoracic and 
mediastinal disorders 

Common Apnoea# 

Skin and subcutaneous 
tissue disorders 

Very common  
 
Uncommon 

Rash  
 
Urticaria# 

General disorders and 
administrative site 
conditions 

Very common  
 
Common 

Pyrexia 
 
Injection site reaction 

 *For full study description, see Section 5.1 Clinical studies 
 # ADRs identified from post-marketing surveillance 
 
Description of selected adverse reactions 
Post-marketing experience 
Post-marketing serious spontaneous adverse reactions reported during palivizumab treatment between 
1998 and 2002 covering four RSV seasons were evaluated.  A total of 1,291 serious reports were 
received where palivizumab had been administered as indicated and the duration of therapy was within 
one season.  The onset of the adverse reactions occurred after the sixth or greater dose in only 22 of 
these reports (15 after the sixth dose, 6 after the seventh doses and 1 after the eight dose).  These 
adverse reactions are similar in character to those after the initial five doses.  
 
Palivizumab treatment schedule and adverse reactions were monitored in a group of nearly 20,000 
infants tracked through a patient compliance registry between 1998 and 2000.  Of this group 1,250 
enrolled infants had 6 injections, 183 infants had 7 injections, and 27 infants had either 8 or 9 
injections.  Adverse reactions observed in patients after a sixth or greater dose were similar in 
character and frequency to those after the initial 5 doses.   
 
In an observational, post-marketing, database study, a small increase in the frequency of asthma was 
observed among preterm palivizumab recipients; however, the causal relationship is uncertain. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important.  It 
allows continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.  
 
4.9 Overdose 
 
In clinical studies, three children received an overdose of more than 15 mg/kg.  These doses were 
20.25 mg/kg, 21.1 mg/kg and 22.27 mg/kg.  No medical consequences were identified in these 
instances. 
 
From the post-marketing experience, overdoses with doses up to 85 mg/kg have been reported and in 
some cases, adverse reactions were reported which did not differ from those observed with 15 mg/kg 
dose (see section 4.8).  In case of overdose, it is recommended that the patient be monitored for any 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


6 

signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted 
immediately.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group:  immune sera immunoglobulins, specific immunoglobulins; ATC Code: 
J06BB16 
 
Palivizumab is a humanised IgG1κ monoclonal antibody directed to an epitope in the A antigenic site 
of the fusion protein of respiratory syncytial virus (RSV).  This humanised monoclonal antibody is 
composed of human (95%) and murine (5%) antibody sequences.  It has potent neutralising and 
fusion-inhibitory activity against both RSV subtype A and B strains.   
 
Palivizumab serum concentrations of approximately 30 µg/ml have been shown to produce a 99% 
reduction in pulmonary RSV replication in the cotton rat model. 
 
In vitro studies of antiviral activity 
The antiviral activity of palivizumab was assessed in a microneutralization assay in which increasing 
concentrations of antibody were incubated with RSV prior to addition of the human epithelial cells 
HEp-2.  After incubation for 4-5 days, RSV antigen was measured in an enzyme-linked 
immunosorbent assay (ELISA).  The neutralization titre (50% effective concentration [EC50]) is 
expressed as the antibody concentration required to reduce detection of RSV antigen by 50% 
compared with untreated virus-infected cells.  Palivizumab exhibited median EC50 values of 0.65 
µg/ml (mean [standard deviation] = 0.75 [0.53] µg/ml; n=69, range 0.07–2.89 µg/ml) and 0.28 µg/ml 
(mean [standard deviation] = 0.35 [0.23] µg/ml; n=35, range 0.03–0.88 µg/ml) against clinical RSV A 
and RSV B isolates, respectively.  The majority of clinical RSV isolates tested (n=96) were collected 
from subjects in the United States.  
 
Resistance 
Palivizumab binds a highly conserved region on the extracellular domain of mature RSV F protein, 
referred to as antigenic site II or A antigenic site, which encompasses amino acids 262 to 275.  In a 
genotypic analysis of 126 clinical isolates from 123 children who failed immunoprophylaxis, all RSV 
mutants that exhibited resistance to palivizumab (n=8) were shown to contain amino acid changes in 
this region of the F protein.  No polymorphic or non-polymorphic sequence variations outside of the A 
antigenic site on the RSV F protein were shown to render RSV resistant to neutralisation by 
palivizumab.  At least one of the palivizumab resistance-associated substitutions, N262D, K272E/Q, 
or S275F/L was identified in these 8 clinical RSV isolates resulting in a combined resistance-
associated mutation frequency of 6.3% in these patients.  A review of clinical findings did not reveal 
an association between A antigenic site sequence changes and RSV disease severity among children 
receiving palivizumab immunoprophylaxis who develop RSV lower respiratory tract disease.  
Analysis of 254 clinical RSV isolates collected from immunoprophylaxis-naïve subjects revealed 
palivizumab resistance-associated substitutions in 2 (1 with N262D and 1 with S275F), resulting in a 
resistance associated mutation frequency of 0.79%. 
 
Immunogenicity  
Antibody to palivizumab was observed in approximately 1% of patients in the IMpact-RSV during the 
first course of therapy.  This was transient, low titre, resolved despite continued use (first and second 
season), and could not be detected in 55 of 56 infants during the second season (including 2 with titres 
during the first season).  Immunogenicity was not studied in the congenital heart disease study.  
Antibody to palivizumab was evaluated in four additional studies in 4337 patients (children born at 35 
weeks of gestation or less and 6 months of age or less, or  24 months of age or less with  
bronchopulmonary dysplasia, or with haemodynamically significant congenital heart disease were 
included in these studies) and was observed in 0% – 1.5% of patients at different study timepoints.  



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There was no association observed between the presence of antibody and adverse events.  Therefore, 
anti-drug antibody (ADA) responses appear to be of no clinical relevance. 
 
Studies using lyophilised palivizumab  
In a placebo-controlled trial of RSV disease prophylaxis in (IMpact-RSV trial) 1502 high-risk children 
(1002 Synagis; 500 placebo), 5 monthly doses of 15 mg/kg reduced the incidence of RSV related 
hospitalisation by 55% (p = < 0.001).  The RSV hospitalisation rate was 10.6% in the placebo group.  
On this basis, the absolute risk reduction is 5.8% which means the number needed to treat is 17 to 
prevent one hospitalisation.  The severity of RSV disease in children hospitalised despite prophylaxis 
with palivizumab in terms of days in ICU stay per 100 children and days of mechanical ventilation per 
100 children was not affected. 
 
A total of 222 children were enrolled in two separate studies to examine the safety of palivizumab 
when it is administered for a second RSV season.  One hundred and three (103) children received 
monthly palivizumab injections for the first time, and 119 children received palivizumab for two 
consecutive seasons.  No difference between groups regarding immunogenicity was observed in either 
study.  However, as the efficacy of palivizumab when administered to patients as a second course of 
treatment during an ensuing RSV season has not been formally investigated in a study performed with 
this objective, the relevance of these data in terms of efficacy is unknown. 
 
In an open label prospective trial designed to evaluate pharmacokinetics, safety and immunogenicity 
after administration of 7 doses of palivizumab within a single RSV season, pharmacokinetic data 
indicated that adequate mean palivizumab levels were achieved in all 18 children enrolled.  Transient, 
low levels of antipalivizumab antibody were observed in one child after the second dose of 
palivizumab that dropped to undetectable levels at the fifth and seventh dose. 
 
In a placebo-controlled trial in 1,287 patients ≤ 24 months of age with haemodynamically significant 
congenital heart disease (639 Synagis; 648 placebo), 5 monthly doses of 15 mg/kg Synagis reduced 
the incidence of RSV hospitalisations by 45% (p = 0.003) (congenital heart disease study).  Groups 
were equally balanced between cyanotic and acyanotic patients.  The RSV hospitalisation rate was 
9.7% in the placebo group and 5.3% in the Synagis group.  Secondary efficacy endpoints showed 
significant reductions in the Synagis group compared to placebo in total days of RSV hospitalisation 
(56% reduction, p = 0.003) and total RSV days with increased supplemental oxygen (73% reduction, 
p = 0.014) per 100 children.   
 
A retrospective observational study was conducted in young children with hemodynamically 
significant congenital heart disease (HSCHD) comparing the occurrence of primary serious adverse 
events (PSAEs: infection, arrhythmia, and death) between those who did (1009) and did not receive 
Synagis prophylaxis (1009) matched by age, type of cardiac lesion, and prior corrective surgery. The 
incidence of arrhythmia and death PSAEs was similar in children who did and did not receive 
prophylaxis. The incidence of infection PSAEs was lower in children who received prophylaxis as 
compared to those children who did not receive prophylaxis. The results of the study indicate no 
increased risk of serious infection, serious arrhythmia, or death in children with HSCHD associated 
with Synagis prophylaxis compared with children who did not receive prophylaxis 
 
Studies using liquid palivizumab 
Two clinical studies were conducted to directly compare liquid and lyophilised formulations of 
palivizumab.  In the first study, all 153 premature infants received both formulations in different 
sequences.   In the second study, 211 and 202 premature infants or children with chronic lung disease 
received liquid and lyophilised palivizumab, respectively.  In two additional studies, liquid 
palivizumab was used as an active control (3918 pediatric subjects) to evaluate an investigational 
monoclonal antibody for prophylaxis of serious RSV disease in premature infants or children with 
BPD or hemodynamically significant CHD (see below for further details of these two studies).  The 
overall rate and pattern of adverse events, study drug discontinuation due to AEs, and the number of 
deaths reported in these clinical studies were consistent with those observed during the clinical 
development programs for the lyophilised formulation.  No deaths were considered related to 
palivizumab and no new ADRs were identified in these studies.  



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Pre-term infants and children with Chronic Lung Disease of Prematurity (CLDP): this trial, conducted 
at 347 centers in the North America, European Union and 10 other countries, studied patients less than 
or equal to 24 months of age with CLDP and patients 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.  Patients with 
hemodynamically significant congenital heart disease were excluded from enrollment in this study and 
were studied in a separate study.  In this trial, patients were randomized to receive 5 monthly 
injections of 15mg/kg of liquid palivizumab (N=3306) used as active control for an investigational 
monoclonal antibody (N=3329).  Subjects were followed for safety and efficacy for 150 days.  Ninety-
eight percent of all subjects receiving palivizumab completed the study and 97% received all five 
injections.  The primary endpoint was the incidence of RSV hospitalisation.  RSV hospitalisations 
occurred among 62 of 3306 (1.9%) patients in the palivizumab group.  The RSV hospitalisation rate 
observed in patients enrolled with a diagnosis of CLDP was 28/723 (3.9%) and in patients enrolled 
with a diagnosis of prematurity without CLDP was 34/2583 (1.3%).  
 
CHD Study 2: this trial, conducted at 162 centers in North America, European Union and 4 other 
countries over two RSV seasons, studied patients less than or equal to 24 months of age with 
hemodynamically significant CHD.  In this trial, patients were randomized to receive 5 monthly 
injections of 15mg/kg of liquid palivizumab (N=612) used as active control for an investigational 
monoclonal antibody (N=624).  Subjects were stratified by cardiac lesion (cyanotic vs. other) and were 
followed for safety and efficacy for 150 days.  Ninety-seven percent of all subjects receiving 
palivizumab completed the study and 95% received all five injections.  The primary endpoint was a 
summary of adverse events and serious adverse events, and the secondary endpoint was the incidence 
of RSV hospitalisation.  The incidence of RSV hospitalisation was 16 of 612 (2.6%) in the 
palivizumab group. 
 
5.2 Pharmacokinetic properties 
 
Lyophilised formulation of palivizumab 
In studies in adult volunteers, palivizumab had a pharmacokinetic profile similar to a human IgG1 
antibody with regard to volume of distribution (mean 57 ml/kg) and half-life (mean 18 days).  In 
prophylactic studies in premature and bronchopulmonary dysplasia paediatric populations, the mean 
half-life of palivizumab was 20 days and monthly intramuscular doses of 15 mg/kg achieved mean 
30 day trough serum active substance concentrations of approximately 40 µg/ml after the first 
injection, approximately 60 µg/ml after the second injection, approximately 70 µg/ml after the third 
injection and fourth injection.  In the congenital heart disease study, monthly intramuscular doses of 
15 mg/kg achieved mean 30 day trough serum active substance concentrations of approximately 
55 µg/ml after the first injection and approximately 90 µg/ml after the fourth injection. 
 
Among 139 children in the congenital heart disease study receiving palivizumab who had 
cardio-pulmonary bypass and for whom paired serum samples were available, the mean serum 
palivizumab concentration was approximately 100 µg/ml pre-cardiac bypass and declined to 
approximately 40 µg/ml after bypass. 
 
5.3 Preclinical safety data 
 
Single dose toxicology studies have been conducted in cynomolgus monkeys (maximum dose 
30 mg/kg), rabbits (maximum dose 50 mg/kg) and rats (maximum dose 840 mg/kg).  No significant 
findings were observed. 
 
Studies carried out in rodents gave no indication of enhancement of RSV replication, or RSV-induced 
pathology or generation of virus escape mutants in the presence of palivizumab under the chosen 
experimental conditions. 
 



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6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder: 
Histidine  
Glycine 
Mannitol (E421) 
 
Solvent: 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product should not be mixed with other medicinal products or diluents other than water 
for injections. 
 
6.3 Shelf-life 
 
4 years. 
 
After reconstitution, the product should be used immediately.  However in-use stability has been 
demonstrated for 3 hours at 20oC - 24oC. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2ºC to 8ºC).  
Do not freeze. 
Keep the vial in the carton in order to protect from light. 
 
6.5 Nature and contents of container 
 
50 mg of powder in a 4 ml vial (type I glass) with a stopper (butyl rubber) and a flip-off seal 
(aluminium). 
1ml of water for injections in an ampoule (type I glass). 
 
Pack size of 1. 
 
6.6 Special precautions for disposal and other handling 
 
The 50 mg vial contains an overfill to allow the withdrawal of 50 mg when reconstituted if following 
the directions described below.   

 
To reconstitute, remove the tab portion of the vial cap and clean the rubber stopper with 70% ethanol 
or equivalent. 
 
Slowly add 0.6 ml of water for injections along the inside wall of the vial to minimise foaming.  After 
the water is added, tilt the vial slightly and gently rotate the vial for 30 seconds.  Do not shake the vial.  
Palivizumab solution should stand at room temperature for a minimum of 20 minutes until the solution 
clarifies.  Palivizumab solution does not contain a preservative and should be administered within 
3 hours of preparation.   
 
When reconstituted as recommended, the final concentration is 100 mg/ml.  
The appearance of the reconstituted solution is clear to slightly opalescent.  
 



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Single-use vial. Any unused product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/99/117/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 13 August 1999 
Date of latest renewal: 27 July 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency: 
http://www.ema.europa.eu.   

http://www.ema.europa.eu/


11 

1. NAME OF THE MEDICINAL PRODUCT 
 
Synagis 100 mg powder and solvent for solution for injection  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains 100 mg palivizumab*, providing 100 mg/ml of palivizumab when reconstituted as 
recommended. 
 
*Palivizumab is a recombinant humanised monoclonal antibody produced by DNA technology in 
mouse myeloma host cells. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection 
 
The powder is a white to off-white cake. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Synagis is indicated for the prevention of serious lower respiratory tract disease requiring 
hospitalisation caused by respiratory syncytial virus (RSV) in children at high risk for RSV disease:  
 
• Children born at 35 weeks of gestation or less and less than 6 months of age at the onset of the 

RSV season 
• Children less than 2 years of age and requiring treatment for bronchopulmonary dysplasia 

within the last 6 months. 
• Children less than 2 years of age and with haemodynamically significant congenital heart 

disease. 
 

4.2 Posology and method of administration 
 
Posology 
The recommended dose of palivizumab is 15 mg/kg of body weight, given once a month during 
anticipated periods of RSV risk in the community.   
 
The volume (expressed in mL) of // Palivizumab // to be administered at one-monthly intervals = 
[patient weight in kg] multiplied by 0.15 
 
Where possible, the first dose should be administered prior to commencement of the RSV season.  
Subsequent doses should be administered monthly throughout the RSV season.  The efficacy of 
palivizumab at doses other than 15 mg per kg or of dosing differently from monthly throughout the 
RSV season, has not been established. 
 
The majority of experience including the pivotal phase III clinical trials with palivizumab has been 
gained with 5 injections during one season (see section 5.1).  Data, although limited, are available on 
greater than 5 doses (see sections 4.8 and 5.1), therefore the benefit in terms of protection beyond 5 
doses has not been established. 
 



12 

To reduce risk of rehospitalisation, it is recommended that children receiving palivizumab who are 
hospitalised with RSV continue to receive monthly doses of palivizumab for the duration of the RSV 
season. 
 
For children undergoing cardiac bypass, it is recommended that a 15 mg/kg of body weight injection 
of palivizumab be administered as soon as stable after surgery to ensure adequate palivizumab serum 
levels.  Subsequent doses should resume monthly through the remainder of the RSV season for 
children that continue to be at high risk of RSV disease (see section 5.2). 
 
Method of administration 
Palivizumab is administered intramuscularly, 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 injection should be given using standard aseptic technique.  
 
Injection volumes over 1 ml should be given as a divided dose. 
 
To ensure the correct volume is reconstituted for Synagis, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or other 
humanised monoclonal antibodies. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Allergic reactions including very rare cases of anaphylaxis and anaphylactic shock have been reported 
following palivizumab administration.  In some cases, fatalities have been reported (see section 4.8).   
 
Medicinal products for the treatment of severe hypersensitivity reactions, including anaphylaxis and 
anaphylactic shock, should be available for immediate use following administration of palivizumab. 
 
A moderate to severe acute infection or febrile illness may warrant delaying the use of palivizumab, 
unless, in the opinion of the physician, withholding palivizumab entails a greater risk.  A mild febrile 
illness, such as mild upper respiratory infection, is not usually reason to defer administration of 
palivizumab. 
 
Palivizumab should be given with caution to patients with thrombocytopaenia or any coagulation 
disorder. 
 
The efficacy of palivizumab when administered to patients as a second course of treatment during an 
ensuing RSV season has not been formally investigated in a study performed with this objective.  The 
possible risk of enhanced RSV infection in the season following the season in which the patients were 
treated with palivizumab has not been conclusively ruled out by studies performed aiming at this 
particular point. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No formal interactions studies with other medicinal products were conducted.  In the phase III IMpact-
RSV study in the premature and bronchopulmonary dysplasia paediatric populations, the proportions 
of patients in the placebo and palivizumab groups who received routine childhood vaccines, influenza 
vaccine, bronchodilators or corticosteroids were similar and no incremental increase in adverse 
reactions was observed among patients receiving these agents. 
 



13 

Since the monoclonal antibody is specific for RSV, palivizumab is not expected to interfere with the 
immune response to vaccines. 
 
Palivizumab may interfere with immune-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. 
 
4.6 Fertility, pregnancy and lactation 
 
Not relevant.  Synagis is not indicated for use in adults.  Data on fertility, pregnancy and lactation are 
not available. 
 
4.7 Effects on ability to drive and use machines 
 
Not relevant. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most serious adverse reactions occurring with palivizumab are anaphylaxis and other acute 
hypersensitivity reactions.  Common adverse reactions occurring with palivizumab are fever, rash, and 
injection site reaction. 
 
Tabulated list of adverse reactions 
Adverse reactions both clinical and laboratory, are displayed by system organ class and frequency 
(very common  ≥ 1/10; common ≥ 1/100 to < 1/10; uncommon  ≥ 1/1,000 to < 1/100; rare ≥ 1/10,000 
to < 1/1,000) in studies conducted in premature and bronchopulmonary dysplasia paediatric patients, 
and paediatric congenital heart disease patients.  
 
The adverse reactions identified via post-marketing surveillance 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 palivizumab exposure.  The frequency for these "ADRs" as presented in the 
table below was estimated using the safety data of the two registration clinical studies.  The incidences 
of these reactions in these studies showed no difference between the palivizumab and placebo groups 
and the reactions were not drug related. 



14 

 
Undesirable effects in clinical studies* and post-marketing reports in paediatric patients 
MedDRA system organ 
class 

Frequency  ADR  

Blood and lymphatic 
system disorders 

Uncommon Thrombocytopenia# 

Immune system disorders Not known Anaphylaxis, anaphylactic 
shock (in some cases, 
fatalities have been 
reported.)# 

Nervous system disorders Uncommon Convulsion# 
Respiratory, thoracic and 
mediastinal disorders 

Common Apnoea# 

Skin and subcutaneous 
tissue disorders 

Very common  
 
Uncommon 

Rash  
 
Urticaria# 

General disorders and 
administrative site 
conditions 

Very common  
 
Common 

Pyrexia 
 
Injection site reaction 

 *For full study description, see Section 5.1 Clinical studies 
 # ADRs identified from post-marketing surveillance. 
 
Description of selected adverse reactions 
Post-marketing experience 
Post-marketing serious spontaneous adverse reactions reported during palivizumab treatment between 
1998 and 2002 covering four RSV seasons were evaluated.  A total of 1,291 serious reports were 
received where palivizumab had been administered as indicated and the duration of therapy was within 
one season.  The onset of the adverse reactions occurred after the sixth or greater dose in only 22 of 
these reports (15 after the sixth dose, 6 after the seventh doses and 1 after the eight dose).  These 
adverse reactions are similar in character to those after the initial five doses.  
 
Palivizumab treatment schedule and adverse reactions were monitored in a group of nearly 20,000 
infants tracked through a patient compliance registry between 1998 and 2000.  Of this group 1,250 
enrolled infants had 6 injections, 183 infants had 7 injections, and 27 infants had either 8 or 9 
injections.  Adverse reactions observed in patients after a sixth or greater dose were similar in 
character and frequency to those after the initial 5 doses.   
 
In an observational, post-marketing, database study, a small increase in the frequency of asthma was 
observed among preterm palivizumab recipients; however, the causal relationship is uncertain. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important.  It 
allows continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.  
 
4.9 Overdose 
 
In clinical studies, three children received an overdose of more than 15 mg/kg.  These doses were 
20.25 mg/kg, 21.1 mg/kg and 22.27 mg/kg.  No medical consequences were identified in these 
instances. 
 
From the post-marketing experience, overdoses with doses up to 85 mg/kg have been reported and in 
some cases, adverse reactions were reported which did not differ from those observed with 15 mg/kg 
dose (see section 4.8).  In case of overdose, it is recommended that the patient be monitored for any 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


15 

signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted 
immediately.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: immune sera immunoglobulins, specific immunoglobulins; ATC Code: 
J06BB16 
 
Palivizumab is a humanised IgG1κ monoclonal antibody directed to an epitope in the A antigenic site 
of the fusion protein of respiratory syncytial virus (RSV).  This humanised monoclonal antibody is 
composed of human (95%) and murine (5%) antibody sequences.  It has potent neutralising and 
fusion-inhibitory activity against both RSV subtype A and B strains.   
 
Palivizumab serum concentrations of approximately 30 µg/ml have been shown to produce a 99% 
reduction in pulmonary RSV replication in the cotton rat model. 
 
In vitro studies of antiviral activity 
The antiviral activity of palivizumab was assessed in a microneutralization assay in which increasing 
concentrations of antibody were incubated with RSV prior to addition of the human epithelial cells 
HEp-2.  After incubation for 4-5 days, RSV antigen was measured in an enzyme-linked 
immunosorbent assay (ELISA).  The neutralization titre (50% effective concentration [EC50]) is 
expressed as the antibody concentration required to reduce detection of RSV antigen by 50% 
compared with untreated virus-infected cells.  Palivizumab exhibited median EC50 values of 0.65 
µg/ml (mean [standard deviation] = 0.75 [0.53] µg/ml; n=69, range 0.07–2.89 µg/ml) and 0.28 µg/ml 
(mean [standard deviation] = 0.35 [0.23] µg/ml; n=35, range 0.03–0.88 µg/ml) against clinical RSV A 
and RSV B isolates, respectively.  The majority of clinical RSV isolates tested (n=96) were collected 
from subjects in the United States. 
 
Resistance 
Palivizumab binds a highly conserved region on the extracellular domain of mature RSV F protein, 
referred to as antigenic site II or A antigenic site, which encompasses amino acids 262 to 275  In a 
genotypic analysis of 126 clinical isolates from 123 children who failed immunoprophylaxis, all RSV 
mutants that exhibited resistance to palivizumab (n=8) were shown to contain amino acid changes in 
this region of the F protein. No polymorphic or non-polymorphic sequence variations outside of the A 
antigenic site on the RSV F protein were shown to render RSV resistant to neutralisation by 
palivizumab. At least one of the palivizumab resistance-associated substitutions, N262D, K272E/Q, or 
S275F/L was identified in these 8 clinical RSV isolates resulting in a combined resistance-associated 
mutation frequency of 6.3% in these patients.  A review of clinical findings did not reveal an 
association between A antigenic site sequence changes and RSV disease severity among children 
receiving palivizumab immunoprophylaxis who develop RSV lower respiratory tract disease.  
Analysis of 254 clinical RSV isolates collected from immunoprophylaxis-naïve subjects revealed 
palivizumab resistance-associated substitutions in 2 (1 with N262D and 1 with S275F), resulting in a 
resistance associated mutation frequency of 0.79%. 
 
Immunogenicity  
Antibody to palivizumab was observed in approximately 1% of patients in the IMpact-RSV during the 
first course of therapy.  This was transient, low titre, resolved despite continued use (first and second 
season), and could not be detected in 55 of 56 infants during the second season (including 2 with titres 
during the first season).  Immunogenicity was not studied in the congenital heart disease study. 
Antibody to palivizumab was evaluated in four additional studies in 4337 patients (children born at 35 
weeks of gestation or less and 6 months of age or less, or  24 months of age or less with 
bronchopulmonary dysplasia, or with haemodynamically significant congenital heart disease were 
included in these studies) and was observed in 0% – 1.5% of patients at different study timepoints.  



16 

There was no association observed between the presence of antibody and adverse events.  Therefore, 
anti-drug antibody (ADA) responses appear to be of no clinical relevance. 
 
Studies using lyophilised palivizumab 
In a placebo-controlled trial of RSV disease prophylaxis in (IMpact-RSV trial) 1502 high-risk children 
(1002 Synagis; 500 placebo), 5 monthly doses of 15 mg/kg reduced the incidence of RSV related 
hospitalisation by 55% (p = < 0.001).  The RSV hospitalisation rate was 10.6% in the placebo group.  
On this basis, the absolute risk reduction is 5.8% which means the number needed to treat is 17 to 
prevent one hospitalisation.  The severity of RSV disease in children hospitalised despite prophylaxis 
with palivizumab in terms of days in ICU stay per 100 children and days of mechanical ventilation per 
100 children was not affected. 
 
A total of 222 children were enrolled in two separate studies to examine the safety of palivizumab 
when it is administered for a second RSV season.  One hundred and three (103) children received 
monthly palivizumab injections for the first time, and 119 children received palivizumab for two 
consecutive seasons.  No difference between groups regarding immunogenicity was observed in either 
study.  However, as the efficacy of palivizumab when administered to patients as a second course of 
treatment during an ensuing RSV season has not been formally investigated in a study performed with 
this objective, the relevance of these data in terms of efficacy is unknown. 
 
In an open label prospective trial designed to evaluate pharmacokinetics, safety, and immunogenicity 
after administration of 7 doses of palivizumab within a single RSV season, pharmacokinetic data 
indicated that adequate mean palivizumab levels were achieved in all 18 children enrolled.  Transient, 
low levels of antipalivizumab antibody were observed in one child after the second dose of 
palivizumab that dropped to undetectable levels at the fifth and seventh dose. 
 
In a placebo-controlled trial in 1,287 patients ≤ 24 months of age with haemodynamically significant 
congenital heart disease (639 Synagis; 648 placebo), 5 monthly doses of 15 mg/kg Synagis reduced 
the incidence of RSV hospitalisations by 45% (p = 0.003) (congenital heart disease study).  Groups 
were equally balanced between cyanotic and acyanotic patients.  The RSV hospitalisation rate was 
9.7% in the placebo group and 5.3% in the Synagis group.  Secondary efficacy endpoints showed 
significant reductions in the Synagis group compared to placebo in total days of RSV hospitalisation 
(56% reduction, p = 0.003) and total RSV days with increased supplemental oxygen (73% reduction, 
p = 0.014) per 100 children.   
 
A retrospective observational study was conducted in young children with hemodynamically 
significant congenital heart disease (HSCHD) comparing the occurrence of primary serious adverse 
events (PSAEs: infection, arrhythmia, and death) between those who did (1009) and did not receive 
Synagis prophylaxis (1009) matched by age, type of cardiac lesion, and prior corrective surgery.  The 
incidence of arrhythmia and death PSAEs was similar in children who did and did not receive 
prophylaxis.  The incidence of infection PSAEs was lower in children who received prophylaxis as 
compared to those children who did not receive prophylaxis.  The results of the study indicate no 
increased risk of serious infection, serious arrhythmia, or death in children with HSCHD associated 
with Synagis prophylaxis compared with children who did not receive prophylaxis. 
 
Studies using liquid palivizumab 
Two clinical studies were conducted to directly compare liquid and lyophilised formulations of 
palivizumab.  In the first study, all 153 premature infants received both formulations in different 
sequences.  In the second study, 211 and 202 premature infants or children with chronic lung disease 
received liquid and lyophilised palivizumab, respectively.  In two additional studies, liquid 
palivizumab was used as an active control (3918 pediatric subjects) to evaluate an investigational 
monoclonal antibody for prophylaxis of serious RSV disease in premature infants or children with 
BPD or hemodynamically significant CHD (see below for further details of these two studies).  The 
overall rate and pattern of adverse events, study drug discontinuation due to AEs, and the number of 
deaths reported in these clinical studies were consistent with those observed during the clinical 
development programs for the lyophilised formulation.  No deaths were considered related to 
palivizumab and no new ADRs were identified in these studies.  



17 

 
Pre-term infants and children with Chronic Lung Disease of Prematurity (CLDP): this trial, conducted 
at 347 centers in the North America, European Union and 10 other countries, studied patients less than 
or equal to 24 months of age with CLDP and patients 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.  Patients with 
hemodynamically significant congenital heart disease were excluded from enrollment in this study and 
were studied in a separate study.  In this trial, patients were randomized to receive 5 monthly 
injections of 15mg/kg of liquid palivizumab (N=3306) used as active control for an investigational 
monoclonal antibody (N=3329).  Subjects were followed for safety and efficacy for 150 days.  Ninety-
eight percent of all subjects receiving palivizumab completed the study and 97% received all five 
injections.  The primary endpoint was the incidence of RSV hospitalisation.  RSV hospitalisations 
occurred among 62 of 3306 (1.9%) patients in the palivizumab group.  The RSV hospitalisation rate 
observed in patients enrolled with a diagnosis of CLDP was 28/723 (3.9%) and in patients enrolled 
with a diagnosis of prematurity without CLDP was 34/2583 (1.3%).  
 
CHD Study 2: this trial, conducted at 162 centers in North America, European Union and 4 other 
countries over two RSV seasons, studied patients less than or equal to 24 months of age with 
hemodynamically significant CHD.  In this trial, patients were randomized to receive 5 monthly 
injections of 15mg/kg of liquid palivizumab (N=612) used as active control for an investigational 
monoclonal antibody (N=624).  Subjects were stratified by cardiac lesion (cyanotic vs. other) and were 
followed for safety and efficacy for 150 days.  Ninety-seven percent of all subjects receiving 
palivizumab completed the study and 95% received all five injections.  The primary endpoint was a 
summary of adverse events and serious adverse events, and the secondary endpoint was the incidence 
of RSV hospitalisation.  The incidence of RSV hospitalisation was 16 of 612 (2.6%) in the 
palivizumab group. 
 
5.2 Pharmacokinetic properties 
 
Lyophilised formulation of palivizumab 
In studies in adult volunteers, palivizumab had a pharmacokinetic profile similar to a human IgG1 
antibody with regard to volume of distribution (mean 57 ml/kg) and half-life (mean 18 days).  In 
prophylactic studies in premature and bronchopulmonary dysplasia paediatric populations, the mean 
half-life of palivizumab was 20 days and monthly intramuscular doses of 15 mg/kg achieved mean 
30 day trough serum active substance concentrations of approximately 40 µg/ml after the first 
injection, approximately 60 µg/ml after the second injection, approximately 70 µg/ml after the third 
injection and fourth injection.  In the congenital heart disease study, monthly intramuscular doses of 
15 mg/kg achieved mean 30 day trough serum active substance concentrations of approximately 
55 µg/ml after the first injection and approximately 90 µg/ml after the fourth injection. 
 
Among 139 children in the congenital heart disease study receiving palivizumab who had 
cardio-pulmonary bypass and for whom paired serum samples were available, the mean serum 
palivizumab concentration was approximately 100 µg/ml pre-cardiac bypass and declined to 
approximately 40 µg/ml after bypass. 
 
5.3 Preclinical safety data 
 
Single dose toxicology studies have been conducted in cynomolgus monkeys (maximum dose 
30 mg/kg), rabbits (maximum dose 50 mg/kg) and rats (maximum dose 840 mg/kg).  No significant 
findings were observed. 
 
Studies carried out in rodents gave no indication of enhancement of RSV replication, or RSV-induced 
pathology or generation of virus escape mutants in the presence of palivizumab under the chosen 
experimental conditions. 
 
 



18 

6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder: 
Histidine  
Glycine  
Mannitol (E421) 
 
Solvent: 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product should not be mixed with other medicinal products or diluents other than water 
for injections. 
 
6.3 Shelf-life 
 
4 years. 
 
After reconstitution, the product should be used immediately.  However in-use stability has been 
demonstrated for 3 hours at 20oC - 24oC. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2ºC to 8ºC). 
Do not freeze. 
Keep the vial in the carton in order to protect from light. 
 
6.5 Nature and contents of container 
 
100 mg of powder in a 10 ml vial (type I glass) with a stopper (butyl rubber) and a flip-off seal 
(aluminium). 
1ml of water for injections in an ampoule (type I glass). 
 
Pack size of 1. 
 
6.6 Special precautions for disposal and other handling 
 
The 100 mg vial contains an overfill to allow the withdrawal of 100 mg when reconstituted if 
following the directions described below. 
 
To reconstitute, remove the tab portion of the vial cap and clean the rubber stopper with 70% ethanol 
or equivalent.   
 
Slowly add 1.0 ml of water for injections along the inside wall of the vial to minimise foaming.  After 
the water is added, tilt the vial slightly and gently rotate the vial for 30 seconds.  Do not shake the vial.  
Palivizumab solution should stand at room temperature for a minimum of 20 minutes until the solution 
clarifies.  Palivizumab solution does not contain a preservative and should be administered within 
3 hours of preparation.   
 
When reconstituted as recommended, the final concentration is 100 mg/ml.  
The appearance of the reconstituted solution is clear to slightly opalescent.   
 
Single-use vial.  Any unused product or waste material should be disposed of in accordance with local 
requirements 



19 

 
 
7. MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/99/117/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 13 August 1999 
Date of latest renewal: 27 July 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency: 
http://www.ema.europa.eu.   

http://www.ema.europa.eu/


20 

1. NAME OF THE MEDICINAL PRODUCT 
 
Synagis 50 mg/0.5 ml solution for injection 
Synagis 100 mg/1 ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
1 ml of Synagis solution contains 100 mg of palivizumab*. 
 
Each 0.5 ml vial contains 50 mg of palivizumab. 
Each 1 ml vial contains 100 mg of palivizumab. 
 
*Palivizumab is a recombinant humanised monoclonal antibody produced by DNA technology in 
mouse myeloma host cells. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection. 
 
The solution is clear or slightly opalescent. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Synagis is indicated for the prevention of serious lower respiratory tract disease requiring 
hospitalisation caused by respiratory syncytial virus (RSV) in children at high risk for RSV disease:  
 
• Children born at 35 weeks of gestation or less and less than 6 months of age at the onset of the 

RSV season. 
• Children less than 2 years of age and requiring treatment for bronchopulmonary dysplasia 

within the last 6 months. 
• Children less than 2 years of age and with haemodynamically significant congenital heart 

disease. 
 

4.2 Posology and method of administration 
 
Posology 
The recommended dose of palivizumab is 15 mg/kg of body weight, given once a month during 
anticipated periods of RSV risk in the community.   
 
The volume (expressed in ml) of // Palivizumab // to be administered at one-monthly intervals = 
[patient weight in kg] multiplied by 0.15. 
 
Where possible, the first dose should be administered prior to commencement of the RSV season.  
Subsequent doses should be administered monthly throughout the RSV season.  The efficacy of 
palivizumab at doses other than 15 mg per kg or of dosing differently from monthly throughout the 
RSV season, has not been established.  
 
The majority of experience including the pivotal phase III clinical trials with palivizumab has been 
gained with 5 injections during one season (see section 5.1).  Data, although limited, are available on 



21 

greater than 5 doses (see sections 4.8 and5.1), therefore the benefit in terms of protection beyond 5 
doses has not been established. 
 
To reduce risk of rehospitalisation, it is recommended that children receiving palivizumab who are 
hospitalised with RSV continue to receive monthly doses of palivizumab for the duration of the RSV 
season. 
 
For children undergoing cardiac bypass, it is recommended that a 15 mg/kg of body weight injection 
of palivizumab be administered as soon as stable after surgery to ensure adequate palivizumab serum 
levels.  Subsequent doses should resume monthly through the remainder of the RSV season for 
children that continue to be at high risk of RSV disease (see section 5.2). 
 
Method of administration 
Palivizumab is administered intramuscularly, 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 injection should be given using standard aseptic technique.  
 
Injection volumes over 1 ml should be given as a divided dose. 
 
Synagis solution for injection is a ready to use formulation.  For instructions on special handling 
requirements, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or to other 
humanised monoclonal antibodies. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Allergic reactions including very rare cases of anaphylaxis and anaphylactic shock have been reported 
following palivizumab administration.  In some cases, fatalities have been reported (see section 4.8).   
 
Medicinal products for the treatment of severe hypersensitivity reactions, including anaphylaxis and 
anaphylactic shock, should be available for immediate use following administration of palivizumab. 
 
A moderate to severe acute infection or febrile illness may warrant delaying the use of palivizumab, 
unless, in the opinion of the physician, withholding palivizumab entails a greater risk.  A mild febrile 
illness, such as mild upper respiratory infection, is not usually reason to defer administration of 
palivizumab. 
 
Palivizumab should be given with caution to patients with thrombocytopaenia or any coagulation 
disorder. 
 
The efficacy of palivizumab when administered to patients as a second course of treatment during an 
ensuing RSV season has not been formally investigated in a study performed with this objective.  The 
possible risk of enhanced RSV infection in the season following the season in which the patients were 
treated with palivizumab has not been conclusively ruled out by studies performed aiming at this 
particular point. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No formal interactions studies with other medicinal products were conducted.  In the phase III IMpact-
RSV study in the premature and bronchopulmonary dysplasia paediatric populations, the proportions 



22 

of patients in the placebo and palivizumab groups who received routine childhood vaccines, influenza 
vaccine, bronchodilators or corticosteroids were similar and no incremental increase in adverse 
reactions was observed among patients receiving these agents. 
 
Since the monoclonal antibody is specific for RSV, palivizumab is not expected to interfere with the 
immune response to vaccines. 
 
Palivizumab may interfere with immune-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. 
 
4.6 Fertility, pregnancy and lactation 
 
Not relevant.  Synagis is not indicated for use in adults.  Data on fertility, pregnancy and lactation are 
not available. 
 
4.7 Effects on ability to drive and use machines 
 
Not relevant. 
 
4.8 Undesirable effects  
 
Summary of the safety profile  
The most serious adverse reactions occurring with palivizumab are anaphylaxis and other acute 
hypersensitivity reactions.  Common adverse reactions occurring with palivizumab are fever, rash, and 
injection site reaction. 
 
Tabulated list of adverse reactions 
Adverse reactions  both clinical and laboratory, are displayed by system organ class and frequency 
(very common  ≥ 1/10; common  ≥ 1/100 to < 1/10; uncommon  ≥ 1/1,000 to < 1/100; rare ≥ 1/10,000 
to <1/1,000 ) in studies conducted in premature and bronchopulmonary dysplasia paediatric patients, 
and paediatric congenital heart disease patients.  
 
The adverse reactions identified via post-marketing surveillance 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 palivizumab exposure.  The frequency for these "ADRs" as presented in the 
table below was estimated using the safety data of the two registration clinical studies.  The incidences 
of these reactions in these studies showed no difference between the palivizumab and placebo groups 
and the reactions were not drug related. 



23 

 
Undesirable effects in clinical studies* and post-marketing reports in paediatric patients 
MedDRA system organ 
class 

Frequency  ADR  

Blood and lymphatic 
system disorders 

Uncommon Thrombocytopenia# 

Immune system disorders Not known Anaphylaxis, anaphylactic 
shock (in some cases, 
fatalities have been 
reported.)# 

Nervous system disorders Uncommon Convulsion# 
Respiratory, thoracic and 
mediastinal disorders 

Common Apnoea# 

Skin and subcutaneous 
tissue disorders 

Very common 
 
Uncommon 

Rash 
 
Urticaria# 

General disorders and 
administrative site 
conditions 

Very common  
 
Common 

Pyrexia 
 
Injection site reaction 

 *For full study description, see Section 5.1 Clinical studies 
 # ADRs identified from post-marketing surveillance 
 
Description of selected adverse reactions 
Post-marketing experience 
Post-marketing serious spontaneous adverse reactions reported during palivizumab treatment between 
1998 and 2002 covering four RSV seasons were evaluated.  A total of 1,291 serious reports were 
received where palivizumab had been administered as indicated and the duration of therapy was within 
one season.  The onset of the adverse reactions occurred after the sixth or greater dose in only 22 of 
these reports (15 after the sixth dose, 6 after the seventh doses and 1 after the eight dose).  These 
adverse reactions are similar in character to those after the initial five doses.  
 
Palivizumab treatment schedule and adverse reactions were monitored in a group of nearly 20,000 
infants tracked through a patient compliance registry between 1998 and 2000.  Of this group 1,250 
enrolled infants had 6 injections, 183 infants had 7 injections, and 27 infants had either 8 or 9 
injections.  Adverse reactions observed in patients after a sixth or greater dose were similar in 
character and frequency to those after the initial 5 doses.   
 
In an observational, post-marketing, database study, a small increase in the frequency of asthma was 
observed among preterm palivizumab recipients; however, the causal relationship is uncertain. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important.  It 
allows continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.  
 
4.9 Overdose 
 
In clinical studies, three children received an overdose of more than 15 mg/kg.  These doses were 
20.25 mg/kg, 21.1 mg/kg and 22.27 mg/kg.  No medical consequences were identified in these 
instances. 
 
From the post-marketing experience, overdoses with doses up to 85 mg/kg have been reported and in 
some cases, adverse reactions were reported which did not differ from those observed with 15 mg/kg 
dose (see section 4.8).  In case of overdose, it is recommended that the patient be monitored for any 
signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted 
immediately.  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


24 

5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties  
 
Pharmacotherapeutic group:  immune sera immunoglobulins, specific immunoglobulins; ATC Code: 
J06BB16. 
 
Palivizumab is a humanised IgG1κ monoclonal antibody directed to an epitope in the A antigenic site 
of the fusion protein of respiratory syncytial virus (RSV).  This humanised monoclonal antibody is 
composed of human (95%) and murine (5%) antibody sequences.  It has potent neutralising and 
fusion-inhibitory activity against both RSV subtype A and B strains. 
 
Palivizumab serum concentrations of approximately 30 µg/ml have been shown to produce a 99% 
reduction in pulmonary RSV replication in the cotton rat model. 
 
In vitro studies of antiviral activity 
The antiviral activity of palivizumab was assessed in a microneutralization assay in which increasing 
concentrations of antibody were incubated with RSV prior to addition of the human epithelial cells 
HEp-2.  After incubation for 4-5 days, RSV antigen was measured in an enzyme-linked 
immunosorbent assay (ELISA).  The neutralization titre (50% effective concentration [EC50]) is 
expressed as the antibody concentration required to reduce detection of RSV antigen by 50% 
compared with untreated virus-infected cells.  Palivizumab exhibited median EC50 values of 0.65 
µg/ml (mean [standard deviation] = 0.75 [0.53] µg/ml; n=69, range 0.07–2.89 µg/ml) and 0.28 µg/ml 
(mean [standard deviation] = 0.35 [0.23] µg/ml; n=35, range 0.03–0.88 µg/ml) against clinical RSV A 
and RSV B isolates, respectively.  The majority of clinical RSV isolates tested (n=96) were collected 
from subjects in the United States. 
 
Resistance 
Palivizumab binds a highly conserved region on the extracellular domain of mature RSV F protein, 
referred to as antigenic site II or A antigenic site, which encompasses amino acids 262 to 275.  In a 
genotypic analysis of 126 clinical isolates from 123 children who failed immunoprophylaxis, all RSV 
mutants that exhibited resistance to palivizumab (n=8) were shown to contain amino acid changes in 
this region of the F protein. No polymorphic or non-polymorphic sequence variations outside of the A 
antigenic site on the RSV F protein were shown to render RSV resistant to neutralisation by 
palivizumab. At least one of the palivizumab resistance-associated substitutions, N262D, K272E/Q, or 
S275F/L was identified in these 8 clinical RSV isolates resulting in a combined resistance-associated 
mutation frequency of 6.3% in these patients.  A review of clinical findings did not reveal an 
association between A antigenic site sequence changes and RSV disease severity among children 
receiving palivizumab immunoprophylaxis who develop RSV lower respiratory tract disease.  
Analysis of 254 clinical RSV isolates collected from immunoprophylaxis-naïve subjects revealed 
palivizumab resistance-associated substitutions in 2 (1 with N262D and 1 with S275F), resulting in a 
resistance associated mutation frequency of 0.79%. 
 
Immunogenicity 
Antibody to palivizumab was observed in approximately 1% of patients in the IMpact-RSV during the 
first course of therapy.  This was transient, low titre, resolved despite continued use (first and second 
season), and could not be detected in 55 of 56 infants during the second season (including 2 with titres 
during the first season).  Immunogenicity was not studied in the congenital heart disease study.  
Antibody to palivizumab was evaluated in four additional studies in 4337 patients (children born at 35 
weeks of gestation or less and 6 months of age or less, or 24 months of age or less with 
bronchopulmonary dysplasia, or with haemodynamically significant congenital heart disease were 
included in these studies) and was observed in 0% – 1.5% of patients at different study timepoints.  
There was no association observed between the presence of antibody and adverse events.  Therefore, 
anti-drug antibody (ADA) responses appear to be of no clinical relevance. 
 



25 

Studies using lyophilised palivizumab 
In a placebo-controlled trial of RSV disease prophylaxis in (IMpact-RSV trial) 1502 high-risk children 
(1002 Synagis; 500 placebo), 5 monthly doses of 15 mg/kg reduced the incidence of RSV related 
hospitalisation by 55% (p = < 0.001).  The RSV hospitalisation rate was 10.6% in the placebo group.  
On this basis, the absolute risk reduction is 5.8% which means the number needed to treat is 17 to 
prevent one hospitalisation.  The severity of RSV disease in children hospitalised despite prophylaxis 
with palivizumab in terms of days in ICU stay per 100 children and days of mechanical ventilation per 
100 children was not affected. 
 
A total of 222 children were enrolled in two separate studies to examine the safety of palivizumab 
when it is administered for a second RSV season.  One hundred and three (103) children received 
monthly palivizumab injections for the first time, and 119 children received palivizumab for two 
consecutive seasons.  No difference between groups regarding immunogenicity was observed in either 
study.  However, as the efficacy of palivizumab when administered to patients as a second course of 
treatment during an ensuing RSV season has not been formally investigated in a study performed with 
this objective, the relevance of these data in terms of efficacy is unknown. 
 
In an open label prospective trial designed to evaluate pharmacokinetics, safety, and immunogenicity 
after administration of 7 doses of palivizumab within a single RSV season, pharmacokinetic data 
indicated that adequate mean palivizumab levels were achieved in all 18 children enrolled.  Transient, 
low levels of antipalivizumab antibody were observed in one child after the second dose of 
palivizumab that dropped to undetectable levels at the fifth and seventh dose. 
 
In a placebo-controlled trial in 1,287 patients ≤ 24 months of age with haemodynamically significant 
congenital heart disease (639 Synagis; 648 placebo), 5 monthly doses of 15 mg/kg Synagis; reduced 
the incidence of RSV hospitalisations by 45% (p = 0.003) (congenital heart disease study).  Groups 
were equally balanced between cyanotic and acyanotic patients.  The RSV hospitalisation rate was 
9.7% in the placebo group and 5.3% in the Synagis group.  Secondary efficacy endpoints showed 
significant reductions in the Synagis group compared to placebo in total days of RSV hospitalisation 
(56% reduction, p = 0.003) and total RSV days with increased supplemental oxygen (73% reduction, 
p = 0.014) per 100 children. 
 
A retrospective observational study was conducted in young children with hemodynamically 
significant congenital heart disease (HSCHD) comparing the occurrence of primary serious adverse 
events (PSAEs: infection, arrhythmia, and death) between those who did (1009) and did not receive 
Synagis prophylaxis (1009) matched by age, type of cardiac lesion, and prior corrective surgery.  The 
incidence of arrhythmia and death PSAEs was similar in children who did and did not receive 
prophylaxis.  The incidence of infection PSAEs was lower in children who received prophylaxis as 
compared to those children who did not receive prophylaxis.  The results of the study indicate no 
increased risk of serious infection, serious arrhythmia, or death in children with HSCHD associated 
with Synagis prophylaxis compared with children who did not receive prophylaxis. 
 
Studies using liquid palivizumab 
Two clinical studies were conducted to directly compare liquid and lyophilised formulations of 
palivizumab.  In the first study, all 153 premature infants received both formulations in different 
sequences.   In the second study, 211 and 202 premature infants or children with chronic lung disease 
received liquid and lyophilised palivizumab, respectively.  In two additional studies, liquid 
palivizumab was used as an active control (3918 pediatric subjects) to evaluate an investigational 
monoclonal antibody for prophylaxis of serious RSV disease in premature infants or children with 
BPD or hemodynamically significant CHD (see below for further details of these two studies).  The 
overall rate and pattern of adverse events, study drug discontinuation due to AEs, and the number of 
deaths reported in these clinical studies were consistent with those observed during the clinical 
development programs for the lyophilised formulation.  No deaths were considered related to 
palivizumab and no new ADRs were identified in these studies.  
 
Pre-term infants and children with Chronic Lung Disease of Prematurity (CLDP): this trial, conducted 
at 347 centers in the North America, European Union and 10 other countries, studied patients less than 



26 

or equal to 24 months of age with CLDP and patients 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.  Patients with 
hemodynamically significant congenital heart disease were excluded from enrollment in this study and 
were studied in a separate study.  In this trial, patients were randomized to receive 5 monthly 
injections of 15mg/kg of liquid palivizumab (N=3306) used as active control for an investigational 
monoclonal antibody (N=3329).  Subjects were followed for safety and efficacy for 150 days.  Ninety-
eight percent of all subjects receiving palivizumab completed the study and 97% received all five 
injections.  The primary endpoint was the incidence of RSV hospitalisation.  RSV hospitalisations 
occurred among 62 of 3306 (1.9%) patients in the palivizumab group.  The RSV hospitalisation rate 
observed in patients enrolled with a diagnosis of CLDP was 28/723 (3.9%) and in patients enrolled 
with a diagnosis of prematurity without CLDP was 34/2583 (1.3%).  
 
CHD Study 2: this trial, conducted at 162 centers in North America, European Union and 4 other 
countries over two RSV seasons, studied patients less than or equal to 24 months of age with 
hemodynamically significant CHD.  In this trial, patients were randomized to receive 5 monthly 
injections of 15mg/kg of liquid palivizumab (N=612) used as active control for an investigational 
monoclonal antibody (N=624).  Subjects were stratified by cardiac lesion (cyanotic vs. other) and were 
followed for safety and efficacy for 150 days.  Ninety-seven percent of all subjects receiving 
palivizumab completed the study and 95% received all five injections.  The primary endpoint was a 
summary of adverse events and serious adverse events, and the secondary endpoint was the incidence 
of RSV hospitalisation.  The incidence of RSV hospitalisation was 16 of 612 (2.6%) in the 
palivizumab group. 
 
5.2 Pharmacokinetic properties 
 
Lyophilised formulation of palivizumab 
In studies in adult volunteers, palivizumab had a pharmacokinetic profile similar to a human IgG1 
antibody with regard to volume of distribution (mean 57 ml/kg) and half-life (mean 18 days).  In 
prophylactic studies in premature and bronchopulmonary dysplasia paediatric populations, the mean 
half-life of palivizumab was 20 days and monthly intramuscular doses of 15 mg/kg achieved mean 
30 day trough serum active substance concentrations of approximately 40 µg/ml after the first 
injection, approximately 60 µg/ml after the second injection, approximately 70 µg/ml after the third 
injection and fourth injection.  In the congenital heart disease study, monthly intramuscular doses of 
15 mg/kg achieved mean 30 day trough serum active substance concentrations of approximately 
55 µg/ml after the first injection and approximately 90 µg/ml after the fourth injection. 
 
Among 139 children in the congenital heart disease study receiving palivizumab who had 
cardio-pulmonary bypass and for whom paired serum samples were available, the mean serum 
palivizumab concentration was approximately 100 µg/ml pre-cardiac bypass and declined to 
approximately 40 µg/ml after bypass. 
 
Liquid formulation of palivizumab 
The pharmacokinetics and safety of palivizumab liquid formulation and palivizumab lyophilised 
formulation, following 15 mg/kg intramuscular administration, were compared in a cross-over trial of 
153 infants less than or equal to 6 months of age with a history of prematurity (less than or equal to 35 
weeks gestational age).  The results of this trial indicated that the trough serum concentrations of 
palivizumab were similar between the liquid formulation and the lyophilised formulation and 
bioequivalence of the liquid and the lyophilised formulation was demonstrated. 
 
5.3 Preclinical safety data 
 
Single dose toxicology studies have been conducted in cynomolgus monkeys (maximum dose 
30 mg/kg), rabbits (maximum dose 50 mg/kg) and rats (maximum dose 840 mg/kg).  No significant 
findings were observed. 
 



27 

Studies carried out in rodents gave no indication of enhancement of RSV replication, or RSV-induced 
pathology or generation of virus escape mutants in the presence of palivizumab under the chosen 
experimental conditions. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Histidine  
Glycine 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product should not be mixed with other medicinal products.  
 
6.3 Shelf-life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2ºC to 8ºC).   
Do not freeze. 
Keep the vial in the carton in order to protect from light. 
 
6.5 Nature and contents of container 
 
Single-use vials: 3 ml capacity, clear, colourless type I glass vial with a chlorobutyl stopper and flip-
off seal containing either 0.5 ml or 1 ml of solution for injection. 
 
Pack size of 1. 
 
6.6 Special precautions for disposal and other handling 
 
Do not mix the palivizumab liquid and lyophilised formulations. 
 
Do not dilute the product. 
 
Do not shake the vial. 
 
Both the 0.5 ml and 1 ml vials contain an overfill to allow the withdrawal of 50 mg or 100 mg, 
respectively. 
 
To administer, remove the tab portion of the vial cap and clean the stopper with 70 % ethanol or 
equivalent.  Insert the needle into the vial and withdraw into the syringe an appropriate volume of 
solution. 
 
Palivizumab solution for injection does not contain a preservative, is for single use and should be 
administered immediately after drawing the dose into the syringe.  
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 



28 

7. MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/99/117/003 
EU/1/99/117/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 13 August 1999 
Date of latest renewal: 27 July 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency: 
 http://www.ema.europa.eu.  
  

http://www.ema.europa.eu/


29 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX II 

 
A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE  

SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE 
FOR BATCH RELEASE  

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
  

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 
 

 
  



30 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
 MANUFACTUR ER(S) RESPONSIBLE FOR BATCH RELEASE  
 
Name and address of the manufacturer(s) of the biological active substance 
 
Boehringer Ingelheim Pharma GmbH & Co. KG 
D-88397 Biberach an der Riss 
Germany 
 
AstraZeneca Pharmaceuticals Limited Partnership (AZPLP) 
660 MedImmune Court / 633 Research Court, Frederick, Maryland,  
USA 
 
Name and address of the manufacturer(s) responsible for batch release 
 
AbbVie S.r.l. 
04011 Campoverde di Aprilia (LT) 
Italy 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 

 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and  any 
subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk management plan (RMP)  
 
The marketing authorization holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP.  
An updated RMP should be submitted:  

• At the request of the European Medicines Agency;  
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

  



31 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



32 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A.  LABELLING 
 
 

  



33 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
50 mg Outer Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Synagis 50 mg powder and solvent for solution for injection 
palivizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 50 mg palivizumab, providing 100 mg/ml of palivizumab when reconstituted as 
recommended. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains histidine, glycine and mannitol. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection 
Contents: 
1 vial Synagis 50 mg. 
1 ampoule 1 ml water for injections. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Reconstitute slowly with 0.6 ml water for injections. 
Swirl gently. Do not shake. Let stand for 20 minutes. 
Use within 3 hours of reconstitution.   
 
Intramuscular use. 
 
Single-use vial. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 



34 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the vial in the carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/117/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
  



35 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Synagis 50 mg vial label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Synagis 50 mg powder for solution for injection 
palivizumab 
IM 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
50 mg   
 
 
6. OTHER 
 
  



36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
100 mg Outer Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Synagis 100 mg powder and solvent for solution for injection 
palivizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains: 100 mg palivizumab, providing 100 mg/ml of palivizumab when reconstituted as 
recommended. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: histidine, glycine and mannitol. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection 
Contents: 
1 vial Synagis 100 mg. 
1 ampoule 1 ml water for injections. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Reconstitute slowly with 1.0 ml water for injections.   
Swirl gently. Do not shake. Let stand for 20 minutes. 
Use within 3 hours of reconstitution.   
 
Intramuscular use. 
 
Single-use vial. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 



37 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the vial in the carton in order to protect from light.    
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/117/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



38 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Synagis 100 mg vial label  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Synagis 100 mg powder for solution for injection 
palivizumab 
IM 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
100 mg   
 
 
6. OTHER 
 



39 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Synagis Water for injections ampoule label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Synagis 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml Water for injections 
 
 
6. OTHER 



40 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Outer Carton of 0.5 ml vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Synagis 50 mg/0.5 ml solution for injection 
palivizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 0.5 ml vial contains 50 mg of palivizumab. Concentration of 100 mg/ml solution for injection.   
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: histidine, glycine and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
50 mg/0.5 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Do not shake. 
 
Intramuscular use. 
 
Single-use vial.  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 



41 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 
Keep the vial in the carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/117/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
  



42 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Outer Carton of 1.0 ml vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Synagis 100 mg/1 ml solution for injection 
palivizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml vial contains 100 mg of palivizumab. Concentration of 100 mg/ml solution for injection. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: histidine, glycine and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
100 mg/1 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Do not shake. 
 
Intramuscular use. 
 
Single-use vial.  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 
Keep the vial in the carton in order to protect from light. 



43 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/117/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



44 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Label of 0.5 ml vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Synagis 50 mg/0.5 ml solution for injection 
palivizumab 
IM 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
100 mg/ml 
 
 
6. OTHER 



45 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Label of 1.0 ml vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Synagis 100 mg/1 ml solution for injection 
palivizumab 
IM 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
AbbVie (as logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
100 mg/ml 
 
 
6. OTHER 
  



46 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B.  PACKAGE LEAFLET 
 



47 

Package leaflet: Information for the user 
 

Synagis 50 mg powder and solvent for solution for injection 
Active substance: palivizumab 

 
Read all of this leaflet carefully before your child is given this medicine because it contains 
important information for you and your child.   
− Keep this leaflet. You may need to read it again. 
− If you have any further questions, ask your doctor or pharmacist. 
− If any of the side effects get serious, or if you notice that your child has any side effects not 

listed in this leaflet, please tell your doctor or pharmacist. See section 4 
 
What is in this leaflet 
 
1. What Synagis is and what it is used for 
2. What you need to know before Synagis is given to your child 
3. How will my child receive Synagis 
4. Possible side effects 
5. How to store Synagis 
6. Contents of the pack and other information  
 
 
1.  What Synagis is and what it is used for 
 
Synagis contains an active ingredient called palivizumab which is an antibody that works specifically 
against a virus called respiratory syncytial virus, RSV.   
 
Your child is at high risk of getting an illness caused by a virus called respiratory syncytial virus 
(RSV).  
 
Children who are more likely to get severe RSV disease (high risk children) include babies born 
prematurely (35 weeks or less) or babies born with certain heart or lung problems.  
 
Synagis is a medicine to help protect your child from getting severe RSV illness 
 
 
2.  What you need to know before Synagis is given to your child 
 
Your child should not be given Synagis 
 
If he/she is allergic to palivizumab or any of the other ingredients of this medicine (listed in section 6). 
Signs and symptoms of a severe allergic reaction could include: 
− severe rash, hives, or itching skin 
− swelling of the lips, tongue, or face 
− closing of the throat, difficulty swallowing 
− difficult, rapid, or irregular breathing 
− bluish colour of skin, lips, or under fingernails 
− muscle weakness or floppiness 
− a drop in blood pressure 
− unresponsiveness 

 



48 

Warnings and precautions 
 
Take special care with Synagis 
− if your child is unwell. Please tell your doctor if your child is unwell, as the use of Synagis may 

need to be delayed.  
− if your child has any bleeding disorders as Synagis is usually injected into the thigh. 

 
Other medicines and Synagis 
 
Synagis is not known to interact with other medicines. However, you should inform your doctor of all 
medicines your child is currently taking before starting Synagis. 
 
 
3. How will my child receive Synagis  
 
How often will Synagis be given to my child? 
Synagis should be given to your child at a dose of 15 mg/kg body weight once a month for as long as 
the risk of RSV infection remains. For your child’s best protection, it is necessary to take the doctor’s 
advice about when to return for additional doses of Synagis. 
 
If your child is to have a heart operation (cardiac bypass surgery), he or she may be given an extra 
dose of Synagis after the operation. Your child can then go back to the original planned injection. 
 
How will my child receive Synagis? 
Synagis will be given by injection to your child into a muscle, usually in the outer part of the thigh. 
 
What should you do if your child misses an injection of Synagis? 
If your child misses an injection, you should contact your doctor as soon as possible. Each injection of 
Synagis can only help protect your child for about one month before another injection is needed. 
 
Always use this medicine exactly as your doctor or pharmacist has told you. If you are not sure about 
how this product will be given to your child, ask your doctor or pharmacist. 
 
 
4. Possible side effects  
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Synagis may cause serious side effects including: 
• severe allergic reactions, such reactions may be life-threatening or fatal (see "Your child 

should not be given Synagis" for a list of signs and symptoms). 
• unusual bruising or groups of tiny red spots on the skin. 

 
Call your doctor or get medical help right away if your child has any of the serious side effects listed 
above after receiving any dose of Synagis. 
 
Additional side effects 
Very common (affects at least 1 user in 10): 
• rash 
• fever 
 
Common (affects 1 to 10 users in 100): 
• pain, redness or swelling at the injection site 
• a pause in breathing or other breathing difficulties 
 



49 

Uncommon (affects less than 1 user in 100): 
• fits 
• hives 
 
Reporting of side effects 
 
If your child gets any side effects, talk to your doctor. This includes any possible side effects not listed 
in this leaflet.  You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine.  
 
 
5. How to store Synagis 
 
Keep this medicine out of the sight and reach of children.   
 
Do not use this medicine after the expiry date which is stated on the label after ‘EXP’. The expiry date 
refers to the last day of that month. 
 
Store in a refrigerator. (2ºC-8°C) 
After reconstitution use within 3 hours. 
Do not freeze. 
Keep the vial in the carton in order to protect from light. 
 
 
6. Contents of the pack and other information  
 
What Synagis contains 
 
- The active substance is palivizumab. 50 mg per vial, providing 100 mg/ml of palivizumab when 

reconstituted as recommended. 
- The other ingredients are, - for the powder: histidine, glycine and mannitol. 

- for the solvent: water for injections. 
 
What Synagis looks like and contents of the pack  
 
Synagis is presented as a powder and solvent for solution for injection (50 mg of powder in vial) + 1 
ml of solvent in ampoule - Pack size of 1. 
 
Synagis is a white to off-white cake. 
 
Marketing Authorisation holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
Manufacturer 
 
AbbVie S.r.l. 
04011 Campoverde di Aprilia (LT) 
Italy 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


50 

België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България  
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811 

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600 

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201 

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0 

Nederland 
AbbVie B.V. 
Tel: +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00 

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U.  
Tel:  +34 9 1 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00  

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400 

Hrvatska  
AbbVie d.o.o. 
Tel: +385 (0)1 5625 501 

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35 

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900 

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060 

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777 

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel: +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ: +357 22 34 74 40 

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600 

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090 

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
  

http://www.ema.europa.eu/


51 

The following information is intended for medical or healthcare professionals only: 
 
Administrator’s Instructions 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
The 50 mg vial contains an overfill to allow the withdrawal of 50 mg when reconstituted if following 
the directions described below. 
 
To reconstitute, remove the tab portion of the vial cap and clean the rubber stopper with 70% ethanol 
or equivalent 
 
Slowly add 0.6 ml of water for injections along the inside wall of the vial to minimise foaming. After 
the water is added, tilt the vial slightly and gently rotate the vial for 30 seconds.  
 
Do not shake the vial.   
 
Palivizumab solution should stand at room temperature for a minimum of 20 minutes until the solution 
clarifies. Palivizumab solution does not contain a preservative and should be administered within 3 
hours of preparation. Single-use vial. Any remaining contents should be discarded after use. 
 
When reconstituted as recommended the final concentration is 100 mg/ml. 
 
Palivizumab should not be mixed with any medicinal products or diluents other than water for 
injections. 
 
Palivizumab is administered once a month intramuscularly, 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 injection should be given using standard aseptic technique. Injection 
volumes over 1 ml should be given as a divided dose. 
 
When using Palivizumab 100 mg/ml, the volume (expressed in ml) of Palivizumab to be administered 
at one-monthly intervals = [patient weight in kg] multiplied by 0.15 
 
For example, for a baby with a body weight of 3 kg, the calculation becomes: 
 
(3 x 0.15) ml = 0.45 ml palivizumab per month 



52 

Package leaflet: Information for the user 
 

Synagis 100 mg powder and solvent for solution for injection 
Active substance: palivizumab 

 
Read all of this leaflet carefully before your child is given this medicine because it contains 
important information for you and your child. 
 
− Keep this leaflet. You may need to read it again. 
− If you have any further questions, ask your doctor or pharmacist. 
− If any of the side effects get serious, or if you notice that your child has any side effects not 

listed in this leaflet, please tell your doctor or pharmacist. See section 4. 
 
What is in this leaflet 
 
1. What Synagis is and what it is used for 
2. What you need to know before Synagis is given to your child 
3. How will my child receive Synagis 
4. Possible side effects 
5. How to store Synagis 
6. Contents of the pack and other information  
 
 
1. What Synagis is and what it is used for  
 
Synagis contains an active ingredient called palivizumab which is an antibody that works specifically 
against a virus called respiratory syncytial virus, RSV.   
 
Your child is at high risk of getting an illness caused by a virus called respiratory syncytial virus 
(RSV). 
 
 Children who are more likely to get severe RSV disease (high risk children) include babies born 
prematurely (35 weeks or less) or babies born with certain heart or lung problems. 
 
Synagis is a medicine to help protect your child from getting severe RSV illness. 
 
 
2. What do you need to know before Synagis is given to your child 
 
Your child should not be given Synagis 
 
If he/she is allergic to palivizumab or any of the other ingredients of this medicine (listed in Section 
6). Signs and symptoms of a severe allergic reaction could include: 
− severe rash, hives, or itching skin 
− swelling of the lips, tongue, or face 
− closing of the throat, difficulty swallowing 
− difficult, rapid, or irregular breathing 
− bluish colour of skin, lips, or under fingernails 
− muscle weakness or floppiness 
− a drop in blood pressure 
− unresponsiveness 
 



53 

Warnings and precautions 
 
Take special care with Synagis 
− if your child is unwell. Please tell your doctor if your child is unwell, as the use of Synagis may 

need to be delayed.  
− if your child has any bleeding disorders as Synagis is usually injected into the thigh. 
−  
Other medicines and Synagis 
 
Synagis is not known to interact with other medicines. However, you should inform your doctor of all 
medicines your child is currently taking before starting Synagis. 
 
 

3. How will my child receive Synagis  

 
How often will Synagis be given to my child? 
Synagis should be given to your child at a dose of 15 mg/kg body weight once a month for as long as 
the risk of RSV infection remains. For your child’s best protection, it is necessary to take the doctor’s 
advice about when to return for additional doses of Synagis. 
 
If your child is to have a heart operation (cardiac bypass surgery), he or she may be given an extra 
dose of Synagis after the operation. Your child can then go back to the original planned injections. 
 
How will my child receive Synagis? 
Synagis will be given by injection to your child into a muscle, usually in the outer part of the thigh. 
 
What should you do if your child misses an injection of Synagis? 
If your child misses an injection, you should contact your doctor as soon as possible. Each injection of 
Synagis can only help protect your child for about one month before another injection is needed. 
 
Always use this medicine exactly as your doctor or pharmacist has told you. If you are not sure about 
how this product will be given to your child, ask your doctor or pharmacist. 
 
 
4. Possible side effects  
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Synagis may cause serious side effects including: 
• severe allergic reactions, such reactions may be life-threatening or fatal (see “Your child 

should not be given Synagis” for a list of signs and symptoms). 
• unusual bruising or groups of tiny red spots on the skin. 

 
Call your doctor or get medical help right away if your child has any of the serious side effects listed 
above after receiving any dose of Synagis. 
 
Additional side effects 
Very common (affects at least 1 user in 10): 
• rash 
• fever 
 
Common (affects 1 to 10 users in 100): 
• pain, redness or swelling at the injection site  
• a pause in breathing or other breathing difficulties 
 



54 

Uncommon (affects less than 1 users in 100): 
• fits 
• hives 
 
Reporting of side effects 
If your child gets any side effects, talk to your doctor. This includes any possible side effects not listed 
in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine.  
 
 
5.  How to store Synagis 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label after ‘EXP’. The expiry date 
refers to the last day of that month 
 
Store in a refrigerator. (2ºC-8°C) 
After reconstitution use within 3 hours. 
Do not freeze.  
Keep the vial in the carton in order to protect form light.  
 
 
6.  Contents of the pack and other information  
 
What Synagis contains 
 
- The active substance is palivizumab. 100 mg per vial, providing 100 mg/ml of palivizumab 

when reconstituted as recommended. 
- The other ingredients are, - for the powder: histidine, glycine and mannitol. 

  - for the solvent: water for injections. 
 
What Synagis looks like and contents of the pack 
 
Synagis is presented as a powder and solvent for solution for injection (100 mg of powder in vial) + 1 
ml of solvent in ampoule - Pack size of 1. 
 
Synagis is a white to off-white cake.  
 
Marketing Authorisation holder 
 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
Manufacturer 
 
AbbVie S.r.l.  
04011 Campoverde di Aprilia (LT) 
Italy 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


55 

België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България  
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811 

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600 

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201 

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0 

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00 

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U.  
Tel: +34 9 1 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00  

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel: +351 (0)21 1908400 

Hrvatska  
AbbVie d.o.o. 
Tel: +385 (0)1 5625 501 

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35 

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900 

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060 

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777 

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel: +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ: +357 22 34 74 40 

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600 

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090 

 
This leaflet was last approved in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
  

http://www.ema.europa.eu/


56 

The following information is intended for medical or healthcare professionals only: 
 
Administrator’s Instructions 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
The 100 mg vial contains an overfill to allow the withdrawal of 100 mg when reconstituted if 
following the directions described below. 
 
To reconstitute, remove the tab portion of the vial cap and clean the rubber stopper with 70% ethanol 
or equivalent 
 
Slowly add 1.0 ml of water for injections along the inside wall of the vial to minimise foaming. After 
the water is added, tilt the vial slightly and gently rotate the vial for 30 seconds.   
 
Do not shake the vial.   
 
Palivizumab solution should stand at room temperature for a minimum of 20 minutes until the solution 
clarifies. Palivizumab solution does not contain a preservative and should be administered within 
3 hours of preparation. Single-use vial. Any remaining contents should be discarded after use. 
 
When reconstituted as recommended the final concentration is 100 mg/ml. 
 
Palivizumab should not be mixed with any medicinal products or diluents other than water for 
injections. 
 
Palivizumab is administered once a month intramuscularly, 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 injection should be given using standard aseptic technique. Injection 
volumes over 1 ml should be given as a divided dose. 
 
When using Palivizumab 100 mg/ml, the volume (expressed in ml) of Palivizumab to be administered 
at one-monthly intervals = [patient weight in kg] multiplied by 0.15 
 
For example, for a baby with a body weight of 3 kg, the calculation becomes: 
 
(3 x 0.15) ml = 0.45 ml palivizumab per month 



57 

Package leaflet: Information for the user 
 

Synagis 50 mg/0.5 ml solution for injection 
Synagis 100 mg/1 ml solution for injection 

Active substance: palivizumab 
 

Read all of this leaflet carefully before your child is given this medicine because it contains 
important information for you and your child.   
− Keep this leaflet. You may need to read it again. 
− If you have any further questions, ask your doctor or your pharmacist. 
− If any of the side effects get serious, or if you notice that your child has any side effects not 

listed in this leaflet, please tell your doctor or pharmacist. See section 4. 
 
What is in this leaflet  
 
1. What Synagis is and what it is used for 
2. What you need to know before Synagis is given to your child 
3. How will my child receive Synagis 
4. Possible side effects 
5. How to store Synagis 
6. Contents of the pack and other information 
 
 
1. What Synagis is and what it is used for 
 
Synagis contains an active ingredient called palivizumab which is an antibody that works specifically 
against a virus called respiratory syncytial virus, RSV. 
 
Your child is at high risk of getting an illness caused by a virus called respiratory syncytial virus 
(RSV).  
 
Children who are more likely to get severe RSV disease (high-risk children) include babies born 
prematurely (35 weeks or less) or babies born with certain heart or lung problems. 
 
Synagis is a medicine to help protect your child from getting severe RSV illness. 
 
 
2. What you need to know before Synagis is given to your child 
 
Your child should not be given Synagis 
If he/she is allergic to palivizumab or any of the other ingredients of this medicine (listed in section 6). 
Signs and symptoms of a severe allergic reaction include: 
− severe rash, hives, or itching skin 
− swelling of the lips, tongue, or face 
− closing of the throat, difficulty swallowing 
− difficult, rapid, or irregular breathing 
− bluish colour of skin, lips, or under fingernails 
− muscle weakness or floppiness 
− a drop in blood pressure 
− unresponsiveness 

 



58 

Warnings and precautions 
Take special care with Synagis 
− if your child is unwell. Please tell your doctor if your child is unwell, as the use of Synagis may 

need to be delayed.  
− if your child has any bleeding disorders as Synagis is usually injected into the thigh.   
 
Other medicines and Synagis 
Synagis is not known to interact with other medicines. However, you should inform your doctor of all 
medicines your child is currently taking before starting Synagis. 
 
 
3. How will my child receive Synagis 
 
How often will Synagis be given to my child? 
Synagis should be given to your child at a dose of 15 mg/kg body weight once a month for as long as 
the risk of RSV infection remains. For your child’s best protection, it is necessary to take the doctor’s 
advice about when to return for additional doses of Synagis. 
 
If your child is to have a heart operation (cardiac bypass surgery), he or she may be given an extra 
dose of Synagis after the operation. Your child can then go back to the original planned injections. 
 
How will my child receive Synagis? 
Synagis will be given by injection to your child into a muscle, usually in the outer part of the thigh. 
 
What should you do if your child misses an injection of Synagis? 
If your child misses an injection, you should contact your doctor as soon as possible. Each injection of 
Synagis can only help protect your child for about one month before another injection is needed. 
 
Always use this medicine exactly as your doctor or pharmacist has told you. If you are not sure about 
how this product will be given to your child, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Synagis may cause serious side effects including: 
• severe allergic reactions, such reactions may be life threatening or fatal (see "Your child 

should not be given Synagis" for a list of signs and symptoms). 
• unusual bruising or groups of tiny red spots on the skin. 

 
Call your doctor or get medical help right away if your child has any of the serious side effects listed 
above after receiving any dose of Synagis. 
 
Additional side effects 
Very common (affects at least 1 user in 10): 
• rash 
• fever 
 
Common (affects 1 to 10 users in 100): 
• pain, redness or swelling at the injection site  
• a pause in breathing or other breathing difficulties 
 



59 

Uncommon (affects less than 1 user in 100): 
• fits 
• hives 
 
Reporting of side effects 
If your child gets any side effects, talk to your doctor. This includes any possible side effects not listed 
in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V.  By reporting side effects you can help provide more information on the safety of this 
medicine.  
 
 
5. How to store Synagis 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label after ‘EXP’. The expiry date 
refers to the last day of that month. 
 
Store in a refrigerator (2ºC to 8ºC). 
Do not freeze.   
Keep the vial in the carton in order to protect from light.  
 
 
6.  Contents of the pack and other information 
 
What Synagis contains 
- The active substance is palivizumab.  One ml of Synagis solution for injection contains 100 mg 

of palivizumab.   
- Each 0.5 ml vial contains 50 mg of palivizumab. 
- Each 1 ml vial contains 100 mg of palivizumab. 
- The other ingredients are histidine, glycine and water for injections.  
 
What Synagis looks like and contents of the pack 
Synagis solution for injection is a clear or slightly opalescent solution and is available in vials of either 
0.5 ml or 1 ml.  
Pack size of 1. 
 
Marketing Authorisation holder 
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse 
67061 Ludwigshafen 
Germany  
 
Manufacturer 
AbbVie S.r.l.  
04011 Campoverde di Aprilia (LT) 
Italy 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


60 

België/Belgique/Belgien 
AbbVie SA 
Tél/Tel: +32 10  477811 

Lietuva 
AbbVie UAB  
Tel: +370 5 205 3023 

България  
АбВи ЕООД 
Тел.:+359 2 90 30 430 

Luxembourg/Luxemburg 
AbbVie SA 
Belgique/Belgien 
Tél/Tel: +32 10 477811 

Česká republika 
AbbVie s.r.o.  
Tel: +420 233 098 111 

Magyarország 
AbbVie Kft. 
Tel.:+36 1 455 8600 

Danmark 
AbbVie A/S 
Tlf: +45 72 30-20-28 

Malta 
V.J.Salomone Pharma Limited  
Tel: +356 22983201 

Deutschland 
AbbVie Deutschland GmbH & Co. KG 
Tel: 00800 222843 33 (gebührenfrei) 
Tel: +49 (0) 611 / 1720-0 

Nederland 
AbbVie B.V. 
Tel:  +31 (0)88 322 2843 

Eesti 
AbbVie Biopharmaceuticals GmbH Eesti filiaal  
Tel: +372 623 1011 

Norge 
AbbVie AS 
Tlf: +47 67 81 80 00 

Ελλάδα 
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. 
Τηλ: +30 214 4165 555 

Österreich 
AbbVie GmbH  
Tel: +43 1 20589-0 

España 
AbbVie Spain, S.L.U  
Tel:  +34 9 1 384 09 10 

Polska 
AbbVie Polska Sp. z o.o. 
Tel.: +48 22 372 78 00  

France 
AbbVie 
Tél: +33 (0) 1 45 60 13 00 

Portugal 
AbbVie, Lda.  
Tel:  +351 (0)21 1908400 

Hrvatska  
AbbVie d.o.o. 
Tel + 385 (0)1 5625 501 

România 
AbbVie S.R.L. 
Tel: +40 21 529 30 35 

Ireland 
AbbVie Limited  
Tel: +353 (0)1 4287900 

Slovenija 
AbbVie Biofarmacevtska družba d.o.o. 
Tel: +386 (1)32 08 060 

Ísland 
Vistor hf. 
Tel: +354 535 7000 

Slovenská republika 
AbbVie s.r.o. 
Tel: +421 2 5050 0777 

Italia 
AbbVie S.r.l.  
Tel: +39 06 928921 

Suomi/Finland 
AbbVie Oy  
Puh/Tel:  +358 (0)10 2411 200 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Τηλ.: +357 22 34 74 40 

Sverige 
AbbVie AB 
Tel:  +46 (0)8 684 44 600 

Latvija 
AbbVie SIA  
Tel: +371 67605000 

United Kingdom 
AbbVie Ltd  
Tel: +44 (0)1628 561090 

 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the 
local representative of the Marketing Authorisation Holder. 
  

http://www.ema.europa.eu/


61 

The following information is intended for medical or healthcare professionals only: 
 
Administrator’s Instructions 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Palivizumab should not be mixed with any medicinal products or diluents. 
Both the 0.5 ml and 1 ml vials contain an overfill to allow the withdrawal of 50 mg or 100 mg 
respectively. 
 
Do not dilute the product. 
 
Do not shake the vial. 
 
To administer, remove the tab portion of the vial cap and clean the stopper with 70 % ethanol or 
equivalent. Insert the needle into the vial and withdraw into the syringe an appropriate volume of 
solution. Palivizumab solution for injection does not contain a preservative, is for single use and 
should be administered immediately after drawing the dose into the syringe. 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
Palivizumab is administered once a month intramuscularly, 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 injection should be given using standard aseptic technique. 
Injection volumes over 1 ml should be given as a divided dose. 
 
When using Palivizumab 100 mg/1 ml, the volume (expressed in ml) of Palivizumab to be 
administered at one-monthly intervals = [patient weight in kg] multiplied by 0.15 
 
For example, for a baby with a body weight of 3 kg, the calculation becomes: 
 
(3 x 0.15) ml = 0.45 ml palivizumab per month. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND  MANUFACTUR ER(S) RESPONSIBLE FOR BATCH RELEASE 
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT  
	A.  LABELLING
	B.  PACKAGE LEAFLET