Fabrazyme
1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS  



 2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Fabrazyme 35 mg powder for concentrate for solution for infusion 
Fabrazyme 5 mg powder for concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Fabrazyme 35 mg powder for concentrate for solution for infusion 
Each vial of Fabrazyme contains a nominal value of 35 mg of agalsidase beta. After reconstitution 
with 7.2 ml water for injections, each vial of Fabrazyme contains 5 mg/ml (35 mg/7 ml) of agalsidase 
beta. The reconstituted solution must be diluted further (see section 6.6). 
 
Fabrazyme 5 mg powder for concentrate for solution for infusion 
Each vial of Fabrazyme contains a nominal value of 5 mg of agalsidase beta. After reconstitution with 
1.1 ml water for injections, each vial of Fabrazyme contains 5 mg/ml of agalsidase beta. The 
reconstituted solution must be diluted further (see section 6.6). 
 
Agalsidase beta is a recombinant form of human α-galactosidase A and is produced by recombinant 
DNA technology using a mammalian Chinese Hamster Ovary (CHO) cell culture. The amino acid 
sequence of the recombinant form, as well as the nucleotide sequence which encoded it, are identical 
to the natural form of α-galactosidase A. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for concentrate for solution for infusion. 
White to off-white lyophilised cake or powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Fabrazyme is indicated for long-term enzyme replacement therapy in patients with a confirmed 
diagnosis of Fabry disease (α-galactosidase A deficiency).  
 
Fabrazyme is indicated in adults, children and adolescents aged 8 years and older. 
 
4.2 Posology and method of administration 
 
Fabrazyme treatment should be supervised by a physician experienced in the management of patients 
with Fabry disease or other inherited metabolic diseases. 
 
Posology 
The recommended dose of Fabrazyme is 1 mg/kg body weight administered once every 2 weeks as an 
intravenous infusion.  
 
Lower dosing regimens have been used in clinical studies. In one of these studies, performed in adult 
male patients, after an initial dose of 1.0 mg/kg every 2 weeks for 6 months, 0.3 mg/kg every 2 weeks 
may maintain clearance of GL-3 in certain cell types in some patients; however, the long term clinical 
relevance of these findings has not been established (see section 5.1). 
 
The initial infusion rate should be no more than 0.25 mg/min (15 mg/hour) to minimise the potential 
occurrence of infusion-associated reactions. After patient tolerance is established, the infusion rate 
may be increased gradually with subsequent infusions. 



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Infusion of Fabrazyme at home may be considered for patients who are tolerating their infusions well. 
The decision to have a patient move to home infusion should be made after evaluation and 
recommendation by the treating physician. Patients experiencing adverse events during the home 
infusion need to immediately stop the infusion process and seek the attention of a healthcare 
professional. Subsequent infusions may need to occur in a clinical setting. Dose and infusion rate 
should remain constant while at home, and not be changed without supervision of a healthcare 
professional. 
 
Special populations 
Renal impairment 
No dose adjustment is necessary for patients with renal insufficiency.  
 
Hepatic impairment 
Studies in patients with hepatic insufficiency have not been performed. 
 
Elderly 
The safety and efficacy of Fabrazyme in patients older than 65 years have not been established and no 
dosage regimen can presently be recommended in these patients. 
 
Paediatric population 
The safety and efficacy of Fabrazyme in children aged 0 to7 years have not yet been established. 
Currently available data are described in sections 5.1 and 5.2 but no recommendation on posology can 
be made in children aged 5 to 7 years. No data are available in children 0 to 4 years 
No dose adjustment is necessary for children 8-16 years 
 
Method of administration 
For instructions on reconstitution and dilution of the medicinal product before administration, see 
section 6.6. 
 
4.3 Contraindications 
 
Life threatening hypersensitivity (anaphylactic reaction) to the active substance or any of the 
excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Immunogenicity 
Since agalsidase beta (r-hαGAL) is a recombinant protein, the development of IgG antibodies is 
expected in patients with little or no residual enzyme activity. The majority of patients developed IgG 
antibodies to r-hαGAL, typically within 3 months of the first infusion with Fabrazyme. Over time, the 
majority of seropositive patients in clinical trials demonstrated either a downward trend in titers 
(based on a ≥ 4-fold reduction in titer from the peak measurement to the last measurement) (40% of 
the patients), tolerised (no detectable antibodies confirmed by 2 consecutive radioimmuno-
precipitation (RIP) assays) (14% of the patients) or demonstrated a plateau (35% of the patients). 
 
Infusion associated reactions 
Patients with antibodies to r-hαGAL have a greater potential to experience infusion-associated 
reactions (IARs), which are defined as any related adverse event occurring on the infusion day. These 
patients should be treated with caution when re-administering agalsidase beta (see section 4.8). 
Antibody status should be regularly monitored. 
 
In clinical trials, sixty seven percent (67 %) of the patients experienced at least one infusion-
associated reaction (see section 4.8). The frequency of IARs decreased over time. Patients 
experiencing mild or moderate infusion-associated reactions when treated with agalsidase beta during 
clinical trials have continued therapy after a reduction in the infusion rate (~0.15 mg/min; 10 mg/hr) 
and/or pre-treatment with antihistamines, paracetamol, ibuprofen and/or corticosteroids. 
 



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Hypersensitivity 
As with any intravenous protein medicinal product, allergic-type hypersensitivity reactions are 
possible. 
 
A small number of patients have experienced reactions suggestive of immediate (Type I) 
hypersensitivity. If severe allergic or anaphylactic-type reactions occur, immediate discontinuation of 
the administration of Fabrazyme should be considered and appropriate treatment initiated. The current 
medical standards for emergency treatment are to be observed. With careful rechallenge Fabrazyme 
has been re-administered to all 6 patients who tested positive for IgE antibodies or had a positive skin 
test to Fabrazyme in a clinical trial. In this trial, the initial rechallenge administration was at a low 
dose and a lower infusion rate (1/2 the therapeutic dose at 1/25 the initial standard recommended rate). 
Once a patient tolerates the infusion, the dose may be increased to reach the therapeutic dose of 
1 mg/kg and the infusion rate may be increased by slowly titrating upwards, as tolerated. 
 
Patients with advanced renal disease 
The effect of Fabrazyme treatment on the kidneys may be limited in patients with advanced renal 
disease. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies and no in vitro metabolism studies have been performed. Based on its 
metabolism, agalsidase beta is an unlikely candidate for cytochrome P450 mediated drug-drug 
interactions. 
 
Fabrazyme should not be administered with chloroquine, amiodarone, benoquin or gentamycin due to 
a theoretical risk of inhibition of intra-cellular α-galactosidase A activity. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate data from the use of agalsidase beta in pregnant women.  
 
Animal studies do not indicate direct or indirect harmful effects with respect to embryonal/foetal 
development (see section 5.3). 
 
Fabrazyme should not be used during pregnancy unless clearly necessary. 
 
Breast-feeding 
Agalsidase beta may be excreted in milk. Because there are no data available on effects in neonates 
exposed to agalsidase beta via breast milk, it is recommended to stop breast-feeding when Fabrazyme 
is used. 
 
Fertility 
Studies have not been conducted to assess the potential effects of Fabrazyme on impairment of 
fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Fabrazyme may have a minor influence on the ability to drive or use machines on the day of 
Fabrazyme administration because dizziness, somnolence, vertigo and syncope may occur (see section 
4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
Since agalsidase beta (r-hαGAL) is a recombinant protein, the development of IgG antibodies is 
expected in patients with little or no residual enzyme activity. Patients with antibodies to r-hαGAL 
have a greater potential to experience infusion-associated reactions (IARs). Reactions suggestive of 



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immediate (Type I) hypersensitivity have been reported in a small number of patients (see section 
4.4).  
 
Very common adverse reactions included chills, pyrexia, feeling cold, nausea, vomiting, headache and 
paraesthesia. Sixty seven percent (67%) of the patients experienced at least one infusion-associated 
reaction. Anaphylactoid reactions have been reported in the postmarketing setting.  
 
Tabulated list of adverse reactions 
Adverse reactions reported from clinical trials with a total of 168 patients (154 males and 14 females) 
treated with Fabrazyme administered at a dose of 1 mg/kg every 2 weeks for a minimum of one 
infusion up to a maximum of 5 years are listed by System Organ Class and frequency (very common 
≥ 1/10; common ≥ 1/100 to < 1/10 and uncommon ≥ 1/1000 to < 1/100) in the table below. The 
occurrence of an adverse reaction in a single patient is defined as uncommon in light of the relatively 
small number of patients treated. Adverse reactions only reported during the Post Marketing period 
are also included in the table below at a frequency category of “not known” (cannot be estimated from 
the available data). Adverse reactions were mostly mild to moderate in severity: 
 



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Incidence of adverse reactions with Fabrazyme treatment 
System organ 
class 

Very common Common Uncommon Not known 

Infections and 
infestations  

--- nasopharyngitis rhinitis  

Immune system 
disorders 

--- --- --- anaphylactoid 
reaction 

Nervous system 
disorders 

headache, 
paraesthesia 

dizziness, somnolence, 
hypoaesthesia, burning 
sensation, lethargy, 
syncope 

hyperaesthesia, 
tremor 

--- 

Eye disorders --- lacrimation increased eye pruritus, ocular 
hyperaemia 

--- 

Ear and 
labyrinth 
disorders 

--- tinnitus, vertigo auricular swelling, 
ear pain 

--- 

Cardiac 
Disorders 

--- tachycardia, 
palpitations, bradycardia 

sinus bradycardia --- 

Vascular 
disorders 

--- flushing, hypertension, 
pallor, hypotension, hot 
flush 

peripheral coldness  --- 

Respiratory, 
thoracic and 
mediastinal 
disorders 

--- dyspnoea, nasal 
congestion, throat 
tightness, wheezing, 
cough, dyspnoea 
exacerbated 

bronchospasm, 
pharyngolaryngeal 
pain, rhinnorhoea, 
tachypnoea, upper 
respiratory tract 
congestion 

 hypoxia 

Gastrointestinal 
Disorders 

nausea, vomiting abdominal pain, 
abdominal pain upper, 
abdominal discomfort, 
stomach discomfort, 
hypoaesthesia oral, 
diarrhoea 

dyspepsia, dysphagia  --- 

Skin and 
subcutaneous 
tissue disorders 

--- pruritus, urticaria, rash, 
erythema, pruritus 
generalized, 
angioneurotic oedema, 
swelling face, rash 
maculo-papular 

livedo reticularis, 
rash erythematous, 
rash pruritic, skin 
discolouration, skin 
discomfort 

leukocytoclastic 
vasculitis 

Musculoskeletal 
and connective 
tissue disorders 

--- pain in extremity, 
myalgia, back pain, 
muscle spasms, 
arthralgia, muscle 
tightness, 
musculoskeletal 
stiffness 

musculoskeletal pain  --- 

General 
disorders and 
administration 
site conditions 

chills, pyrexia, 
feeling cold 

fatigue, chest 
discomfort, feeling hot, 
oedema peripheral, pain, 
asthenia, chest pain, face 
oedema, hyperthermia 

feeling hot and cold, 
influenza-like illness, 
infusion site pain, 
infusion site reaction, 
injection site 
thrombosis, malaise, 
oedema 

 --- 

Investigations    oxygen saturation 
decreased 

For the purpose of this table, ≥1% is defined as reactions occurring in 2 or more patients. 
Adverse reaction terminology is based upon the Medical Dictionary for Regulatory Activities (MedDRA) 



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Description of selected adverse reactions 
Infusion associated reactions 
Infusion associated reactions consisted most often of fever and chills. Additional symptoms included 
mild or moderate dyspnoea, hypoxia (oxygen saturation decreased), throat tightness, chest discomfort, 
flushing, pruritus, urticaria, face oedema, angioneurotic oedema, rhinitis, bronchospasm, tachypnoea, 
wheezing, hypertension, hypotension, tachycardia, palpitations, abdominal pain, nausea, vomiting, 
infusion-related pain including pain at the extremities, myalgia, and headache. 
 
The infusion-associated reactions were managed by a reduction in the infusion rate together with the 
administration of non-steroidal anti-inflammatory medicinal products, antihistamines and/or 
corticosteroids. Sixty seven percent (67%) of the patients experienced at least one infusion-associated 
reaction. The frequency of these reactions decreased over time. The majority of these reactions can be 
attributed to the formation of IgG antibodies and/or complement activation. In a limited number of 
patients IgE antibodies were demonstrated (see section 4.4). 
 
Paediatric population 
Limited information from clinical trials suggests that the safety profile of Fabrazyme treatment in 
paediatric patients ages 5-7, treated with either 0.5 mg/kg every 2 weeks or 1.0 mg/kg every 4 weeks 
is similar to that of patients (above the age of 7) treated at 1.0 mg/kg every 2 weeks. 
 
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 trials doses up to 3 mg/kg body weight were used. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other alimentary tract and metabolism products, enzymes. ATC code: 
A16AB04.  
 
Fabry disease 
Fabry disease is an inherited heterogeneous and multisystemic progressive disease, that affects both 
males and females. It is characterised by the deficiency of α-galactosidase. Reduced or absent α-
galactosidase activity results in the accumulation of GL-3 in the lysosomes of many cell types 
including the endothelial and parenchymal cells, ultimately leading to life-threatening clinical 
deteriorations as a result of renal, cardiac and cerebrovascular complications.  
 
Mechanism of action 
The rationale for enzyme replacement therapy is to restore a level of enzymatic activity sufficient to 
clear the accumulating substrate in the organ tissues; thereby, preventing, stabilizing or reversing the 
progressive decline in function of these organs before irreversible damage has occurred. 
 
After intravenous infusion, agalsidase beta is rapidly removed from the circulation and taken up by 
vascular endothelial and parenchymal cells into lysosomes, likely through the mannose-6 phosphate, 
mannose and asialoglycoprotein receptors. 
 



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Clinical efficacy and safety 
Efficacy and safety of Fabrazyme was evaluated in two studies with children, one dose-finding study, 
two double-blind placebo-controlled studies, and one open-label extension study in both male and 
female patients. 
 
In the dose finding study, the effects of 0.3, 1.0 and 3.0 mg/kg once every 2 weeks and 1.0 and 
3.0 mg/kg once every 2 days were evaluated. A reduction in GL-3 was observed in kidney, heart, skin 
and plasma at all doses. Plasma GL-3 was cleared in a dose dependent manner, but was less consistent 
at the dose of 0.3 mg/kg. In addition, infusion-associated reactions were dose dependent. 
 
In the first placebo-controlled clinical trial, Fabrazyme was effective in clearing GL-3 from the 
vascular endothelium of the kidney after 20 weeks of treatment. This clearance was achieved in 69% 
(20/29) of the Fabrazyme treated patients, but in none of the placebo patients (p<0.001). This finding 
was further supported by a statistically significant decrease in GL-3 inclusions in kidney, heart and 
skin combined and in the individual organs in patients treated with agalsidase beta compared to 
placebo patients (p<0.001). Sustained clearance of GL-3 from kidney vascular endothelium upon 
agalsidase beta treatment was demonstrated further in the open label extension of this trial. This was 
achieved in 47 of the 49 patients (96%) with available information at month 6, and in 8 of the 
8 patients (100%) with available information at the end of the study (up to a total of 5 years of 
treatment). Clearance of GL-3 was also achieved in several other cell types from the kidney. Plasma 
GL-3 levels rapidly normalised with treatment and remained normal through 5 years. 
 
Renal function, as measured by glomerular filtration rate and serum creatinine, as well as proteinuria, 
remained stable in the majority of the patients. However, the effect of Fabrazyme treatment on the 
kidney function was limited in some patients with advanced renal disease. 
 
Although no specific study has been conducted to assess the effect on the neurological signs and 
symptoms, the results also indicate that patients may achieve reduced pain and enhanced quality of 
life upon enzyme replacement therapy.  
 
Another double-blind, placebo-controlled study of 82 patients was performed to determine whether 
Fabrazyme would reduce the rate of occurrence of renal, cardiac, or cerebrovascular disease or death. 
The rate of clinical events was substantially lower among Fabrazyme-treated patients compared to 
placebo-treated patients (risk reduction = 53% intent-to-treat population (p=0.0577); risk reduction = 
61 % per-protocol population (p=0.0341)). This result was consistent across renal, cardiac and 
cerebrovascular events.  
 
The results of these studies indicate that Fabrazyme treatment at 1 mg/kg every other week provides 
clinical benefit on key clinical outcomes in patients with early and advanced Fabry disease. Because 
this condition is slowly progressive, early detection and treatment is critical to achieve the best 
outcomes. 
 
In an additional study, 21 male patients were enrolled to follow GL3 clearance in kidney and skin 
tissues at an alternative dosing regimen. Following treatment with 1 mg/kg every other week for 
24 weeks, a dose regimen of 0.3 mg/kg every 2 weeks for 18 months was able to maintain the 
clearance of cellular GL-3 in the capillary endothelium of the kidney, other kidney cell types and skin 
(superficial skin capillary endothelium) in the majority of patients. However, at the lower dose, IgG 
antibodies may play a role with respect to GL-3 clearance in some patients. Due to the limitations of 
the study design (small number of patients), no definitive conclusion regarding the dose maintenance 
regimen can be drawn, but these findings suggest that, after an initial debulking dose of 1.0 mg/kg 
every 2 weeks, 0.3 mg/kg every 2 weeks may be sufficient in some patients to maintain clearance of 
GL-3. 
 
In the postmarketing setting, experience was gained in patients who initiated treatment at a dose of 
1 mg/kg every 2 weeks and subsequently received a reduced dose for an extended period. In some of 
these patients, an increase of some of the following symptoms was spontaneously reported: pain, 
paraesthesia and diarrhoea, as well as cardiac, central nervous system and renal manifestations. These 
reported symptoms resemble the natural course of Fabry disease. 



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Paediatric population 
In one open-label paediatric study, sixteen patients with Fabry disease (8-16 years old; 14 males, 
2 females) had been treated for one year at 1.0 mg/kg every 2 weeks. Clearance of GL-3 in the 
superficial skin vascular endothelium was achieved in all patients who had accumulated GL-3 at 
baseline. The 2 female patients had little or no GL-3 accumulation in the superficial skin vascular 
endothelium at baseline, making this conclusion applicable in male patients only. 
 
In an additional 5-year open-label paediatric study,  31 male patients aged 5 to 18 years were 
randomized prior to the onset of clinical symptoms involving major organs and treated with two lower 
dose regimens of agalsidase beta, 0.5 mg/kg every 2 weeks or 1.0 mg/kg every 4 weeks. Results were 
similar between the two treatment groups. Superficial skin capillary endothelium GL-3 scores were 
reduced to zero or maintained at zero at all time points post-baseline upon treatment in 19/27 patients 
completing the study without a dose increase. Both baseline and 5-year kidney biopsies were obtained 
in a subset of 6 patients: in all, kidney capillary endothelium GL-3 scores were reduced to zero but 
highly variable effects were observed in podocyte GL-3, with a reduction in 3 patients. Ten (10) 
patients met per protocol dose increase criteria, two (2) had a dose increase to the recommended dose 
of 1.0 mg/kg every 2 weeks.  
 
5.2 Pharmacokinetic properties 
 
Following an intravenous administration of agalsidase beta to adults at doses of 0.3 mg, 1 mg and 
3 mg/kg body weight, the AUC values increased more than dose proportional, due to a decrease in 
clearance, indicating a saturated clearance. The elimination half-life was dose independent and ranged 
from 45 to 100 minutes. 
 
After intravenous administration of agalsidase beta to adults with an infusion time of approximately 
300 minutes and at a dose of 1 mg/kg body weight, biweekly, mean Cmax plasma concentrations   
ranged from 2000-3500 ng/ml, while the AUCinf ranged from 370-780 µg min/ml. Vss ranged from 
8.3-40.8 l, plasma clearance from 119-345 ml/min and the mean elimination half-life from 
80-120 minutes.  
 
Agalsidase beta is a protein and is expected to be metabolically degraded through peptide hydrolysis. 
Consequently, impaired liver function is not expected to affect the pharmacokinetics of agalsidase 
beta in a clinically significant way. Renal elimination of agalsidase beta is considered to be a minor 
pathway for clearance. 
 
Paediatric population 
Fabrazyme pharmacokinetics was also evaluated in two paediatric studies. In one of these studies, 15 
paediatric patients with available pharmacokinetics data, aged 8.5 to 16 years weighing 27.1 to 64.9 
kg were treated with 1.0 mg/kg every 2 weeks. Agalsidase beta clearance was not influenced by 
weight in this population. Baseline CL was 77 ml/min with a Vss of 2.6 l; half-life was 55 min. After 
IgG seroconversion, CL decreased to 35 ml/min, Vss increased to 5.4 l, and half-life increased to 240 
min. The net effect of these changes after seroconversion was an increase in exposure of 2- to 3-fold 
based on AUC and Cmax. No unexpected safety issues were encountered in patients with an increase in 
exposure after seroconversion. 
In another study with 30 paediatric patients with available pharmacokinetics data, aged 5 to 18 years, 
treated with two lower dose regimens of 0.5 mg/kg every 2 weeks and 1.0 mg/kg every 4 weeks, mean 
CL was 4.6 and 2.3 ml/min/kg, respectively, mean Vss was 0.27 and 0.22 l/kg, respectively, and mean 
elimination half-life was 88 and 107 minutes, respectively. After IgG seroconversion, there was no 
apparent change in CL (+24% and +6%, resp.), while Vss was 1.8 and 2.2 fold higher, with the net 
effect being a small decrease in Cmax (up to -34% and -11%, resp.) and no change in AUC (-19% and -
6%, resp.).  
 



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5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, single 
dose toxicity, repeated dose toxicity and embryonal/foetal toxicity. Studies with regard to other stages 
of the development have not been carried out. Genotoxic and carcinogenic potential are not expected. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol 
Sodium phosphate monobasic, monohydrate 
Sodium phosphate dibasic, heptahydrate  
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other 
medicinal products in the same infusion. 
 
6.3 Shelf life 
 
3 years. 
 
Reconstituted and diluted solutions 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage and conditions prior to use are the responsibility of the user. The 
reconstituted solution cannot be stored and should be promptly diluted; only the diluted solution can 
be held for up to 24 hours at 2°C-8°C. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). 
 
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Fabrazyme 35 mg powder for concentrate for solution for infusion 
Fabrazyme 35 mg is supplied in clear Type I glass 20 ml vials. The closure consists of a siliconised 
butyl stopper and an aluminium seal with a plastic flip-off cap. 
 
Package sizes: 1, 5 and 10 vials per carton. 
Not all pack sizes may be marketed. 
 
Fabrazyme 5 mg powder for concentrate for solution for infusion 
Fabrazyme 5 mg is supplied in clear Type I glass 5 ml vials. The closure consists of a siliconised 
butyl stopper and an aluminium seal with a plastic flip-off cap. 
 
Package sizes: 1, 5 and 10 vials per carton. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
The powder for concentrate for solution for infusion has to be reconstituted with water for injections, 
diluted with 0.9% sodium chloride intravenous solution and then administered by intravenous 
infusion. Use Aseptic Technique  
 



 11 

Determine the number of vials to be reconstituted based on the individual patient’s weight and remove 
the required vials from the refrigerator in order to allow them to reach room temperature (in 
approximately 30 minutes). Each vial of Fabrazyme is intended for single use only. 
 
Reconstitution  
 
Fabrazyme 35 mg powder for concentrate for solution for infusion 
Reconstitute each vial of Fabrazyme 35 mg with 7.2 ml water for injections. Avoid forceful impact of 
the water for injections on the powder and avoid foaming. This is done by slow drop-wise addition of 
the water for injection down the inside of the vial and not directly onto the lyophilized cake. Roll and 
tilt each vial gently. Do not invert, swirl or shake the vial. 
 
Fabrazyme 5 mg powder for concentrate for solution for infusion 
Reconstitute each vial of Fabrazyme 5 mg with 1.1 ml water for injections. Avoid forceful impact of 
the water for injections on the powder and avoid foaming. This is done by slow drop-wise addition of 
the water for injection down the inside of the vial and not directly onto the lyophilized cake. Roll and 
tilt each vial gently. Do not invert, swirl or shake the vial.  
 
The reconstituted solution contains 5 mg agalsidase beta per ml, and appears as a clear colourless 
solution. The pH of the reconstituted solution is approximately 7.0. Before further dilution, visually 
inspect the reconstituted solution in each vial for particulate matter and discoloration. Do not use the 
solution if foreign particles are observed or if the solution is discoloured. 
 
After reconstitution it is recommended to promptly dilute the vials, to minimise protein particle 
formation over time. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
Dilution 
 
Fabrazyme 35 mg powder for concentrate for solution for infusion 
Prior to adding the reconstituted volume of Fabrazyme required for the patient dose, it is 
recommended to remove an equal volume of 0.9% sodium chloride intravenous solution, from the 
infusion bag. 
 
Remove the airspace within the infusion bag to minimize the air/liquid interface. 
 
Slowly, withdraw 7.0 ml (equal to 35 mg) of the reconstituted solution from each vial up to the total 
volume required for the patient dose. Do not use filter needles and avoid foaming. 
 
Then slowly inject the reconstituted solution directly into the 0.9% sodium chloride intravenous 
solution (not in any remaining airspace) to a final concentration between 0.05 mg/ml and 0.7 mg/ml. 
Determine the total volume of sodium chloride 0.9% solution for infusion (between 50 and 500 ml) 
based on the individual dose. For doses lower than 35 mg use a minimum of 50 ml, for doses 35 to 
70 mg use a minimum of 100 ml, for doses 70 to 100 mg use a minimum of 250 ml and for doses 
greater than 100 mg use only 500 ml. Gently invert or lightly massage the infusion bag to mix the 
diluted solution. Do not shake or excessively agitate the infusion bag. 
 
Fabrazyme 5 mg powder for concentrate for solution for infusion 
Prior to adding the reconstituted volume of Fabrazyme required for the patient dose, it is 
recommended to remove an equal volume of 0.9% sodium chloride intravenous solution, from the 
infusion bag. 
 
Remove the airspace within the infusion bag to minimize the air/liquid interface.  
 
Slowly, withdraw 1.0 ml (equal to 5 mg) of the reconstituted solution from each vial up to the total 
volume required for the patient dose. Do not use filter needles and avoid foaming. 



 12 

 
Then slowly inject the reconstituted solution directly into the 0.9% sodium chloride intravenous 
solution (not in any remaining airspace) to a final concentration between 0.05 mg/ml and 0.7 mg/ml. 
Determine the total volume of sodium chloride 0.9% solution for infusion (between 50 and 500 ml) 
based on the individual dose. For doses lower than 35 mg use a minimum of 50 ml, for doses 35 to 
70 mg use a minimum of 100 ml, for doses 70 to 100 mg use a minimum of 250 ml and for doses 
greater than 100 mg use only 500 ml. Gently invert or lightly massage the infusion bag to mix the 
diluted solution. Do not shake or excessively agitate the infusion bag. 
 
Administration 
 
It is recommended to administer the diluted solution through an in-line low protein-binding 0.2 µm 
filter to remove any protein particles which will not lead to any loss of agalsidase beta activity. The 
initial infusion rate should be no more than 0.25 mg/min (15 mg/hour) to minimise the potential 
occurrence of infusion-associated reactions. After patient tolerance is established, the infusion rate 
may be increased gradually with subsequent infusions. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Genzyme Europe B.V., Paasheuvelweg 25, 1105 BP Amsterdam, The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBERS  
 
EU/1/01/188/001  Fabrazyme 35 mg 1 vial of powder for concentrate for solution for infusion 
EU/1/01/188/002  Fabrazyme 35 mg 5 vials of powder for concentrate for solution for infusion 
EU/1/01/188/003  Fabrazyme 35 mg 10 vials of powder for concentrate for solution for infusion 
EU/1/01/188/004  Fabrazyme 5 mg 1 vial of powder for concentrate for solution for infusion 
EU/1/01/188/005  Fabrazyme 5 mg 5 vials of powder for concentrate for solution for infusion 
EU/1/01/188/006  Fabrazyme 5 mg 10 vials of powder for concentrate for solution for infusion 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 03 August 2001 
Date of last renewal: 03 August 2006 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 

  

http://www.emea.europa.eu./


 13 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 

SUBSTANCE 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 
 



 14 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  

 
Name and address of the manufacturer of the biological active substance 
 
Genzyme Corporation 
45, 51, 68, 74, 76 and 80 New York Avenue 
Framingham 
MA 01701 United States 
 
Name and address of the manufacturer responsible for batch release 
 
Genzyme Ireland Limited 
IDA Industrial Park 
Old Kilmeaden Road 
Waterford 
Ireland 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2) 
 
 
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 authorisation 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. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 



 15 

• Additional risk minimisation measures 
 
Prior to the use of FABRAZYME in each Member State in the home setting the Marketing 
Authorisation Holder (MAH) must agree about the content and format of the educational programme, 
including communication media, distribution modalities, and any other aspects of the programme, 
with the National Competent Authority.  

The MAH shall ensure that in each Member State where FABRAZYME is marketed, all Healthcare 
Professionals (HCP) who are expected to prescribe FABRAZYME are provided with the following 
educational pack which includes HCP and Patient/Caregiver guides;  
 
HCP Educational Material: 
HCPs’ educational materials include the following elements: 

• The HCP’s guide 
• The Summary of Product Characteristics 

 
HCP guide: 
In order to minimize the risk of hypersensitivity reactions and medication errors in the home infusion 
setting, the HCP’s guide contains the following key safety information to support HCPs (prescribing 
and/or administering FABRAZYME) in the management of patients receiving FABRAZYME in the 
home setting: 
 
Information for HCPs prescribing FABRAZYME: 

• Information on the risk of medication errors potentially related to the use of FABRAZYME in 
the home setting, 

• Criteria to determine eligibility for home infusion,   
• Use of the logbook,  
• Information on the need to provide the patients material to all patients receiving home infusions 

of FABRAZYME. 
 

Information for HCPs administering FABRAZYME: 
• Information on the risk of medication errors potentially related to the use of FABRAZYME in 

the home setting with focus on the actions needed to prevent medication errors that may occur 
in the home setting, 

• Information on the risk of hypersensitivity reactions including the signs and symptoms of 
hypersensitivity and the recommended actions when symptoms occur, 

• Use of the logbook, 
• Information on the preparation and administration of FABRAZYME infusion, 
• Training on the preparation and administration of FABRAZYME infusion (for patients who are 

going to self administer the product), 
• Information on the need to provide the patients material to all patients receiving home infusions 

of FABRAZYME. 
 

Patient Educational Material: 
The patients’ educational materials include the following elements: 

• The patient’s guide 
• The patient information leaflet. 

 
Patient guide: 
The patient’s guide contains the following elements: 

• Information on the risk of hypersensitivity reactions including the signs and symptoms of 
hypersensitivity and the recommended actions when symptoms occur, 

• Use of the logbook, 
• Clear step by step instructions on the reconstitution and administration of the product (only 

applicable to those who self-administer). 
  



 16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
  



 17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING  
  



 18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON (1 VIAL, 5 VIALS, 10 VIALS) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Fabrazyme 35 mg powder for concentrate for solution for infusion 
agalsidase beta 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial of powder contains 35 mg of agalsidase beta. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients:  
mannitol 
sodium phosphate monobasic, monohydrate 
sodium phosphate dibasic, heptahydrate 
See the leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 vial of powder for concentrate for solution for infusion. 
5 vials of powder for concentrate for solution for infusion. 
10 vials of powder for concentrate for solution for infusion. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only. 
Read the package leaflet before use. 
Intravenous use. 
 
 
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 (2°C – 8°C). 



 19 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution should be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Genzyme Europe B.V. 
Paasheuvelweg 25 
1105 BP Amsterdam 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/01/188/001 1 vial of powder for concentrate for solution for infusion 
EU/1/01/188/002 5 vials of powder for concentrate for solution for infusion 
EU/1/01/188/003 10 vials of powder for concentrate for solution for infusion 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Fabrazyme 35 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 
  



 20 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Fabrazyme 35 mg powder for concentrate for solution for infusion 
agalsidase beta 
Intravenous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
Genzyme Europe B.V.-NL 
 
Store in a refrigerator (2°C – 8°C). 
  



 21 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON (1 VIAL, 5 VIALS, 10 VIALS) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Fabrazyme 5 mg powder for concentrate for solution for infusion 
agalsidase beta 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial of powder contains 5 mg of agalsidase beta. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients:  
mannitol 
sodium phosphate monobasic, monohydrate 
sodium phosphate dibasic, heptahydrate 
See the leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 vial of powder for concentrate for solution for infusion. 
5 vials of powder for concentrate for solution for infusion. 
10 vials of powder for concentrate for solution for infusion. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only. 
Read the package leaflet before use. 
Intravenous use. 
 
 
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 (2°C – 8°C). 



 22 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution should be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Genzyme Europe B.V. 
Paasheuvelweg 25 
1105 BP Amsterdam 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/01/188/004 1 vial of powder for concentrate for solution for infusion 
EU/1/01/188/005 5 vials of powder for concentrate for solution for infusion 
EU/1/01/188/006 10 vials of powder for concentrate for solution for infusion 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Fabrazyme 5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 



 23 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Fabrazyme 5 mg powder for concentrate for solution for infusion 
agalsidase beta 
Intravenous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
Genzyme Europe B.V.- NL 
 
Store in a refrigerator (2°C – 8°C) 
 

 
  



 24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET  



 25 

Package leaflet: Information for the user 
 

Fabrazyme 35 mg powder for concentrate for solution for infusion 
Agalsidase beta 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet  
1. What Fabrazyme is and what it is used for 
2. What you need to know before you use Fabrazyme 
3. How to use Fabrazyme 
4. Possible side effects 
5. How to store Fabrazyme  
6. Contents of the pack and other information 
 
 
1. What Fabrazyme is and what it is used for 
 
Fabrazyme contains the active substance agalsidase beta and is used as enzyme replacement therapy 
in Fabry disease, where the level of α-galactosidase enzyme activity is absent or lower than normal. If 
you suffer from Fabry disease a fat substance, called globotriaosylceramide (GL-3), is not removed 
from the cells of your body and starts to accumulate in the walls of the blood vessels of your organs. 
 
Fabrazyme is indicated for use as long-term enzyme replacement therapy in patients with a confirmed 
diagnosis of Fabry disease. 
 
Fabrazyme is indicated in adults, children and adolescents aged 8 years and older. 
 
 
2. What you need to know before you use Fabrazyme 
 
Do not use Fabrazyme 
- if you are allergic to agalsidase beta or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions 
Talk to your doctor  or pharmacist before using Fabrazyme. 
 
If you are treated with Fabrazyme, you may develop infusion associated reactions. An infusion-
associated reaction is any side effect occurring during the infusion or until the end of the infusion day 
(see section 4). If you experience a reaction like this, you should tell your doctor immediately. You 
may need to be given additional medicines to prevent such reactions from occurring. 
 
Children and adolescents 
No clinical studies have been performed in children 0-4 years old. The risks and benefits of 
Fabrazyme in children  aged 5 to 7 years have not yet been established and therefore no dose can be 
recommended for this age group. 
 



 26 

Other medicines and Fabrazyme 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
Tell your doctor if you use any medicines containing chloroquine, amiodarone, benoquin or 
gentamicin. There is a theoretical risk of decreased agalsidase beta activity.   
 
Pregnancy, breast-feeding and fertility 
Use of Fabrazyme during pregnancy is not recommended. There is no experience with the use of 
Fabrazyme in pregnant women. Fabrazyme may get into breast milk. Use of Fabrazyme during breast-
feeding is not recommended. Studies have not been performed to examine the effects of Fabrazyme 
on fertility. 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
Do not drive or use machines if you experience dizziness, sleepiness, vertigo or fainting during or 
shortly after administration of Fabrazyme (see section 4). Talk to your doctor first. 
 
 
3. How to use Fabrazyme 
 
Fabrazyme is given through a drip into a vein (by intravenous infusion). It is supplied as a powder 
which will be mixed with sterile water before it is given (see information for Health Care 
Professionals at the end of this leaflet). 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
Fabrazyme is only used under the supervision of a doctor who is knowledgeable in the treatment of 
Fabry disease. Your doctor may advise that you can be treated at home provided you meet certain 
criteria. Please contact your doctor if you would like to be treated at home. 
 
The recommended dose of Fabrazyme for adults is 1 mg/kg body weight, once every 2 weeks. No 
changes in dose are necessary for patients with kidney disease.  
 
Use in children and adolescents 
The recommended dose of Fabrazyme for children and adolescents 8 – 16 years is 1 mg/kg body 
weight, once every 2 weeks. No changes in dose are necessary for patients with kidney disease.  
 
If you use more Fabrazyme than you should 
Doses up to 3 mg/kg body weight have shown to be safe. 
 
If you forget to use Fabrazyme 
If you have missed an infusion of Fabrazyme, please contact your doctor.  
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects  
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
In clinical studies side effects were mainly seen while patients were being given the medicine or 
shortly after (“infusion related reactions”). Severe life-threatening allergic reactions (“anaphylactoid 
reactions”) have been reported in some patients. If you experience any serious side effect, you should 
contact your doctor immediately. 
 



 27 

Very common symptoms (may affect more than 1 in 10 people) include chills, fever, feeling cold, 
nausea, vomiting, headache and abnormal feelings in the skin such as burning or tingling. Your doctor 
may decide to lower the infusion rate or give you additional medicines to prevent such reactions from 
occurring. 
 
List of other side effects: 
   
Common (may affect up to 1 in 10 people):  
• chest pain • sleepiness • fatigue 
• difficulty in breathing • increased heart beat • flushing 
• pallor • abdominal pain • pain 
• itching • back pain • throat tightness 
• abnormal tear secretion • rash • dizziness 
• feeling weak • low heart rate • palpitations 
• tinnitus • lethargy • decreased sensitivity to pain 
• nasal congestion • syncope • burning sensation 
• diarrhoea • cough • wheezing 
• redness • abdominal discomfort • urticaria 
• muscle pain • swelling face • pain at the extremities 
• increased blood pressure • joint pain • nasopharyngitis 
• sudden swelling of the face 

or throat 
• decreased blood pressure • hot flush 

• oedema in extremities • chest discomfort • feeling hot  
• vertigo • face oedema  • hyperthermia 
• stomach discomfort • exacerbated difficulty in 

breathing 
• decreased mouth sensitivity 

• muscle spasms • muscle tightness • musculoskeletal stiffness 
   
Uncommon (may affect up to 1 in 100 people): 
• tremor • itching eyes • low heart rate due to conduction 

disturbances 
• red eyes • ear swelling • increased sensitivity to pain 
• ear pain • bronchospasm • upper respiratory tract congestion 
• throat pain • runny nose • red rash 
• fast breathing • heart burn • (mottled purplish) skin discoloration 
• itchy rash • skin discomfort • coldness of the extremities 
• feeling hot and cold • musculoskeletal pain • injection site blood clotting 
• difficulty swallowing • rhinitis • skin discoloration 
• infusion site pain • influenza-like illness • oedema 
• infusion site reaction • malaise  
   
Not known (frequency cannot be estimated from the available data): 
• lower blood oxygen levels • serious inflammation of the 

vessels 
 

 
In some patients initially treated at the recommended dose, and whose dose was later reduced for an 
extended period, some symptoms of Fabry disease were reported more frequently. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. 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. 
 
 

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


 28 

5. How to store Fabrazyme 
 
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. 
 
Unopened vials 
Store in a refrigerator (2°C – 8°C). 
 
Reconstituted and diluted solutions 
The reconstituted solution cannot be stored and should be promptly diluted. The diluted solution can 
be held for up to 24 hours at 2°C – 8°C. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Fabrazyme contains 
- The active substance is agalsidase beta, one vial contains 35 mg.  
- The other ingredients are:  

- Mannitol 
- Sodium phosphate monobasic, monohydrate 
- Sodium phosphate dibasic, heptahydrate. 

 
What Fabrazyme looks like and contents of the pack 
Fabrazyme is supplied as a white to off-white powder. After reconstitution it is a clear, colourless 
liquid, free from foreign matter. The reconstituted solution must be further diluted.  
Package sizes: 1, 5 and 10 vials per carton. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing authorisation holder 
Genzyme Europe B.V., Paasheuvelweg 25, 1105 BP Amsterdam, The Netherlands 
 
Manufacturer  
Genzyme Ireland Limited, IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland 
 



 29 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien/ 
Luxembourg/Luxemburg 
Sanofi Belgium 
Tél/Tel: + 32 2 710 54 00 
 

Lietuva 
UAB „SANOFI-AVENTIS LIETUVA“ 
Tel. +370 5 275 5224 
 

България 
SANOFI BULGARIA EOOD 
Tел: +359 2 9705300 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel: +36 1 505 0050 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Malta 
Sanofi S.p.A. 
Tel: +39 02 39394275 
 

Danmark 
Sanofi A/S 
Tlf: +45 45 16 70 00 
 

Nederland 
Genzyme Europe B.V. 
Tel: +31 20 245 4000 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 04 36 996 
Tel. aus dem Ausland: +49 69 305 70 13 
 

Norge 
sanofi-aventis Norge AS 
Tlf: + 47 67 10 71 00 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel. +372 6 273 488 
 

Österreich 
sanofi-aventis GmbH 
Tel: + 43 1 80 185 - 0 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 1600 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
  

Portugal 
Sanofi – Produtos Farmacêuticos, Lda.  
Tel: +351 21 35 89 400 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger: +33 1 57 63 23 23 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 4800 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel.:  +421 2 33 100 100 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: + 358 201 200 300 
 

Italia 
Sanofi S.p.A. 
Tel: 800536389 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 



 30 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 

United Kingdom 
Sanofi  
Tel +44 (0)845 372 7101 

 
Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

 

This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 
 
--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Instructions for use – reconstitution, dilution and administration 
 
The powder for concentrate for solution for infusion has to be reconstituted with water for injections, 
diluted with 0.9% sodium chloride intravenous solution and then administered by intravenous 
infusion.  
 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage and conditions are the responsibility of the user. The reconstituted 
solution cannot be stored and should be promptly diluted; only the diluted solution can be held for up 
to 24 hours at 2ºC -8ºC.  
 
Use Aseptic Technique  
 
1. Determine the number of vials to be reconstituted based on the individual patient's weight and 

remove the required vials from the refrigerator in order to allow them to reach room 
temperature (in approximately 30 minutes). Each vial of Fabrazyme is intended for single use 
only. 

 
Reconstitution  
 
2. Reconstitute each vial of Fabrazyme 35 mg with 7.2 ml water for injections. Avoid forceful 

impact of the water for injections on the powder and avoid foaming. This is done by slow drop-
wise addition of the water for injection down the inside of the vial and not directly onto the 
lyophilized cake. Roll and tilt each vial gently. Do not invert, swirl or shake the vial.  

 
3. The reconstituted solution contains 5 mg agalsidase beta per ml, and appears as a clear 

colourless solution. The pH of the reconstituted solution is approximately 7.0. Before further 
dilution, visually inspect the reconstituted solution in each vial for particulate matter and 
discoloration. Do not use the solution if foreign particles are observed or if the solution is 
discoloured. 

 
4. After reconstitution it is recommended to promptly dilute the vials, to minimise protein particle 

formation over time. 
 
5. Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 
 

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


 31 

Dilution  
 
6. Prior to adding the reconstituted volume of Fabrazyme required for the patient dose, it is 

recommended to remove an equal volume of 0.9% sodium chloride intravenous solution, from 
the infusion bag. 

 
7. Remove the airspace within the infusion bag to minimize the air/liquid interface.  
 
8. Slowly, withdraw 7.0 ml (equal to 35 mg) of the reconstituted solution from each vial up to the 

total volume required for the patient dose. Do not use filter needles and avoid foaming. 
 
9. Then slowly inject the reconstituted solution directly into the 0.9% sodium chloride intravenous 

solution (not in any remaining airspace) to a final concentration between 0.05 mg/ml and 
0.7 mg/ml. Determine the total volume of sodium chloride 0.9% solution for infusion (between 
50 and 500 ml) based on the individual dose. For doses lower than 35 mg use a minimum of 
50 ml, for doses 35 to 70 mg use a minimum of 100 ml, for doses 70 to 100 mg use a minimum 
of 250 ml and for doses greater than 100 mg use only 500 ml. Gently invert or lightly massage 
the infusion bag to mix the diluted solution. Do not shake or excessively agitate the infusion 
bag. 

 
Administration 
 
10. It is recommended to administer the diluted solution through an in-line low protein-binding 

0.2 µm filter to remove any protein particles which will not lead to any loss of agalsidase beta 
activity. The initial infusion rate should be no more than 0.25 mg/min (15 mg/hour) to 
minimise the potential occurrence of infusion-associated reactions. After patient tolerance is 
established, the infusion rate may be increased gradually with subsequent infusions. 



 32 

Package leaflet: Information for the user 
 

Fabrazyme 5 mg powder for concentrate for solution for infusion 
Agalsidase beta 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet  
1. What Fabrazyme is and what it is used for 
2. What you need to know before you use Fabrazyme 
3. How to use Fabrazyme 
4. Possible side effects 
5. How to store Fabrazyme 
6. Contents of the pack and other information 
 
 
1. What Fabrazyme is and what it is used for 
 
Fabrazyme contains the active substance agalsidase beta and is used as enzyme replacement therapy 
in Fabry disease, where the level of α-galactosidase enzyme activity is absent or lower than normal. If 
you suffer from Fabry disease a fat substance, called globotriaosylceramide (GL-3), is not removed 
from the cells of your body and starts to accumulate in the walls of the blood vessels of your organs. 
 
Fabrazyme is indicated for use as long-term enzyme replacement therapy in patients with a confirmed 
diagnosis of Fabry disease. 
 
Fabrazyme is indicated in adults, children and adolescents aged 8 years and older. 
 
 
2. What you need to know before you use Fabrazyme 
 
Do not use Fabrazyme 
- if you are allergic to agalsidase beta or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions 
Talk to your doctor  or pharmacist before using Fabrazyme. 
 
If you are treated with Fabrazyme, you may develop infusion associated reactions. An infusion-
associated reaction is any side effect occurring during the infusion or until the end of the infusion day 
(see section 4). If you experience a reaction like this, you should tell your doctor immediately. You 
may need to be given additional medicines to prevent such reactions from occurring. 
 
Children and adolescents 
No clinical studies have been performed in children 0-4 years old. The risks and benefits of 
Fabrazyme in children  aged 5 to 7 years have not yet been established and therefore no dose can be 
recommended for this age group. 
 



 33 

Other medicines and Fabrazyme 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
Tell your doctor if you use any medicines containing chloroquine, amiodarone, benoquin or 
gentamicin. There is a theoretical risk of decreased agalsidase beta activity.  
 
Pregnancy, breast-feeding and fertility 
Use of Fabrazyme during pregnancy is not recommended. There is no experience with the use of 
Fabrazyme in pregnant women. Fabrazyme may get into breast milk. Use of Fabrazyme during breast-
feeding is not recommended. Studies have not been performed to examine the effects of Fabrazyme 
on fertility.  
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
Do not drive or use machines if you experience dizziness, sleepiness, vertigo or fainting during or 
shortly after administration of Fabrazyme (see section 4). Talk to your doctor first. 
 
 
3. How to use Fabrazyme 
 
Fabrazyme is given through a drip into a vein (by intravenous infusion). It is supplied as a powder 
which will be mixed with sterile water before it is given (see information for Health Care 
Professionals at the end of this leaflet). 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
Fabrazyme is only used under the supervision of a doctor who is knowledgeable in the treatment of 
Fabry disease. Your doctor may advise that you can be treated at home provided you meet certain 
criteria. Please contact your doctor if you would like to be treated at home. 
 
The recommended dose of Fabrazyme for adults is 1 mg/kg body weight, once every 2 weeks. No 
changes in dose are necessary for patients with kidney disease.  
 
Use in children and adolescents 
The recommended dose of Fabrazyme for children and adolescents 8 – 16 years is 1 mg/kg body 
weight, once every 2 weeks. No changes in dose are necessary for patients with kidney disease. 
 
If you use more Fabrazyme than you should 
Doses up to 3 mg/kg body weight have shown to be safe. 
 
If you forget to use Fabrazyme 
If you have missed an infusion of Fabrazyme, please contact your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4.  Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
In clinical studies side effects were mainly seen while patients were being given the medicine or 
shortly after (“infusion related reactions”). Severe life-threatening allergic reactions (“anaphylactoid 
reactions”) have been reported in some patients. If you experience any serious side effect, you should 
contact your doctor immediately. 
 



 34 

Very common symptoms (may affect more than 1 in 10 people) include chills, fever, feeling cold, 
nausea, vomiting, headache and abnormal feelings in the skin such as burning or tingling.  Your 
doctor may decide to lower the infusion rate or give you additional medicines to prevent such 
reactions from occurring. 
 
List of other side effects: 
   
Common (may affect up to 1 in 10 people):  
• chest pain • sleepiness • fatigue 
• difficulty in breathing • increased heart beat • flushing 
• pallor • abdominal pain • pain 
• itching • back pain • throat tightness 
• abnormal tear secretion • rash • dizziness 
• feeling weak • low heart rate • palpitations 
• tinnitus • lethargy • decreased sensitivity to pain 
• nasal congestion • syncope • burning sensation 
• diarrhoea • cough • wheezing 
• redness • abdominal discomfort • urticaria 
• muscle pain • swelling face • pain at the extremities 
• increased blood pressure • joint pain • nasopharyngitis 
• sudden swelling of the face 

or throat 
• decreased blood pressure • hot flush 

• oedema in extremities • chest discomfort • feeling hot  
• vertigo • face oedema  • hyperthermia 
• stomach discomfort • exacerbated difficulty in 

breathing 
• decreased mouth sensitivity 

• muscle spasms • muscle tightness • musculoskeletal stiffness 
   
Uncommon (may affect up to 1 in 100 people): 
• tremor • itching eyes • low heart rate due to conduction 

disturbances 
• red eyes • ear swelling • increased sensitivity to pain 
• ear pain • bronchospasm • upper respiratory tract congestion 
• throat pain • runny nose • red rash 
• fast breathing • heart burn • (mottled purplish) skin discoloration 
• itchy rash • skin discomfort • coldness of the extremities 
• feeling hot and cold • musculoskeletal pain • injection site blood clotting 
• difficulty swallowing • rhinitis • skin discoloration 
• infusion site pain • influenza-like illness • oedema 
• infusion site reaction • malaise  
   
Not known (frequency cannot be estimated from the available data): 
• lower blood oxygen levels  • serious inflammation of the 

vessels 
 

 
In some patients initially treated at the recommended dose, and whose dose was later reduced for an 
extended period, some symptoms of Fabry disease were reported more frequently. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. 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. 
 
 

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


 35 

5. How to store Fabrazyme 
 
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. 
 
Unopened vials 
Store in a refrigerator (2°C – 8°C). 
 
Reconstituted and diluted solutions 
The reconstituted solution cannot be stored and should be promptly diluted. The diluted solution can 
be held for up to 24 hours at 2°C – 8°C. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Fabrazyme contains 
- The active substance is agalsidase beta, one vial contains 5 mg.  
- The other ingredients are:  

- Mannitol 
- Sodium phosphate monobasic, monohydrate 
- Sodium phosphate dibasic, heptahydrate. 

 
What Fabrazyme looks like and contents of the pack 
Fabrazyme is supplied as a white to off-white powder. After reconstitution it is a clear, colourless 
liquid, free from foreign matter. The reconstituted solution must be further diluted.  
Package sizes: 1, 5 and 10 vials per carton. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing authorisation holder 
Genzyme Europe B.V., Paasheuvelweg 25, 1105 BP Amsterdam, The Netherlands 
 
Manufacturer 
Genzyme Ireland Limited, IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland 
 



 36 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien/ 
Luxembourg/Luxemburg 
Sanofi Belgium 
Tél/Tel: + 32 2 710 54 00 
 

Lietuva 
UAB „SANOFI-AVENTIS LIETUVA“ 
Tel. +370 5 275 5224 
 

България 
SANOFI BULGARIA EOOD 
Tел: +359 2 9705300 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel: +36 1 505 0050 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Malta 
Sanofi S.p.A. 
Tel: +39 02 39394275 
 

Danmark 
Sanofi A/S 
Tlf: +45 45 16 70 00 
 

Nederland 
Genzyme Europe B.V. 
Tel: +31 20 245 4000 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 04 36 996 
Tel. aus dem Ausland: +49 69 305 70 13 
 

Norge 
sanofi-aventis Norge AS 
Tlf: + 47 67 10 71 00 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel. +372 6 273 488 
 

Österreich 
sanofi-aventis GmbH 
Tel: + 43 1 80 185 - 0 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 1600 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
  

Portugal 
Sanofi – Produtos Farmacêuticos, Lda.  
Tel: +351 21 35 89 400 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger: +33 1 57 63 23 23 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 4800 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel.:  +421 2 33 100 100 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: + 358 201 200 300 
 

Italia 
Sanofi S.p.A. 
Tel: 800536389 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 



 37 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 

United Kingdom 
Sanofi  
Tel +44 (0)845 372 7101 

 
Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

 

This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 
 
--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Instructions for use – reconstitution, dilution and administration 
 
The powder for concentrate for solution for infusion has to be reconstituted with water for injections, 
diluted with 0.9% sodium chloride intravenous solution and then administered by intravenous 
infusion.  
 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage and conditions are the responsibility of the user. The reconstituted 
solution cannot be stored and should be promptly diluted; only the diluted solution can be held for up 
to 24 hours at 2ºC -8ºC.  
 
Use Aseptic Technique 
  
1. Determine the number of vials to be reconstituted based on the individual patient's weight and 

remove the required vials from the refrigerator in order to allow them to reach room 
temperature (in approximately 30 minutes). Each vial of Fabrazyme is intended for single use 
only. 

 
Reconstitution  
 
2. Reconstitute each vial of Fabrazyme 5 mg with 1.1 ml water for injections. Avoid forceful 

impact of the water for injections on the powder and avoid foaming. This is done by slow drop-
wise addition of the water for injection down the inside of the vial and not directly onto the 
lyophilized cake. Roll and tilt each vial gently. Do not invert, swirl or shake the vial.  

 
3. The reconstituted solution contains 5 mg agalsidase beta per ml, and appears as a clear 

colourless solution. The pH of the reconstituted solution is approximately 7.0. Before further 
dilution, visually inspect the reconstituted solution in each vial for particulate matter and 
discoloration. Do not use the solution if foreign particles are observed or if the solution is 
discoloured. 

 
4. After reconstitution it is recommended to promptly dilute the vials, to minimise protein particle 

formation over time. 
 
5. Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 
 

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


 38 

Dilution  
 
6. Prior to adding the reconstituted volume of Fabrazyme required for the patient dose, it is 

recommended to remove an equal volume of 0.9% sodium chloride intravenous solution, from 
the infusion bag. 

 
7. Remove the airspace within the infusion bag to minimize the air/liquid interface.  
 
8. Slowly, withdraw 1.0 ml (equal to 5 mg) of the reconstituted solution from each vial up to the 

total volume required for the patient dose. Do not use filter needles and avoid foaming. 
 

9. Then slowly inject the reconstituted solution directly into the 0.9% sodium chloride intravenous 
solution (not in any remaining airspace) to a final concentration between 0.05 mg/ml and 
0.7 mg/ml. Determine the total volume of sodium chloride 0.9% solution for infusion (between 
50 and 500 ml) based on the individual dose. For doses lower than 35 mg use a minimum of 
50 ml, for doses 35 to 70 mg use a minimum of 100 ml, for doses 70 to 100 mg use a minimum 
of 250 ml and for doses greater than 100 mg use only 500 ml. Gently invert or lightly massage 
the infusion bag to mix the diluted solution. Do not shake or excessively agitate the infusion 
bag. 

 
Administration 
 
10. It is recommended to administer the diluted solution through an in-line low protein-binding 

0.2 µm filter to remove any protein particles which will not lead to any loss of agalsidase beta 
activity. The initial infusion rate should be no more than 0.25 mg/min (15 mg/hour) to 
minimise the potential occurrence of infusion-associated reactions. After patient tolerance is 
established, the infusion rate may be increased gradually with subsequent infusions. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	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
	A. LABELLING
	B. PACKAGE LEAFLET
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{'Title': '2. what you need to know before you use fabrazyme', 'Section_Content': 'do not use fabrazyme - if you are allergic to agalsidase beta or any of the other ingredients of this medicine (listed in section 6). warnings and precautions talk to your doctor or pharmacist before using fabrazyme. if you are treated with fabrazyme, you may develop infusion associated reactions. an infusion- associated reaction is any side effect occurring during the infusion or until the end of the infusion day (see section 4). if you experience a reaction like this, you should tell your doctor immediately. you may need to be given additional medicines to prevent such reactions from occurring. children and adolescents no clinical studies have been performed in children 0-4 years old. the risks and benefits of fabrazyme in children aged 5 to 7 years have not yet been established and therefore no dose can be recommended for this age group. other medicines and fabrazyme tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. tell your doctor if you use any medicines containing chloroquine, amiodarone, benoquin or gentamicin. there is a theoretical risk of decreased agalsidase beta activity. pregnancy, breast-feeding and fertility use of fabrazyme during pregnancy is not recommended. there is no experience with the use of fabrazyme in pregnant women. fabrazyme may get into breast milk. use of fabrazyme during breast- feeding is not recommended. studies have not been performed to examine the effects of fabrazyme on fertility. if you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. driving and using machines do not drive or use machines if you experience dizziness, sleepiness, vertigo or fainting during or shortly after administration of fabrazyme (see section 4). talk to your doctor first.', 'Entity_Recognition': [{'Text': 'fabrazyme', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 2, 'BeginOffset': 11, 'EndOffset': 20, 'Score': 0.9993020296096802, 'Text': 'fabrazyme', 'Category': 'MEDICATION', 'Type': 'BRAND_NAME', 'Traits': [{'Name': 'NEGATION', 'Score': 0.7928767204284668}]}, {'Text': 'allergic', 'Type': 'PROBLEM', 'BeginOffset': 34, 'EndOffset': 42}, {'Id': 3, 'BeginOffset': 46, 'EndOffset': 61, 'Score': 0.9883444309234619, 'Text': 'agalsidase beta', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 97, 'EndOffset': 110}, {'Id': 4, 'BeginOffset': 206, 'EndOffset': 215, 'Score': 0.9993284940719604, 'Text': 'fabrazyme', 'Category': 'MEDICATION', 'Type': 'BRAND_NAME', 'Traits': []}, {'Id': 5, 'BeginOffset': 241, 'EndOffset': 250, 'Score': 0.9994924068450928, 'Text': 'fabrazyme', 'Category': 'MEDICATION', 'Type': 'BRAND_NAME', 'Traits': []}, {'Text': 'infusion associated reactions', 'Type': 'PROBLEM', 'BeginOffset': 268, 'EndOffset': 297}, {'Text': 'an infusion', 'Type': 'TREATMENT', 'BeginOffset': 299, 'EndOffset': 310}, {'Text': 'associated reaction', 'Type': 'PROBLEM', 'BeginOffset': 312, 'EndOffset': 331}, {'Text': 'any side effect', 'Type': 'PROBLEM', 'BeginOffset': 335, 'EndOffset': 350}, {'Text': 'the infusion', 'Type': 'TREATMENT', 'BeginOffset': 368, 'EndOffset': 380}, {'Text': 'a reaction', 'Type': 'PROBLEM', 'BeginOffset': 453, 'EndOffset': 463}, {'Text': 'additional medicines', 'Type': 'TREATMENT', 'BeginOffset': 541, 'EndOffset': 561}, {'Text': 'such reactions', 'Type': 'PROBLEM', 'BeginOffset': 573, 'EndOffset': 587}, {'Text': 'clinical studies', 'Type': 'TEST', 'BeginOffset': 632, 'EndOffset': 648}, {'Id': 6, 'BeginOffset': 722, 'EndOffset': 731, 'Score': 0.9957439303398132, 'Text': 'fabrazyme', 'Category': 'MEDICATION', 'Type': 'BRAND_NAME', 'Traits': []}, {'Text': '5', 'Type': 'NUMBER', 'BeginOffset': 749, 'EndOffset': 750}, {'Text': '7', 'Type': 'NUMBER', 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{'Title': '3. how to use fabrazyme', 'Section_Content': 'fabrazyme is given through a drip into a vein (by intravenous infusion). it is supplied as a powder which will be mixed with sterile water before it is given (see information for health care professionals at the end of this leaflet). always use this medicine exactly as your doctor has told you. check with your doctor if you are not sure. fabrazyme is only used under the supervision of a doctor who is knowledgeable in the treatment of fabry disease. your doctor may advise that you can be treated at home provided you meet certain criteria. please contact your doctor if you would like to be treated at home. the recommended dose of fabrazyme for adults is 1 mg/kg body weight, once every 2 weeks. no changes in dose are necessary for patients with kidney disease. use in children and adolescents the recommended dose of fabrazyme for children and adolescents 8 16 years is 1 mg/kg body weight, once every 2 weeks. no changes in dose are necessary for patients with kidney disease. if you use more fabrazyme than you should doses up to 3 mg/kg body weight have shown to be safe. if you forget to use fabrazyme if you have missed an infusion of fabrazyme, please contact your doctor. if you have any further questions on the use of this medicine, ask your doctor.', 'Entity_Recognition': [{'Text': 'fabrazyme', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 3, 'BeginOffset': 0, 'EndOffset': 9, 'Score': 0.9986385703086853, 'Text': 'fabrazyme', 'Category': 'MEDICATION', 'Type': 'BRAND_NAME', 'Traits': [], 'Attributes': [{'Type': 'FORM', 'Score': 0.3069871962070465, 'RelationshipScore': 0.9999351501464844, 'RelationshipType': 'FORM', 'Id': 4, 'BeginOffset': 29, 'EndOffset': 33, 'Text': 'drip', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'ROUTE_OR_MODE', 'Score': 0.31000423431396484, 'RelationshipScore': 0.999909520149231, 'RelationshipType': 'ROUTE_OR_MODE', 'Id': 5, 'BeginOffset': 50, 'EndOffset': 61, 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{'Title': '4. possible side effects', 'Section_Content': 'like all medicines, this medicine can cause side effects, although not everybody gets them. in clinical studies side effects were mainly seen while patients were being given the medicine or shortly after ("infusion related reactions"). severe life-threatening allergic reactions ("anaphylactoid reactions") have been reported in some patients. if you experience any serious side effect, you should contact your doctor immediately. very common symptoms (may affect more than 1 in 10 people) include chills, fever, feeling cold, nausea, vomiting, headache and abnormal feelings in the skin such as burning or tingling. your doctor may decide to lower the infusion rate or give you additional medicines to prevent such reactions from occurring. list of other side effects: common (may affect up to 1 in 10 people): chest pain sleepiness fatigue difficulty in breathing increased heart beat flushing pallor abdominal pain pain itching back pain throat tightness abnormal tear secretion rash dizziness feeling weak low heart rate palpitations tinnitus lethargy decreased sensitivity to pain nasal congestion syncope burning sensation diarrhoea cough wheezing redness abdominal discomfort urticaria muscle pain swelling face pain at the extremities increased blood pressure joint pain nasopharyngitis sudden swelling of the face or throat decreased blood pressure hot flush oedema in extremities chest discomfort feeling hot vertigo face oedema hyperthermia stomach discomfort exacerbated difficulty in breathing decreased mouth sensitivity muscle spasms muscle tightness musculoskeletal stiffness uncommon (may affect up to 1 in 100 people): tremor itching eyes low heart rate due to conduction disturbances red eyes ear swelling increased sensitivity to pain ear pain bronchospasm upper respiratory tract congestion throat pain runny nose red rash fast breathing heart burn (mottled purplish) skin discoloration itchy rash skin discomfort coldness of the extremities feeling hot and cold musculoskeletal pain injection site blood clotting difficulty swallowing rhinitis skin discoloration infusion site pain influenza-like illness oedema infusion site reaction malaise not known (frequency cannot be estimated from the available data): lower blood oxygen levels serious inflammation of the vessels in some patients initially treated at the recommended dose, and whose dose was later reduced for an extended period, some symptoms of fabry disease were reported more frequently. reporting of side effects if you get any side effects, talk to your doctor or pharmacist. 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.', 'Entity_Recognition': [{'Text': 'fabrazyme', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, 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{'Title': '5. how to store fabrazyme', 'Section_Content': "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. unopened vials store in a refrigerator (2 8). reconstituted and diluted solutions the reconstituted solution cannot be stored and should be promptly diluted. the diluted solution can be held for up to 24 hours at 2 8. do not throw away any medicines via wastewater or household waste. ask your pharmacist how to throw away medicines you no longer use. these measures will help protect the environment.", 'Entity_Recognition': [{'Text': 'fabrazyme', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 70, 'EndOffset': 83}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 242, 'EndOffset': 243}, {'Text': '8.', 'Type': 'NUMBER', 'BeginOffset': 244, 'EndOffset': 246}, {'Text': 'reconstituted and diluted solutions the reconstituted solution', 'Type': 'TREATMENT', 'BeginOffset': 248, 'EndOffset': 310}, {'Text': 'the diluted solution', 'Type': 'TREATMENT', 'BeginOffset': 360, 'EndOffset': 380}, {'Text': '24', 'Type': 'NUMBER', 'BeginOffset': 403, 'EndOffset': 405}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 415, 'EndOffset': 416}, {'Text': '8.', 'Type': 'NUMBER', 'BeginOffset': 417, 'EndOffset': 419}]}
{'Title': '6. contents of the pack and other information', 'Section_Content': 'what fabrazyme contains - the active substance is agalsidase beta, one vial contains 35 mg. - the other ingredients are: - mannitol - sodium phosphate monobasic, monohydrate - sodium phosphate dibasic, heptahydrate. what fabrazyme looks like and contents of the pack fabrazyme is supplied as a white to off-white powder. after reconstitution it is a clear, colourless liquid, free from foreign matter. the reconstituted solution must be further diluted. package sizes: 1, 5 and 10 vials per carton. not all pack sizes may be marketed.', 'Entity_Recognition': [{'Text': 'fabrazyme', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 5, 'EndOffset': 14, 'Score': 0.9955282807350159, 'Text': 'fabrazyme', 'Category': 'MEDICATION', 'Type': 'BRAND_NAME', 'Traits': []}, {'Id': 1, 'BeginOffset': 50, 'EndOffset': 65, 'Score': 0.9974604845046997, 'Text': 'agalsidase beta', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'DOSAGE', 'Score': 0.8287563323974609, 'RelationshipScore': 0.9999680519104004, 'RelationshipType': 'DOSAGE', 'Id': 2, 'BeginOffset': 67, 'EndOffset': 75, 'Text': 'one vial', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'DOSAGE', 'Score': 0.9371939301490784, 'RelationshipScore': 0.9999420642852783, 'RelationshipType': 'DOSAGE', 'Id': 3, 'BeginOffset': 85, 'EndOffset': 91, 'Text': '35 mg.', 'Category': 'MEDICATION', 'Traits': []}]}, {'Text': '35', 'Type': 'NUMBER', 'BeginOffset': 85, 'EndOffset': 87}, {'Id': 4, 'BeginOffset': 123, 'EndOffset': 160, 'Score': 0.8202411532402039, 'Text': 'mannitol - sodium phosphate monobasic', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'DOSAGE', 'Score': 0.9371939301490784, 'RelationshipScore': 0.8540677428245544, 'RelationshipType': 'DOSAGE', 'Id': 3, 'BeginOffset': 85, 'EndOffset': 91, 'Text': '35 mg.', 'Category': 'MEDICATION', 'Traits': []}]}, {'Id': 5, 'BeginOffset': 162, 'EndOffset': 200, 'Score': 0.2954811751842499, 'Text': 'monohydrate - sodium phosphate dibasic', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'heptahydrate', 'Type': 'TREATMENT', 'BeginOffset': 202, 'EndOffset': 214}, {'Id': 6, 'BeginOffset': 221, 'EndOffset': 230, 'Score': 0.9964727759361267, 'Text': 'fabrazyme', 'Category': 'MEDICATION', 'Type': 'BRAND_NAME', 'Traits': []}, {'Text': 'the pack fabrazyme', 'Type': 'TREATMENT', 'BeginOffset': 258, 'EndOffset': 276}, {'Text': 'white powder', 'Type': 'TREATMENT', 'BeginOffset': 307, 'EndOffset': 319}, {'Text': 'reconstitution', 'Type': 'TREATMENT', 'BeginOffset': 327, 'EndOffset': 341}, {'Text': 'the reconstituted solution', 'Type': 'TREATMENT', 'BeginOffset': 402, 'EndOffset': 428}, {'Text': '1', 'Type': 'NUMBER', 'BeginOffset': 469, 'EndOffset': 470}, {'Text': '5', 'Type': 'NUMBER', 'BeginOffset': 472, 'EndOffset': 473}, {'Text': '10', 'Type': 'NUMBER', 'BeginOffset': 478, 'EndOffset': 480}]}