Firazyr

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Firazyr 30 mg solution for injection in pre-filled syringe 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
Each pre-filled syringe of 3 ml contains icatibant acetate equivalent to 30 mg icatibant.  
Each ml of the solution contains 10 mg of icatibant. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection. 
The solution is a clear and colourless liquid.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Firazyr is indicated for symptomatic treatment of acute attacks of hereditary angioedema (HAE) in 
adults, adolescents and children aged 2 years and older, with C1-esterase-inhibitor deficiency.  
 
4.2 Posology and method of administration 
 
Firazyr is intended for use under the guidance of a healthcare professional.  
 
Posology 
 
Adults 
The recommended dose for adults is a single subcutaneous injection of Firazyr 30 mg.  
 
In the majority of cases a single injection of Firazyr is sufficient to treat an attack. In case of 
insufficient relief or recurrence of symptoms, a second injection of Firazyr can be administered after 
6 hours. If the second injection produces insufficient relief or a recurrence of symptoms is observed, a 
third injection of Firazyr can be administered after a further 6 hours. No more than 3 injections of 
Firazyr should be administered in a 24 hour period.  
 
In the clinical trials, not more than 8 injections of Firazyr per month have been administered.  
 
Paediatric population 
The recommended dose of Firazyr based on body weight in children and adolescents (aged 2 to 17 
years) is provided in table 1 below.   
 



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Table 1: Dosage regimen for paediatric patients 
 

Body Weight Dose (Injection Volume) 

12 kg to 25 kg 10 mg (1.0 ml) 

26 kg to 40 kg 15 mg (1.5 ml) 

41 kg to 50 kg 20 mg (2.0 ml) 

51 kg to 65 kg 25 mg (2.5 ml) 

>65 kg 30 mg (3.0 ml) 

 
In the clinical trial, not more than 1 injection of Firazyr per HAE attack has been administered. 
 
No dosage regimen for children aged less than 2 years or weighing less than 12 kg can be 
recommended as the safety and efficacy in this paediatric group has not been established. 
 
Elderly 
Limited information is available on patients older than 65 years of age.  
 
Elderly people have been shown to have increased systemic exposure to icatibant. The relevance of 
this to the safety of Firazyr is unknown (see section 5.2).   
 
Hepatic impairment 
No dose adjustment is required in patients with hepatic impairment. 
 
Renal impairment 
No dose adjustment is required in patients with renal impairment.  
 
Method of administration  
 
Firazyr is intended for subcutaneous administration preferably in the abdominal area.   
 
Firazyr solution for injection should be injected slowly due to the volume to be administered. 
 
Each Firazyr syringe is intended for single use only. 
 
Refer to the patient information leaflet for instructions for use. 
 
Caregiver/self-administration 
The decision on initiating caregiver or self-administration of Firazyr should only be taken by a 
physician experienced in the diagnosis and treatment of hereditary angioedema (see section 4.4).  
 
Adults 
Firazyr may be self-administered or administered by a caregiver only after training in subcutaneous 
injection technique by a healthcare professional. 
 
Children and adolescents aged 2-17 years 
Firazyr may be administered by a caregiver only after training in subcutaneous injection technique by 
a healthcare professional. 
 



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4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Laryngeal attacks 
 
Patients with laryngeal attacks should be managed in an appropriate medical institution after injection 
until the physician considers discharge to be safe. 
 
Ischemic heart disease 
 
Under ischemic conditions, a deterioration of cardiac function and a decrease in coronary blood flow 
could theoretically arise from antagonism of bradykinin receptor type 2. Caution should therefore be 
observed in the administration of Firazyr to patients with acute ischemic heart disease or unstable 
angina pectoris (see section 5.3). 
 
Stroke 
 
Although there is evidence to support a beneficial effect of B2 receptor blockade immediately 
following a stroke, there is a theoretical possibility that icatibant may attenuate the positive late phase 
neuroprotective effects of bradykinin. Accordingly, caution should be observed in the administration 
of icatibant to patients in the weeks following a stroke. 
 
Caregiver/self-administration  
 
For patients who have never received Firazyr previously, the first treatment should be given in a 
medical institution or under the guidance of a physician. 
 
In case of insufficient relief or recurrence of symptoms after self-treatment or administration by a 
caregiver, it is recommended that the patient or caregiver should seek medical advice. For adults, 
subsequent doses that may be required for the same attack should be administered within a medical 
institution (see section 4.2). There are no data on administering subsequent doses for the same attack 
in adolescents or children.   
 
Patients experiencing a laryngeal attack should always seek medical advice and be observed in a 
medical institution also after having taken the injection at home. 
 
Paediatric population 
 
There is limited experience with treatment of more than one HAE attack with Firazyr in the paediatric 
population. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Pharmacokinetic drug interactions involving CYP450 are not expected (see section 5.2). 
 
Co-administration of Firazyr with angiotensin-converting-enzyme (ACE) inhibitors has not been 
studied. ACE inhibitors are contraindicated in HAE patients due to possible enhancement of 
bradykinin levels. 
 



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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
For icatibant, no clinical data on exposed pregnancies are available. Animal studies showed effects on 
uterine implantation and parturition (see section 5.3), but the potential risk for humans is unknown.  
 
Firazyr should be used during pregnancy only, if the potential benefit justifies the potential risk for the 
foetus, (e.g for treatment of potentially life threatening laryngeal attacks). 
 
Breast-feeding 
 
Icatibant is excreted in the milk of lactating rats at concentrations similar to those in maternal blood. 
No effects were detected in the post-natal development of rat pups.  
 
It is unknown whether icatibant is excreted in human breast milk but it is recommended that 
breastfeeding women, who wish to take Firazyr, should not breastfeed for 12 hours after treatment. 
 
Fertility 
 
In both rats and dogs, repeated use of icatibant resulted in effects on reproductive organs. Icatibant had 
no effect on the fertility of male mice and rats (see section 5.3). In a study of 39 healthy adult men and 
women treated with 30 mg every 6 hours for 3 doses every 3 days for a total of 9 doses, there were no 
clinically significant changes from baseline in basal and GnRH-stimulated concentration of 
reproductive hormones in either females or males. There were no significant effects of icatibant on the 
concentration of luteal phase progesterone and luteal function, or on menstrual cycle length in females 
and there were no significant effects of icatibant on sperm count, motility and morphology in males. 
The dosing regimen used for this study is unlikely to be sustained in the clinical setting. 
 
4.7 Effects on ability to drive and use machines 
 
Firazyr has minor influence on the ability to drive and use machines. Fatigue, lethargy, tiredness, 
somnolence, and dizziness have been reported following the use of Firazyr. These symptoms may 
occur as a result of an attack of HAE. Patients should be advised not to drive and use machines if they 
feel tired or dizzy. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
In clinical studies used for registration, a total of 999 HAE attacks have been treated with 30 mg 
Firazyr administered subcutaneously by a healthcare professional. Firazyr 30 mg SC has been 
administered by a healthcare professional to 129 healthy subjects and 236 patients with HAE. 
 
Almost all subjects who were treated with subcutaneous icatibant in clinical trials developed reactions 
at the site of injection (characterised by skin irritation, swelling, pain, itchiness, erythema, burning 
sensation). These reactions were generally mild to moderate in severity, transient, and resolved 
without further intervention.  
 
Tabulated list of adverse reactions 
 
The frequency of adverse reactions listed in Table 1 is defined using the following convention: 
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); very rare (<1/10,000). 
All adverse reactions from post-marketing experience are italicised. 
 



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Table 2: Adverse reactions reported with icatibant  
 

System Organ Class 
(incidence category) 

Preferred Term 

Nervous system disorders  

(Common, ≥1/100 to <1/10) Dizziness 
Headache 

Gastrointestinal disorders  

(Common, ≥1/100 to <1/10) Nausea 

Skin and subcutaneous tissue disorders  

(Common, ≥1/100 to <1/10) Rash  
Erythema 
Pruritus 

(Unknown) Urticaria 

General disorders and administration site 
conditions 

 

(Very Common, ≥1/10) Injection site reactions* 

(Common, ≥1/100 to <1/10) Pyrexia 

Investigations  

(Common, ≥1/100 to <1/10) Transaminases increased 
* Injection site bruising, Injection site hematoma, Injection site burning, Injection site erythema, Injection site 
hypoesthesia, Injection site irritation, Injection site numbness, Injection site edema, Injection site pain, 
Injection site pressure sensation, Injection site pruritus, Injection site swelling, Injection site urticaria, and 
Injection site warmth. 

 
Paediatric Population 
 
A total of 32 paediatric patients (8 children aged 2 to 11 years and 24 adolescents aged 12 to 17 years) 
with HAE were exposed to treatment with icatibant during clinical studies. Thirty-one patients 
received a single dose of icatibant and 1 patient (an adolescent) received icatibant for two HAE attacks 
(in total, two doses). Firazyr was administered by subcutaneous injection at a dose of 0.4 mg/kg based 
on body weight to a maximum dose of 30 mg.   
 
The majority of paediatric patients who were treated with subcutaneous icatibant experienced injection 
site reactions such as erythema, swelling, burning sensation, skin pain and itching/pruritus; these were 
found to be mild to moderate in severity and consistent with reactions that have been reported in 
adults. Two paediatric patients experienced injection site reactions which were assessed as severe and 
which were completely resolved within 6 hours. These reactions were erythema, swelling, burning and 
warm sensation.  
 
No clinically significant changes in reproductive hormones were observed during clinical studies. 
 
Description of selected adverse reactions 
 
Immunogenicity 
Across repeated treatment in adults in the controlled phase III trials, transient positivity to anti-
icatibant antibodies was observed in rare cases. All patients maintained efficacy. One Firazyr-treated 
patient tested positive for anti-icatibant antibodies before and after treatment with Firazyr. This patient 
was followed for 5 months and further samples were negative for anti-icatibant antibodies. No 
hypersensitivity or anaphylactic reactions were reported with Firazyr.   



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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 
 
No clinical information on overdose is available. 
 
A dose of 3.2 mg/kg intravenously (approximately 8 times the therapeutic dose) caused transient 
erythema, itching, flushing or hypotension in healthy subjects. No therapeutic intervention was 
necessary.  
 
 
5. PHARMACOLOGICAL PROPERTIES  
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other haematological agents, drugs used to treat hereditary angioedema; 
ATC code: B06AC02. 
 
Mechanism of action 
 
HAE (an autosomal dominant disease) is caused by an absence or dysfunction of C1-esterase-
inhibitor. HAE attacks are accompanied by an increased release of bradykinin, which is the key 
mediator in the development of the clinical symptoms.  
 
HAE manifests as intermittent attacks of subcutaneous and/or sub mucosal oedema involving the 
upper respiratory tract, the skin and the gastrointestinal tract. An attack usually lasts between 2 to 5 
days. 
 
Icatibant is a selective competitive antagonist at the bradykinin type 2 (B2) receptor. It is a synthetic 
decapeptide with a structure similar to bradykinin, but with 5 non-proteinogenic amino acids. In HAE 
increased bradykinin concentrations are the key mediator in the development of the clinical symptoms.  
 
Pharmacodynamic effects 
 
In healthy young subjects, icatibant administered in doses of 0.8 mg/kg over 4 hours; 1.5 mg/kg/day or 
0.15 mg/kg/day for 3 days, development of bradykinin-induced hypotension, vasodilatation and reflex 
tachycardia was prevented. Icatibant was shown to be a competitive antagonist when the bradykinin 
challenge dose was increased 4-fold.  
 
Clinical efficacy and safety 
 
Efficacy data were obtained from an initial open-label Phase II study and from three controlled Phase 
III studies.  
 
Phase III clinical studies (FAST-1 and FAST-2) were randomized, double-blind, controlled trials and 
had identical designs except for the comparator (one with oral tranexamic acid as the comparator and 
one placebo controlled). A total of 130 patients were randomized to receive either a 30 mg dose of 
icatibant (63 patients) or comparator (either tranexamic acid, - 38 or placebo - 29 patients). 
Subsequent episodes of HAE were treated in an open label extension. Patients with symptoms of 
laryngeal angioedema received open label treatment with icatibant. The primary efficacy endpoint was 
the time to onset of symptom relief using a visual analogue scale (VAS). Table 3 shows the efficacy 
results for these studies. 

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


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FAST-3 was a randomized, placebo-controlled, parallel-group study of 98 adult patients with a median 
age of 36 years. Patients were randomized to receive either icatibant 30 mg or placebo by 
subcutaneous injection. A subset of patients in this study experienced acute HAE attacks while 
receiving androgens, antifibrinolytic agents or Cl inhibitors. The primary endpoint was time to onset 
of symptom relief assessed using a 3-item composite visual analog score (VAS-3) consisting of 
assessments of skin swelling, skin pain, and abdominal pain. Table 4 shows the efficacy results for 
FAST-3.  
 
In these studies, patients on icatibant had a faster median time to onset of symptom relief (2.0, 2.5 and 
2.0 hours, respectively) compared to tranexamic acid (12.0 hours) and placebo (4.6 and 19.8 hours). 
The treatment effect of icatibant was confirmed by secondary efficacy endpoints.  
 
In an integrated analysis of these controlled Phase III studies, the time to onset of symptom relief and 
time to onset of primary symptom relief were similar regardless of age group, sex, race, weight or 
whether or not the patient used androgens or antifibrinolytic agents. 
 
Response was also consistent across repeated attacks in the controlled Phase III trials. A total of 237 
patients were treated with 1,386 doses of 30 mg icatibant for 1,278 attacks of acute HAE. In the first 
15 Firazyr treated attacks (1,114 doses for 1,030 attacks), the median times to onset of symptom relief 
were similar across attacks (2.0 to 2.5 hours). 92.4% of these attacks of HAE were treated with a 
single dose of Firazyr. 
 
Table 3. Efficacy results for FAST-1 and FAST-2 
 

 
Controlled Clinical Study of FIRAZYR vs Tranexamic acid or Placebo: Efficacy Results 

FAST-2 FAST-1 

 Icatibant Tranexamic acid  Icatibant Placebo 

Number of subjects 
in ITT Population 36 38 

Number of subjects 
in ITT Population 27 29 

Baseline 
VAS(mm) 63.7 61.5 

Baseline 
VAS(mm) 69.3 67.7 

Change from 
baseline to 4 hours -41.6 -14.6 

Change from 
baseline to 4 hours -44.8 -23.5 

Difference 
between treatments 
(95% CI, p-value) 

-27.8 (-39.4, -16.2) p < 0.001 
Difference 
between treatments 
(95% CI, p-value) 

-23.3 (-37.1, -9.4) p = 0.002 

Change from 
baseline to 
12 hours 

-54.0 -30.3 
Change from 
baseline to 
12 hours 

-54.2 -42.4 

Difference 
between treatments 
(95% CI, p-value) 

-24.1 (-33.6, -14.6) p < 0.001 
Difference 
between treatments 
(95% CI, p-value) 

-15.2 (-28.6, -1.7) p = 0.028 

Median time to 
onset of symptom 
relief (hours) 

    
Median time to 
onset of symptom 
relief (hours) 

    

All episodes 
(N = 74) 2.0 12.0 

All episodes 
(N = 56) 2.5 4.6 

Response rate  
(%, CI) at 4 hours 
after start of 
treatment 

    

Response rate  
(%, CI) at 4 hours 
after start of 
treatment 

    



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Controlled Clinical Study of FIRAZYR vs Tranexamic acid or Placebo: Efficacy Results 

FAST-2 FAST-1 

 Icatibant Tranexamic acid  Icatibant Placebo 

All episodes 
(N = 74) 

80.0  
(63.1, 91.6) 

30.6  
(16.3, 48.1) 

All episodes 
(N = 56) 

66.7  
(46.0, 83.5) 

46.4  
(27.5, 66.1) 

Median time to 
onset of symptom 
relief: all 
symptoms (hours): 
 Abdominal pain 
 Skin swelling  
 Skin pain  

  
 
 
 

1.6 
2.6 
1.5 

  
 
 
 

3.5 
18.1 
12.0 

Median time to 
onset of symptom 
relief: all 
symptoms (hours): 
 Abdominal pain 
 Skin swelling  
 Skin pain  

 
 
 
  

2.0 
3.1 
1.6 

 
 
 
  

3.3 
10.2 
9.0 

Median time to 
almost complete 
symptom relief 
(hours) 

    

Median time to 
almost complete 
symptom relief 
(hours) 

    

All episodes 
(N = 74) 10.0 51.0 

All episodes 
(N = 56) 8.5 19.4 

Median time to 
regression of 
symptoms, by 
patient (hours) 

    

Median time to 
regression of 
symptoms, by 
patient (hours) 

    

All episodes 
(N = 74) 0.8 7.9 

All episodes 
(N = 56) 0.8 16.9 

Median time to 
overall patient 
improvement, by 
physician (hours) 

    

Median time to 
overall patient 
improvement, by 
physician (hours) 

    

All episodes 
(N = 74) 1.5 6.9 

All episodes 
(N = 56) 1.0 5.7 

 
Table 4. Efficacy results for FAST-3 
 

Efficacy Results: FAST-3; Controlled Phase -- ITT population 

Endpoint Statistic Firazyr Placebo p-value 

  (n = 43) (n=45)  

Primary Endpoint     

Time to Onset of Symptom 
Relief-- Composite VAS (hrs)  

Median 2.0 19.8 <0.001 

Other Endpoints     

Time to Onset of Primary 
Symptom Relief (hrs)  

Median 1.5 18.5 < 0.001 

Change in Composite VAS 
Score at 2 hrs after treatment  

Mean -19.74 -7.49 < 0.001 

Change in Composite 
Subject-Assessed Symptom 
Score at 2 hours  

Mean -0.53 -0.22 < 0.001 



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Efficacy Results: FAST-3; Controlled Phase -- ITT population 

Endpoint Statistic Firazyr Placebo p-value 

  (n = 43) (n=45)  

Change in Composite 
Investigator-Assessed 
Symptom Score at 2 hours  

Mean -0.44 -0.19 < 0.001 

Time to Almost Complete 
Symptom Relief (hrs)  

Median 8.0 36.0 0.012 

Time to Subject-Assessed 
Initial Symptom 
Improvement (hrs)  

Median 0.8 3.5 < 0.001 

Time to Investigator-
Assessed Initial  Visual 
Symptom Improvement (hrs)  

Median 0.8 3.4 < 0.001 

 
 
A total of 66 patients with attacks of HAE affecting the larynx were treated in these controlled Phase 
III clinical trials. The results were similar to patients with non-laryngeal attacks of HAE with respect 
to time to onset of symptom relief. 
 
Paediatric population 
An open label, non-randomised single-arm study (HGT-FIR-086) was performed with a total of 32 
patients. All patients received at least one dose of icatibant (0.4mg/kg body weight up to a maximum 
dose of 30 mg) and the majority of patients were followed up for a minimum of 6 months. Eleven 
patients were of prepubertal status and 21 patients were either pubertal or postpubertal. 
 
The efficacy population consisted of 22 patients who had been treated with icatibant (11 prepubertal 
and 11 pubertal/postpubertal) for HAE attack. 
 
The primary efficacy endpoint was the time to onset of symptom relief (TOSR) measured using a 
composite investigator-reported symptom score. Time to symptom relief was defined as the duration 
of time (in hours) taken for improvement of symptoms to occur by a magnitude of 20%.  
 
Overall the median time to onset of symptom relief was 1.0 hour (95% confidence interval, 1.0-1.1 
hours). At 1 and 2 hours post treatment, approximately 50% and 90% of patients experienced onset of 
symptom relief, respectively.   
Overall, the median time to minimal symptoms (earliest time post treatment when all symptoms were 
either mild or absent) was 1.1 hours (95% confidence interval, 1.0-2.0 hours). 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of icatibant has been characterized by studies using both intravenous and 
subcutaneous administration to healthy volunteers and patients. The pharmacokinetic profile of 
icatibant in patients with HAE is similar to that in healthy volunteers. 
 
Absorption 
 
Following subcutaneous administration, the absolute bioavailability of icatibant is 97%. The time to 
maximum concentration is approximately 30 minutes.  
 
Distribution  
 
Icatibant volume of distribution (Vss) is about 20-25 L. Plasma protein binding is 44%.  



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Elimination 
 
Icatibant is mainly eliminated by metabolism with less than 10% of the dose eliminated in the urine as 
unchanged drug. Clearance is about 15-20 l/h and independent of dose. The terminal plasma half-life 
is about 1-2 hours.  
 
Biotransformation  
 
Icatibant is extensively metabolized by proteolytic enzymes to inactive metabolites that are primarily 
excreted in the urine. 
 
In vitro studies have confirmed that icatibant is not degraded by oxidative metabolic pathways and is 
not an inhibitor of major cytochrome P450 (CYP) isoenzymes (CYP 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 
2D6, 2E1, and 3A4) and is not an inducer of CYP 1A2 and 3A4.  
 
Special populations 
 
Elderly 
Data suggest an age-related decline in clearance resulting in about 50-60% higher exposure in older 
people (75-80 years) compared to patients aged 40 years.  
 
Gender 
Data suggest that there is no difference in the clearance between females and males after correcting for 
body weight.  
 
Hepatic and Renal Impairment 
Limited data suggest that icatibant exposure is not influenced by hepatic or renal impairment.  
 
Race 
Information on individual race effect is limited. Available exposure data suggest no difference in the 
clearance between non-White (n=40) and White (n=132) subjects. 
 
Paediatric population 
The pharmacokinetics of icatibant were characterized in paediatric HAE patients in study HGT-FIR-
086 (see section 5.1). Following a single subcutaneous administration (0.4 mg/kg up to a maximum of 
30 mg), the time to maximum concentration is approximately 30 minutes and the terminal half-life is 
about 2 hours. There are no observed differences in the exposure to icatibant between HAE patients 
with and without an attack. Population pharmacokinetic modelling using both adult and paediatric data 
showed that clearance of icatibant is related to body weight with lower clearance values noted for 
lower body weights in the paediatric HAE population. Based on modelling for weight banded dosing, 
the predicted exposure to icatibant in the paediatric HAE population (see section 4.2) is lower than the 
observed exposure in studies conducted with adult HAE patients. 
 
 
5.3 Preclinical safety data  
 
Repeated-dose studies of up to 6-months duration in rats and 9-months duration in dogs have been 
conducted. In both rats and dogs, there was a dose-related reduction in circulating sex hormone levels 
and the repeated use of icatibant reversibly delayed sexual maturation. 
 
Maximum daily exposures defined by area under the curve (AUC) at the No Observed Adverse Effect 
Levels (NOAEL) in the 9-month study in dog were 2.3 times the AUC in adult humans after a 
subcutaneous dose of 30 mg. A NOAEL was not measurable in the rat study, however, all of the 
findings from that study showed either completely or partially reversible effects in treated rats. 
Adrenal gland hypertrophy was observed at all doses tested in rats.  Adrenal gland hypertrophy was 



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seen to reverse after cessation of icatibant treatment. The clinical relevance of the adrenal gland 
findings is unknown. 
 
Icatibant had no effect on the fertility of male mice (top dose 80.8 mg/kg/day) and rats (top dose 
10 mg/kg/day). 
 
In a 2 year study to evaluate the carcinogenic potential of icatibant in rats, daily doses giving exposure 
levels up to approximately 2-fold that achieved after a therapeutic dose in humans had no effect on the 
incidence or morphology of tumours. Results do not indicate a carcinogenic potential for icatibant. 
 
In a standard battery of in vitro and in vivo tests icatibant was not genotoxic.  
 
Icatibant was not teratogenic when administered by SC injection during early embryonic and fetal 
development in rat (top dose 25 mg/kg/day) and rabbit (top dose 10 mg/kg/day). Icatibant is a potent 
antagonist of bradykinin and therefore, at high dose levels, treatment can have effects on the uterine 
implantation process and subsequent uterine stability in early pregnancy. These uterine effects also 
manifest in late stage pregnancy where icatibant exhibits a tocolytic effect resulting in delayed 
parturition in the rat, with increased fetal distress and perinatal death at high doses (10 mg/kg/day). 
 
A 2-week subcutaneous dose range finding study in juvenile rats identified 25 mg/kg/day as a 
maximally tolerated dose. In the pivotal juvenile toxicity study in which sexually immature rats were 
treated daily with 3 mg/kg/day for 7 weeks, atrophy of testes and epididymides were observed; the 
observed microscopic findings were partially reversible. Similar effects of icatibant on reproductive 
tissue were seen in sexually mature rats and dogs. These tissue findings were consistent with reported 
effects on gonadotrophins and during the subsequent treatment-free period appear to be reversible.  
 
Icatibant did not elicit any cardiac conduction change in vitro (hERG channel) or in vivo in normal 
dogs or in various dog models (ventricular pacing, physical exertion and coronary ligation) where no 
associated hemodynamic changes were observed. Icatibant has been shown to aggravate induced 
cardiac ischemia in several non-clinical models, although a detrimental effect has not consistently 
been shown in acute ischemia.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Sodium chloride 
Acetic acid, glacial (for pH adjustment) 
Sodium hydroxide (for pH adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
24 months. 
 
6.4 Special precautions for storage 
 
Do not store above 25○C. 
 
Do not freeze. 
 



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6.5 Nature and contents of container 
 
3 ml of solution in a 3 ml pre-filled syringe (type I glass) with plunger stopper (bromobutyl coated 
with fluorocarbon polymer). A hypodermic needle (25 G; 16 mm) is included in the pack. 
 
Pack size of one pre-filled syringe with one needle or a multipack containing three pre-filled syringes 
with three needles. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
The solution should be clear and colourless and free from visible particles.   
 
Paediatric use 
 
The appropriate dose to be administered is based on body weight (see section 4.2). 
 
Where the required dose is less than 30 mg (3 ml), the following equipment is required to extract and 
administer the appropriate dose: 
 

• Adapter (proximal and/or distal female luer lock connector/coupler) 
• 3 ml (recommended) graduated syringe 

 
The pre-filled icatibant syringe and all other components are for single use only. 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
All needles and syringes should be disposed of in a sharps container. 
 
 
7. MARKETING AUTHORISATION HOLDER  
 
Shire Pharmaceuticals Ireland Limited 
Block 2 & 3 Miesian Plaza 
50 – 58 Baggot Street Lower 
Dublin 2 
D02 Y754, Ireland 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/461/001 
EU/1/08/461/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 11 July 2008 
Date of latest renewal: 13 March 2013 
 
 
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/


14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. 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 

 
  

 



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A MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Shire Pharmaceuticals Ireland Limited 
Block 2 & 3 Miesian Plaza 
50 – 58 Baggot Street Lower 
Dublin 2 
D02 Y754, Ireland. 
 
 
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 
 
The requirements for submission of periodic safety update reports 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 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. 

 



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



18 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON OF UNIT PACK 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Firazyr 30 mg solution for injection in pre-filled syringe 
Icatibant 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 3 ml pre-filled syringe contains icatibant acetate equivalent to 30 mg icatibant. 
Each ml of the solution contains 10 mg of icatibant. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains: acetic acid glacial, sodium hydroxide, sodium chloride, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
One pre-filled syringe 
One 25G needle 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use 
Read the package leaflet before use 
For single use only 
 
 
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 
 
Do not store above 25ºC. Do not freeze. 
 



19 

 
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 
 
Shire Pharmaceuticals Ireland Limited 
Dublin 2 
D02 Y754, Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/461/001  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Firazyr 30 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



20 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON OF MULTI-PACK (INCLUDING BLUE BOX)  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Firazyr 30 mg solution for injection in pre-filled syringe 
Icatibant 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 3 ml pre-filled syringe contains icatibant acetate equivalent to 30 mg icatibant. 
Each ml of the solution contains 10 mg of icatibant. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains: acetic acid glacial, sodium hydroxide, sodium chloride, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection  
Multipack containing three pre-filled syringes and three 25G needles 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use 
Read the package leaflet before use 
For single use only 
 
 
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 
 
Do not store above 25ºC. Do not freeze. 
 
 



21 

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 
 
Shire Pharmaceuticals Ireland Limited 
Dublin 2 
D02 Y754, Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/461/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Firazyr 30 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



22 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INTERMEDIATE CARTON OF MULTI-PACK (WITHOUT BLUE BOX)  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Firazyr 30 mg solution for injection in pre-filled syringe 
Icatibant 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 3 ml pre-filled syringe contains icatibant acetate equivalent to 30 mg icatibant. 
Each ml of the solution contains 10 mg of icatibant. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains: acetic acid glacial, sodium hydroxide, sodium chloride, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection  
One pre-filled syringe and one 25G needle. 
Component of a multipack, can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use 
Read the package leaflet before use 
For single use only 
 
 
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 
 
Do not store above 25ºC. Do not freeze. 
 
 



23 

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 
 
Shire Pharmaceuticals Ireland Limited 
Dublin 2 
D02 Y754, Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/461/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Firazyr 30 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



24 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
{BLISTER TRAY LID} 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Firazyr 30 mg solution for injection in pre-filled syringe 
Icatibant 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Shire Pharmaceuticals Ireland Limited 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Subcutaneous use 



25 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Firazyr 30 mg  
Icatibant 
sc 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
30 mg/3 ml 
 
 
6. OTHER 
 
Shire Pharmaceuticals Ireland Limited 
 



26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



27 

 
Package Leaflet: Information for the user 

 
Firazyr 30 mg solution for injection pre-filled syringe 

Icatibant 
 
 
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 Firazyr is and what it is used for 
2. What you need to know before you use Firazyr  
3. How to use Firazyr 
4. Possible side effects 
5. How to store Firazyr 
6. Contents of the pack and other information  
 
 
1. What Firazyr is and what it is used for 
 
Firazyr contains the active substance icatibant. 
 
Firazyr is used for treating the symptoms of hereditary angioedema (HAE) in adults, adolescents and 
children aged 2 years and older. 
In HAE levels of a substance in your bloodstream called bradykinin are increased and this leads to 
symptoms like swelling, pain, nausea, and diarrhoea. 
Firazyr blocks the activity of bradykinin and therefore ends the further progression of the symptoms.  
 
 
2. What you need to know before you use Firazyr  
 
Do not use Firazyr  
 
- If you are allergic to icatibant, or any of the other ingredients of this medicine (listed in 

section 6).  
 
Warnings and precautions 
 
Talk to your doctor before taking Firazyr: 
- if you are suffering from angina (reduced blood flow to the heart muscle)  
- if you have recently suffered a stroke 

 
Some of the side effects connected with Firazyr are similar to the symptoms of your disease. Tell your 
doctor immediately if you notice that your symptoms of the attack get worse after you received Firazyr 

 
In addition: 
- You or your caregiver must be trained on subcutaneous (under the skin) injection technique 

before you self-inject or your caregiver injects you with Firazyr. 



28 

 
- Immediately after you self-inject Firazyr or your caregiver injects you with Firazyr while you 

are experiencing a laryngeal attack (obstruction of the upper airway), you must seek medical 
care in a medical institution. 

 
- If your symptoms are not resolved following one self- or caregiver administered injection of 

Firazyr, you should seek medical advice regarding additional injections of Firazyr. For adult 
patients, up to 2 additional injections may be given within 24 hours. 

 
Children and adolescents  
 
Firazyr is not recommended for use in children under 2 years of age or weighing less than 12 kg 
because it has not been studied in these patients.  
 
Other medicines and Firazyr 
 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Firazyr is not known to interact with other medicines. If you are taking a medicine known as an 
Angiotensin Converting Enzyme (ACE) inhibitor (for example: captopril, enalapril, ramipril, 
quinapril, lisinopril) which is used to lower your blood pressure or for any other reason, you should 
inform your doctor before receiving Firazyr. 
 
Pregnancy and breast feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor before starting to use Firazyr. 
 
If you are breast-feeding you should not breast-feed for 12 hours after you have last received Firazyr. 
 
Driving and using machines 
 
Do not drive or use machines if you feel tired or dizzy as a result of your HAE attack or after using 
Firazyr. 
 
Firazyr contains a small amount of sodium 
 
The injection solution contains less than 1 mmol (23 milligrams) of sodium, so it is essentially 
‘sodium-free’. 
 
 
3. How to use Firazyr 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure.  
 
If you have never received Firazyr previously, your first dose of Firazyr will always be injected by 
your doctor or nurse. Your doctor will tell you when it is safe for you to go home. After discussion 
with your doctor or nurse and after training in subcutaneous (under the skin) injection technique, you 
may be able to inject yourself with Firazyr or your caregiver may inject Firazyr for you when you have 
an HAE attack.  It is important that Firazyr is injected subcutaneously (under the skin) as soon as you 
notice an attack of angioedema. Your healthcare provider will teach you and your caregiver how to 
safely inject Firazyr by following the instructions in the Package Leaflet.   
 
When and how often should you use Firazyr? 
 
Your doctor has determined the exact dose of Firazyr and will tell you how often it should be used. 



29 

 
Adults 
- The recommended dose of Firazyr is one injection (3 ml, 30 mg) injected subcutaneously (under 

the skin) as soon as you notice the attack of angioedema (for example increased skin swelling, 
particularly affecting the face and neck, or increasing tummy pain). 
 

- If you experience no relief of symptoms after 6 hours, you should seek medical advice regarding 
additional injections of Firazyr. For adults, up to 2 additional injections may be given within 24 
hours. 

 
- You should not have more than 3 injections in a 24 hour period and if you require more than 

8 injections in a month, you should seek medical advice. 
 
Children and adolescents aged 2 to 17 years 
- The recommended dose of Firazyr is one injection of 1 ml up to a maximum of 3 ml based on 

body weight injected subcutaneously (under the skin) as soon as you develop symptoms of an 
angioedema attack (for example increased skin swelling, particularly affecting the face and neck, 
increasing tummy pain).   

 
- See section on instructions for use for the dose to inject. 
 
- If you are not sure which dose to inject, ask your doctor, pharmacist or nurse. 
 
- If your symptoms get worse or do not improve, you must seek immediate medical help. 
 
How should Firazyr be administered? 
 
Firazyr is intended for subcutaneous injection (under the skin).  Each syringe should only be used 
once. 
 
Firazyr is injected with a short needle into the fatty tissue under the skin in the abdomen (tummy).  
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
The following step-by step instructions are intended for: 

- self-administration (adults)  
- administration by a caregiver or healthcare professional to adults, adolescents or children 

aged over 2 years (weighing at least 12 kg). 
 
The instructions include the following main steps: 
 
1)  General Information 
2a)  Preparing the syringe for children and adolescents (2-17 years) weighing 65 kg or less 
2b)  Preparing the syringe and needle for injection (all patients) 
3)  Preparing the injection site 
4)  Injecting the solution 
5)  Disposal of the injection material 
 
 



30 

Step-by-Step Instructions for Injection 
 

1) General Information 
 

• Clean the work area (surface) to be used before beginning the process. 
 

• Wash your hands with soap and water. 
 

• Open the tray by peeling back the seal. 
 

• Remove the pre-filled syringe from the tray. 
 

• Remove the cap from the end of the pre-filled syringe by unscrewing the cap. 
 

• Put down the pre-filled syringe after unscrewing the cap. 
2a) Preparing the syringe for  

children and adolescents (2-17 years) 
weighing 65 kg or less: 

 
Important information for healthcare professionals and caregivers: 

 
Where the dose is less than 30 mg (3 ml), the following equipment is required to extract the 
appropriate dose (see below): 
 

a) Firazyr pre-filled syringe (containing icatibant solution) 
 

b) Connector (adapter) 
 

c) 3 ml graduated syringe 
 

 

 
 
The required injection volume in ml should be drawn up in an empty 3 ml graduated syringe (see table 
below). 
 
 
 
 
 
 
 
 
 
 



31 

Table 1: Dosage regimen for children and adolescents 
 

Body Weight Injection Volume 

12 kg to 25 kg 1.0 ml 

26 kg to 40 kg 1.5 ml 

41 kg to 50 kg 2.0 ml 

51 kg to 65 kg 2.5 ml 

 
Patients weighing more than 65 kg will use the full contents of the pre-filled syringe (3 ml). 
 
 

If you are not sure which volume of solution to extract, ask your doctor, pharmacist or 
nurse 
 
 
1) Remove the caps on each end of the connector. 
 
 

Avoid touching the ends of the connector and syringe tips, to prevent contamination 
 
 
2) Screw the connector onto the pre-filled syringe. 
 
3) Attach the graduated syringe to the other end of the connector ensuring that both connections fit 

securely. 
 

 

 
 

Transferring the icatibant solution to the graduated syringe: 
 
1) To start transfer of icatibant solution, push the pre-filled syringe plunger (on far left of below 

image). 

 

 



32 

 

2) If the icatibant solution does not begin to transfer to the graduated syringe, pull slightly on the 
graduated syringe plunger until the icatibant solution starts to flow into the graduated syringe (see 
below image). 

 

 

3) Continue to push on the pre-filled syringe plunger until the required injection volume (dose) is 
transferred to the graduated syringe.  Refer to table 1 for dosage information. 

 
 

If there is air in the graduated syringe: 

• Turn the connected syringes so that the pre-filled syringe is on top (see below image). 

 

• Push the plunger of the graduated syringe so that any air is transferred back into the pre-filled 
syringe (this step may need to be repeated several times). 
 



33 

• Withdraw the required volume of icatibant solution. 
 

4) Remove the pre-filled syringe and connector from the graduated syringe. 
 
5) Discard the pre-filled syringe and connector into the sharps container. 
 

2b) Preparing the syringe and needle for injection: 
All patients (adults, adolescents and children) 

 
 
 
 
 
 
 
 
 
 
 

 
 

• Remove the needle cap from the blister. 
 
• Remove the seal from the needle cap (the needle should be still in the needle cap). 

 

 
 
 
 
 
 
 
 
 
 
 

 
 
• Grip the syringe firmly.  Carefully attach the needle to the syringe containing the colourless 

solution. 
 
• Screw the syringe on the needle still fixed in the needle cap. 
 
• Remove the needle from the needle cap by pulling the syringe. Do not pull up on the plunger. 
 
• The syringe is now ready for injection. 
 

 
 



34 

3) Preparing the injection site 
 

 
 
 

• Choose the injection site. The injection site should be a skin fold on your abdomen approximately 
5-10 cm (2-4 inches) below your navel on either side. This area should be at least 5 cm (2 inches) 
away from any scars. Do not choose an area that is bruised, swollen, or painful.  

 
• Clean the injection site with a rubbing alcohol pad and allow it to dry. 

 
 

4) Injecting the solution 
 

 
 
 
 
 
 
 
 
 
 
 
 
 

 
• Hold the syringe in one hand between two fingers with your thumb at the bottom of the plunger. 
 
• Make sure that there is no air bubble in the syringe by pressing the plunger until the first drop 

appears on the tip of the needle. 
 

 
 



35 

 
 
 

• Hold syringe between 45-90 degrees angle to skin with needle facing the skin. 
 
• Keeping the syringe in one hand, use your other hand to gently hold a fold of skin between your 

thumb and fingers at the previously disinfected injection site. 
 
• Hold the fold of skin, bring the syringe to the skin and quickly insert the needle into the skin 

fold. 
 
• Slowly push the plunger of the syringe with a steady hand until all the fluid is injected into the 

skin and no liquid remains in the syringe. 
 
• Press slowly so that this takes approximately 30 seconds. 

 
• Release the skin fold and gently pull the needle out. 
 
 
 

5) Disposal of the injection material 
 

 
 

• Discard the syringe, needle and needle cap into the sharp container for throwing away waste that 
might hurt others if not handled properly. 

 
 
 
 



36 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Almost all 
patients receiving Firazyr will experience a reaction at the site of the injection (such as skin irritation, 
swelling, pain, itchiness, redness of the skin and burning sensation). These effects are usually mild and 
clear up without the need for any additional treatment. 
 
Very common (may affect more than 1 in 10 people) : 
Additional injection site reactions (pressure sensation, bruising, reduced sensation and/or numbness, 
raised itchy skin rash and warmth). 
 
Common (may affect up to 1 in 10 people) : 
Feeling sick 
Headache 
Dizziness 
Fever 
Itching 
Rash 
Skin redness 
Abnormal liver function test 
 
Not known (frequency cannot be estimated from the available data) : 
Hives (urticaria) 
 
 
Tell your doctor immediately if you notice that the symptoms of your attack get worse after you 
received Firazyr. 
 
If you get any side effects talk to your doctor. This includes any possible side effects not listed in this 
leaflet. 
 
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. 
 
 
5. How to store Firazyr 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date stated on the label after ‘EXP’. The expiry date refers to 
the last day of that month.  
 
Do not store above 25○C. Do not freeze. 
 
Do not use this medicine if you notice that the syringe or needle packaging is damaged or if there are 
any visible signs of deterioration, for example if the solution is cloudy, if it has floating particles, or if 
the colour of the solution has changed. 
 
Do not throw away any medicines via waste water or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

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


37 

6. Contents of the pack and other information 
 
What Firazyr contains  
 
The active substance is icatibant. Each pre-filled syringe contains 30 milligrams of icatibant (as 
acetate). The other ingredients are sodium chloride, acetic acid glacial, sodium hydroxide and water 
for injection. 
 
What Firazyr looks like and contents of the pack 
 
Firazyr is presented as a clear, colourless solution for injection in a pre-filled glass syringe of 3 ml. 
Hypodermic needle is included in the pack. 
 
Firazyr is available as a single pack containing one pre-filled syringe with one needle or as a 
multipack containing three pre-filled syringes with three needles. 
 
Not all pack sizes may be marketed. 
 
 
Marketing Authorisation Holder and Manufacturer 
 
Shire Pharmaceuticals Ireland Limited 
Block 2 & 3 Miesian Plaza 
50 – 58 Baggot Street Lower 
Dublin 2 
D02 Y754, Ireland 
Tel:  +44(0)1256 894 959 
E-mail: medinfoEMEA@shire.com 
 
 
This leaflet was last revised in . 
 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 

mailto:medinfoEMEA@shire.com
http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A 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