Ruconest

1 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Ruconest 2100 Units powder for solution for injection. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial contains 2100 units of conestat alfa, corresponding to 2100 units per 14 ml after reconstitution, or a 
concentration of 150 units/ml.  
 
Conestat alfa is a recombinant analogue of the human C1 esterase inhibitor (rhC1-INH) produced by 
recombinant DNA technology in the milk of transgenic rabbits.  
 
1 unit of conestat alfa activity is defined as the equivalent of C1 esterase inhibiting activity present in 1 ml of 
pooled normal plasma. 
 
Excipient with known effect: 
Each vial contains approximately 19.5 mg sodium.  
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for solution for injection. 
White to off-white powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Ruconest is indicated for treatment of acute angioedema attacks in adults, adolescents, and children (aged 
2 years and above) with hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency. 
 
4.2 Posology and method of administration 
 
Ruconest should be initiated under the guidance and supervision of a physician experienced in the diagnosis 
and treatment of hereditary angioedema. 
 
Posology in adults, adolescents and children aged 2 years and above 
Body weight up to 84 kg 
- One intravenous injection of 50 U/kg body weight. 
 
Body weight of 84 kg or greater  
- One intravenous injection of 4200 U (2 vials). 
 
In the majority of cases, a single dose of Ruconest is sufficient to treat an acute angioedema attack.  
In case of an insufficient clinical response, an additional dose (50 U/kg body weight up to 4200 U) can be 
administered at the discretion of the physician (see section 5.1). 
 
- In adults and adolescents an additional dose may be administered if the patient has not responded 

adequately after 120 minutes.  
- In children an additional dose may be administered if the patient has not responded adequately after 60 

minutes. 
 
Not more than two doses should be administered within 24 hours. 
 



3 
 

Dose calculation 
Determine the patient’s body weight. 
 
Body weight up to 84 kg 
- For patients up to 84 kg calculate the volume required to be administered according to the formula below: 
 

Volume to be 
administered (ml)  = 

body weight (kg) times 50 (U/kg) 
150 (U/ml) = 

body weight (kg) 
3 

 
Body weight of 84 kg or greater  
- For patients of 84 kg or above the volume required to be administered is 28 ml, corresponding to 4200 U 

(2 vials). 
 
Paediatric population  
Ruconest may be used in paediatric patients (2 years and older) at the same dose as in adults (50 U/kg body 
weight).  
The safety and efficacy of Ruconest in children less than 2 years old have not been established. No clinical 
data are available.  
 
Elderly (≥65 years old)  
Data in patients older than 65 years are limited.  
There is no rationale for patients older than 65 years to respond differently to Ruconest.  
 
Renal impairment 
No dose adjustment is necessary in patients with renal impairment since conestat alfa does not undergo renal 
clearance. 
 
Hepatic impairment 
There is no clinical experience with Ruconest in patients with hepatic impairment. Hepatic impairment may 
prolong the plasma half-life of conestat alfa, but this is not thought to be a clinical concern. No 
recommendation on a dose adjustment can be made. 
 
Method of administration 
For intravenous use. 
Ruconest should be administered by a healthcare professional. 
For instructions on reconstitution of Ruconest before administration, see section 6.6. 
The required volume of the reconstituted solution should be administered as a slow intravenous injection 
over approximately 5 minutes. 
 
4.3 Contraindications 
 
• Known or suspected allergy to rabbits (see section 4.4)  
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number of the 
administered products should be clearly recorded. 
 
Conestat alfa is derived from milk of transgenic rabbits and contains traces of rabbit protein. Before initiating 
treatment with Ruconest, patients should be queried about prior exposure to rabbits and signs and symptoms 
suggestive of an allergic reaction. 
 
Hypersensitivity reactions cannot be excluded.  
All patients must be closely monitored and carefully observed for any symptoms of hypersensitivity during 



4 
 

and after the administration period. Patients should be informed of the early signs of hypersensitivity 
reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension and 
anaphylaxis. If these symptoms occur after administration, they should alert their physician. 
In case of anaphylactic reactions or shock, emergency medical treatment should be administered. 
Although cross-reactivity between cow milk and rabbit milk is considered unlikely, the possibility of such a 
cross-reactivity in a patient who has evidence of clinical allergy to cow milk cannot be excluded and the 
patient should be observed for signs and symptoms of hypersensitivity following Ruconest administration. 
 
Sodium 
Each vial of Ruconest contains 19.5 mg of sodium. To be taken into consideration by patients on a controlled 
sodium diet. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. 
 
Scientific literature indicates an interaction of tissue-type plasminogen activator (tPA) and C1-INH 
containing medicinal products. Ruconest should not be administered simultaneously with tPA. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy and breast-feeding 
There is no experience with the use of Ruconest in pregnant and breast-feeding women. 
In one animal study reproductive toxicity was observed (see section 5.3). Ruconest is not recommended for 
use during pregnancy or breast-feeding, unless the treating physician judges the benefits to outweigh the 
possible risks.  
 
Fertility 
There are no data on the effects of Ruconest on male or female fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Based on the known pharmacology and adverse reaction profile of Ruconest, effects on the ability to drive 
and use machines are not expected. However, headache, vertigo and dizziness have been reported following 
the use of Ruconest, but may also occur as a result of an attack of HAE. Patients should be advised not to 
drive and use machines if they experience headache, vertigo or dizziness. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
One case of hypersensitivity was observed in clinical trials with Ruconest. The most common adverse 
reaction observed after administration of Ruconest is nausea. 
 
Tabulated lists of adverse reactions 
Adverse reactions obtained from clinical trials in patients with HAE following acute attack treatment with 
Ruconest are tabulated below. Adverse reactions were usually mild to moderate in severity. The incidence of 
adverse reactions was similar for all dose groups and did not increase upon repeated administration. 
 
The frequency of adverse reactions listed below 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),  
Not known (cannot be estimated from the available data). 
 



5 
 

System Organ Class Adverse reaction Frequency 

Nervous system disorders 

Headache Uncommon 

Vertigo Uncommon 

Hypoaesthesia Uncommon 

Dizziness Uncommon 

Ear and labyrinth disorders Auricular swelling Uncommon 

Respiratory, thoracic and 
mediastinal disorders 

Throat irritation Uncommon 

Gastrointestinal disorders 

Nausea  Common 

Diarrhoea Uncommon 

Abdominal discomfort Uncommon 

Oral paraesthesia Uncommon 

Skin and subcutaneous tissue 
disorders 

Urticaria Uncommon 

 
Paediatric population 
In the clinical development program, 37 children and adolescents (aged 5 to 17 years) with HAE were 
treated for 124 acute angioedema attacks. Frequency, type and severity of adverse reactions in children and 
adolescents were similar to those in adults. 
 
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.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other haematological agents, drugs used in hereditary angioedema, ATC code: 
B06AC04. 
 
The plasma protein C1-INH is the main regulator of activation of the contact and complement systems in 
vivo. HAE patients have a heterozygous deficiency of the plasma protein C1-INH. As a result they may 
suffer from uncontrolled activation of contact and complement systems, with formation of inflammatory 
mediators, which clinically becomes manifest as the occurrence of acute angioedema attacks. 
 
Conestat alfa, a recombinant human complement component 1 (C1) esterase inhibitor (rhC1-INH), is an 
analogue of human C1-INH and is obtained from the milk of rabbits expressing the gene coding for human 
C1-INH. The amino acid sequence of conestat alfa is identical to that of endogenous C1-INH. 
 
C1-INH exerts an inhibitory effect on several proteases (target proteases) of the contact and complement 
systems. The effect of conestat alfa on the following target proteases was assessed in vitro: activated C1s, 
kallikrein, factor XIIa and factor XIa. Inhibition kinetics were found to be comparable with those observed 
for plasma-derived human C1-INH. 
 



6 
 

The complement component (protein) C4, is a substrate for activated C1s. Patients with HAE have low 
levels of C4 in the circulation. As for plasma-derived C1-INH, the pharmacodynamic effects of conestat alfa 
on C4 show dose-dependent restoration of complement homeostasis in HAE patients at a plasma C1-INH 
activity level greater than 0.7 U/ml, which is the lower limit of the normal range. In HAE patients, Ruconest 
at a dose of 50 U/kg increases plasma C1-INH activity level to greater than 0.7 U/ml for approximately 
2 hours (see section 5.2). 
 
The efficacy and safety of Ruconest as a treatment of acute angioedema attacks in adult and adolescent 
patients with HAE has been evaluated in two double blind randomized placebo controlled and four open 
label clinical studies. The doses evaluated in the clinical studies ranged from a single vial of 2100 U 
(corresponding to 18-40 U/kg), to 50 and 100 U/kg. Efficacy of Ruconest as a treatment for acute 
angioedema attacks was demonstrated by significantly shorter time to beginning of relief of symptoms and 
time to minimal symptoms and few therapeutic failures. The table below shows the results (primary and 
secondary endpoints) of the two randomized controlled trials: 
 

 
Study 

 
Treatment  

Time (minutes) to  
beginning of relief 
median (95% CI) 

Time (minutes) to  
minimal symptoms 
median (95% CI) 

C1 1205 RCT 100 U/kg 
n =13 

68 (62, 132) 
p = 0.001 

245 (125, 270) 
p = 0.04 

50 U/kg 
n =12 

122 (72, 136) 
p < 0.001 

247 (243, 484) 
 

Saline 
n = 13 

258 (240, 495) 1101 (970, 1494) 

C1 1304 RCT 100 U/kg 
n =16 

62 (40, 75) 
p = 0.003 

480 (243, 723) 
p = 0.005 

Saline 
n = 16 

508 (70, 720) 
 

1440 (720, 2885) 
 

 
The results of the open label studies were consistent with the above findings and support the repeated use of 
Ruconest in the treatment of subsequent attacks of angioedema. 
 
In the randomized controlled trials 39/41 (95%) of patients treated with Ruconest reached time to beginning 
of relief within 4 hours. In an open label study 146/151 (97%) attacks treated with a single dose of 50 U/kg 
reached time to beginning of relief within 4 hours. An additional dose of 50 U/kg was administered for 
17/168 (10%) attacks. 
 
Paediatric population 
Children 
In an open label study with 20 children with HAE (aged 5 to 14 years), 64/67 (96%) attacks treated with a 
single dose of 50 U/kg reached time to beginning of relief within 4 hours. An additional dose of 50 U/kg was 
administered for 3/73 (4%) attacks. 
 
Adolescents 
Ten adolescent HAE patients (aged 13 to 17 years) were treated with 50 U/kg for 27 acute angioedema 
attacks, and 7 (aged 16 to 17 years) with 2100 U for 24 acute angioedema attacks.  
 
The efficacy and safety results in children and adolescents were consistent with those in adults. 
 
5.2 Pharmacokinetic properties 
 
Distribution 
No formal distribution studies have been performed. The distribution volume of conestat alfa was 
approximately 3 L, comparable to plasma volume.  
 
Biotransformation and elimination 



7 
 

Based on animal data, conestat alfa is cleared from the circulation by the liver via receptor-mediated 
endocytosis followed by complete hydrolysis/degradation. 
 
After administration of Ruconest (50 U/kg) to asymptomatic HAE patients, a Cmax of 1.36 U/ml was 
observed. The elimination half-life of conestat alfa was approximately 2 hours. 
 
Excretion 
There is no excretion, as conestat alfa is cleared from the circulation via receptor-mediated endocytosis 
followed by complete hydrolysis/degradation in the liver. 
 
Paediatric population 
Children 
After receiving a conestat alfa dose of 50 U/kg, a total of 18/20 children had concentrations of functional C1-
INH that were >70% of normal (the lower limit of the normal range) at the 5-minute and/or 2-4 hour post-
dose time points. The arithmetic mean functional C1-INH Cmax for the first attack was 123% of normal 
(range 62% to 168%) and the AUC0-3 was 171% of normal (range 95% to 244%). 
 
A population PK model shows that a dose of 50 U/kg will achieve concentrations of functional C1-INH that 
are >70% of normal in 96.0% of children aged 2 to ≤13 years and in 90.5% of children aged 2 to <5 years. 
 
5.3 Preclinical safety data 
 
Preclinical data do not indicate any safety concern for the use of conestat alfa in humans based on studies of 
safety pharmacology, single-dose toxicity, two-week sub-chronic toxicity and local tolerance in various 
animal species including rats, dogs, rabbits and cynomolgus monkeys. Genotoxic and carcinogenic potential 
is not expected. 
 
Embryofoetal studies in rat and rabbit; Daily single doses of vehicle or 625 U/kg/administration of conestat 
alfa were administered intravenously to mated rats and rabbits. In the study in rats there were no malformed 
foetuses in either the conestat alfa or the control group. In a rabbit embryotoxicity study an increase in the 
incidence of foetal cardiac vessel defects (1.12% in the treatment group versus 0.03% in historical controls) 
was observed for animals that were administered conestat alfa. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sucrose 
Sodium citrate (E331) 
Citric acid  
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
4 years. 
 
Reconstituted solution 
Chemical and physical in-use stability has been demonstrated for 48 hours between 5˚C and 25˚C. From a 
microbiological point of view, the medicinal product should be used immediately. If not used immediately, 
in-use storage times and conditions prior to use are the responsibility of the user and would normally not be 
longer than 24 hours at 2 to 8ºC, unless reconstitution has taken place in controlled and validated aseptic 



8 
 

conditions. 
 
6.4 Special precautions for storage 
 
Do not store above 25°C. 
Store in the original package in order to protect from light. 
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
2100 units of conestat alfa powder in a 25 ml vial (type 1 glass) with a stopper (siliconized chlorobutyl 
rubber) and a flip-off seal (aluminium and coloured plastic). 
Pack size of 1. 
 
6.6 Special precautions for disposal 
 
Each vial of Ruconest is for single use only. 
An aseptic technique should be used for reconstitution, combining and mixing the solutions. 
 
Reconstitution 
Each vial of Ruconest (2100 U) should be reconstituted with 14 ml water for injections. Water for injections 
should be added slowly to avoid forceful impact on the powder and mixed gently to minimise foaming of the 
solution. The reconstituted solution contains 150 U/ml conestat alfa and appears as a clear colourless 
solution. 
 
The reconstituted solution in each vial should be visually inspected for particulate matter and discoloration. 
A solution exhibiting particulates or discoloration should not be used. The medicinal product should be used 
immediately (see section 6.3). 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Pharming Group N.V.  
Darwinweg 24  
2333 CR Leiden  
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/641/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28 October 2010 
Date of latest renewal: 18 September 2015 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 



9 
 

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

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


10 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Ruconest 2100 Units powder and solvent for solution for injection. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Powder vial: 
One vial contains 2100 units of conestat alfa, corresponding to 2100 units per 14 ml after reconstitution, or a 
concentration of 150 units/ml.  
 
Conestat alfa is a recombinant analogue of the human C1 esterase inhibitor (rhC1-INH) produced by 
recombinant DNA technology in the milk of transgenic rabbits.  
 
1 unit of conestat alfa activity is defined as the equivalent of C1 esterase inhibiting activity present in 1 ml of 
pooled normal plasma. 
 
Excipient with known effect: 
Each powder vial contains approximately 19.5 mg sodium.  
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection. 
White to off-white powder. 
The solvent is a clear, colourless liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Ruconest is indicated for treatment of acute angioedema attacks in adults, adolescents, and children (aged 
2 years and above) with hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency. 
 
4.2 Posology and method of administration 
 
Ruconest should be initiated under the guidance and supervision of a physician experienced in the diagnosis 
and treatment of hereditary angioedema. 
 
Posology in adults, adolescents and children aged 2 years and above 
Body weight up to 84 kg  
- One intravenous injection of 50 U/kg body weight. 
 
Body weight of 84 kg or greater  
- One intravenous injection of 4200 U (2 vials). 
 
In the majority of cases, a single dose of Ruconest is sufficient to treat an acute angioedema attack.  
In case of an insufficient clinical response, an additional dose (50 U/kg body weight up to 4200 U) can be 
administered (see section 5.1). 
 
- In adults and adolescents an additional dose may be administered if the patient has not responded 

adequately after 120 minutes.  
- In children an additional dose may be administered if the patient has not responded adequately after 60 

minutes. 
 



11 
 

Not more than two doses should be administered within 24 hours. 
 
Dose calculation 
Determine the patient’s body weight. 
 
Body weight up to 84 kg  
- For patients up to 84 kg calculate the volume required to be administered according to the formula below: 
 

Volume to be 
administered (ml)  = 

body weight (kg) times 50 (U/kg) 
150 (U/ml) = 

body weight (kg) 
3 

 
Body weight of 84 kg or greater  
- For patients of 84 kg or above the volume required to be administered is 28 ml, corresponding to 4200 U 

(2 vials). 
 
Paediatric population  
Ruconest may be used in paediatric patients (2 years and older) at the same dose as in adults (50 U/kg body 
weight).  
The safety and efficacy of Ruconest in children less than 2 years old have not been established. No clinical 
data are available. 
 
Elderly (≥65 years old)  
Data in patients older than 65 years are limited.  
There is no rationale for patients older than 65 years to respond differently to Ruconest.  
 
Renal impairment 
No dose adjustment is necessary in patients with renal impairment since conestat alfa does not undergo renal 
clearance. 
 
Hepatic impairment 
There is no clinical experience with Ruconest in patients with hepatic impairment. Hepatic impairment may 
prolong the plasma half-life of conestat alfa, but this is not thought to be a clinical concern. No 
recommendation on a dose adjustment can be made. 
 
Method of administration 
For intravenous use. 
Ruconest must be administered by a healthcare professional until the patient (or caregiver) is competent to 
administer after having been properly trained and in agreement with the healthcare professional. 
For instructions on reconstitution of Ruconest before administration, see section 6.6. 
The required volume of the reconstituted solution should be administered as a slow intravenous injection 
over approximately 5 minutes. 
 
4.3 Contraindications 
 
• Known or suspected allergy to rabbits (see section 4.4)  
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number of the 
administered products should be clearly recorded. 
 
Conestat alfa is derived from milk of transgenic rabbits and contains traces of rabbit protein. Before initiating 
treatment with Ruconest, patients should be queried about prior exposure to rabbits and signs and symptoms 
suggestive of an allergic reaction.  



12 
 

 
Hypersensitivity reactions cannot be excluded.  
All patients must be closely monitored and carefully observed for any symptoms of hypersensitivity during 
and after the administration period. Patients should be informed of the early signs of hypersensitivity 
reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension and 
anaphylaxis. If these symptoms occur after administration, they should alert their physician. 
In case of anaphylactic reactions or shock, emergency medical treatment should be administered. 
Although cross-reactivity between cow milk and rabbit milk is considered unlikely, the possibility of such a 
cross-reactivity in a patient who has evidence of clinical allergy to cow milk cannot be excluded and the 
patient should be observed for signs and symptoms of hypersensitivity following Ruconest administration.  
 
Sodium 
Each vial of Ruconest contains 19.5 mg of sodium. To be taken into consideration by patients on a controlled 
sodium diet. 
 
Home-treatment and self-administration 
There are limited data on the use of this medicinal product in home- or self-administration. Potential risks 
associated with home-treatment are related to the administration itself as well as the handling of adverse 
reactions, particularly hypersensitivity. The decision on the use of home-treatment for an individual patient 
should be made by the treating physician, who should ensure that appropriate training is provided and the use 
reviewed at intervals. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. 
 
Scientific literature indicates an interaction of tissue-type plasminogen activator (tPA) and C1-INH 
containing medicinal products. Ruconest should not be administered simultaneously with tPA. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy and breast-feeding 
There is no experience with the use of Ruconest in pregnant and breast-feeding women. 
In one animal study reproductive toxicity was observed (see section 5.3). Ruconest is not recommended for 
use during pregnancy or breast-feeding, unless the treating physician judges the benefits to outweigh the 
possible risks.  
 
Fertility 
There are no data on the effects of Ruconest on male or female fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Based on the known pharmacology and adverse reaction profile of Ruconest, effects on the ability to drive 
and use machines are not expected. However headache, vertigo and dizziness have been reported following 
the use of Ruconest, but may also occur as a result of an attack of HAE. Patients should be advised not to 
drive and use machines if they experience headache, vertigo or dizziness. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
One case of hypersensitivity was observed in clinical trials with Ruconest. The most common adverse 
reaction observed after administration of Ruconest is nausea.  
 
Tabulated lists of adverse reactions 
Adverse reactions obtained from clinical trials in patients with HAE following acute attack treatment with 
Ruconest are tabulated below. Adverse reactions were usually mild to moderate in severity. The incidence of 
adverse reactions was similar for all dose groups and did not increase upon repeated administrations. 



13 
 

 
The frequency of adverse reactions listed below 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),  
Not known (cannot be estimated from the available data). 
 

System Organ Class Adverse reaction Frequency 

Nervous system disorders 

Headache Uncommon 

Vertigo Uncommon 

Hypoaesthesia Uncommon 

Dizziness Uncommon 

Ear and labyrinth disorders Auricular swelling Uncommon 

Respiratory, thoracic and 
mediastinal disorders 

Throat irritation Uncommon 

Gastrointestinal disorders 

Nausea  Common 

Diarrhoea Uncommon 

Abdominal discomfort Uncommon 

Oral paraesthesia Uncommon 

Skin and subcutaneous tissue 
disorders 

Urticaria Uncommon 

 
Paediatric population 
In the clinical development program, 37 children and adolescents (aged 5 to 17 years) with HAE were 
treated for 124 acute angioedema attacks. Frequency, type and severity of adverse reactions in children and 
adolescents were similar to those in adults. 
 
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.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other haematological agents, drugs used in hereditary angioedema, ATC code: 
B06AC04. 
 
The plasma protein C1-INH is the main regulator of activation of the contact and complement systems in 
vivo. HAE patients have a heterozygous deficiency of the plasma protein C1-INH. As a result they may 
suffer from uncontrolled activation of contact and complement systems, with formation of inflammatory 
mediators, which clinically becomes manifest as the occurrence of acute angioedema attacks. 
 



14 
 

Conestat alfa, a recombinant human complement component 1 (C1) esterase inhibitor (rhC1-INH), is an 
analogue of human C1-INH and is obtained from the milk of rabbits expressing the gene coding for human 
C1-INH. The amino acid sequence of conestat alfa is identical to that of endogenous C1-INH. 
 
C1-INH exerts an inhibitory effect on several proteases (target proteases) of the contact and complement 
systems. The effect of conestat alfa on the following target proteases was assessed in vitro: activated C1s, 
kallikrein, factor XIIa and factor XIa. Inhibition kinetics were found to be comparable with those observed 
for plasma-derived human C1-INH. 
 
The complement component (protein) C4, is a substrate for activated C1s. Patients with HAE have low 
levels of C4 in the circulation. As for plasma-derived C1-INH, the pharmacodynamic effects of conestat alfa 
on C4 show dose-dependent restoration of complement homeostasis in HAE patients at a plasma C1-INH 
activity level greater than 0.7 U/ml, which is the lower limit of the normal range. In HAE patients, Ruconest 
at a dose of 50 U/kg increases plasma C1-INH activity level to greater than 0.7 U/ml for approximately 
2 hours (see section 5.2). 
 
The efficacy and safety of Ruconest as a treatment of acute angioedema attacks in adult and adolescent 
patients with HAE has been evaluated in two double blind randomized placebo controlled and four open 
label clinical studies. The doses evaluated in the clinical studies ranged from a single vial of 2100 U 
(corresponding to 18-40 U/kg), to 50 and 100 U/kg. Efficacy of Ruconest as a treatment for acute 
angioedema attacks was demonstrated by significantly shorter time to beginning of relief of symptoms and 
time to minimal symptoms and few therapeutic failures. The table below shows the results (primary and 
secondary endpoints) of the two randomized controlled trials: 
 

 
Study 

 
Treatment  

Time (minutes) to  
beginning of relief 
median (95% CI) 

Time (minutes) to  
minimal symptoms 
median (95% CI) 

C1 1205 RCT 100 U/kg 
n =13 

68 (62, 132) 
p = 0.001 

245 (125, 270) 
p = 0.04 

50 U/kg 
n =12 

122 (72, 136) 
p < 0.001 

247 (243, 484) 
 

Saline 
n = 13 

258 (240, 495) 1101 (970, 1494) 

C1 1304 RCT 100 U/kg 
n =16 

62 (40, 75) 
p = 0.003 

480 (243, 723) 
p = 0.005 

Saline 
n = 16 

508 (70, 720) 
 

1440 (720, 2885) 
 

 
The results of the open label studies were consistent with the above findings and support the repeated use of 
Ruconest in the treatment of subsequent attacks of angioedema. 
 
In the randomized controlled trials 39/41 (95%) of patients treated with Ruconest reached time to beginning 
of relief within 4 hours. In an open label study 146/151 (97%) attacks treated with a single dose of 50 U/kg 
reached time to beginning of relief within 4 hours. An additional dose of 50 U/kg was administered for 
17/168 (10%) attacks. 
 
Paediatric population 
Children 
In an open label study with 20 children with HAE (aged 5 to 14 years), 64/67 (96%) attacks treated with a 
single dose of 50 U/kg reached time to beginning of relief within 4 hours. An additional dose of 50 U/kg was 
administered for 3/73 (4%) attacks. 
 
Adolescents 
Ten adolescent HAE patients (aged 13 to 17 years) were treated with 50 U/kg for 27 acute angioedema 
attacks, and 7 (aged 16 to 17 years) with 2100 U for 24 acute angioedema attacks.  
 



15 
 

The efficacy and safety results in children and adolescents were consistent with those in adults. 
 
5.2 Pharmacokinetic properties 
 
Distribution 
No formal distribution studies have been performed. The distribution volume of conestat alfa was 
approximately 3 L, comparable to plasma volume.  
 
Biotransformation and elimination 
Based on animal data, conestat alfa is cleared from the circulation by the liver via receptor-mediated 
endocytosis followed by complete hydrolysis/degradation. 
 
After administration of Ruconest (50 U/kg) to asymptomatic HAE patients, a Cmax of 1.36 U/ml was 
observed. The elimination half-life of conestat alfa was approximately 2 hours. 
 
Excretion 
There is no excretion, as conestat alfa is cleared from the circulation via receptor-mediated endocytosis 
followed by complete hydrolysis/degradation in the liver. 
 
Paediatric population 
Children 
After receiving a conestat alfa dose of 50 U/kg, a total of 18/20 children had concentrations of functional C1-
INH that were >70% of normal (the lower limit of the normal range) at the 5-minute and/or 2-4 hour post-
dose time points. The arithmetic mean functional C1-INH Cmax for the first attack was 123% of normal 
(range 62% to 168%) and the AUC0-3 was 171% of normal (range 95% to 244%). 
 
A population PK model shows that a dose of 50 U/kg will achieve concentrations of functional C1-INH that 
are >70% of normal in 96.0% of children aged 2 to ≤13 years and in 90.5% of children aged 2 to <5 years. 
 
5.3 Preclinical safety data 
 
Preclinical data do not indicate any safety concern for the use of conestat alfa in humans based on studies of 
safety pharmacology, single-dose toxicity, two-week sub-chronic toxicity and local tolerance in various 
animal species including rats, dogs, rabbits and cynomolgus monkeys. Genotoxic and carcinogenic potential 
is not expected. 
 
Embryofoetal studies in rat and rabbit; Daily single doses of vehicle or 625 U/kg/administration of conestat 
alfa were administered intravenously to mated rats and rabbits. In the study in rats there were no malformed 
foetuses in either the conestat alfa or the control group. In a rabbit embryotoxicity study an increase in the 
incidence of foetal cardiac vessel defects (1.12% in the treatment group versus 0.03% in historical controls) 
was observed for animals that were administered conestat alfa. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder vial: 
Sucrose 
Sodium citrate (E331) 
Citric acid  
 
Solvent vial: 
Water for injections 
 
6.2 Incompatibilities 



16 
 

 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
4 years. 
 
Reconstituted solution 
Chemical and physical in-use stability has been demonstrated for 48 hours between 5˚C and 25˚C. From a 
microbiological point of view, the medicinal product should be used immediately. If not used immediately 
in-use storage times and conditions prior to use are the responsibility of the user and would normally not be 
longer than 24 hours at 2 to 8ºC, unless reconstitution has taken place in controlled and validated aseptic 
conditions. 
 
6.4 Special precautions for storage 
 
Powder vial: 
Do not store above 25°C. 
Store in the original package in order to protect from light. 
 
Solvent vial: 
Do no store above 25°C. 
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Powder vial: 2100 units of conestat alfa powder in a vial (type 1 glass) with a stopper (siliconized 
chlorobutyl rubber) and a flip-off seal (aluminium and coloured plastic). 
 
Solvent vial: 20 ml of water for injections in a vial (type 1 glass) with a stopper (siliconized chlorobutyl 
rubber) and a flip-off seal (aluminium and coloured plastic). 
 
Administration kit: 
- 1 powder vial 
- 1 solvent vial 
- 2 vial adapters 
- 1 syringe 
- 1 infusion set with 35 cm tubing and 25G needle 
- 2 alcohol pads 
- 1 sterile non-woven pad 
- 1 self-adhesive plaster 
 
6.6 Special precautions for disposal and other handling 
 
Preparation and handling 
Each vial of Ruconest is for single use only. 
Ruconest is intended for intravenous administration after reconstitution with water for injections. An aseptic 
technique should be used for reconstitution, combining and mixing the solutions. 
 
Reconstitution 
1. Each vial of Ruconest (2100 U) should be reconstituted with 14 ml of solvent. 
2. Disinfect the rubber stoppers of the powder and solvent vials and put a vial adapter onto each solvent 

and powder vial until it snaps onto the vial neck. 
3. Attach the syringe to the adapter on the solvent vial and turn clockwise until it locks. Draw in 14 ml of 

solvent. Unlock the syringe from the adapter by turning counter clockwise and discard the vial with 



17 
 

adapter. 
4. Attach the syringe with solvent to the adapter on the powder vial and turn clockwise until it locks. The 

solvent should be added slowly to avoid forceful impact on the powder and mixed gently to minimise 
foaming of the solution. Leave the syringe on the adapter. Repeat steps 3 and 4 if you need to prepare 
a second solution (this requires a second kit). 

5. The reconstituted solution contains 150 U/ml conestat alfa and appears as a clear colourless solution. 
The reconstituted solution in each vial should be visually inspected for particulate matter and 
discoloration. A solution exhibiting particulates or discoloration should not be used. Small amounts of 
foam are acceptable. The medicinal product should be used immediately (see section 6.3). 

 
Administration 
1. Draw in the required volume of prepared solution. Never exceed 14 ml per syringe. Unlock the 

syringe(s) by turning counter clockwise and discard the vial with adapter. 
2. Attach the infusion set to the syringe and turn clockwise until it locks. Hold the syringe with the tip 

pointing upwards and gently press the plunger to fill the infusion set with the solution. 
3. Disinfect the injection site with an alcohol pad. Remove the needle cap from the needle of the infusion 

set and carefully insert the needle into the vein. 
4. Ensure that the tourniquet is released. Gently inject the solution into the vein – inject over about 5 

minutes. 
5. If two syringes were prepared: fold over the tubing to prevent backflow, unscrew the empty syringe 

from the infusion set (counter clockwise) and immediately replace it with the second syringe. Gently 
inject the solution of the second syringe.  

 
Disposal 
Please safely dispose of the used infusion set with needle, any unused solution, the syringe and the empty 
vial in an appropriate medical waste container as these materials may hurt others if not disposed of properly. 
Do not reuse equipment. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Pharming Group N.V.  
Darwinweg 24  
2333 CR Leiden  
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/641/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28 October 2010 
Date of latest renewal: 18 September 2015 
 
 
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.ema.europa.eu/


18 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

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

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND 

USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 

SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 



19 
 

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

 
Name and address of the manufacturers of the biological active substance 
 
Pharming Technologies B.V. 
Darwinweg 24 
2333 CR Leiden 
The Netherlands 
 
Broekman Institute B.V. 
Schoolstraat 21 
5711 CP Someren 
The Netherlands 
 
Sanofi-Chimie 
Route d’Avignon 
Aramon 30390 
France 
 
Name and address of the manufacturer responsible for batch release 
 
Pharming Technologies B.V. 
Darwinweg 24 
2333 CR Leiden 
The Netherlands 
 
 
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 



20 
 

(pharmacovigilance or risk minimisation) milestone being reached. 
 
• Additional risk minimisation measures 
 
Prior to launch of the product in each member state, the MAH shall agree the content and format of the 
educational material with the national competent authority (NCA). 
 
The MAH should ensure that, at launch, all Healthcare Professionals who are expected to prescribe Ruconest 
are provided with an educational pack. 
 
The educational pack should contain the following: 
• Summary of Product Characteristics and Package Leaflet for Ruconest 
• Educational material for the Healthcare Professional. 
• Educational material for non-Healthcare Professionals. 
• Diary to be given to patients before they receive Ruconest. 
• Copies of the patient card to be given to patients before they receive Ruconest. 
 
The educational material for the Healthcare Professional should include information on the following key 
elements: 
 
• That Ruconest should be initiated under the guidance and supervision of a physician experienced in 

the diagnosis and treatment of hereditary angioedema. 
 
• That patients treated with Ruconest should be monitored for clinical signs and symptoms of 

hypersensitivity during administration. Emergency medical treatment should be available immediately 
to be administered in case of anaphylactic reactions or shock. 

 
• The fact that Ruconest is derived from milk of transgenic rabbits and contains trace of rabbit proteins 

(Host -Related Impurities, HRI). 
 
• That Ruconest is contra indicated in all patients with known or suspected rabbit allergy. 
 
• That patients with clinical evidence of cow’s milk allergy may have antibodies cross reacting with the 

rabbit milk impurities in Ruconest. 
 
• The need to inform patients about the early signs of hypersensitivity reactions including hives, 

generalised urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis, and that they 
should alert their physician if these symptoms occur. 

 
• The potential risk of an immune complex-mediated type III hypersensitivity reaction due to the 

formation of antibodies directed against HRI. Advice about the immunogenicity laboratory testing 
program for detecting these antibodies for following up suspected immune complex-mediated disease, 
and about the procedure to follow for the collection and shipment of a blood sample to the company’s 
central laboratory. This testing should be provided free of charge. 

 
• The risk of formation of anti-C1-INH antibodies and therefore the potential risk of formation of 

neutralising antibodies. Advice about the immunogenicity laboratory testing program for these 
antibodies provided by the company for following up suspected emergence of neutralising antibodies 
and information about the procedure to follow for the collection and shipment of a blood sample to the 
company’s central laboratory. This testing should be provided free of charge. 

 
• There are limited data on the use of this medicinal product in home or self-administration. 
 
• The decision on the use of home treatment for an individual patient should be made by the treating 

physician. 
 



21 
 

• Use of Ruconest is only approved in acute attacks of hereditary angioedema. 
 
• It is the responsibility of the physician to provide the patient or a caregiver with instructions and 

training on administration outside of a clinic setting. 
 
• The training to be provided should address the following elements 

- Precaution for storage 
- Dose calculation and indication (i.e. only acute HAE attacks) 
- Preparation of one dose of Ruconest (50 U/kg, up to 4200 U) by reconstituting one or two vials 
- Method of reconstitution of each powder vial 
- Technique of intravenous injection 
- Guidance on use of a second dose of Ruconest 
- Instruction to immediately seek medical attention in case of failure to gain venous access, in case 

of lack of efficacy, in the event of any adverse reaction including hypersensitivity, or after self-
administering Ruconest for an acute laryngeal HAE attack. 

- Instruction in handling possible adverse drug reactions including an acute hypersensitivity reaction 
- Information on the need to keep a diary to document each treatment administered at home and to 

bring it at each visit. The information recorded should include: 
- Date and time of treatment 
- Batch number and dose 
- Response to treatment 
- Any adverse events 

 
• It is the responsibility of the physician to verify that all the necessary skills have been acquired by the 

non-Healthcare Professional and that Ruconest may be safely and effectively administered outside of a 
Healthcare Professional setting. 

 
• The existence of a postmarketing registry in which healthcare professionals are encouraged to enter 

patients. 
 
The educational material for non-Healthcare Professionals should include information on the following key 
elements: 
 
• There are limited data on the use of this medicinal product in home or self-administration. 
 
• For some patients the physician may decide that Ruconest may be administered outside of a clinic 

setting by a non-Healthcare Professional such as a family member or by self-administration. 
 
• Use of Ruconest is only approved in acute attacks of hereditary angioedema. 
 
• Necessary skills have to be acquired by non-Healthcare Professionals before Ruconest may be safely 

and effectively administered outside of a Healthcare Professional setting. 
 
• A physician will provide training on the following elements: 

- Precaution for storage 
- Dose calculation and indication (i.e. only acute HAE attacks) 
- Preparation of one dose of Ruconest (50 U/kg, up to 4200 U) by reconstituting one or two vials 
- Method of reconstitution of each powder vial 
- Technique of intravenous injection 
- Method and rate of administration of one dose of Ruconest 
- Guidance on use of a second dose of Ruconest 
- Instruction to immediately seek medical attention in case of failure to gain venous access, in case 

of lack of efficacy, in the event of any adverse reaction including hypersensitivity, or after self-
administering Ruconest for an acute laryngeal HAE attack.  

- Information on the need to keep a diary to document each treatment administered at home and to 
bring it at each visit. The information collected should include: 



22 
 

- Date and time of treatment 
- Batch number and dose 
- Response to treatment 
- Any adverse events 

 
The patient diary should contain the following key elements: 
• Date and time of treatment 
• Batch number and dose 
• Response to treatment 
• Any adverse events 
 
The patient card should contain the following key elements: 
• That they are receiving Ruconest for treatment of an acute attack of hereditary angioedema. 
• That Ruconest is derived from milk of transgenic rabbits and contains trace of rabbit proteins. 
• The importance of monitoring for clinical signs and symptoms of hypersensitivity and that patients 

should immediately seek medical care if they develop such symptoms during or after receiving 
Ruconest.  

• That they should be asked to carry the card and always show it to any Healthcare Professional treating 
them for acute attacks of hereditary angioedema. 

 
  



23 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



24 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



25 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
VIAL CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ruconest 2100 Units powder for solution for injection 
conestat alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial contains 2100 U of conestat alfa, corresponding to 2100 U/14 ml after reconstitution, or a 
concentration of 150 U/ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
Sucrose, 
Sodium Citrate (E331), 
Citric Acid. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection  
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For 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 
 
 
 
 
 



26 
 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Pharming Group N.V. 
Darwinweg 24 
2333 CR Leiden 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/641/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ruconest 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



27 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
ADMINISTRATION KIT OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ruconest 2100 Units powder and solvent for solution for injection 
conestat alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One powder vial contains 2100 U of conestat alfa, corresponding to 2100 U/14 ml after reconstitution, or a 
concentration of 150 U/ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients:  
Sucrose,  
Sodium Citrate (E331),  
Citric Acid. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection 
 
One administration kit contains: 
 
1 powder vial  
1 solvent vial  
2 vial adapters 
1 syringe 
1 infusion set with needle 
2 alcohol pads 
1 sterile non-woven pad 
1 adhesive plaster 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use. 
For single 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. 
 
 
 



28 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. 
Keep the powder vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Pharming Group N.V. 
Darwinweg 24 
2333 CR Leiden 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/641/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ruconest 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



29 
 

 
PC: 
SN: 
NN: 
 
  



30 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
ADMINISTRATION KIT VIAL CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ruconest 2100 Units powder for solution for injection 
conestat alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial contains 2100 U of conestat alfa, corresponding to 2100 U/14 ml after reconstitution, or a 
concentration of 150 U/ml. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
Sucrose, 
Sodium Citrate (E331), 
Citric Acid. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection  
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For 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 
 
Do not store above 25°C. 
Keep the vial in the original package in order to protect from light. 



31 
 

 
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 
 
Pharming Group N.V. 
Darwinweg 24 
2333 CR Leiden 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/641/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ruconest 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN: 
 



32 
 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Ruconest  2100 Units powder for solution for injection 
conestat alfa  
For IV use.  
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2100 U of conestat alfa. 
After reconstitution with 14 ml water for injections, the solution contains 150 U conestat alfa per ml. 
 
 
6. OTHER 
 
 



33 
 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SOLVENT VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Ruconest 
Water for injections 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
20 ml 
 
 
6. OTHER 
 
 
  



34 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



35 
 

Package leaflet: Information for the patient 
 

Ruconest 2100 Units powder for solution for injection  
conestat alfa 

 
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. 
- 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. This includes any possible side effects not listed in this 

leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Ruconest is and what it is used for 
2. What you need to know before you use Ruconest 
3. How to use Ruconest 
4. Possible side effects 
5. How to store Ruconest 
6. Contents of the pack and other information 
 
 
1. What Ruconest is and what it is used for 
 
Ruconest contains conestat alfa as the active substance. Conestat alfa is a recombinant (not blood-derived) 
form of human C1 inhibitor (rhC1-INH).  
 
Ruconest is to be used by adults, adolescents, and children (aged 2 years and above) with a rare inherited 
blood disorder, called Hereditary Angioedema (HAE). These patients have a shortage of the C1 inhibitor 
protein in their blood. This can lead to repeated attacks of swelling, pain in the abdomen, difficulty breathing 
and other symptoms. 
 
The administration of Ruconest is to resolve the shortage of C1 inhibitor and will lead to reduction of 
symptoms of an acute attack of HAE. 
 
 
2. What you need to know before you use Ruconest  
 
Do not use Ruconest 
• If you are or think you are allergic to rabbits. 
• If you are allergic to conestat alfa or any of the other ingredients of this medicine (listed in section 6). 
 
Warnings and precautions  
Talk to your doctor before using Ruconest. 
If you experience allergic reactions e.g. hives, rash, itching, dizziness, wheezing, difficulty breathing or your 
tongue swells up following the administration of Ruconest, you should seek emergency medical assistance so 
that symptoms of your allergic reaction can be treated urgently. 
 
Children and adolescents 
Do not give this medicine to children under 2 years old. Ruconest has not been studied in children younger 
than 5 years of age. Your doctor will determine whether treatment of your child with Ruconest is 
appropriate. Additional monitoring of your child for symptoms of allergic reactions during and after 
administration is needed. 
 



36 
 

Other medicines and Ruconest 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
If you are receiving tissue type plasminogen activator as acute treatment for blood clots, you should not be 
treated with Ruconest at the same time. 
 
Pregnancy and breast-feeding 
It is not recommended to use Ruconest during pregnancy or breast-feeding.  
If you plan becoming pregnant, discuss with your doctor before starting to use Ruconest. 
 
Driving and using machines 
Do not drive or use machinery if you feel dizzy or suffer from headache after using Ruconest.  
 
Ruconest contains sodium (19.5 mg per vial) 
This should be taken into consideration by patients on a controlled sodium diet. 
 
 
3. How to use Ruconest 
 
Ruconest will be initiated by a doctor who is specialised in the diagnosis and treatment of hereditary 
angioedema. 
 
Ruconest will be given to you directly into a vein over a period of approximately 5 minutes by your doctor or 
by a nurse. Your dose, up to 2 vials, will be worked out based on your weight. 
 
Most of the time a single dose is sufficient. Your doctor may decide that an additional dose should be 
administered if your symptoms do not improve after 120 minutes (for adults and adolescents) or 60 minutes 
(for children). No more than 2 doses should be given within 24 hours. 
 
The instructions for use are clearly described in the doctor’s information leaflet and are attached. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
If your symptoms get worse and/or you develop a rash, tingling, difficulty breathing or your face or tongue 
swells up, get medical attention immediately. This may indicate that you have developed an allergy to 
Ruconest. 
 
Some side effects may occur during treatment with Ruconest:  
Common: may affect up to 1 in 10 people 
• Nausea 
 
Uncommon: may affect up to 1 in 100 people 
• Abdominal pain, diarrhoea 
• Sensation of tingling, prickling or numbness in the mouth 
• Headache, dizziness 
• Reduced sense of touch or sensation in skin or limbs 
• Throat irritation 
• Hives 
• Swelling of the ears or the area around the ears  
 
Reporting of side effects 
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in the leaflet. 



37 
 

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 Ruconest 
 
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 carton and on the label of the vial after 
EXP. The expiry date refers to the last day of that month. 
 
Do not store above 25°C. 
Store in the original package in order to protect from light. 
  
Before Ruconest can be administered, it needs to be dissolved in water for injections, by a healthcare 
professional. 
Once reconstituted, the product should be used immediately.  
Do not use this medicine if you notice particles in the solution or if the solution is discoloured. 
 
 
6. Contents of the pack and other information 
 
What Ruconest contains  
The active substance is conestat alfa. Each vial contains 2100 units of conestat alfa, corresponding to 2100 
units per 14 ml after reconstitution, or a concentration of 150 units/ml. 
 
The other ingredients are sucrose, sodium citrate (E331) and citric acid. 
 
What Ruconest looks like and contents of the pack 
Ruconest is presented as a single glass vial containing a white to off-white powder for solution for injection. 
After dissolving the powder in water for injections, the solution is clear and colourless. 
Ruconest is supplied in a carton box containing one vial. 
 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder: 
Pharming Group N.V. 
Darwinweg 24 
2333 CR Leiden 
The Netherlands 
 
Manufacturer: 
Pharming Technologies B.V. 
Darwinweg 24 
2333 CR Leiden 
The Netherlands 
 
 
This leaflet was last revised in  
 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
------------------------------------------------------------------------------------------------------------------------------- 
 

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


38 
 

The following information is intended for healthcare professionals only: 
 
 
POSOLOGY AND METHOD OF ADMINISTRATION 
 
Posology 
Body weight up to 84 kg 
- One intravenous injection of 50 U/kg body weight.  
Body weight of 84 kg or greater  
- One intravenous injection of 4200 U (two vials). 
 
In the majority of cases a single dose of Ruconest is sufficient to treat an acute angioedema attack.  
In case of an insufficient clinical response, an additional dose (50 U/kg body weight up to 4200 U) can be 
administered. 
Not more than two doses should be administered within 24 hours. 
 
Dose calculation 
Determine the patient’s body weight. 
Body weight up to 84 kg  
- For patients up to 84 kg calculate the volume required to be administered according to the formula below: 
 

Volume to be 
administered (ml)  = 

body weight (kg) times 50 (U/kg) 
150 (U/ml) = 

body weight (kg) 
3 

 
Body weight of 84 kg or greater  
- For patients of 84 kg or above the volume required to be administered is 28 ml, corresponding to 4200 U 

(2 vials). 
 
Reconstitute each vial with 14 ml water for injections (see section on Reconstitution below). 
The reconstituted solution in each vial contains 2100 U conestat alfa at 150 U/ml. 
 
The required volume of the reconstituted solution should be administered as a slow intravenous injection 
over approximately 5 minutes. 
 
 
SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING 
 
Each vial of Ruconest is for single use only. 
An aseptic technique should be used for reconstitution, combining and mixing the solutions. 
 
Reconstitution 
Each vial of Ruconest (2100 U) should be reconstituted with 14 ml water for injections. Water for injections 
should be added slowly to avoid forceful impact on the powder and mixed gently to minimise foaming of the 
solution. The reconstituted solution in each vial contains 2100 U conestat alfa at 150 U/ml and appears as a 
clear colourless solution. 
 
The reconstituted solution in each vial should be inspected for particulate matter and discoloration. A 
solution exhibiting particulates or discoloration should not be used. The medicinal product should be used 
immediately.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 



39 
 

Package leaflet: Information for the patient 
 

Ruconest 2100 Units powder and solvent for solution for injection  
conestat alfa 

 
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. 
- 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. This includes any possible side effects not listed in this 

leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Ruconest is and what it is used for 
2. What you need to know before you use Ruconest 
3. How to use Ruconest 
4. Possible side effects 
5. How to store Ruconest 
6. Contents of the pack and other information 
 
 
1. What Ruconest is and what it is used for 
 
Ruconest contains conestat alfa as the active substance. Conestat alfa is a recombinant (not blood-derived) 
form of human C1 inhibitor (rhC1-INH).  
 
Ruconest is to be used by adults, adolescents, and children (aged 2 years and above) with a rare inherited 
blood disorder, called Hereditary Angioedema (HAE). These patients have a shortage of the C1 inhibitor 
protein in their blood. This can lead to repeated attacks of swelling, pain in the abdomen, difficulty breathing 
and other symptoms. 
 
The administration of Ruconest is to resolve the shortage of C1 inhibitor and will lead to reduction of 
symptoms of an acute attack of HAE. 
 
 
2. What you need to know before you use Ruconest  
 
Do not use Ruconest 
• If you are or think you are allergic to rabbits. 
• If you are allergic to conestat alfa or any of the other ingredients of this medicine (listed in section 6). 
 
Warnings and precautions  
Talk to your doctor before using Ruconest. 
If you experience allergic reactions e.g. hives, rash, itching, dizziness, wheezing, difficulty breathing or your 
tongue swells up following the administration of Ruconest, you should seek emergency medical assistance so 
that symptoms of your allergic reaction can be treated urgently. 
 
Children and adolescents 
Do not give this medicine to children under 2 years old. Ruconest has not been studied in children younger 
than 5 years of age. Your doctor will determine whether treatment of your child with Ruconest is 
appropriate. Additional monitoring of your child for symptoms of allergic reactions during and after 
administration is needed. 
 



40 
 

Other medicines and Ruconest 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
If you are receiving tissue type plasminogen activator as acute treatment for blood clots, you should not be 
treated with Ruconest at the same time. 
 
Pregnancy and breast-feeding 
It is not recommended to use Ruconest during pregnancy or breast-feeding.  
If you plan becoming pregnant, discuss with your doctor before starting to use Ruconest. 
 
Driving and using machines 
Do not drive or use machinery if you feel dizzy or suffer from headache after using Ruconest.  
 
Ruconest contains sodium (19.5 mg per vial) 
This should be taken into consideration by patients on a controlled sodium diet. 
 
 
3. How to use Ruconest 
 
Ruconest will be initiated by a doctor who is specialised in the diagnosis and treatment of hereditary 
angioedema. 
 
Ruconest must be administered by a healthcare professional until you or your caregiver are properly trained 
and capable to administer Ruconest. 
 
Always use this medicine exactly as described in this leaflet or as your doctor or nurse have told you. Check 
with your doctor or nurse if you are not sure.  
 
Ruconest is administered into a vein over about 5 minutes. Your dose will be worked out based on your body 
weight.  
 
Most of the time a single dose is sufficient. An additional dose could be administered if your symptoms do 
not improve after 120 minutes (for adults and adolescents) or 60 minutes (for children). No more than 
2 doses, calculated according to step 7, should be given within 24 hours. 
 
You or your caregiver may inject Ruconest only after receiving adequate instructions and training from your 
doctor or nurse. 
 
Instructions for use 
Do not mix or administer Ruconest with other medicines or solutions. The following describes how Ruconest 
solution must be prepared and administered. 
 
Before you begin 
• Ensure the kit package is complete and contains all components listed in section 6 of this leaflet. 
• In addition to the kit, the following is required: 

- a tourniquet 
- plaster for securing the needle 

• Inspect vials and other components. 
- All vials must be sealed with plastic lid and aluminium cap and without visible damage, such as 

cracks in glass. 
- Check the expiry date. Never use any kit component after the expiry date stated on the big outer 

carton. 
Within a single kit box, different components may have different expiry dates. The expiry date on 
the outer carton reflects the date of the component with the shortest shelf-life.  

• Allow the number of powder and solvent vials required according to step 1, to reach room 
temperature. 



41 
 

 
 
Preparation of solution 
Step 1: Cleaning and other requirements 
• Wash your hands carefully. 
• Put the powder and solvent vials required on a flat and clean surface. 

- body weight 42 kg or less: 1 powder and 1 solvent vial 
- body weight over 42 kg: 2 powder and 2 solvent vials 

• Put the vial adapters on the work surface. Do not remove the adapter packaging.  
- 2 adapters if 1 powder and 1 solvent vial is required 
- 4 adapters if 2 powder and 2 solvent vials are required 

• Put the syringe(s) on the work surface. Do not remove the syringe packaging. 
- 1 syringe if 1 powder and 1 solvent vial is required 
- 2 syringes if 2 powder and 2 solvent vials are required 

 
Step 2: Disinfection of vial stoppers 
• Remove the plastic flip-off cap from the powder and solvent vials. 
• Use one alcohol pad to disinfect all vial stoppers and wait for at least 30 seconds until the stoppers 

have dried. 

 
 
• After disinfection, do not touch the stoppers with your fingers or anything else. 
 
Step 3: Mounting of adapters on vials 
• Take a packaged adapter in one hand and remove the lid. The adapter must remain in its plastic 

packaging.  
• Put the adapter onto a powder vial, piercing the stopper, until it snaps onto the vial neck. 

 
 
• Leave the packaging on the adapter until you attach the syringe in steps 4 and 5. 
• Repeat the above steps for mounting an adapter on the solvent vial. All adapters supplied with the kit 

are identical. 



42 
 

• If you need to use a second powder and solvent vial, repeat the above steps. 
 
Step 4: Drawing up solvent 
• Take a sterile syringe out of its packaging. 
• Remove the packaging from the adapter on the solvent vial. 

 
 
• Hold the adapter with one hand. With the other hand, attach the syringe and secure by turning it 

clockwise until it stops. 

 
 
• Turn the whole – solvent vial with adapter and syringe – upside down. While keeping it vertical, 

slowly draw in 14 ml solvent. 
If air bubbles appear, minimise as far as possible by gently tapping the syringe and applying gentle 
pressure by pushing the plunger into the syringe. Continue to fill the syringe with 14 ml solvent. 

 
 
• Unlock the syringe from the adapter by turning counter-clockwise. 

 
 



43 
 

• Leave the remainder of the solvent in the vial and discard the vial. 
• Place the syringe on the work surface, taking care not to touch the surface or any other object with the 

syringe tip. 
 
Step 5: Adding solvent to powder and dissolving 
• Remove the packaging from the adapter on the powder vial. 
• Take the syringe with solvent that you prepared in step 4. 
• Hold the adapter with the other hand and attach the syringe. Secure the syringe by turning it clockwise 

until it stops.  
• Push the solvent slowly, in a single motion, into the powder vial in order to minimise foaming. 
 

 
 
• Leave the syringe on the adapter and gently swirl the vial for approximately half a minute. Do not 

shake. 
After swirling, leave the vial on the surface for several minutes until the solution has become clear. If 
undissolved powder is still present, repeat the procedure. 

 
 
• Repeat steps 4 and 5 if you need to prepare a second solution. 
 
Step 6: Check prepared solutions 
• Check whether the powder in the vial(s) has dissolved completely and the plunger is completely 

pushed down in the syringe. 
• After the powder has dissolved, the solution should be clear and colourless. 
• Do not use the prepared solution if it is cloudy, contains particles or has changed colour. Inform your 

healthcare professional if this occurs. Small amounts of foam are acceptable. 

 
 



44 
 

Step 7: Drawing up prepared solution 
• Calculate the millilitres of prepared solution to be injected. 

Body weight Millilitres of prepared solution to be injected 
below 84 kg Body weight in kg divided by three 
84 kg and above  28 ml 

 
• Draw in the volume of prepared solution, while keeping the syringe in the vertical position. If you 

have prepared: 
- one vial with solution, draw up the volume as calculated 
- two vials and your body weight is below 84 kg, draw up in a similar way: 

a) 14 ml from the first vial 
b) from the second vial, the difference between your calculated volume and the 14 ml from the 

first vial 
- two vials and your body weight is 84 kg or more, draw up 14 ml from each vial into each syringe 
If air bubbles appear, minimise as far as possible by gently tapping the syringe and applying gentle 
pressure by pushing the plunger into the syringe. Continue to fill the syringe with the volume required. 

 
 

• Never exceed the volume of 14 ml per syringe. 
• Unlock the syringe(s) by turning it counter-clockwise and discard the vial(s) with adapter. 
• Place the syringe(s) on the work surface, taking care not to touch the surface or any other object with 

the syringe tip. 
 
Step 8: Check prepared syringes 
• Recheck that the volume in the syringe(s) you prepared in step 7 is correct. 
 
Administration into a vein 
It is very important that the prepared solution is injected directly into a vein and not into an artery or the 
surrounding tissue. 
Inject the Ruconest solution immediately after preparation, preferably while seated. 
 
Step 9: Required components 
• Check that all required components are on the work surface: 

- 1 or 2 syringes with prepared solution 
- 1 infusion set with 25G needle 
- 1 alcohol pad 
- 1 sterile non-woven pad 
- 1 self-adhesive plaster 
- 1 tourniquet 
- 1 plaster for securing the needle 

 
Step 10: Preparation of the infusion set 
• Remove the screw cap from the end of the infusion set. This is the end which has no needle. 
• Hold this end with one hand, attach the syringe tip end and secure by turning clockwise until it stops. 
• Hold the syringe with the tip pointing upwards. Gently press the syringe plunger to carefully fill the 



45 
 

infusion set with the prepared solution. 

 
 
• Check that no air is present in the syringe, infusion tube or the needle. 
 
Step 11: Preparing the injection site 
• Position the tourniquet above the injection site – preferably the middle part of the upper arm. Tighten 

it to compress the vein. This should be boosted by tightening your fist. 
• Feel, with your other hand, for an appropriate vein. 
• Disinfect the injection site thoroughly with an alcohol pad and let the skin dry. 

 
 
Step 12: Administration of the prepared solution  
• Remove the needle cap. 
• Carefully insert the needle of the infusion set, at the flattest possible angle, into the vein. 

 
 
• Secure the needle by applying the plaster, around 7 cm long, over the wings of the needle. 
• Carefully pull back the syringe plunger slightly until you see blood being drawn into the tubing, to 

ensure that the needle is in the vein.  
• Release the tourniquet. 
• If there is no blood in the tubing, remove the needle, repeat all steps from beginning of step 11 and 

reposition the needle. 
• If blood is present, gently inject the solution into the vein, as shown in the picture. Inject over about 

5 minutes. 



46 
 

 
 
• If you have prepared two syringes: 

- fold over the tubing near the connector of the infusion set to prevent backflow 
- unscrew the empty syringe from the infusion set and immediately replace it with the second syringe 

 
 

- unfold the tubing and gently inject this solution, similar to the first syringe 
 
Step 13: After administration 
• Carefully remove the plaster for securing the needle and withdraw the needle from the vein. 
• Immediately after removing the needle, press the sterile pad on the injection site for a few minutes to 

reduce bleeding. 

 
 
• Next, put the self-adhesive plaster on the injection site. 
• Fold down the yellow protection cap over the needle. 
• Safely dispose of the used infusion set with needle, any unused solution, the syringe and the empty 

vial in an appropriate medical waste container as these materials may hurt others if not disposed of 
properly. Do not reuse equipment. 

 
Step 14: Documenting the administration 
Please record (e.g. in your diary): 
• date and time of the administration 
• the batch number written on the label of the powder vial 
 
If you use more Ruconest than you should 
Contact your doctor or nearest hospital if this occurs.  
 
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. 
 
If your symptoms get worse and/or you develop a rash, tingling, difficulty breathing or your face or tongue 



47 
 

swells up, get medical attention immediately. This may indicate that you have developed an allergy to 
Ruconest. 
 
Some side effects may occur during treatment with Ruconest:  
Common: may affect up to 1 in 10 people 
• Nausea 
 
Uncommon: may affect up to 1 in 100 people 
• Abdominal pain, diarrhoea 
• Sensation of tingling, prickling or numbness in the mouth 
• Headache, dizziness 
• Reduced sense of touch or sensation in skin or limbs  
• Throat irritation 
• Hives 
• Swelling of the ears or the area around the ears 
 
Reporting of side effects 
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in the 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 Ruconest 
 
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 carton and on the label of the vial after 
EXP. The expiry date refers to the last day of that month. 
 
Do not store above 25°C. 
Keep the powder vial in the vial carton in order to protect from light. 
  
Before Ruconest can be administered, the powder needs to be dissolved in the solvent included in the 
package (see section 3). 
Once reconstituted, the product should be used immediately.  
Do not use this medicine if, after dissolving, you notice particles in the solution or if the solution is 
discoloured. Small amounts of foam are acceptable. 
 
 
6. Contents of the pack and other information 
 
What Ruconest contains  
Powder vial: 
• The active substance is conestat alfa. Each powder vial contains 2100 units of conestat alfa, 

corresponding to 2100 units per 14 ml after reconstitution, or a concentration of 150 units/ml. 
• The other ingredients of the powder are sucrose, sodium citrate (E331) and citric acid. 
 
Solvent vial: 
• The ingredient of the solvent is water for injections. 
 
What Ruconest looks like and contents of the pack 
Ruconest is presented as a single glass vial containing a white to off-white powder for solution for injection 
together with one glass vial containg a clear, colourless solvent to dissolve the powder. After dissolving the 
powder in water for injections, the solution is clear and colourless. 
 
Ruconest is supplied with an administration kit in a carton box containing: 



48 
 

- 1 vial of 2100 U powder 
- 1 vial of 20 ml solvent 
- 2 vial adapters 
- 1 syringe 
- 1 infusion set with 35 cm tubing and 25G needle 
- 2 alcohol pads 
- 1 sterile non-woven pad 
- 1 self-adhesive plaster 
 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder: 
Pharming Group N.V. 
Darwinweg 24 
2333 CR Leiden 
The Netherlands 
 
Manufacturer: 
Pharming Technologies B.V. 
Darwinweg 24 
2333 CR Leiden 
The Netherlands 
 
 
This leaflet was last revised in  
 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
------------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
 
POSOLOGY AND METHOD OF ADMINISTRATION 
 
Posology 
Body weight up to 84 kg 
- One intravenous injection of 50 U/kg body weight.  
Body weight of 84 kg or greater  
- One intravenous injection of 4200 U (two vials). 
 
In the majority of cases a single dose of Ruconest is sufficient to treat an acute angioedema attack.  
In case of an insufficient clinical response, an additional dose (50 U/kg body weight up to 4200 U) can be 
administered. 
Not more than two doses should be administered within 24 hours. 
 
Dose calculation 
Determine the patient’s body weight. 
Body weight up to 84 kg  
- For patients up to 84 kg calculate the volume required to be administered according to the formula below: 
 

Volume to be 
administered (ml)  = 

body weight (kg) times 50 (U/kg) 
150 (U/ml) = 

body weight (kg) 
3 

 

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


49 
 

Body weight of 84 kg or greater  
- For patients of 84 kg or above the volume required to be administered is 28 ml, corresponding to 4200 U 

(2 vials). 
 
Reconstitute each vial with 14 ml water for injections (see section on Reconstitution below). 
The reconstituted solution in each vial contains 2100 U conestat alfa at 150 U/ml. 
 
The required volume of the reconstituted solution should be administered as a slow intravenous injection 
over approximately 5 minutes. 
 
 
SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING 
 
Preparation and handling 
Each vial of Ruconest is for single use only. 
Ruconest is intended for intravenous administration after reconstitution with water for injections. An aseptic 
technique should be used for reconstitution, combining and mixing the solutions. 
 
Reconstitution 
1. Each vial of Ruconest (2100 U) should be reconstituted with 14 ml water for injections. 
2. Disinfect the rubber stoppers of the powder and solvent vials and put a vial adapter onto each solvent 

and powder vial until it snaps onto the vial neck. 
3. Attach a syringe to the adapter on a solvent vial and turn clockwise until it locks. Draw in 14 ml of 

solvent. Unlock the syringe from the adapter by turning counter clockwise. Repeat this step if two 
powder vials need to be reconstituted. 

4. Attach a syringe with solvent to the adapter on a powder vial and turn clockwise until it locks. Water 
for injections should be added slowly to avoid forceful impact on the powder and mixed gently to 
minimise foaming of the solution. Leave the syringe on the adapter. Repeat this step if a second 
powder vial needs to be reconstituted. 

5. The reconstituted solution in each vial contains 150 U/ml and appears as a clear colourless solution. 
The reconstituted solution in each vial should be inspected for particulate matter and discoloration. A 
solution exhibiting particulates or discoloration should not be used. Small amounts of foam are 
acceptable. The medicinal product should be used immediately.  

 
Administration 
1. Draw in the required volume of prepared solution. Never exceed 14 ml per syringe. Unlock the 

syringe(s) by turning counter clockwise and discard vial(s) with adapter 
2. Attach the infusion set to the syringe and turn clockwise until it locks. Hold the syringe with the tip 

pointing upwards and gently press the plunger to fill the infusion set with the solution 
3. Disinfect the injection site with an alcohol pad. Remove the needle cap from the needle of the infusion 

set and carefully insert the needle into the vein. 
4. Ensure that the tourniquet is released. Gently inject the solution into the vein – inject over about 5 

minutes. 
5. If two syringes were prepared: fold over the tubing to prevent backflow, unscrew the empty syringe 

from the infusion set (counter clockwise) and immediately replace it with the second syringe. Gently 
inject the solution of the second syringe.  

 
Disposal 
Please safely dispose of the used infusion set with needle, any unused solution, the syringe and the empty 
vial in an appropriate medical waste container as these materials may hurt others if not disposed of properly. 
Do not reuse equipment. 


	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