ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Soliris 300 mg concentrate for solution for infusion
2.
2.1
General description
Eculizumab is a humanised monoclonal IgG
2/4κ
antibody produced in NS0 cell line by recombinant
DNA technology.
2.2 Qualitative and quantitative composition
Each vial of 30 ml contains 300 mg of eculizumab (10 mg/ml).
After dilution, the final concentration of the solution to be infused is 5mg/ml.
Excipients: Sodium (5.00 mmol per dose (1 vial))
For a full list of excipients, see section 6.1.
3.
Concentrate for Solution for Infusion.
Clear, colorless, pH 7.0 solution.
4.
Soliris (eculizumab) is indicated for the treatment of patients with paroxysmal nocturnal
haemoglobinuria (PNH).
Evidence of clinical benefit of Soliris in the treatment of patients with PNH is limited to patients with
history of transfusions.
To reduce the risk of meningococcal infection (
Neisseria meningitidis
), all patients must be vaccinated
at least 2 weeks prior to receiving Soliris and must be re-vaccinated according to current medical
guidelines for vaccination use (see section 4.4).
Soliris should be administered by a healthcare professional and under the supervision of a physician
experienced in the management of patients with haematological disorders.
Posology
The dosing regimen consists of a 5-week initial phase followed by a maintenance phase:
Initial phase: 600 mg of Soliris via a 25 - 45 minute intravenous infusion every week for the
first 4 weeks, followed by 900 mg of Soliris for the fifth week of the initial phase.
2
Maintenance phase: 900 mg of Soliris administered via a 25 - 45 minute intravenous infusion
every 14 ± 2 days (see Section 5.1).
Method of administration
For instructions on dilution of the medicinal product before administration, see section 6.6.
Do not administer as an intravenous push or bolus injection. Soliris should only be administered via
intravenous infusion as described below.
The diluted solution of Soliris should be administered by intravenous infusion over 25 – 45 minutes
via gravity feed, a syringe-type pump, or an infusion pump. It is not necessary to protect the diluted
solution of Soliris from light during administration to the patient.
Patients should be monitored for one hour following infusion. If an adverse event occurs during the
administration of Soliris, the infusion may be slowed or stopped at the discretion of the physician. If
the infusion is slowed, the total infusion time may not exceed two hours.
Paediatric Population
: No data is available.
Elderly:
Soliris may be administered to patients aged 65 years and over. There is no evidence to
suggest that any special precautions are needed when older people are treated – although experience
with Soliris in this patient population is still limited.
Renal impairment:
The safety and efficacy of Soliris have not been studied in patients with renal
impairment.
Hepatic impairment:
The safety and efficacy of Soliris have not been studied in patients with hepatic
impairment.
Hypersensitivity to eculizumab, murine proteins or to any of the excipients.
Do not initiate Soliris therapy in patients:
•
with unresolved
Neisseria meningitidis
infection.
•
who are not currently vaccinated against
Neisseria meningitidis.
•
who have known or suspected hereditary complement deficiencies.
Soliris is not expected to affect the aplastic component of anaemia in patients with PNH.
Meningococcal Infection:
Due to its mechanism of action, the use of Soliris increases the patient’s
susceptibility to meningococcal infection (
Neisseria meningitidis
). These patients might be at risk of
disease by uncommon serogroups (particularly Y, W135 and X), although meningococcal disease due
to any serogroup may occur. To reduce the risk of infection, all patients must be vaccinated at least 2
weeks prior to receiving Soliris and must be re-vaccinated according to current medical guidelines for
vaccination use. Tetravalent vaccines against serotypes A, C, Y and W135 are strongly recommended,
preferably conjugated ones. Vaccination may not be sufficient to prevent meningococcal infection.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Cases of serious or fatal meningococcal infections have been reported in Soliris treated patients. All
patients should be monitored for early signs of meningococcal infection, evaluated immediately if
infection is suspected, and treated with antibiotics if necessary. Patients should be informed of these
signs and symptoms and steps taken to seek medical care immediately (see Patient Information Leaflet
for a description).
3
Other Systemic Infections:
Due to its mechanism of action, Soliris therapy should be administered
with caution to patients with active systemic infections. The overall severity and frequency of
infections in Soliris treated patients was similar to placebo treated patients in clinical studies, although
an increase in the number and severity of infections, particularly due to encapsulated bacteria, cannot
be excluded. Patients should be provided with information from the Patient Information Leaflet to
increase their awareness of potential serious infections and the signs and symptoms of them.
Infusion Reactions:
As with all therapeutic proteins, administration of Soliris may result in infusion
reactions or immunogenicity that could cause allergic or hypersensitivity reactions (including
anaphylaxis), though immune system disorders within 48 hours of Soliris administration did not differ
from placebo treatment in PNH and non-PNH studies conducted with Soliris. In clinical trials, no
PNH patients experienced an infusion reaction which required discontinuation of Soliris. Soliris
administration should be interrupted in all patients experiencing severe infusion reactions and
appropriate medical therapy administered.
Immunogenicity:
Infrequent, low titre antibody responses have been detected in Soliris treated patients
across all PNH and non-PNH studies with a frequency (3.4%) similar to that of placebo (4.8%). No
patients have been reported to develop neutralizing antibodies following therapy with Soliris, and
there has been no observed correlation of antibody development to clinical response or adverse events.
Immunization:
Prior to initiating Soliris therapy, it is recommended that PNH patients should receive
immunizations according to current immunization guidelines. Additionally, all patients must be
vaccinated against meningococcus at least 2 weeks prior to receiving Soliris. If available, tetravalent,
conjugated vaccines are recommended (see meningococcal disease).
Anticoagulant therapy:
Treatment with Soliris should not alter anticoagulant management.
Laboratory Monitoring:
PNH patients should be monitored for signs and symptoms of intravascular
haemolysis, including serum lactate dehydrogenase (LDH) levels. PNH patients receiving Soliris
therapy should be similarly monitored for intravascular haemolysis by measuring LDH levels, and
may require dose adjustment within the recommended 14±2 day dosing schedule during the
maintenance phase (up to every 12 days).
Treatment Discontinuation
: Patients who discontinue treatment with Soliris should be monitored for
signs and symptoms of serious intravascular haemolysis. Serious haemolysis is identified by serum
LDH levels greater than the pre-treatment level, along with any of the following: greater than 25%
absolute decrease in PNH clone size (in the absence of dilution due to transfusion) in one week or less;
a haemoglobin level of <5 g/dL or a decrease of >4 g/dL in one week or less; angina; change in mental
status; a 50% increase in serum creatinine level; or thrombosis. Monitor any patient who discontinues
Soliris for at least 8 weeks to detect serious haemolysis and other reactions.
If serious haemolysis occurs after Soliris discontinuation, consider the following
procedures/treatments: blood transfusion (packed RBCs), or exchange transfusion if the PNH RBCs
are >50% of the total RBCs by flow cytometry; anticoagulation; corticosteroids; or reinstitution of
Soliris. In PNH clinical studies, 16 patients discontinued the Soliris treatment regimen. Serious
haemolysis was not observed.
Excipients
: This medicinal product contains 5.00 mmol sodium per dose (1 vial). To be taken into
consideration by patients on a controlled sodium diet.
No interaction studies have been performed.
Pregnancy:
4
For Soliris, no clinical data on exposed pregnancies are available.
Animal reproduction studies have not been conducted with eculizumab (see section 5.3).
Human IgG are known to cross human placental barrier, and thus eculizumab may potentially cause
terminal complement inhibition in the foetal circulation. Therefore, Soliris should be given to a
pregnant woman only if clearly needed. Woman of childbearing potential have to use adequate
contraception methods during treatment and up to 5 months after treatment.
Lactation:
It is not known whether eculizumab is secreted into human milk. Since many medicinal products and
immunoglobulins are secreted into human milk, and because of the potential for serious adverse
reactions in nursing infants, lactation should be discontinued during treatment and up to 5 months after
treatment.
No studies on the effects on the ability to drive and use machines have been performed.
Eculizumab for the treatment of PNH was studied in three clinical studies that included 195
eculizumab-treated patients and most of these patients have been enrolled in the E05-001 extension
study. There was one pivotal trial comparing the eculizumab-treatment arm to a placebo-treatment
arm.
The most commonly reported adverse reactions are headache, dizziness, nausea and pyrexia each
occurring in 5% or more..
Adverse reactions reported at a very common (
1/10) common (≥1/100 to <1/10) or uncommon
(≥1/1,000 to <1/100) frequency with eculizumab in a total of 195 patients in PNH clinical studies are
listed by system organ class and preferred term in Table 1. Adverse reactions were mostly mild to
moderate in severity.
Table 1: Adverse Reactions Reported in 195 patients included in PNH Studies and in postmarketing
setting
MedDRA System
Organ Class
Very Common
(≥1/10);
Common
(≥1/100 to <1/10)
Uncommon
(≥1/1,000 to <1/100)
Blood and lymphatic
system disorders
Thrombocytopenia, Haemolysis* Coagulopathy, Red blood cell
agglutination
Cardiac disorders
Palpitation
Ear and labyrinth
disorders
Tinnitus, Vertigo
E
ndocrine disorders
Basedow’s disease
Eye disorders
Conjunctival irritation,
Vision blurred
Gastrointestinal
disorders
Abdominal pain, Constipation,
Diarrhea, Dyspepsia, Nausea,
Vomiting
Abdominal distension,
Gastrooesophagal reflux
disease, Gingival pain
General disorders
Chest discomfort, Chills, Fatigue, Chest pain, Influenza like
5
and administration
site condition
Asthenia*, Infusion related
reaction, Oedema, Pyrexia
illness, Infusion site
paraesthesia, Infusion site
pain*, Feeling hot*
Hepatobiliary
disorders
Jaundice
Immune system
disorders
Anaphylactic reaction*
Hypersensitivity
Infection and
infestations
Bronchitis, Pneumonia*,
Gastrointestinal infection,
Nasopharyngitis, Oral Herpes,
Sepsis, Septic shock, Upper
respiratory tract infection, Urinary
tract infection, Cystitis*,Viral
infection, Meningococcal sepsis,
Meningococcal meningitis*,
Arthritis bacterial*
Abscess, Cellulitis, Fungal
infection, Gingival infection,
Haemophilus infection,
Infection, Influenza, Lower
respiratory tract infection,
Neisseria infection, Sinusitis,
Tooth infection
Investigations
Coombs test positive*
Alanine aminotransferase
increased, Aspartate
aminotransferase increased,
Gamma-glutamyltransferase
increased
Metabolism and
n
utrition disorders
Anorexia, Decreased appetite
Musculoskeletal and
connective tissue
disorders
Arthralgia, Back pain, Myalgia,
Neck pain, Pain in extremity
Bone pain, Joint swelling,
Muscle spasms, Trismus
Neoplasms benign,
malignant and
unspecified
Malignant melanoma,
Myelodysplastic syndrome
Nervous system
disorders
Headache
Dizziness, Dysgeusia, Paraesthesia Syncope
Psychiatric disorders
Abnormal dreams, Anxiety,
Depression Insomnia, Mood
swings, Sleep disorder
Renal and urinary
disorders
Dysuria
Renal impairment
Reproductive system
and breast disorders
Spontaneous penile erection
Menstrual disorder
Respiratory, thoracic
and mediastinal
disorders
Cough, Nasal congestion,
Pharyngolaryngeal pain, Throat
irritation
Epistaxis, Rhinorrhea,
Skin and
subcutaneous tissue
disorders
Alopecia, Dry skin, Pruritus, Rash, Hyperhidrosis, Petechiae,
Skin depigmentation, ,
Urticaria
Vascular disorders
Haematoma, Hypotension,
Hot flush
*
Adverse reactions reported in the postmarketing setting.
In the C04-001 study, headache was the most common adverse reactions observed with eculizumab.
Headaches were observed in 34.9% (15/43 patients) of patients treated with eculizumab and 4.5%
(2/44 patients) in placebo-treated patients and were mild/moderate in all but 1 eculizumab treated and
1 placebo-treated patients. Most headaches did not persist after the initial administration phase of
Soliris. In addition, fatigue was the only adverse reactions with an increase in frequency by 5% or
more with Soliris as compared to placebo. There was no evidence of an increased incidence of
6
infection across PNH studies with eculizumab as compared to placebo, including serious infections,
severe infections or multiple infections.
In all PNH clinical studies the most serious adverse reaction was meningococcal septicaemia in two
vaccinated PNH patients (see section 4.4).
Low titres of antibodies were detected in 2% patients with PNH treated with Soliris. As with all
proteins there is a potential for immunogenicity.
Cases of haemolysis have been reported in the setting of missed or delayed Soliris dose (see also
Section 4.2).
Safety Data From Other Clinical Studies
Supportive safety data were obtained in 11 clinical studies that included 716 patients exposed to
eculizumab in six disease populations other than PNH. There was an un-vaccinated patient diagnosed
with idiopathic membranous glomerulonephropathy who experienced meningococcal meningitis. With
regard to other AEs and considering all double-blind, placebo-controlled studies in patients diagnosed
with diseases other than PNH (N=526 patients with Soliris; N=221 patients with placebo), AEs
reported with Soliris at a frequency of 2% or greater than the frequency reported with placebo were:
upper respiratory tract infection, rash, and injury.
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Immunomodulators, ATC code: L04AA25
Soliris is a recombinant humanised monoclonal IgG
2/4k
antibody that binds to the human C5
complement protein and inhibits the activation of terminal complement. The Soliris antibody contains
human constant regions and murine complementarity-determining regions grafted onto the human
framework light- and heavy-chain variable regions. Soliris is composed of two 448 amino acid heavy
chains and two 214 amino acid light chains and has a molecular weight of approximately 148kDa.
Soliris is produced in a murine myeloma (NS0 cell line) expression system and purified by affinity and
ion exchange chromatography. The bulk drug substance manufacturing process also includes specific
viral inactivation and removal steps.
Mechanism of Action
Eculizumab, the active ingredient in Soliris, is a terminal complement inhibitor that specifically binds
to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and
preventing the generation of the terminal complement complex C5b-9. Soliris therefore restores
terminal complement regulation in the blood of PNH patients and inhibits terminal complement
mediated intravascular haemolysis in PNH patients. Eculizumab preserves the early components of
complement activation that are essential for opsonization of microorganisms and clearance of immune
complexes.
Administration of Soliris results in a rapid and sustained reduction in terminal complement activity.
Eculizumab serum concentrations of approximately 35 microgram/ml are sufficient for essentially
complete inhibition of terminal complement-mediated intravascular haemolysis in most PNH patients.
7
Administration of Soliris resulted in a rapid and sustained reduction in complement-mediated
haemolytic activity.
Clinical efficacy and safety
The safety and efficacy of Soliris in PNH patients with haemolysis were assessed in a randomized,
double-blind, placebo-controlled 26 week study (C04-001); PNH patients were also treated with
Soliris in a single arm 52 week study (C04-002); and in a long term extension study (E05-001).
Patients received meningococcal vaccination prior to receipt of Soliris. In all studies, the dose of
eculizumab was 600 mg every 7 ± 2 days for 4 weeks, followed by 900 mg 7 2 days later, then 900
mg every 14 ± 2 days for the study duration. Eculizumab was administered as an intravenous infusion
over 25 – 45 minutes.
In study C04-001 (TRIUMPH) PNH patients with at least 4 transfusions in the prior 12 months, flow
cytometric confirmation of at least 10% PNH cells and platelet counts of at least 100,000/microliter
were randomized to either Soliris (n = 43) or placebo (n = 44). Prior to randomization, all patients
underwent an initial observation period to confirm the need for RBC transfusion and to identify the
haemoglobin concentration (the "set-point") which would define each patient’s haemoglobin
stabilization and transfusion outcomes. The haemoglobin set-point was less than or equal to 9 g/dL in
patients with symptoms and was less than or equal to 7 g/dL in patients without symptoms. Primary
efficacy endpoints were haemoglobin stabilization (patients who maintained a haemoglobin
concentration above the haemoglobin set-point and avoid any RBC transfusion for the entire 26 week
period) and blood transfusion requirement. Fatigue and health-related quality of life were relevant
secondary endpoints. Haemolysis was monitored mainly by the measurement of serum LDH levels,
and the proportion of PNH RBCs was monitored by flow cytometry. Patients receiving anticoagulants
and systemic corticosteroids at baseline continued these medications. Major baseline characteristics
were balanced (see table 2).
In the non-controlled study C04-002 (SHEPHERD), PNH patients with at least one transfusion in the
prior 24 months and at least 30,000 platelets/microliter received Soliris over a 52-week period.
Concomitant medications included anti-thrombotic agents in 63% of the patients and systemic
corticosteroids in 40% of the patients. Baseline characteristics are shown in Table 2.
Table 2: Patient Demographics and Characteristics in C04-001 and C04-002
C04-001
C04-002
Parameter
Placebo
N = 44
Soliris
N = 43
Soliris
N = 97
Mean Age (SD)
38.4 (13.4)
42.1 (15.5)
41.1 (14.4)
Gender - Female (%)
29 (65.9)
23 (53.5)
49 (50.5)
History of Aplastic Anemia or MDS (%)
12 (27.3)
8 (18.7)
29 (29.9)
Concomitant Anticoagulants (%)
20 (45.5)
24 (55.8)
59 (61)
Concomitant Steroids/Immunosuppressant
Treatments (%)
16 (36.4)
14 (32.6)
46 (47.4)
Discontinued treatment
10
2
1
PRBC in previous 12 months (median (Q1,Q3))
17.0 (13.5, 25.0)
18.0 (12.0,
24.0)
8.0 (4.0, 24.0)
4
Mean Hgb level (g/dL) at setpoint (SD)
7.7 (0.75)
7.8 (0.79)
N/A
Pre-treatment LDH levels (median, U/L)
2,234.5
2,032.0
2,051.0
Free Haemoglobin at baseline (median, mg/dL)
46.2
40.5
34.9
8
In TRIUMPH, study patients treated with Soliris had significantly reduced (p< 0.001) haemolysis
resulting in improvements in anaemia as indicated by increased haemoglobin stabilization and reduced
need for RBC transfusions compared to placebo treated patients (see table 3). These effects were seen
among patients within each of the three pre-study RBC transfusion strata (4 - 14 units; 15 - 25 units; >
25 units). After 3 weeks of Soliris treatment, patients reported less fatigue and improved health-
related quality of life. Because of the study sample size and duration, the effects of Soliris on
thrombotic events could not be determined. In SHEPHERD study, 96 of the 97 enrolled patients
completed the study (one patient died following a thrombotic event). A reduction in intravascular
haemolysis as measured by serum LDH levels was sustained for the treatment period and resulted in
increased transfusion avoidance, a reduced need for RBC transfusion and less fatigue. See Table 3.
Table 3: Efficacy Outcomes in C04-001 and C04-002
C04-001
C04-002*
Placebo
N = 44
Soliris
N = 43
P – Value
Soliris
N = 97
P – Value
Percentage of patients with
stabilized Hemoglobin levels at
end of study
0
49
< 0.001
N/A
PRBC transfused during
treatment (median)
10
0
< 0.001
0
< 0.001
Transfusion Avoidance during
treatment (%)
0
51
< 0.001
51
< 0.001
LDH levels at end of study
(median, U/L)
2,167
239
< 0.001
269
< 0.001
LDH AUC at end of study
(median, U/L x Day)
411,822
58,587
< 0.001
-632,264
< 0.001
Free Hemoglobin at end of study
(median, mg/dL)
62
5
< 0.001
5
< 0.001
FACIT-Fatigue (effect size)
1.12
< 0.001
1.14
< 0.001
* Results from study C04-002 refer to pre- versus post-treatment comparisons.
From the 195 patients that originated in C04-001, C04-002 and other initial studies, Soliris-treated
PNH patients were enrolled in a long term extension study (E05-001). All patients sustained a
reduction in intravascular haemolysis over a total Soliris exposure time ranging from 10 to 54 months.
There were fewer thrombotic events with Soliris treatment than during the same period of time prior to
treatment. However, this finding was shown in non-controlled clinical trials.
5.2 Pharmacokinetic properties
Pharmacokinetics and Drug Metabolism:
Metabolism
:
Human antibodies undergo endocytotic digestion in the cells of the reticuloendothelial
system. Eculizumab contains only naturally occurring amino acids and has no known active
metabolites. Human antibodies are predominately catabolized by lysosomal enzymes to small peptides
and amino acids.
Elimination:
No specific studies have been performed to evaluate the hepatic, renal, lung, or
gastrointestinal routes of excretion/elimination for Soliris. In normal kidneys, antibodies are not
excreted and are excluded from filtration by their size.
Pharmacokinetic Parameters:
9
In 40 patients with PNH, a 1-compartmental model was used to estimate pharmacokinetic parameters
after multiple doses. Mean clearance was 0.31 0.12 ml/hr/kg, mean volume of distribution was 110.3
17.9 ml/kg, and mean elimination half-live was 11.3 3.4 days. Based on these data, the onset of
steady state is predicted to be approximately 49 – 56 days.
Pharmacodynamic activity correlates directly with eculizumab serum concentrations and maintenance
of trough levels above 35 microgram/ml results in essentially complete blockade of haemolytic
activity in the majority of patients.
Special Populations:
Formal studies have not been conducted to evaluate the pharmacokinetics of Soliris administration in
special patient populations based on gender, race, age (paediatric or geriatric), or renal or hepatic
impairment.
5.3 Preclinical safety data
The specificity of eculizumab for C5 in human serum was evaluated in two
in vitro
studies.
The tissue cross-reactivity of eculizumab was evaluated by assessing binding to a panel of 38 human
tissues. C5 expression in the human tissue panel examined in this study is consistent with published
reports of C5 expression, as C5 has been reported in smooth muscle, striated muscle, and renal
proximal tubular epithelium. No unexpected tissue cross-reactivity was observed.
In a 26 week toxicity study performed in mice with a surrogate antibody directed against murine C5,
treatment did not affect any of the toxicity parameters examined. Haemolytic activity during the
course of the study was effectively blocked in both female and male mice.
Animal reproduction studies have not been conducted with eculizumab. No clear treatment-related
effects or adverse effects were observed in reproductive toxicology studies in mice with a surrogate
terminal complement inhibitory antibody. When maternal exposure to the antibody occurred during
organogenesis, two cases of retinal dysplasia and one case of umbilical hernia were observed among
230 offspring born to mothers exposed to the higher antibody dose (approximately 4 times the
maximum recommended human Soliris dose, based on a body weight comparison); however, the
exposure did not increase foetal loss or neonatal death.
No animal studies have been conducted to evaluate the genotoxic and
carcinogenic potential
of eculizumab or its effect on fertility.
6.
6.1 List of excipients
Sodium phosphate monobasic
Sodium phosphate dibasic
Sodium chloride
Polysorbate 80
Water for injections
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in
section 6.6.
10
6.3 Shelf life
30 months.
After dilution, the medicinal product should be used immediately. However, chemical and physical
stability has been demonstrated for 24 hours at 2 – 8 °C.
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8º C).
Do not freeze.
Store in the original package in order to protect from light.
For storage conditions of the diluted medicinal product, see section 6.3.
6.5
Nature and contents of container
30 ml of concentrate in a vial (Type I glass) with a stopper (butyl, siliconised), and a seal (aluminium)
with flip-off cap (polypropylene).
6.6
Special precautions for disposal and other handling
Soliris should be administered by a health care professional. Soliris therapy must not be initiated
without prior vaccination against
Neisseria meningitidis
at least 2 weeks prior to initial administration.
All patients should be administered a meningococcal vaccine at least two weeks prior to the first dose
of Soliris (see section 4.4).
Prior to administration, the Soliris solution should be visually inspected for particulate matter and
discolouration.
Instructions:
Reconstitution and dilution should be performed in accordance with good practices rules, particularly
for the respect of asepsis.
Withdraw the total amount of Soliris from the vial(s) using a sterile syringe.
Transfer the recommended dose to an infusion bag.
Dilute Soliris to a final concentration of 5 mg/ml by addition to the infusion bag using 0.9% sodium
chloride, 0.45% sodium chloride, or 5% Dextrose in water, as the diluent.
The final volume of a 5 mg/ml diluted solution is 120 ml for 600 mg doses or 180 ml for 900 mg
doses. The solution should be clear and colourless.
Gently agitate the infusion bag containing the diluted solution to ensure thorough mixing of the
product and diluent.
The diluted solution should be allowed to warm to room temperature prior to administration by
exposure to ambient air.
Discard any unused portion left in a vial, as the product contains no preservatives.
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.
7.
Alexion Europe SAS
11
25 Boulevard de l’Amiral Bruix
75016 Paris
FRANCE
8.
EU/1/07/393/001
9.
20 June 2007
Detailed information on this medicinal product is available on the website of the European Medicines
Agency
http://www.ema.europa.eu
/.
12
ANNEX II
A.
MANUFACTURERS OF THE BIOLOGICAL ACTIVE
SUBSTANCE AND MANUFACTURING AUTHORISATION
HOLDER RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
13
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturers of the biological active substance
Lonza Biologics, Inc.
101 International Drive
Pease International Tradeport
Portsmouth, New Hampshire 03801
U.S.A.
Lonza Biologics, plc.
228 Bath Road
Slough
Berkshire SL1 4DX
United Kingdom
Alexion Rhode Island Manufacturing Facility (ARIMF)
100 Technology Way
Smithfield, Rhode Island 02917
U.S.A.
Name and address of the manufacturer responsible for batch release
Almac Pharma Services
22 Seagoe Industrial Estate
Craigavon BT63 5QD
United Kingdom
B. CONDITIONS OF THE MARKETING AUTHORISATION
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product
Characteristics, section 4.2).
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
1. The MAH shall agree the details of a distribution system with the National Competent
Authorities and must implement such programme nationally to ensure that:
drug distribution will only be possible after checking that the patient has effectively
received a meningococcal vaccination with a written confirmation.
prior to administration, all health care professionals are provided with information on the
following key safety concerns:
o
Headache
o
Infusion reaction
o
Neisseria and general infection
o
Risk of serious haemolysis following eculizumab discontinuation and proposed management
o
Pregnancy and need of adequate contraception in women of childbearing potential
o
Immunogenicity
o
Renal and hepatic impairment.
14
2. Prior to launch, the MAH shall agree on the implementation of a patient card system in each
Member State. This patient card will provide details of the signs and symptoms of infection
as well as instruction for the patient to immediately seek medical care. The card will also
provide information to health care professionals that the patient is receiving Soliris
treatment.
3. The MAH will assess the compliance of the prescribers with the recommended Risk Management
Plan (RMP) tool by examination of data collected in the PNH Registry.
The effectiveness of the risk minimization measures will therefore be assessed by actual clinical
practice. Review and assessment of the information collected will be presented in each PSUR.
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance presented in Module 1.8.1. of the
Marketing Authorisation Application, is in place and functioning before and whilst the product is on
the market.
Risk Management Plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan, as agreed in version 4 of the RMP presented in Module 1.8.2. of the
Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the
updated RMP should be submitted at the same time as the next Periodic Safety Update Report
(PSUR).
In addition, an updated RMP should be submitted:
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached
At the request of the European Medicines Agency.
15
ANNEX III
LABELLING AND PACKAGE LEAFLET
16
A.LABELLING
17
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
Carton Label
1.
Soliris 300 mg concentrate for solution for infusion
Eculizumab
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each vial of 30 ml contains 300 mg of eculizumab (10mg/ml)
Eculizumab is a humanised monoclonal IgG
2/4 k
antibody produced in
NS0 cell line by recombinant
DNA technology.
After dilution, the final concentration of the solution to be infused is 5 mg/ml.
3.
LIST OF EXCIPIENTS
Sodium as chloride, phosphate dibasic, phosphate monobasic; polysorbate 80 and water for injections.
See package leaflet for further information
4.
Concentrate for solution for infusion
1 x 30 ml (10 mg/ml)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For intravenous use.
Must be diluted before use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP:
After dilution, the medicinal product should be used immediately within 24 hours.
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator (2C – 8C).
18
Do not Freeze.
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
Any unused product or waste material should be disposed of in accordance with local requirements.
Marketing Authorisation Holder:
Alexion Europe SAS
25 Boulevard de l’Amiral Bruix
75016 PARIS
France
EU/1/07/393/001
13. BATCH NUMBER
LOT:
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
19
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
Single use Type I glass vial
1.
Soliris 300 mg concentrate for solution for infusion
Eculizumab
For intravenous use
2.
METHOD OF ADMINISTRATION
To be diluted before use.
Read the package leaflet before use.
3.
EXPIRY DATE
EXP:
4.
BATCH NUMBER
LOT:
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
30 ml (10 mg/ml)
6.
OTHER
20
B. PACKAGE LEAFLET
21
PACKAGE LEAFLET: INFORMATION FOR THE USER
Soliris 300 mg, concentrate for solution for infusion
Eculizumab
Read all of this leaflet carefully before you start using this medicine.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist
- If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
In this leaflet
:
1. What Soliris is and what it is used for
2. Before you use Soliris
3. How to use Soliris
4. Possible side effects
5.
How to store Soliris
6.
Further information
1.
WHAT SOLIRIS IS AND WHAT IT IS USED FOR
The active substance of Soliris is eculizumab and it belongs to a class of medicines called monoclonal
antibodies. Eculizumab binds to and inhibits a specific protein in the body that causes inflammation.
Soliris is used for the treatment of patients with a certain type of disease affecting the blood system
called Paroxysmal Nocturnal Haemoglobinuria (PNH). In patients with PNH, their red blood cells can
be destroyed which can lead to low blood counts (anaemia), tiredness, difficulty in functioning, pain,
dark urine, shortness of breath, and blood clots. Eculizumab can block the body’s inflammatory
response, and its ability to attack and destroy its own vulnerable PNH blood cells. There is only
experience in the treatment of patients with previous history of transfusions.
2.
BEFORE YOU USE SOLIRIS
Do not use Soliris
-
If you are allergic (hypersensitive) to eculizumab, proteins derived from mouse products, have
had an allergic reaction to other monoclonal antibodies, or any of the other ingredients of
Soliris. (See Section 6, What Soliris contains).
-
If you have not been vaccinated against meningitis infection.
-
If you have a meningitis infection.
-
If you have a disease that alters your immune system.
Take special care with Soliris
Meningitis alert:
Soliris treatment may reduce your natural resistance to infections, especially against certain organisms
that cause meningitis.
Consult your doctor before you take Soliris to be sure that you receive vaccination against
Neisseria
meningitidis
, an organism that causes meningitis, at least 2 weeks before beginning therapy, or that
your current meningitis vaccination is up to date. You should also be aware that vaccination may not
prevent this type of infection. In accordance with national recommendations, your doctor might
consider that you need supplementary measures to prevent infection.
22
Meningitis symptoms
Because of the importance of rapidly identifying and treating certain types of infection in patients who
receive Soliris, you will be provided a card to carry with you, listing specific trigger symptoms. This
card is named: “Patient Safety Card”.
If you experience any of the following symptoms, you should immediately inform your doctor :
-
bothersome headache with nausea or vomiting
-
bothersome headache with a stiff neck or back
-
fever
-
fever and a rash
-
confusion
-
severe muscle aches combined with flu-like symptoms
-
sensitivity to light
Treatment for meningitis while travelling
If you are travelling in a remote region where you are unable to contact your doctor or in which you
find yourself temporarily unable to receive medical treatment, your doctor can make arrangements to
issue, as a preventive measure, a prescription for an antibiotic to counter
Neisseria meningitidis
that
you keep with you. If you experience any of the symptoms amongst those cited above, you should take
the antibiotics as prescribed. You should bear in mind that you should see a doctor as soon as possible,
even if you feel better after having taken the antibiotics.
Infections
Inform your doctor before you take Soliris if you have any infections.
Allergic reactions
Soliris contains a protein and proteins can cause allergic reactions in some people.
Using Soliris with other medicines:
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Using Soliris with food and drink:
Interactions between your treatment with Soliris and food or drink are unlikely.
Woman of childbearing potential:
Women who are able to get pregnant should use adequate contraception methods during treatment and
up to 5 months after treatment.
Pregnancy and breast-feeding
Ask your doctor or pharmacist for advice before using any medicine.
Pregnancy
Tell your doctor before starting treatment with Soliris if you are pregnant or plan to become pregnant.
Soliris is not recommended during pregnancy.
Breast-feeding
Soliris may pass through your breast milk to your baby. Therefore, you should not breast-feed while
using Soliris.
Driving and using machines:
The effects on the ability to drive and to use machines have not been studied. As with all medicines,
you should ask for advice from your doctor.
Elderly people
23
There is no evidence to suggest that any special precautions are needed when older people (65 years
and over) are treated – although experience is still limited.
Children and adolescents
Soliris has not been administered to patients less than 18 years of age.
Important information about some of the ingredients of Soliris
This medicinal product contains 5.00 mmol sodium per dose (1 vial). To be taken into consideration
by patients on a controlled sodium diet.
3. HOW TO USE SOLIRIS
Prior to beginning treatment, your doctor will discuss with you the importance of:
-
Receiving a vaccine against meningitis,
-
Becoming knowledgeable about symptoms associated with infections, and
-
Being carefully monitored by your doctor following any discontinuation of Soliris treatment.
At least 14 days before you start treatment with Soliris, your doctor will administer a vaccine against
meningitis if it was not previously administered or if your vaccination is outdated.
Instructions for proper use
The treatment will be given by your doctor or other health care provider by infusing a dilution of the
Soliris vial from a drip bag through a tube directly into one of your veins. It is recommended that the
beginning of your treatments, called the initial phase, will extend over 5 weeks, followed by a
maintenance phase:
Initial Phase:
Every week for the first four weeks, your doctor will administer an intravenous infusion of
diluted Soliris
.
Each infusion will consist of a dose of 600 mg (2 vials of 30 ml) and will take
approximately 30 minutes.
In the fifth week your doctor will administer an intravenous infusion of diluted Soliris at a
dose of 900 mg (3 vials of 30 ml) over a 30 minute period.
Maintenance Phase:
After the fifth week, your doctor will administer 900 mg of diluted Soliris every two weeks as
a long-term treatment.
Following each infusion, you will be monitored for about one hour. Your doctor’s instructions should
be carefully observed.
If you receive more Soliris than you should
If you suspect that you have been accidentally administered a higher dose of Soliris than prescribed,
please contact your doctor for advice.
If you forget an appointment to receive Soliris
If you forget an appointment, please contact your doctor immediately for advice and see section below
“If you stop using Soliris”.
If you stop using
Soliris
Interrupting or ending treatment with Soliris may cause your PNH symptoms to come back more
severely soon after stopping Soliris treatment. If you stop treatment with Soliris, your doctor will
discuss the possible side effects with you and explain the risks. Your doctor will want to continue to
monitor you closely.
The risks of stopping Soliris include an increase in the destruction of your red blood cells, which may
cause:
24
-
A significant fall in your red blood cell counts (anaemia),
-
You to be confused or unalert,
-
Chest pain, or angina,
-
An increase in your serum creatine level (problems with your kidneys), or
-
Thrombosis (blood clotting).
If you have any of these symptoms, contact your doctor.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Soliris can cause side effects, although not everybody gets them. The side effects
caused by Soliris are usually mild or moderate. Your doctor will discuss the possible side effects with
you and explain the risks and benefits of Soliris with you prior to treatment.
If you are not sure what the side effects below are, ask your doctor to explain them to you.
Very common side effects
(occurring in at least 1 in 10 patients) include: headaches.
Common side effects
(occurring in 1 or more out of 100 patients and less than 10 in 100 patients) include: relatively few
platelets in blood (thrombocytopenia), destruction of red blood cells (haemolysis), abdominal pain,
constipation, vomiting, diarrhea, stomach discomfort after meals (dyspepsia), nausea, chest
discomfort, chills, infusion related reaction, swelling (edema), fever (pyrexia), feeling tired (fatigue),
feeling of weakness (asthenia), serious allergic reaction which causes difficulty in breathing or
dizziness (anaphylactic reaction), cold sores (herpes simplex), common cold (nasopharyngitis), viral
infection, stomach flu (gastrointestinal infection), bronchitis, cystitis, severe infection (sepsis, septic
shock, meningococcal sepsis), infection of the joint (arthritis bacterial), infection of the lung
(pneumonia), infection of the meninges (meningococcal meningitis), muscle aches, back and neck
pain, pain in the limbs or joints (arms and legs), dizziness, taste disorders (dysgeusia), tingling in part
of the body (paresthesia), difficulties or pain when urinating (dysuria), spontaneous penile erection,
upper respiratory tract infection, infection of the urinary system (urinary tract infection), cough, throat
irritation or pain (pharyngolaryngeal pain), stuffy nose (nasal congestion), itchy skin (pruritus), rash,
hair loss (alopecia), dry skin.
Uncommon side effects
(occurring in 1 or more out of 1000 patients and less than 10 in 1000 patients) include:
Abnormal blood clotting, clumping of cells, feeling your heartbeat, ringing in the ears, disease with
thyroid overactivity (Basedow’s disease), irritation of eye, vision blurred, unusual backflow of food
from stomach, gum pain, chest pain, influenza like illness, feeling hot, infusion site pain, yellowing of
the skin and/or eyes (jaundice), collection of pus (abscess), type of infection of the skin (cellulitis),
fungal infection, gum infection, infection, influenza, sinusitis, tooth infection, increase of liver
enzymes, loss of appetite, spasm of mouth muscle, muscle cramp, skin tumor (melanoma), bone
marrow disorder, fainting, abnormal dreams, anxiety, depression, inability to sleep, mood swings,
sleep disorder, kidney disorder, menstrual disorder, nose bleed, runny nose, increased sweating, red or
purple spots under the skin, skin color disorder, hives, bruise, low blood pressure, hot flush.
If any of these side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
5. HOW TO STORE SOLIRIS
Keep out of the reach and sight of children.
25
Store in a refrigerator (2°C – 8C).
Do not freeze.
Store in the original package in order to protect from light.
Do not use Soliris after the expiry date which is stated on the label after “EXP”.
After dilution, the product should be used immediately within 24 hours.
6.
FURTHER INFORMATION
What Soliris contains
The active substance is eculizumab (300 mg/30 ml in a vial corresponding to 10 mg/ml).
The other ingredients are:
- sodium phosphate monobasic
- sodium phosphate dibasic
- sodium chloride
- polysorbate 80 (vegetable origin)
Solvent: water for injections
What Soliris looks like and contents of the pack
Soliris is presented as a concentrate for solution for infusion (30 ml in a vial – pack size of 1).
Soliris is a clear and colorless solution.
Marketing Authorisation Holder and Manufacturer :
Marketing Authorisation Holder
:
Alexion Europe SAS
25 Boulevard de l’Amiral Bruix
75016 Paris
Tel: +33 (0) 1 53 64 38 00
France
Manufacturer:
Almac Pharma Service
22 Seagoe Industrial Estate
Craigavon BT63 5QD
United Kingdom
For any information about this medicinal product, please contact the local representative of the
Marketing Authorisation Holder:
België/Belgique/Belgien
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Bruxelles / Brussel
Belgique / België
Luxembourg/Luxemburg
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Bruxelles
Belgique
Tél/Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Tél/Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com
България
Alexion Pharma France
15 Boulevard de l’Amiral Bruix 75016 Paris
Франция
Magyarország
Alexion Pharma France
15 Boulevard de l’Amiral Bruix 75016 Paris
Franciaország
Teл.: +33 (0) 1 53 64 39 50
alexion.france@alxn.com
Tel: +33 (0) 1 53 64 39 50
alexion.france@alxn.com
26
Česká republika
Alexion Pharma France
15 Boulevard de l’Amiral Bruix 75016 Paris
Francie
Malta
Alexion Pharma UK
Unit 14, Horizon Business Village
1, Brooklands Road, Weybridge,
Surrey KT13 OTJ
UK
Tel: +44 (0) 1 932 35 9220
alexion.uk@alxn.com
Tel: +33 (0) 1 53 64 39 50
alexion.france@alxn.com
Danmark
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Bruxelles
Belgien
Nederland
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Brussel
België
Tlf: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Deutschland
Alexion Pharma Germany
Arnulfstr. 19
80335 München
Deutschland
Norge
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Brussel
Belgia
Tel : +49 89 45 70 91 300
alexion.germany@alxn.com
Tlf: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Eesti
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Brüssel
Belgia
Österreich
Alexion Pharma Germany
Arnulfstr. 19
80335 München
Deutschland
Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Tel : +49 89 45 70 91 300
alexion.germany@alxn.com
Ελλάδα
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Βρυξέλλες
Βέλγιο
Polska
Alexion Pharma France
15 Boulevard de l’Amiral Bruix 75016 Paris
Francja
Τηλ: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Tel: +33 (0) 1 53 64 39 50
alexion.france@alxn.com
España
Alexion Pharma Spain
Passeig de Gràcia,
85, 4a Planta
Barcelona 08008
España
Portugal
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Bruxelas
Bélgica
Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com
27
Tel : +34 93 272 30 05
alexion.spain@alxn.com
France
Alexion Pharma France
15 Boulevard de l’Amiral Bruix 75016 Paris
France
România
Alexion Pharma France
15 Boulevard de l’Amiral Bruix 75016 Paris
Franţa
Tel: +33 (0) 1 53 64 39 50
alexion.france@alxn.com
Tel: +33 (0) 1 53 64 39 50
alexion.france@alxn.com
Ireland
Alexion Pharma UK
Unit 14, Horizon Business Village
1, Brooklands Road, Weybridge,
Surrey KT13 OTJ
UK
Slovenija
Alexion Pharma France
15 Boulevard de l’Amiral Bruix 75016 Paris
Francija
Tel: +33 (0) 1 53 64 39 50
alexion.france@alxn.com
Tel: +44 (0) 1 932 35 9220
alexion.uk@alxn.com
Ísland
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Brussel
Belgía
Slovenská republika
Alexion Pharma France
15 Boulevard de l’Amiral Bruix 75016 Paris
Francúzsko
Sími: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Tel: +33 (0) 1 53 64 39 50
alexion.france@alxn.com
Italia
Alexion Pharma Italy S.r.l.
Largo Corsia Dei Servi 3
20122 Milano
Italia
Suomi/Finland
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Bryssel
Belgien
Puh/Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Tel: 800 915 921
alexion.italy@alxn.com
Κύπρος
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Βρυξέλλες
Βέλγιο
Sverige
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Bryssel
Belgia
Τηλ: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Latvija
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Brisele
Beļģija
United Kingdom
Alexion Pharma UK
Unit 14, Horizon Business Village
1, Brooklands Road, Weybridge,
Surrey KT13 OTJ
UK
Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com
Tel: +44 (0) 1 932 35 9220
alexion.uk@alxn.com
28
Lietuva
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Briuselis
Belgija
Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com
This leaflet was last approved in .
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu
/. There are also links to other websites about rare diseases and treatments.
29
---------------------------------------------------------------------------------------------------------------------------
-------
Instructions for Use for Healthcare Professionals
Handling Soliris
The following information is intended for medical or healthcare professionals only:
1- How is Soliris supplied?
Each vial of Soliris contains 300 mg of active ingredient in 30 ml of product solution.
2- Before Administration
Reconstitution and dilution should be performed in accordance with good practices rules, particularly
for the respect of asepsis.
Soliris should be prepared for administration by a qualified healthcare professional using aseptic
technique.
Inspect visually Soliris solution for particulate matter and discolouration.
Withdraw the required amount of Soliris from the vial(s) using a sterile syringe.
Transfer the recommended dose to an infusion bag.
Dilute Soliris to a final concentration of 5 mg/ml (initial concentration divided by 2) by adding the
appropriate amount of diluent to the infusion bag. For 600mg doses, use 60 ml of Soliris
(10mg/ml) and add the same volume of diluent. For 900 mg use 90 ml of Soliris and add 90 ml of
diluent. The final volume of a 5 mg/ml diluted Soliris solution is
120 ml for 600 mg doses
or
180
ml for 900 mg doses
.
Diluents are 0.9% Sodium chloride, 0.45% Sodium chloride or 5% Dextrose in Water.
Gently agitate the infusion bag containing the diluted Soliris solution to ensure thorough mixing of
the medicinal product and diluent.
The diluted solution should be allowed to warm to room temperature [18°-25° C] prior to
administration by exposure to ambient air.
The diluted solution must not be heated in a microwave or with any heat source other than the
prevailing room temperature.
Discard any unused portion left in a vial as the medicinal product contains no preservatives.
Diluted solution of Soliris may be stored at 2°C -8 C for up to 24 hours prior to administration.
3- Administration
Do not administer Soliris as an intravenous Push or Bolus Injection.
Soliris should only be administered via intravenous infusion.
The diluted solution of Soliris should be administered by intravenous infusion over 25 to 45
minutes via gravity feed, a syringe-type pump, or an infusion pump. It is not necessary to protect
the diluted solution of Soliris from light during administration to the patient.
The patient should be monitored for one hour following infusion. If an adverse event occurs during
the administration of Soliris, the infusion may be slowed or stopped at the discretion of the physician.
If the infusion is slowed, the total infusion time may not exceed two hours.
4- Special Handling and Storage
Soliris vials must be stored in the original carton until time of use under refrigerated conditions at 2-
8ºC and protected from light. Do not use beyond the expiration date stamped on the carton.
30
Source: European Medicines Agency
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