Soliris - instructions for use, doses, side effects, contraindications

Active substanceEkulizumabEkulizumab

Similar drugsTo uncover

Soliris®

concentrate d / infusion

Alexion Pharma International Sarl Switzerland

Dosage form: & nbspconcentrate for solution for infusion

Composition:

1 ml of the preparation contains:

active substance: ekulizumab 10.0 mg

Excipients: sodium dihydrogen phosphate monohydrate 0.46 mg, sodium hydrogen phosphate heptahydrate 1.78 mg, sodium chloride 8.77 mg, polysorbate-80 0.22 mg, water for injection up to 1.0 ml.

Description:

A clear, colorless solution.

Pharmacotherapeutic group:immunosuppressive agent

ATX: & nbsp

L.04.A.A.25 Ekulizumab

Pharmacodynamics:

Eculizumab is a recombinant humanized monoclonal antibody - kappa-immunoglobulin (IgG2 / 4k), which binds to the human complement protein C5 and suppresses the activation of complement-mediated cell lysis. The antibody consists of human immunoglobulin constant regions and complementarily deterministic mouse immunoglobulin regions embedded in the light and heavy chain variable regions of the human antibody. The composition of ekulizumab includes two heavy chains, 448 amino acids each, and two light chains, each having 214 amino acids. The molecular weight is 147870 Da.

Euculizumab is produced in cell line culture NS0 myeloma of the mouse and purified by affinity and ion exchange chromatography. In the process of production of the substance, specific inactivation and virus removal processes are also included.

Ekulizumab inhibits the activity of human complement terminal complex, having a high affinity for its C5 component. As a consequence, the splitting of the component C5 into C5a and C5b and the formation of the terminal complex of complement C5b-9. Thus, ekulizumab restores regulation of complement activity in the blood and prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH), but also prevents excessive terminal complex activity in patients with atypical hemolytic uremic syndrome (Agus) where the cause of the disease is genetically determined dysregulation of the complement system. FROM other hand, the terminal complex of complement deficiency associated with increased incidence of infections by microorganisms encapsulated mainly meningococcal infection. Wherein ekulizumab supports the content of early complement activation products necessary for opsonization of microorganisms and excretion of immune complexes.

Appointment of patients with the drug Soliris® is accompanied by a rapid and stable decrease in the activity of the terminal complement complex. In the majority of APG patients, the concentration of euculizumab in the blood plasma is about 35 μg / ml sufficient for complete inhibition intravascular hemolysis, induced by activation of the terminal complement complex.

Patients with atypical hemolytic-uremic syndrome (aHUS) chronic uncontrolled activation of the complement, which, in turn, induces the development of thrombotic microangiopathy (TMA), is also blocked during treatment with Soliris®. All patients who received the preparation of Soliris® at the recommended doses had a rapid and stable decrease in the activity of the terminal complement complex. In all patients with AChS, the concentration of euculizumab in blood plasma of about 50-100 μg / ml is sufficient for the almost complete inhibition of the activation of the terminal complement complex.

The results of the experimental studies did not show the presence of cross reactivity, as well as signs of reproductive toxicity. The genotoxicity of ekulizumab, its carcinogenic potential and the effect on fertility in animals have not been studied.

Clinical efficacy and safety

Paroxysmal nocturnal hemoglobinuria The effectiveness and safety of the preparation Soliris® (Triumph, 87 patients), a 52-week open non-randomized study (Shepherd, 97 patients), as well as an open, expanded study, in which patients were included in the study, were assessed in patients with APG and hemolysis symptoms during a double-blind, placebo-controlled 26-week study of the first two studies and 11 patients from the Phase 2 study.

Patients receiving the preparation of Soliris ® showed a significant stable decrease (by 86%, p <0.001) of intravascular hemolysis, assessed by the activity of lactate dehydrogenase (LDH). As a consequence, the severity of anemia decreased, which was confirmed by the stabilization of the need for blood transfusions. Patients noted a decrease in weakness and improved quality of life. There was a decrease in the frequency of thromboembolic complications.

The efficacy and safety of Soliris was evaluated in the pediatric population of APG patients (study M07-005). Seven patients aged 11 to 17 years received Soliris for 12 weeks. Treatment with Soliris in accordance with the recommended dosing regimen was accompanied by a decrease in intravascular hemolysis, measured by the LDH level. There was also a significant reduction in the number or total elimination of blood transfusions, an improvement in the overall condition of patients. The efficacy of eculizumab in this study was comparable to that obtained with the study of echulizumab in adult patients (TRIUMPH C04-001 and SHEPHERD C04-002).

Atypical hemolytic-uremic syndrome

The efficacy and safety of Soliris® was studied in prospective clinical trials in adult and pediatric populations with a total of 100 patients. The studies involved groups: patients with recent diagnosed aguas and signs of TMA (thrombocytopenia below 150,000 / μL, LDH and creatinine above the upper limit of the norm), as well as patients with a long-lasting AGU without obvious hematologic manifestations of TMA.

After initiation of therapy with Soliris®, a decrease in the activity of the terminal complement complex was achieved in all patients. Normalization of the platelet count was also observed (according to two studies - in 82% and 90% of patients, respectively), which lasted for two years (88% and 90% of patients, respectively). The therapy resulted in the inhibition of complement-mediated TMA and the absence of symptoms of TMA (in 80% and 88% of patients, respectively) that persisted for two years: 88% and 95% of patients, respectively [95%].

During therapy with Soliris®, there was a significant improvement in renal function, assessed by the level of the calculated glomerular filtration rate (rSCF): improvement of rSCP> 15 mL / min / 1.73 m2 was observed in both studies in 4% and 53% of patients, respectively, and persisted in for two years in 59% and 40% of patients, respectively. Normalization of hematological parameters reached 76% and 90% of patients, respectively, in both studies with a positive dynamics for two years in 88% and 90% of patients, respectively [95% CI].

Pharmacokinetics:

Metabolism

Human antibodies under the action of lysosomal enzymes in the cells of the reticuloendothelial system are cleaved to small peptides and amino acids.

Excretion

No special studies have been conducted to evaluate the ways of excretion of ekulizumab. Because of the large molecular weight (148 kD) ekulizumab Not excreted unchanged in the urine. The average clearance is 0.31 ± 0.12 ml / h / kg, the average volume of distribution is 110.3 ± 17.9 ml / kg, and the average half-life is 11.3 ± 3.4 days. Based on these data, the equilibrium state is reached after 49-56 days.

The pharmacodynamic activity of ekulizumab was directly proportional to its concentration in the plasma. While maintaining the concentration of ekulizumab in the blood plasma> 35 mcg / ml, in most patients almost complete blockage of hemolytic activity was noted.

In the study M07-005, the parameters of the pharmacokinetics of ekulizumab in the pediatric population of patients with APG were evaluated. In seven patients aged 11 to 17 years, with the recommended dosage regimen as a function of weight, the lowest clearance of eukulizumab was 0.0105 l / h.

The dependence of the pharmacokinetics of Soliris® on sex, race, functional activity of the liver or kidneys has not been studied.

Indications:

Soliris® is indicated for the treatment of patients with:

- Paroxysmal nocturnal hemoglobinuria (APG)

The effectiveness of the drug Soliris® was confirmed only in patients with APG who previously had blood transfusion or its components.

- Atypical hemolytic-uremic syndrome (AGU)

Contraindications:

Hypersensitivity to ekulizumab, mouse proteins or other components of the drug

- The period of breastfeeding.

For patients with APG

- Active infection of Neisseria meningitidis

- Lack of vaccination against Neisseria meningitidis

For patients with AGU

- Active infection of Neisseria meningitidis

- Lack of vaccination against Neisseria meningitides or failure to receive an appropriate preventive course of antibiotic therapy within 2 weeks after vaccination.

Carefully:

Given the mechanism of action of the drug Soliris®, he must be cautiously assigned to patients with active systemic infections.

In patients with impaired hepatic function due to lack of clinical experience

Pregnancy and lactation:

There were no controlled studies of the drug during pregnancy.

It is known that human immunoglobulin G (IgG) passes through the placental barrier, in connection with which, ekulizumab is potentially capable of inhibiting the terminal activity of complement in fetal blood.Soliris® should not be used during pregnancy, except when the benefit to the mother exceeds the possible risk to the fetus.

It is not established whether the ekulizumab in breast milk, but, taking into account the potential undesirable effects of the drug, it is recommended that breastfeeding be canceled during treatment with the drug and within 5 months after its completion (see "Contraindications").

Dosing and Administration:

Intravenously drip for 25-45 minutes for adults and for 1-4 hours for patients of childhood.

Paroxysmal nocturnal hemoglobinuria

The course of treatment for adults (> 18 years old) includes a 4-week initial cycle followed by a cycle of maintenance therapy.

Initial cycle: 600 mg of Soliris® once a week for 4 weeks. Maintenance therapy - 900 mg of the preparation Soliris® at week 5, followed by the introduction of 900 mg of Soliris® every 14 ± 2 days.

For patients with APG under 18 years of age, the dose Soliris® is determined according to the weight of the child:

The weight the patient	Elementary cycle	Supportive therapy
> 40 kg	600 mg once a week x 4	900 mg at the 5th week; then 900 mg every 2 weeks
30 - <40 kg	600 mg once a week x 2	900 mg at the 3rd week; then 900 mg every 2 weeks
20 - <30 kg	600 mg 1 time per week x 2	600 mg on the 3rd a week; then 600 mg every 2 weeks
10 - <20 kg	600 mg once a week x 1	300 mg on the 2nd week; then 300 mg every 2 weeks
5 - <10 kg	300 mg once a week х 1	300 mg on the 2nd week; then 300 mg every 3 weeks

Atypical hemolytic-uremic syndrome

The course of treatment for adults (> 18 years old) includes a 4-week primary cycle followed by a cycle of maintenance therapy:

Initial cycle: 900 mg of the preparation Soliris® 1 time per week for 4 weeks. Standing / shining therapy - 1200 mg of the preparation Soliris® at the 5th week, followed by the administration of 1200 mg of the preparation Soliris® every 14 ± 2days.

For patients with ASUS younger than 18 years, the dose of Soliris® depends on the weight of the child:

The weight the patient	Elementary cycle	Supportive therapy
> 40 kg	900 mg once a week x 4	1200 mg at the 5th week; then 1200 mg every 2 weeks
30 - <40 kg	600 mg once a week x 2	900 mg at the 3rd week; then 900 mg every 2 weeks
20 - <30 kg	600 mg once a week x 2	600 mg at the 3rd week; then 600 mg every 2 weeks
10 - <20 kg	600 mg once a week x 1	300 mg on the 2nd week; then 300 mg every 2 weeks
5 - <10 kg	300 mg once a week х 1	300 mg on the 2nd week; then 300 mg every 3 weeks

Introduction of an additional dose of Soliris® It is required in the case of plasmapheresis,exchange plasma transfusion or infusion of fresh frozen plasma:

View plasma procedures	Previous dose of the drug Soliris®	Additional dose preparation Soliris® after each plasma procedures	Time introduction of additional dose preparation Soliris®
Plasmapheresis or exchange transfusion plasma	300 mg	300 mg per each plasmapheresis or exchange plasma transfusion	Within 60 min after of each plasmapheresis or exchange transfusion of plasma
Plasmapheresis or exchange transfusion plasma	> 600 mg	600 mg per each plasmapheresis or exchange plasma transfusion
Infusion Fresh-born plasma	> 300 mg	300 mg per every unit freshly frozen plasma	In 60 minutes before infusion each units fresh-frozen plasma

Control during treatment In the course of treatment of patients with ASUS, symptoms of TMA should be monitored.

Recommended lifelong treatment with Soliris® With the exception of cases where there is medical evidence for discontinuing treatment.

For intravenous administration of a diluted solution of Soliris® it is necessary to use special infusion systems with controlled delivery.It is not necessary to protect the reconstituted drug solution from light during administration.

After the end of the drug, the patient should be monitored for 1 hour. If adverse events develop during the administration of the drug, the infusion rate may be reduced until the injection is completely stopped at the doctor's discretion. When reducing the speed Soliris® drug administration, total infusion time should not exceed 2 hours in adults and children aged 12 to 18 years and 4 watches - for children under 12 years.

Side effects:

The most common adverse event in the treatment of eculizumab was headache (noted mainly in the initial cycle of therapy).

The most serious undesirable phenomenon was meningococcal sepsis.

Below is presented a summary of the adverse reactions noted in clinical studies and also in post-marketing period in patients with APG or Agus treated ekulizumabIn accordance with a lesion of organs and organ systems (MedDRA) and WHO classification by frequency of occurrence, 'very often' (> or = 1/10); "often" (> or = 1/100, <1/10); "Infrequently" (> or = 1/1000, <1/100), "rarely" (> or = 1/10000, <1/1000) and "very rarely" (<1/10000).

Violations from the blood and lymphatic system:

Often - leukopenia, thrombocytopenia, hemolysis *;

Infrequently - coagulopathy, agglutination of erythrocytes, blood clotting disorders, anemia, lymphopenia.

Benign, malignant and unspecified neoplasms:

Infrequently - myelodysplastic syndrome, melanoma.

Heart Disease:

Infrequent - a feeling of palpitations.

Vascular disorders:

Often - lowering blood pressure;

Infrequent - hematoma, increased blood pressure, malignant hypertension, "hot flashes" of blood, venous disease.

Hearing disorders and labyrinthine disturbances:

Infrequent - ringing in the ears, vertigo (vestibular dizziness).

Disorders from the endocrine system:

Infrequent - hyperthyroidism.

Disorders from the side of the organ of vision:

Infrequent irritation of the conjunctiva, vague vision.

Disturbances from the gastrointestinal tract:

Often - abdominal pain, constipation, diarrhea, indigestion, nausea, vomiting;

Infrequent - bloating, gastroesophageal reflux, pain in the gums, peritonitis.

Disorders from the metabolism and nutrition:

Often - decreased appetite;

Infrequently, anorexia.

Disorders from the liver and bile ducts:

Infrequent - jaundice.

Impaired nervous system:

Very often - headache;

Often - peripheral dizziness, dysgeusia.

Infrequent - syncope, tremor, paresthesia.

Disturbances from the respiratory system, chest and mediastinal organs:

Often - cough, swelling of the nasal mucosa, pain in the larynx and pharynx, dyspnoea, rhinorrhea;

Infrequent - hemoptysis, choking in the throat.

Disorders of the psyche:

Uncommon - unusual dreams, anxiety, depression, insomnia, mood swings, sleep disturbances.

Disorders from the kidneys and urinary tract:

Infrequent - hematuria, dysuria, renal dysuria.

Disturbances from the skin and subcutaneous tissues:

Often - alopecia, itching, rash;

Infrequent - urticaria, dermatitis, erythema, petechia, a violation of skin pigmentation, hyperhidrosis, dry skin.

Disturbances from the musculoskeletal and connective tissue:

Often - arthralgia, back pain, myalgia, neck pain, pain in the extremities, bone pain, muscle spasms;

Infrequent - swelling of the joints, trismus.

Infectious and parasitic diseases:

Often - infections of the upper respiratory tract,urinary tract infections, including viral, nasopharyngitis, bronchitis, mucosa of oral herpes, meningococcal sepsis, bacterial arthritis, aspergillosis;

Infrequently - lower respiratory tract infections, gastrointestinal tract, cystitis, sinusitis, infections of dental tissues and gums, abscesses and subcutaneous tissue inflammation, fungal infection, influenza, of Neisseria infection and of Haemophilus, impetigo, meningococcal meningitis, sepsis, septic shock, pneumonia.

Immune system disorders:

Often - anaphylactic reactions;

Infrequent reactions are hypersensitivity.

Violations of the genitals and breast:

Infrequent - violations of the menstrual cycle, spontaneous erection.

General disorders and disorders at the site of administration:

Often - a sense of discomfort in the chest, chills, weakness, swelling, fever, fatigue, flu-like symptoms;

It is not often - pain in the chest, paresthesia, bruising and pain at the injection site, feeling of "heat".

Laboratory and instrumental data:

Often - a positive test of Coombs *;

It is not often - increasing the activity of aspartate aminotransferase, increased alanine aminotransferase activity, increased activity of gamma-glutamyl transferase, decreased hemoglobin concentration and hematocrit.

Injuries, poisonings and procedural complications:

Infrequently - nonspecific reactions at the site of administration

* - for more information, see the "Additional Information" section.

Additional Information

Among the side effects recorded during all clinical studies in patients with APG or AGU, the most severe was meningococcal septicemia.

Antibodies to Soliris® were determined in 2% of patients with APG and in 3% of patients with AGU treated with the drug.

An increase in the immunogenicity of the body is characteristic of all protein preparations.

Hemolysis cases were noted during the miss or delay in the introduction of a regular dose of Soliris® in patients with APG.

Clinical manifestations of thrombotic microangiopathy were noted on admission

or delayed introduction of a regular dose of Soliris® in patients with ASUS.

Children

A generalized analysis of safety data did not reveal differences in the safety profile in children aged 11-18 years and in adult APG patients. Children most often had a headache. According to studies in children aged 2 months to 18 years, the safety profile does not differ from that in adult patients with ASUS.

Patients with other diseases

Safety data from other clinical trials

A generalized analysis of data from all clinical studies performed with the Soliris® preparation (11 studies, 716 patients) with 6 other nosological forms than APG and AGU revealed 1 case of meningococcal meningitis in an unvaccinated patient with idiopathic membranous glomerulonephropathy.

For other AEs, analysis of data from all double-blind, placebo-controlled studies in patients without APG (526 patients receiving Soliris®, 221 patients received a placebo), with a frequency of 2% or more than in the placebo group, revealed the following AEs: infections upper respiratory tract, rash and injury.

Overdose:

Cases of an overdose of eculisumab are unknown.

Interaction:

Pharmaceutical

The preparation of Soliris® can be mixed only with 0.9% sodium chloride solution, 0.45% sodium chloride solution or 5% dextrose (glucose) solution for injection

Special instructions:

The use of Soliris® should be performed under the supervision of a physician.

Do not inject intravenously! Soliris® does not affect the aplastic component of anemia in patients with APG.

Women of childbearing age Women of reproductive age should use reliable contraceptive methods during treatment with Soliris® and within 5 months after its completion.

Meningococcal infection: the mechanism of action of the drug Soliris® involves an increased risk of developing meningococcal infection (Neisseria meningitidis) against its background. As pathogenic, any serotypes, including atypical ones, for example Y, W135 and X can be considered. In order to reduce the likelihood of infection, all patients should be vaccinated against meningococcus 2 weeks prior to use of the Soliris® preparation. Patients with ASUS who received Soliris® treatment earlier than 2 weeks after vaccination against meningococcal infection should receive appropriate prophylactic antibiotic therapy within 2 weeks after vaccination. All patients should also be revaccinated according to the existing standards in the Russian Federation. Most preferred is a conjugated tetravalent vaccine against serotypes A, C, Y and W135. In some cases, vaccination does not have a sufficient protective effect.When choosing an antibacterial drug for the treatment of this complication, it is necessary to strictly follow the official recommendations.

All patients should be informed of the early symptoms of meningococcal infection and the need to seek medical help immediately.

Other Systemic Infections The mechanism of action of the Soliris® drug also suggests the possibility of activating a latent infection, although clinical studies have not revealed differences in incidence, severity, or location of infections in patients receiving Soliris® and placebo.

Nevertheless, patients should be warned about the possibility of activating the infection against the background of treatment with Soliris® and its possible symptoms.

Infusion reactions

Intravenous administration of the preparation Soliris®, as well as the introduction of other protein preparations, may be accompanied by hypersensitivity reactions, including anaphylaxis. Despite the lack of clinical data on the development of such reactions in the treatment with the preparation Soliris 8 ', in the case of a severe infusion reaction, the drug should be discontinued and symptomatic therapy should be prescribed.

Immunogenicity

A low antibody titer was detected in patients treated with Soliris® (3.4%) and placebo (4.8%). In patients with ASUS who received Soliris ®, the appearance of antibodies to Soliris was reported in 3 cases out of 100 (3%).

In 1 case, out of 100 (1%) patients with AGU registered the appearance of neutralizing antibodies. No correlation was found between the antibody titer and the clinical efficacy of the drug or its side effect.

Immunization

Before starting therapy with Soliris®, all patients with APG and AGU should undergo a full vaccination in accordance with the National Vaccination Pro- gramme. In addition, at least 2 weeks before the start of treatment with Soliris®, all patients must necessarily be given a meningococcal vaccine, preferably tetravalent conjugate.

Patients who received Soliris® treatment earlier than 2 weeks after vaccination against meningococcal infection should receive appropriate prophylactic antibiotic therapy within 2 weeks after vaccination. Patients younger than 18 years of age should also be vaccinated against hemophilic rods and pneumococci in strict accordance with the national vaccination calendar.

Anticoagulant therapy

Recommendations for anticoagulant therapy should not be changed in connection with the appointment of Soliris®.

Laboratory control in the treatment of APG

In patients with APG on the background of treatment with Soliris ® to control the expression of intravascular hemolysis, it is necessary to determine the activity of lactate dehydrogenase in the blood serum. If it is necessary to correct the dose during the period of maintenance therapy, the frequency of administration of the drug, determined within 14 ± 2 days, can be increased up to 1 time every 12 days.

Laboratory control in the treatment of ASUS

In patients with AGU on the background of treatment with Soliris®, TMA should be monitored by regular monitoring of platelet count, lactate dehydrogenase activity and serum creatinine. If it is necessary to correct the dose during the period of maintenance therapy, the frequency of administration of the drug, determined by 14 ± 2 days, can be increased up to 1 time every 12 days.

Discontinuation of treatment of APG patients Patients for whom Soliris® therapy has been discontinued should be under medical supervision to ensure control of intravascular hemolysis.Signs of severe hemolysis are: LDH activity in the serum is higher than before the initiation of therapy with Soliris®, in combination with one of the following indicators: a decrease of more than 25% in the APG cell population (in the absence of the dilution effect in case of blood transfusion) for 1 week or before; the concentration of hemoglobin is less than 50 g / l or its decrease by more than 40 g / l for 1 week or earlier; the appearance of angina pectoris or an increase in its severity; mental disorders; an increase in the concentration of creatinine in the blood by 50% or thrombosis. The duration of follow-up of patients after discontinuation of Soliris® should be at least 8 weeks.

In case of signs of severe hemolysis after discontinuation of treatment with Soliris®, it is recommended to appoint blood transfusion (erythrocyte mass) or exchange blood transfusion if, according to flow cytometry, the population of APG cells is> 50% of the total number of erythrocytes; and also to prescribe anticoagulants, corticosteroids or to resume therapy with Soliris®. Data from observations of 16 patients with APG, whose therapy with Soliris® was discontinued, did not reveal an increase in intravascular hemolysis intensity.

Discontinuation of treatment of patients with ASUS In the course of the clinical study of the preparation of Soliris®, the development of severe complications of thrombotic microangiopathy in patients with ASUS was observed after the abolition of therapy. Patients with ASUS who have been discontinued with Soliris® should be under medical supervision to monitor the signs and symptoms of severe complications of thrombotic microangiopathy.

Signs of severe complications of TMA after the discontinuation of Soliris® are: (1) any two or repeated detectable changes in one of the following: a decrease in the number of platelets by 25% and lower than the baseline value or the maximum platelet count during treatment with Soliris®; an increase in the serum creatinine concentration by 25% or more, as compared with the baseline or minimum level during therapy with Soliris®; or an increase in serum LDH activity of 25% or more, as compared with the baseline value or the minimum value during therapy with Soliris®; or (2) any of the following symptoms: a change in the psyche or seizures; angina or shortness of breath; thrombosis.

The duration of follow-up after the discontinuation of Soliris® for the detection of severe complications of TMA should be at least 12 weeks.

In case of severe complications of TMA after discontinuation of treatment with Soliris®, it is recommended to resume Soliris® therapy, prescribe maintenance treatment with plasmapheresis or exchange plasma transfusions or appropriate specific maintenance therapy, including hemodialysis, pulmonary ventilation or anticoagulant therapy. In the course of clinical studies of the preparation Soliris®, 18 patients with ASUS were abolished by Soliris (in 5 patients in prospective studies) .After passing the next dose of the drug, seven severe complications of TMA developed in five patients, and in 4 of these 5 patients, Soliris ® was resumed.

Training materials All physicians who plan to prescribe Soliris® should read the "Physician's Guide for the use of the Soliris® drug". It is necessary to instruct patients that if the body temperature rises above 39 ° C,the development of a headache in combination with fever and / or a feeling of "stiffness" of the neck or photophobia, they should immediately seek medical help, as this may be signs of a meningococcal infection. Auxiliary substances

For patients on a strict salt-free diet, it should be borne in mind that each vial of the drug contains 5.00 mmol of sodium.

The unused drug remaining in the syringe should be immediately disposed of, since its composition does not include preservatives.

Do not reuse syringe or needles.

Any unused or consumable material must be disposed of in accordance with local requirements.

Effect on the ability to drive transp. cf. and fur:

Studies to study the effect on the ability to drive vehicles and the use of mechanisms have not revealed a negative effect of the preparation of Soliris®; nevertheless, taking into account the possibility of developing unwanted reactions against the background of drug treatment (for example, headache, dizziness, weakness), driving and working with machinery.

Form release / dosage:

Concentrate for the preparation of a solution for infusions of 10 mg / ml.

Packaging:

30 ml of preparation in a bottle of transparent colorless glass (type 1) with a capacity of 30 ml, sealed with a rubber stopper, sealed on top by an aluminum cap with a detachable plastic lid.

1 bottle with instructions for use in a cardboard pack.

Storage conditions:

In a dark place at a temperature of 2 to 8 ° C, do not freeze. Keep out of the reach of children.

Shelf life:

2.5 years

Do not use after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001159

Date of registration:11.11.2011

The owner of the registration certificate:Alexion Pharma International SarlAlexion Pharma International Sarl Switzerland

Manufacturer: & nbsp

PATHEON ITALIA, S.p.A. Italy

DSM Pharmaceuticals, Inc. USA

Representation: & nbspRAYFARM, LLCRAYFARM, LLC

Information update date: & nbsp21.10.2015

Illustrated instructions

Instructions

Soliris® (Soliris®)