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Instruction for use: Soliris
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Dosage form: Concentrate for solution for infusion
Active substance: Eculizumabum
ATX
L04AA25 Eculisumab
Pharmacological group:
Immunodepressants
The nosological classification (ICD-10)
D59.3 Hemolytic-uremic syndrome: Hemolytic-uremic syndrome; Gasser's Disease; Gasser's syndrome; Gasser-Carrera disease
D59.5 Paroxysmal nocturnal hemoglobinuria [Marietaafy-Micheli]: Marietaafy-Micheli syndrome; Paroxysmal hemoglobinuria (night and cold)
Composition
Concentrate for solution for infusion - 1 ml
active substance: Ekulizumab 10 mg
Auxiliary substances: 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 ml
Description of dosage form
Clear colorless solution.
Characteristic
Ekulizumab is a recombinant humanized monoclonal antibody - κ-immunoglobulin (IgG2 / 4k), which binds to the human complement C5 protein and suppresses the activation of complement-mediated cell lysis. The antibody consists of human Ig 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.
Ekulizumab is produced in the mouse myeloma line NS0 cell culture and purified by affinity and ion exchange chromatography. The process of production of the substance also includes the processes of specific inactivation and removal of viruses.
Pharmachologic effect
Mode of action - Immunosuppressive.
Pharmacodynamics
Ekulizumab suppresses the activity of the terminal complex of human complement, having a high affinity for its C5-component. As a consequence, the splitting of the C5 component into C5a and C5b and the formation of the terminal complex of the complement C5b-9 is completely blocked. Thus, ekulizumab restores the regulation of complement activity in the blood and prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria (APG), and also prevents excessive activation of the terminal complement complex in patients with atypical hemolytic-uremic syndrome (AGU), where the cause of the disease is genetically determined dysregulation Complement system. On the other hand, the deficiency of the terminal complement complex is accompanied by an increased incidence of infections with encapsulated microorganisms, mainly meningococcal infection. In this case, ekulizumab maintains the content of early complement activation products necessary for opsonization of microorganisms and elimination of immune complexes.
The appointment of patients with the preparation of Soliris® is accompanied by a rapid and stable decrease in the activity of the terminal complement complex. In most patients with APG, the concentration of euculizumab in the blood plasma is about 35 μg / ml sufficient to completely inhibit intravascular hemolysis induced by activation of the terminal complement complex.
In patients with AGU chronic uncontrolled activation of complement, which, in turn, induces the development of thrombotic microangiopathy (TMA), is also blocked against the background of 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 the blood plasma is of the order of 50-100 μg / ml, sufficient for practically complete inhibition of the activity of the terminal complement complex.
The results of 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
APG. The efficacy and safety of Soliris® in patients with APG and with hemolysis was assessed in a double-blind, placebo-controlled 26-week study (Triumph, 87 patients), a 52-week open non-randomized study (Sheperd, 97 patients), and an open expanded study , Which included patients from 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, as measured by LDH activity. As a consequence, the severity of anemia decreased, which was confirmed by the stabilization of hemoglobin and the decrease in 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 international observational study "The Register of Patients with APG" (M07-001) evaluated the efficacy of the drug in patients without blood transfusions in the anamnesis, but with active hemolysis, which was confirmed by an increase in LDH levels 1.5 times higher than IGN and the presence of concomitant clinical symptoms: fatigue , Hemoglobinuria, abdominal pain, dyspnea, anemia (hemoglobin <100 g / l), severe vascular complications (including thrombosis), dysphagia or erectile dysfunction.
The study found that the appointment of the drug Soliris® to such patients was accompanied by a significant (p <0.001) decrease in hemolysis (the evaluation was carried out to reduce LDH) and concomitant clinical symptoms, including fatigue.
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® according to the recommended dosing regimen was accompanied by a decrease in intravascular hemolysis measured by LDH. There was also a significant decrease 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).
AGU
The efficacy and safety of Soliris® was studied in prospective clinical trials in adult and pediatric populations with a total of 100 patients. In the studies, the following groups participated: patients with newly diagnosed ASUS and signs of TMA (thrombocytopenia below 150,000 / μL, LDH and creatinine higher than UGN), as well as patients with a long-term 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 persisted for two years (88 and 90% of patients, respectively). Conducted therapy led to inhibition of complement-mediated TMA and the absence of TMA symptoms (in 80 and 88% of patients, respectively) persisting for 2 years: in 88 and 95% of patients, respectively.
During therapy with Soliris®, there was a significant improvement in kidney function, assessed by the level of the calculated glomerular filtration rate (rSCF): an improvement in rSCP> 15 mL / min / 1.73 m2 was observed in both studies in 4 and 53% of patients, respectively, and persisted For 2 years in 59 and 40% of patients, respectively. Normalization of hematological parameters reached 76 and 90% of patients, respectively, in both studies with positive dynamics for 2 years in 88 and 90% of patients, respectively.
Pharmacokinetics
Metabolism. Human antibodies under the action of lysosomal enzymes in the cells of the reticuloendothelial system are cleaved up 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 kDa), ekulizumab is not excreted unchanged in urine. The average clearance is (0.31 ± 0.12) ml / h / kg, the mean Vd is (110.3 ± 17.9) ml / kg, and the mean T1 / 2 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 blood plasma ≥35 μg / ml, the majority of patients had almost complete blockade of hemolytic activity.
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 depending on weight, the lowest clearance of euculizumab 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.
Indication of the drug Soliris
Paroxysmal nocturnal hemoglobinuria (the efficacy of the drug Soliris® is confirmed in patients with hemolysis and concomitant clinical symptoms, indicating a high activity of the disease, regardless of the need for blood transfusions in the anamnesis);
Atypical hemolytic-uremic syndrome.
Contraindications
Increased sensitivity to ekulizumab, proteins of mouse origin or other components of the drug;
Breastfeeding period
For patients with paroxysmal nocturnal hemoglobinuria
Active infection Neisseria meningitidis;
Lack of vaccination against Neisseria meningitidis.
For patients with atypical hemolytic-uremic syndrome
Active infection Neisseria meningitidis;
The lack of vaccination against Neisseria meningitidis or failure to receive an appropriate preventive course of antibiotic therapy within 2 weeks after vaccination.
With caution: taking into account the mechanism of action of the preparation Soliris®, it must be cautiously prescribed to patients with active systemic infections; As well as patients with impaired liver and kidney function (due to lack of clinical experience).
Application in pregnancy and breastfeeding
There were no controlled studies of the drug during pregnancy.
It is known that human IgG passes through the placental barrier, and therefore, 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 echulizumab penetrates breast milk, but considering 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").
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 are summarized data on adverse reactions noted during clinical trials and in the postmarketing period in patients with APG or AGU receiving eculizumab according to the lesions of organs and systems of organs (MedDRA) and the WHO classification by frequency: very often ( ≥1 / 10); Often (≥1 / 100, <1/10); Infrequently (≥1 / 1000, <1/100); Rarely (≥1 / 10000, <1/1000) and very rarely (<1/10000).
On the part of 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.
From the heart: rarely - a feeling of palpitations.
From the side of the vessels: often - a decrease in blood pressure; Infrequently - hematoma, increased blood pressure, malignant hypertension, hot flushes, venous diseases.
From the side of the organ of hearing and labyrinthine disorders: infrequent - ringing in the ears; Vertigo (vestibular dizziness).
From the endocrine system: infrequently - hyperthyroidism.
From the side of the organ of vision: infrequently - irritation of the conjunctiva, vague vision.
From the digestive tract: often - abdominal pain, constipation, diarrhea, indigestion, nausea, vomiting; Infrequent - bloating, gastroesophageal reflux, pain in the gums, peritonitis.
From the side of metabolism and nutrition: often - a decrease in appetite; Infrequently - anorexia.
From the liver and biliary tract: infrequently - jaundice.
From the nervous system: very often - headache; Often - peripheral dizziness, dysgeusia; Infrequently - a syncope, a tremor, paresthesias.
From the respiratory system, chest and mediastinum: often - cough, swelling of the nasal mucosa, pain in the larynx and pharynx, dyspnoea, rhinorrhea; Infrequently - hemoptysis, choking in the throat.
Disorders of the psyche: infrequent - unusual dreams, anxiety, depression, insomnia, mood swings, sleep disturbances.
From the side of the kidneys and urinary tract: infrequently - hematuria, dysuria, renal dysuria.
From the skin and subcutaneous tissues: often - alopecia, itching, rash; Infrequently - hives, dermatitis, erythema, petechia, skin pigmentation, hyperhidrosis, dry skin.
From the musculoskeletal and connective tissue: often - arthralgia, back pain, myalgia, neck pain, pain in the extremities, bone pain, muscle spasms; Infrequently - swelling of the joints, trismus.
Infectious and parasitic diseases: often - infections of the upper respiratory tract, urinary tract, incl. Viral, nasopharyngitis, bronchitis, herpes mucosa of the oral cavity, meningococcal sepsis, bacterial arthritis, aspergillosis; Infrequently, lower respiratory tract infections, gastrointestinal tract, cystitis, sinusitis, dental and gum tissue infections, abscesses and inflammations of subcutaneous tissue, fungal infections, influenza, Neisseria and Haemophilus infections, impetigo, meningococcal meningitis, sepsis, septic shock, pneumonia.
From the immune system: often - anaphylactic reactions; Infrequently - reactions of hypersensitivity.
From the genitals and the breast: infrequently - violations of the menstrual cycle, spontaneous erection.
General disorders and disorders at the injection site: often - a feeling of discomfort in the chest, chills, weakness, swelling, fever, asthenia, flu-like syndrome; Infrequently - pain in the chest, paresthesia, bruising and pain at the injection site, a feeling of heat.
Laboratory and instrumental data: often - a positive test of Coombs *; Infrequently, an increase in AST activity, an increase in ALT activity, an increase in GGT activity, a decrease in hemoglobin and hematocrit concentration.
Injuries, poisonings and procedural complications: infrequently, nonspecific reactions at the site of administration.
* For more information, see Additional Information.
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 the preparation Soliris® were determined in 2% of APG patients and 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 when a dose of Soliris® was missed or delayed 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 research, 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 with Soliris® (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 adverse events, an analysis of all double-blind, placebo-controlled studies in patients without APG (526 patients receiving Soliris®, 221 patients receiving a placebo), with a frequency of 2% or more than in the placebo group, revealed the following adverse events : Upper respiratory tract infections, rashes and lesions.
Interaction
Pharmaceutical. Soliris ® can be mixed only with 0.9% sodium chloride solution, 0.45% sodium chloride solution or 5% dextrose (glucose) solution for injection.
Dosing and Administration
IV, drop, for 25-45 minutes - for adults and 1-4 hours - for children.
APG. The course of treatment for adult patients (over ≥18 years) includes a 4-week initial cycle followed by a cycle of maintenance therapy. The initial cycle is 600 mg of Soliris® once a week for 4 weeks. Supportive therapy - 900 mg of Soliris® for the 5th week, followed by 900 mg of Soliris® every 14 (± 2) days.
For patients with APG younger than 18 years, the dose of Soliris® is determined according to the weight of the child (Table 1):
Table 1
| Body weight, kg | Initial cycle | Supportive therapy |
| ≥40 | 600 mg once a week × 4 | 900 mg for the 5th week; Then 900 mg every 2 weeks |
| 30 — <40 | 600 mg once a week × 2 | 900 mg for the 3rd week; Then 900 mg every 2 weeks |
| 20 — <30 | 600 mg once a week × 2 | 600 mg for the 3rd week; Then 600 mg every 2 weeks |
| 10 — <20 | 600 mg once a week × 1 | 300 mg for the 2nd week; Then 300 mg every 2 weeks |
| 5 — <10 | 300 mg once a week × 1 | 300 mg for the 2nd week; Then 300 mg every 3 weeks |
For patients with AGU younger than 18 years, the dose of Soliris® is determined according to the weight of the child (see Table 2).
Table 2
| Body weight, kg | Initial cycle | Supportive therapy |
| ≥40 | 600 mg once a week × 4 | 1200 mg for the 5th week; Then 1200 mg every 2 weeks |
| 30 — <40 | 600 mg once a week × 2 | 900 mg for the 3rd week; Then 900 mg every 2 weeks |
| 20 — <30 | 600 mg once a week × 2 | 600 mg for the 3rd week; Then 600 mg every 2 weeks |
| 10 — <20 | 600 mg once a week × 1 | 300 mg for the 2nd week; Then 300 mg every 2 weeks |
| 5 — <10 | 300 mg once a week × 1 | 300 mg for the 2nd week; Then 300 mg every 3 weeks |
| Type of plasma procedure | Previous dose of Soliris® | A further dose of Soliris® after each plasma procedure | Time of administration of an additional dose of Soliris® |
| Plasmapheresis or exchange transfusion of plasma | 300 mg | 300 mg per each plasmapheresis or exchange transfusion of plasma | Within 60 min after each plasmapheresis or exchange transfusion of plasma |
| ≥600 mg | 600 mg per each plasmapheresis or exchange transfusion of plasma | ||
| Infusion of fresh-frozen plasma | ≥300 mg | 300 mg per each freshly frozen plasma | 60 minutes prior to infusion of each freshly frozen plasma unit |
Control during treatment
During treatment of patients with ASUS, symptoms of TMA should be monitored. It is recommended lifelong treatment with Soliris®, except when there are medical indications for discontinuing treatment.
For IV administration of a diluted solution of the Soliris® preparation, special infusion systems with controlled delivery should be used. It is not necessary to protect the diluted drug solution from light during administration.
After the end of the drug administration, 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 physician's discretion. With a decrease in the rate of Soliris® administration, the total infusion time should not exceed 2 hours for adults and children aged 12 to 18 years and 4 hours for children under 12 years of age.
Peculiarities of application in individual patient groups
Elderly patients. The drug can be administered to patients over 65 years of age. Elderly patients do not need a special dosing regimen and adherence to special precautions, although the clinical experience of treating this age group of patients is limited.
Patients with impaired renal function. Correction of the dose of Soliris® in patients with impaired renal function is not required.
Patients with impaired liver function. Special studies of the efficacy and safety of Soliris® in patients with impaired liver function were not performed (see "With caution").
Recommendations for solution preparation and infusion
Do not mix Soliris® for intravenous administration with another drug in one syringe or vial!
Using a sterile syringe with a needle, collect the entire contents of the vial / flasks with the Soliris® preparation and transfer the recommended dose into the vial with the infusion solution.
Dilute Soliris® to a final concentration of 5 mg / ml with 0.9% sodium chloride solution, 0.45% sodium chloride solution or 5% dextrose (glucose) solution for injection.
The final volume of diluted Soliris® preparation to a final concentration of 5 mg / ml is 60 ml (for a dose of 300 mg), 120 ml (for a dose of 600 mg), 180 ml (for a dose of 900 mg) and 240 ml (for a dose of 1200 mg).
The finished solution should be clear and colorless. If the solution is dyed or visible inclusions are detected, its use is not allowed. The finished solution should not be stored for more than 24 hours at a temperature of 2 to 8 ° C. Immediately before administration, the contents of the infusion bottle must be gently shaken to ensure that the preparation and the solvent are mixed. The solution temperature during the injection should be 20-25 ° C.
Overdose
Cases of an overdose of ekulizumab are unknown.
Special instructions
The use of Soliris® should be performed under the supervision of a physician.
Do not administer the drug 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 methods of contraception 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 before using Soliris®.
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. The conjugated tetravalent vaccine against serotypes A, C, Y and W135 is most preferred. 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 activation of a latent infection, although clinical studies have not revealed differences in the incidence, severity, or localization 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. IV the introduction of the preparation Soliris®, as well as the introduction of other protein preparations, can be accompanied by hypersensitivity reactions, including anaphylaxis. Despite the lack of clinical data on the development of such reactions in the treatment with Soliris®, in the case of a severe infusion reaction, the drug should be discontinued and symptomatic therapy is prescribed.
Immunogenicity. A low antibody titer was determined in patients treated with Soliris® (3.4%) and placebo (4.8%). In patients with ASUS who received Soliris ®, the appearance of antibodies to the preparation Soliris ® was registered in 3 cases out of 100 (3%). In 1 case, out of 100 (1%) in patients with ASUS, the appearance of neutralizing antibodies was registered. 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 Calendar for Prophylactic Vaccines. 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 under the age of 18 must also be vaccinated against hemophilic rods and pneumococci in strict accordance with the national immunization schedule.
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, the activity of LDH in serum is necessary. If it is necessary to correct the dose during the period of maintenance therapy, the frequency of drug administration, determined by the frames (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 the 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 drug administration, determined by the frames (14 ± 2) days, can be increased up to 1 time every 12 days.
Termination of treatment of patients with APG. Patients for whom Soliris® therapy has been discontinued should be under medical supervision to monitor intravascular hemolysis. Signs of severe hemolysis are: LDH activity in the serum is higher than before the start 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 after the discontinuation of Soliris® should be at least 8 weeks.
In case of signs of severe hemolysis after stopping treatment with Soliris®, it is recommended to appoint blood transfusion (erythrocyte mass) or exchange blood transfusion if, according to flow cytometry, APG cell population> 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.
Termination of treatment of patients with ASUS. After the cancellation of treatment with Soliris®, some patients with ASUS experienced a resumption of symptoms of TMA, between 4 and 127 weeks after discontinuation of therapy. In clinical trials of the AGU a total of 61 patients (21 of them) stopped taking Soliris®, the average follow-up period was 24 weeks. After the cessation of treatment in 12 patients, there were fifteen serious complications associated with the resumption of TMA. Two more cases of severe manifestations of TMA occurred in 2 patients who received the preparation of Soliris® at a lower dose - outside the approved dosage regimen. Serious manifestations of TMA were observed in patients, regardless of whether they had genetic mutations, a high risk of polymorphism or autoantibodies. These patients had additional serious medical complications, including. A sharp deterioration in kidney function; Diseases requiring hospitalization; And progression of CKD to the terminal stage of renal failure requiring renal replacement therapy. Despite the resumption of Soliris® after the cessation of therapy, one patient developed progression to the terminal stage of renal failure. Patients with ASUS who have been discontinued with Soliris® should be under medical supervision to monitor the signs and symptoms of severe complications of TMA. Monitoring may not be sufficient to predict or prevent severe manifestations of TMA in patients with ASUS after the discontinuation of Soliris®.
Signs of TMA manifestations after the discontinuation of Soliris® are: (1) any two or re-revealed 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 to the baseline or minimum level during therapy with Soliris®; Or an increase in serum LDH activity of 25% or more, as compared to the baseline or minimum value during therapy with Soliris®; Or (2) any of the following symptoms: a change in the psyche, seizures, angina, shortness of breath, thrombosis.
In the case of severe complications of TMA, it is recommended that, following discontinuation of treatment with Soliris®, it be advisable to resume therapy with Soliris®, prescribe maintenance treatment with plasmapheresis or exchange plasma transfusions, or appropriate specific maintenance therapy, including hemodialysis, artificial lung ventilation or anticoagulant therapy.
Teaching materials. All doctors who plan to prescribe Soliris® should read the "Guide for the physician on the use of the Soliris® drug". Patients should be instructed that if the body temperature rises above 39 ° C, the development of a headache in combination with fever and / or a feeling of stiff neck or photophobia, they should immediately seek medical help. It may be signs of meningococcal infection.
Excipients. Patients on a strict salt-free diet should bear in mind that each vial of the drug contains 5 millimoles of sodium.
The unused drug remaining in the syringe should be immediately disposed of, since It does not include preservatives.
Do not reuse the syringe or needles.
Any unused or consumable material must be disposed of in accordance with local requirements.
Effect on the ability to drive and work with machinery. Studies on the effect on the ability to drive vehicles and the use of mechanisms have not revealed a negative effect of the preparation of Soliris®, however, considering the possibility of developing unwanted reactions against the background of drug treatment (for example, headache, dizziness, weakness), care must be taken in managing Car and work with mechanisms.
Release form
Concentrate for solution for infusion, 10 mg / ml. 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 with an aluminum cap with a detachable plastic lid. On 1 ôë. Placed in a cardboard box.
Manufacturer
Production of ready-made dosage form and packing:
1. Pateon Manufakchuring Service, LLS, 5900 Martin Luther King J. Highway, Greenville, North Carolina, 27834, USA.
2. Pateion Italy SpA:
A) Viale G.B. Stukki, 110 - 20900 Monza (MB), Italy;
B) 2 Herbs. SX Via Morolense, 5 - 03013 Ferentino (FR), Italy.
Issued quality control:
1. Almac Pharma Services Ltd., 22 Siago Industrial Estate, Craigavon, Co. Armah VT63 5UA, United Kingdom.
2. Pateion Italy SpA, Viale G.B. Stukki, 110 - 20900 Monza (MB), Italy.
Name and address of the legal entity in whose name the registration certificate was issued (RU owner): Alexion Pharma International Sarl, Avenue du Tribunal Federal 34, 1005 Lausanne, Switzerland.
To receive additional information about the preparation, as well as to send your complaints and information about undesirable phenomena, you can go to the following address in Russia: Alexon Pharma LLC, 143421, Moscow Region
Conditions of supply of pharmacies
On prescription.
Storage conditions of the drug Soliris
In the dark place at a temperature of 2-8 ° C (do not freeze).
Keep out of the reach of children.
Shelf life of the drug Soliris
Concentrate for solution for infusions 10 mg / ml - 2 years 6 months.
Concentrate for solution for infusions 10 mg / ml - 2.5 years.
Do not use after the expiry date printed on the package.
