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

Active substanceSebelipase alfaSebelipase alfa

Similar drugsTo uncover

Kanuma

concentrate d / infusion

Alexion Europe CAC France

Dosage form: & nbspconcentrate for solution for infusion

Composition:

Composition per ml:

active substance: Implipase alpha 2 mg,

auxiliary components:

trisodium citrate dihydrate 13.7 mg, citric acid monohydrate 1.57 mg, human serum albumin 10 mg, water for injection up to 1 ml.

Description:

Transparent to slightly opalescent, from colorless to light yellow with a greenish tinge, without visible foreign particles. Semitransparent protein-like particles may be present.

Pharmacotherapeutic group:Preparations for the treatment of diseases of the digestive tract and metabolic disorders - enzymes

ATX: & nbsp

A.16.A.B.14 Sebelipase alfa

Pharmacodynamics:

Characteristics of the preparation

Sebelipase alpha is a recombinant human lysosomal acid lipase (rhLAL), purified from the egg protein of transgenic chickens, with the same amino acid sequence as the native human enzyme. Purified amylipase alpha is a glycoprotein with 6 N-linked sites of glycosylation. The glycans of the amylipase alpha are mainly composed of N-acetylglucosamine (GlcNAc) and N-linked structures terminating in mannose, as well as mannose-6-phosphate fragments. Described N-glikanovye structure facilitates the absorption of the protein in the macrophage cells via mannose or mannose-6-phosphate receptor.

Farmacodynamics

Sebelipaza alpha - recombinant lysosomal acidic lipase, an enzyme which is used as an enzyme replacement therapy, in order to improve lipid metabolism and reduce the accumulation of cholesterol esters and triglycerides in patients of all ages under deficiency of lysosomal acidic lipase (DLKL).

The deficiency of lysosomal acid lipase (historically Wolman's disease, the accumulation of cholesterol esters) is a rare autosomal recessive lysosomal accumulation disease characterized by a genetic defect LAL gene, and leading to a marked decrease or loss of activity of the enzyme lysosomal acid lipase (LCL). This deficiency is characterized by the absence of cleavage of cholesterol esters and triglycerides in lysosomes.

Lysosomal accumulation of esters of cholesterol and triglycerides in the liver leads to hepatomegaly, an increase in the specific proportion of fat in the hepatic tissue, an increase in the levels of transaminases,signaling chronic liver damage, as well as progression to fibrosis, cirrhosis and complications of the terminal stage of liver failure. In the spleen, DLL causes splenomegaly, in the blood - anemia and thrombocytopenia. The accumulation of lipids in the intestinal wall leads to malabsorption and disruption of growth and development. Dyslipidemia is often accompanied by a rise in low-density lipoprotein (LDL) and triglyceride levels and a decrease in high-density lipoprotein (HDL) and is associated with an increase in the specific percentage of fat in liver tissue and a rise in the level of transaminases in the blood. Patients with DLLL have an increased risk of developing cardiovascular disease and a higher rate of atherosclerosis. Deficiency of the enzyme also leads to a decrease in the production of free cholesterol, which leads to an increase in the synthesis of apo-B-containing lipoproteins and slowing down the formation of HDL particles.

Other lipid-modifying agents can lower LDL cholesterol in patients with LDL, but they do not affect the progression of liver disease, since these drugs do not affect the underlying cause of the enzyme deficiency.

Based on the results of experimental pharmacological data and clinical studies, it was shown that KANUMA preparation, being a pathogenetic agent of DLLL therapy, promotes improvement of lipid metabolism and normalization of hepatic enzymes level in conditions associated with DLLL.

Mechanism of action

Sebelipase alpha binds to cell membrane receptors through glycans expressed on a protein and is subsequently absorbed by lysosomes. Sebelipase alfa catalyzes the lysosomal hydrolysis of esters of cholesterol and triglycerides to free cholesterol, glycerol and free fatty acids. Substitution of enzymatic activity of LCL leads to a decrease in the specific percentage of fat in liver tissue and normalization the level of transaminases in the blood, and also restores the metabolism of cholesterol and triglyceride esters in lysosomes, which leads to lower levels of low-density lipoprotein (LDL) cholesterol and low-density lipoprotein (LNVV), triglycerides, and high-density lipoprotein (HDL) cholesterol. Improved growth and development of the body occurs as a result of a decrease in the accumulation of lipids in the wall of the intestine and, as a consequence,improve the absorption of nutrients.

Clinical efficacy and safety

Research the children with newly diagnosed deficiency of lysosomal acid lipase

Study LAL-CL03 was a multicentre open noncomparative study of the drug KANUMA in 9 patients with DLL with developmental disability or other signs of rapidly progressing disease at the age of up to 6 months. Patients also suffered rapidly progressive insufficiency of liver function and severe hepatosplenomegaly. The age range for inclusion in the study was 1-6 months. Patients received the drug KANUMA at a dose of 0.35 mg / kg once a week for the first 2 weeks and then 1 mg / kg once a week. According to the clinical response, the dose was raised to 3 mg / kg once a week after 1 month and up to 20 months from the start of treatment at a dose of 1 mg / kg. It was allowed to further increase the dose to 5 mg / kg once a week.

Efficacy was assessed by comparing the survival experience of patients treated with KANUMA, who survived to age 12 months and older in the study LAL CL03, with a historical cohort of untreated infants who have been diagnosed with DLL with similar clinical symptoms. In the study LAL CL03 Six out of nine infants who received the drug KANUMA survived to 12 months or more (67% 12 month survival, 95% CI: 30% to 93%). With the continuation of treatment after 12 months of age, 1 patient died at the age of 15 months. In a historical cohort, 0 out of 21 patients experienced an 8-month age (0% 12 month survival, 95 % CI: 0% to 16 %).

Taking the drug KANUMA in doses up to 1 mg / kg once a week led to an improvement in the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (ACT) and to weight gain during the first few weeks of treatment. From baseline to week 48, average ALT decline and ACT were 34.0 U / L and 44.5 U / L, respectively. An increase in the dose to 3 mg / kg once a week was associated with an additional improvement in the indices of weight gain, lymphadenopathy and serum albumin. From baseline to week 48, the average percentile of mass body by age improved from 12.74 % up to 29.83%, and the average serum albumin levels rose from 26.7 g / l to 38.7 g / l.

Children and adults with a deficiency of lysosomal acid lipase

Study LAL-CL02 was a multicenter, double-blind, placebo-controlled study conducted in 66 children and adults with DLLL. Patients were randomized to receive CAIUM preparation at a dose of 1 mg / kg (n = 36) or placebo (n = 30) once every two weeks for 20 weeks of a double-blind period. The age range at the time of randomization was 4-58 years (71% of patients <18 years old). To enter the study, patients were required to have ALT at 1.5 upper limit of the norm (VGN). In the majority of patients (58%), the level of cholesterol was> 190 mg / dl when included in the study; 24% of patients with LDL cholesterol> 190 ml / dL received lipid-lowering medications. Of the 32 patients who underwent liver biopsy at the time of enrollment, 100% had fibrosis and 31 % cirrhosis. The age range of patients with signs of cirrhosis, confirmed by biopsy, was 4-21 years.

The following endpoints were evaluated: normalization of ALT level, lowering of LDL cholesterol level, lowering of LDL cholesterol level, normalization of level ACT, decrease in triglyceride levels, increase in HDL cholesterol level, decrease in the specific percentage of fatty tissue of the liver, assessed by means of magnetic resonance tomography in the regime of multiple gradient echo (MEGE-MRI), and a decrease in the degree of fatty liver dystrophy measured by morphometry.

A statistically significant improvement in multiple endpoints was observed in the group treated with KANUMA compared with the placebo group at the end of the 20-week, double-blind study period. The absolute decrease in the average level of ALT was 57.9 U / l (-53%) in the group treated with CAIUMA and 6.7 U / L (-6 %) in the placebo group.

Paired liver biopsies at baseline and week 20 were available in a subpopulation of patients (n = 26). Of patients with paired liver biopsies in 63 % (10/16) treated with KANUMA, a reduction in fatty liver was recorded (at least 5 % decrease), which was measured by morphometry compared with 40% (4/10) of patients on placebo. This difference was not statistically significant.

Open period

Sixty-five of the 66 patients entered the open period (up to 130 weeks) with the introduction drug KANUMA in a dose of 1 mg / kg once every two weeks. In patients who received the drug KANUMA during the double-blind period, there was a decrease in ALT levels achieved during the first 20 weeks of treatment and further improvement of lipid parameters was observed,including LDL cholesterol and HDL cholesterol levels.

In patients on placebo, elevated levels of serum transaminases and abnormalities in serum lipid levels persisted during the double-blind period. In accordance with the facts observed in patients treated with KANUMA during the double-blind period, the onset of KANUMA treatment during the open period resulted in a rapid improvement in ALT and lipid levels, including LDL cholesterol and LDL cholesterol levels.

In a separate open study (LAL CL01/LAL CL04) in adults with DLLL, an improvement in serum transaminase levels and lipid levels persisted throughout the 104-week treatment period.

Pediatric population

Age 56 of 84 patients (67 %), who received the drug KANUMA during clinical trials (LAL-CL01/LAL-CL04, LAL-CL02 and LAL-CL03), was in the pediatric and adolescent range (from 1 month to 18 years).

Pharmacokinetics:

The pharmacokinetics of the drug KANUMA in children and adults was determined using population pharmacokinetic analysis in 65 patients with DLLL who received intravenous infusions of the drug KANUMA at a dose of 1 mg / kg every two weeks in a study LAL-CL02. The age of 24 patients was 4-11 years, 23 patients from 12 to 17 years and 18 patients ≥ 18 years old. According to a non-compartmental analysis of adult patients (LAL-CL01/LAL-CL-04), the pharmacokinetics of the amylipase alpha looked non-linear with a large dose-proportional increase in the effect observed between dosages of 1 and 3 mg / kg. Cumulation in a dose of 1 mg / kg (once a week or once every two weeks) and 3 mg / kg once a week was not observed.

Infant population (age <6 months)

In the study LAL-CL03 the drug KANUMA was eliminated from the systemic blood flow with the median T1 / 2 0.1 h (range: 0.1-0.2) at a dose of 3 mg / kg once a week (n = 4). Differences in the exposure of amylipase alpha between 0.35 mg / kg once a week and 3 mg / kg once a week were more dose-proportional: an 8.6-fold increase in dose gave a 9.6-fold increase in exposure to AUC and a 10.0-fold increase in the Stach.

Linearity / nonlinearity

On the basis of these data, the pharmacokinetics of the amylipase alpha was considered to be nonlinear, with a large dose-proportional increase in the exposure observed between doses of 1 and 3 mg / kg.

Characteristics in specific patient groups

In the analysis of the covariate of the population-based pharmacokinetic model of amylipase alpha, no significant effect of age, body weight and sex on CL and Vc amylipase alpha. In patients 2 to 4 years of age and patients aged 65 years or older amylipase alpha not investigated.

Information on the pharmacokinetics of amylipase alpha in non-neuropeople ethnic groups is limited.

Sebelipase alpha is a protein; It is expected that in the course of metabolism it will be cleaved by peptide hydrolysis. Therefore, it is not expected that a violation of the liver function will affect the pharmacokinetics of the amylipase alpha.

Renal elimination of amylipase alpha is considered a secondary way of removing the drug. Data in patients with impaired renal function are limited.

The information on the effect of antibodies to the drug on the pharmacokinetics of the amylipase alpha is limited.

Indications:KANUMA is indicated for long-term enzyme replacement therapy (PTA) in patients of all ages with a deficiency of lysosomal acid lipase.

Contraindications:

Life-threatening hypersensitivity (anaphylactic reaction) to the active substance or to any of the auxiliarysubstances with unsuccessful attempts to re-introduce the drug.

Carefully:

Preclinical safety data

Preclinical data revealed no specific threats to humans in traditional pharmacological safety studies and toxicity when re-administered in rats and monkeys.

Studies to assess the mutagenic and carcinogenic potential of the amylipase alpha have not been performed at this time.

Pregnancy and lactation:

Pregnancy

There are no data on the use of amylipase alpha by pregnant women. Research on animals do not indicate the presence of direct or indirect negative effects in terms of reproductive toxicity. For the sake of precaution, whenever possible, avoid using the drug KANUMA during pregnancy. The results of a preclinical study on embryonic and peri- and postnatal development in rats and rabbits did not reveal the effect of the drug on these parameters. At the same time, there were no undesirable results in studies of embryo-fetal development in rats and rabbits in doses at least 50 times higher than human doses.

Lactation

There are no data on studies involving women who are breast-feeding. It is not known whether the blood is excreted amylipase alpha with breast milk. It is necessary to decide whether to stop breastfeeding or stop treatment with KANUMA, taking into account the benefits of breastfeeding for a child and the benefits of treatment for a woman.

Fertility

There are no clinical data on the effects of amylipase alpha on fertility. Studies in animals showed no signs of impaired fertility.

Dosing and Administration:

Treatment with KANUMA should be performed under the guidance of an experienced physician who is well versed in the management of patients with DLL, other metabolic disorders or chronic liver disease. The drug KANUMA should be administered by a trained medical worker who knows how to deal with medical emergency conditions.

It is important to begin treatment with the drug as soon as possible after the diagnosis of DLLL.

Young children (<6 months of age) with recently identified DLLCL

The recommended initial dose in young children (<6 months) with newly diagnosed rapidly progressing DLL is 1 mg / kg and administered as an intravenous infusion once a week.Depending on the clinical response, the possibility of a gradual increase in dosage to 3 mg / kg once a week should be considered.

Children and adults with DLLCL

The recommended dose for children older than 6 months and adults with DLL is 1 mg / kg and is administered as an intravenous infusion once every two weeks.

Patients over 65 years of age

Safety and efficacy of KANUMA in patients older than 65 years was evaluated, therefore, there are no recommendations for alternative dosage in such patients.

Renal or hepatic impairment

Recommendations for dose adjustment in the case of patients with renal or hepatic insufficiency, taking into account current information about the pharmacokinetics and pharmacodynamics of amylipase alpha, are absent.

Pediatric population

Fifty-six of the 84 patients (67%) who received the drug KANUMA during clinical trials were in pediatric and adolescence (1 month to 18 years). Data on the use of amylipase alpha in children from 2 to 4 years of age are limited. The dosage in this pediatric population is the same as that for adults.

Patients with overweight and obesity

The safety and efficacy of Kanuma was not assessed in this category of patients. An alternative dosing regimen depending on the clinical response may be recommended.

Method of administration

The drug KANUMA is intended only for intravenous administration.

The entire infusion volume should be administered for about 2 hours. After ascertaining the tolerability of the drug by the patient, the option of switching to a one-hour infusion may be considered. If the dose is increased, the duration of the infusion can be increased.

The drug KANUMA should be injected through a 0.2 μm filter.

Each flask of the drug KANUMA is intended only for single use. The drug must be diluted Kanuma sodium chloride 9 mg / ml (0.9%) of sodium infusion aseptically.

The dilution was administered to patients via infusions systems with low protein binding, possibly equipped with a weakly binding proteins flow filter with a pore size of 0.2 microns with a surface area greater than 4.5 cm², to avoid occlusion of the filter.

Preparation of the administration of the drug CANUM

Preparation and administration of the drug KANUMA should be carried out in accordance with the following steps. It is necessary to follow the rules of asepsis.

a. Determine the number of vials that will need to be diluted for infusion, based on the patient's body weight and the prescribed dose.

b. Allow the bottles with KANUMA preparation to reach room temperature (15-25 ° C) before dilution (about 30 minutes) in order to minimize the possibility of forming protein particles of amylipase alpha in solution. Do not leave bottles at room temperature for longer than 24 hours, before dilution for infusion. Vials should not be frozen, not heated, do not expose the microwave oven and protect from light.

at. Do not shake. Before breeding, visually examine the solution in the vial (s); the preparation must comply with the description (see section "Description"). Do not use the drug in case of discoloration, turbidity, or the presence of foreign mechanical inclusions. Since this preparation is a protein solution, semi-transparent protein-like particles can be present in the vials.

in Slowly dial up to K) ml of the solution from each vial and dilute with a solution for sodium chloride infusion of 9 mg / ml (0.9%) according to Table 1, which lists the recommended total infusion volumes, depending on the body weight. Mix gently. 11e shake.

Table 1. Recommended volumes of administration (dose 1 mg / kg) *

Body weight (kg)	Total infusion volume (ml)
1-10	10
11-24	25
25-49	50
50-99	100
100-120	250

* The volume of the infusion should be based on the prescribed dose and should be prepared before the final concentration of amylipase alpha 0.1-1.5 mg / ml.

Unused preparation and consumables must be disposed of in accordance with the requirements of the region. For information on preventive measures and monitoring of hypersensitivity reactions, see "Specific guidance". With the development of a hypersensitivity reaction, appropriate preventive measures should be taken in accordance with therapeutic standards.

Side effects:

Summary of security profile

The most serious adverse reactions experienced by 3% of patients in clinical trials had signs and symptoms consistent with anaphylaxis. Symptoms included chest discomfort, conjunctival injection, dyspnea, generalized and itching rash, flushing, mild eyelid edema, rhinorrhea, severe respiratory distress, tachycardia, tachypnea and urticaria.

The list of undesirable reactions

The data in Table 2 reflect the adverse reactions observed in infants who received KANUMA in clinical trials at doses up to 3 mg / kg weekly.The data in Table 3 reflect the adverse reactions observed in children and adults who received the drug KANUMA in clinical trials at a dose of 1 mg / kg once every two weeks.

Undesirable reactions are listed by class of organ systems and frequency. The frequency is defined in the following conditional limits: the most frequent (1/10); Frequent (from 1/100 to <1/10), infrequent (from 1/1 000 to <1/100), rare (from 1/10 000 to <1/1 000), very rare (<1/10 000 ) and possessing an unknown frequency (calculations on the available data can not be made). Undesirable effects are grouped by frequency and in each group are presented in order of severity.

Table 2: Adverse Reactions, marked in infants, who received the drug CANUM

A class of organ systems by MedDRA	Frequency^a	The preferred term for MedDRA
Immune system disorders	The most frequent	Edema of the century
Mental disorders	Most frequent	Excitation^b, irritability^b
Disturbances from the nervous system	Most frequent	Muscular hypotension
Disorders from the cardiovascular system	Most frequent	Arterial hypertension, paleness^b, tachycardia^b
Respiratory, thoracic and mediastinal disorders	The most frequent	Respiratory distress, wheezing, cough, rhinitis, nasal congestion and sneezing
Disorders from the digestive system	Most frequent	Diarrhea, gastroesophageal reflux, urge for vomiting, vomiting^b
Disturbances from the skin and subcutaneous tissue	Most frequent	Hives^b, rash^b (including spotted-nodular), eczema^b, itching
Systemic disorders and complications at the site of administration	Most frequent	Chills, fever, fever^b, swelling
Abnormalities detected in laboratory studies	Most frequent	Increased body temperature, decreased oxygen saturation, increased blood pressure, increased heart rate, increased respiration

^aThe most frequent = marked in ≥ 1 patient receiving the drug CANUM

^b Reported in> 2 patients receiving the drug CANUM

^cAge at time of first injection: 1 to 6 months

Table 3: Undesirable reactions noted in children and adults receiving the drug CANUM

A class of organ systems by MedDRA	Frequency^a	The preferred term for MedDRA
Urinary tract	Frequent	Urinary tract infection
Immune system disorders	Frequent	Anaphylactic reaction, edema of the eyelids
Disorders of nutrition and metabolism	Frequent	Transient hypercholesterolemia, transient hypertriglyceridemia
Mental disorders	Frequent	Anxiety^from, insomnia
Disturbances from the nervous system	Frequent	Dizziness
Disorders from the cardiovascular system	Frequent	Hyperemia^from, arterial hypotension, tachycardia
Respiratory, thoracic and mediastinal disorders	Frequent	Laryngeal edema^from, dyspnea^b^,^c^,^e
Disorders from the digestive system	Frequent	Diarrhea^b^,^c, stomach ache^b^,^c, bloating, nausea^b^,^c
Disturbances from the skin and subcutaneous tissue	Frequent	Hives, rashes^c^,^e (including papular and itchy), itching^e, eczema^e
Disorders from the reproductive system and mammary glands	Frequent	Menorrhagia
Systemic disorders and complications at the site of administration	Frequent	Chills, chest discomfort^c^,^e, swelling, fatigue, seals at the injection site, fever
Abnormalities detected in laboratory studies	Frequent	Increased body temperature^b^,^c
Injury, poisoning and complications of procedures	Frequent	Reaction related to infusion^c

^aFrequent = marked for ≥ 1 patient receiving the drug CANUM

^b Reported with the same frequency in patients receiving the drug or placebo Kanuma, or more frequently in patients receiving placebo in the double-blind period of the study LAL CL02

^cReported as part of an unwanted reaction in one patient who received the drug KANUMA in the study LAL CL02

^dAge at time of first injection: 4 to 58 years

^eReported in ≥2 patients who received the drug KANUMA.

One infant was treated at a dose of 5 mg / kg once a week as part of the study LAL CL03; When this dose was used, no new adverse reactions were reported. In the absence of additional clinical data, this dose is not recommended for use.

Description of individual adverse reactions

Hypersensitivity

Three of the 106 (3 %) patients treated with KANUMA in clinical trials developed signs and symptoms corresponding to anaphylaxis. Anaphylaxis developed during the infusion no later than one year after the start of treatment.

In clinical trials, 21 of 106 (20%) patients treated with KANUMA, including 9 of 14 (64%) infants and 12 of 92 (13%) children and adults, developed signs and symptoms, or corresponding hypersensitivity reactions, or possibly associated with it. The signs and symptoms that occurred in two or more participants included abdominal pain, agitation, chills, diarrhea, eczema, arterial hypertension, irritability, laryngeal edema, nausea, swelling, pallor, itching, fever / fever, rash, tachycardia , hives and vomiting. Most reactions developed during infusion or within 4 hours of the completion of infusion.

Transient hyperlipidemia

According to the known mechanism of action of the drug, asymptomatic elevation of levels circulating in the bloodstream of cholesterol and triglycerides was observed after the start of treatment with the drug KANUMA. These rises usually occurred within the first 2-4 weeks and were weakened for a further 8 weeks of treatment with KANUMA.

Immunogenicity

Patients had antibodies to the drug (ALP) to self-lipase alpha.

In the study LAL CL03 in 4 out of 7 infants (57 %) During treatment with the drug KANUMA ALP appeared. During the first detection of ALP, 3 patients received a dose of 1 mg / kg once a week and 1 patient received a dose of 3 mg / kg once a week. In the majority of patients who developed ALP, this occurred during the first 2 months of exposure. ALP titers fell to undetectable levels with continued treatment in 3 out of 4 patients. Two patients have antibodies that are in vitro inhibit the activity of the enzyme and its uptake by cells.

In the study LAL CL02 in 5 out of 35 children and adults (14%) who received the drug KANUMA during the 20-week double-blind study period, ALPs were formed. All patients received 1 mg / kg once every two weeks. In those patients who developed ALP, this occurred during the first 3 months of exposure. With continued treatment, ALP titers fell to undetectable levels in all patients. Two patients had a positive reaction at only one control point. None of the patients had antibodies, in vitro inhibiting enzyme activity or enzyme uptake by cells.

The relationship between the occurrence of ALP to the self-lipase alpha and the decrease in the effectiveness of treatment or the development of unwanted reactions has not been revealed.

Overdose:

In clinical studies, doses of amylipase alpha to 5 mg / kg once a week were studied. Special symptoms after application of higher doses were not revealed.

In experimental animal studies on the study of chronic toxicity in young Javanica monkeys, the results showed no toxicity at doses up to 30 times higher than the human dose.

Interaction:

Interaction studies have not been conducted. Because the amylipase alpha is a recombinant human protein, the likelihood that it interacts with other drugs, including cytochrome P450 is mediated is small.

Pharmacological Compatibility

Since studies on compatibility with this drug have not been conducted, it should not be confused with other drugs.

Special instructions:

Hypersensitivity reactions, including anaphylaxis

Patients who received the drug KANUMA, hypersensitivity reactions have been reported, including cases of anaphylaxis. For this reason, with the introduction of amylipase alpha, appropriate medical supplies must be available.In the case of the development of such reactions, it is necessary to stop the drug immediately KANUMA and begin appropriate therapeutic treatment. At the same time, it is necessary to follow the current medical standards of emergency care.

We should weigh the risk and benefit of repeated attempts to administer the drug KANUMA, after the onset of severe reactions. With regard to patients, during infusion, experienced allergic reactions, with repeated administration of the drug, it is necessary to exercise caution.

Measures to combat hypersensitivity reactions may include temporary discontinuation of infusion, a reduction in its rate and (or) administration of antihistamines, antipyretics and (or) corticosteroids. When the infusion is temporarily stopped, it can then be resumed at a slower rate, with a subsequent increase, in accordance with tolerability. Preventive treatment with antipyretics and (or) antihistamines may prevent subsequent reactions in cases where symptomatic treatment was required.

In cases of pronounced reaction to infusion, and also when the therapeutic effect is insufficient, patients should be tested for the presence of antibodies.

A medicinal preparation may contain traces of a chicken egg protein. Patients with allergic reactions to a chicken egg were excluded from clinical trials.

After the first infusion of nimipase alpha, including the first infusion after increasing the dose, patients should be monitored for at least an hour to monitor the condition and identify symptoms and signs of anaphylaxis or a pronounced hypersensitivity reaction.

Excipients

This drug contains 33 mg of sodium per bottle and is administered in a solution of sodium chloride 9 mg / ml (0.9%) for infusion. These factors must be taken into account in patients on a diet with limited sodium intake.

Special precautions for disposal and other handling

The unused preparation and the waste material must be disposed of in accordance with the requirements of the region.

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

Care must be taken when driving vehicles and engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Concentrate for solution for infusion 2 mg / ml.

Packaging:

For 10 ml of concentrate in a bottle of clear, colorless glass of hydrolytic class 1, sealed with a rubber stopper, sealed with an aluminum lid with a plastic tear-off cap.

A label is attached to the vial.

For 1 bottle with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of (2-8) ° C. Do not freeze!

Keep in original packaging to protect from light.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004513

Date of registration:31.10.2017

Expiration Date:31.10.2022

The owner of the registration certificate:Alexion Europe CACAlexion Europe CAC France

Manufacturer: & nbsp

PATHEON ITALIA, S.p.A. Italy

Representation: & nbspAleksion Pharma, Open CompanyAleksion Pharma, Open CompanyRussia

Information update date: & nbsp27.12.2017

Illustrated instructions

Instructions

Kanuma (Kanuma)