Naglazim® (Naglazym)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceGalsulfaseGalsulfase
Similar drugsTo uncover
  • Naglazim®
    concentrate d / infusion 
    BioMarin Europe Ltd.     United Kingdom
    • Dosage form: & nbspconcentrate for solution for infusion
    Composition:

    1 ml of concentrate contains:

    active substance: galsulfase 1.0 mg;

    Excipients: sodium chloride 43.78 mg; monobasic sodium phosphate, monohydrate 6.20 mg; dibasic sodium phosphate, heptahydrate 1.34 mg; polysorbate 80 0.25 mg; water for injection 5 ml.

    Description:Colorless or pale yellow, clear or slightly opalescent solution.
    Pharmacotherapeutic group:The drug for the treatment of diseases of the digestive tract and metabolic disorders
    ATX: & nbsp

    A.16.A.B.08   Galsulfase

    Pharmacodynamics:

    Galsulfase is a recombinant form of natural human N-acetylgalactosamine-4-sulphatase produced by recombinant DNA technology on the mammalian cell line of Chinese hamster ovary (CHO) cells.

    Diseases associated with the accumulation of mucopolysaccharides in tissues (diseases of accumulation of mucopolysaccharides) are due to a deficiency of specific lysosomal enzymes required for the catabolism of glycosaminoglycans (GAG). Mucopolysaccharidosis (MPS) of the VI type (Maroto-Lamy syndrome) is a heterogeneous and multisystem disease,which is characterized by the absence or deficiency of the enzyme M-acetylgalactosamine-4-sulfatase (lysosomal hydrolase, catalyzing the hydrolytic cleavage of the sulfate radical from the GAG ​​molecule of dermatan sulfate). The absence or decrease in the activity of this enzyme leads to accumulation of dermatan sulfate in various cells and tissues, and causes various structural and functional disorders. The purpose of enzyme replacement therapy is to restore the level of lysosomal enzyme activity, sufficient to hydrolyze the accumulated dermatan sulfate and prevent its further accumulation.

    Naglazim is a purified galsulfase preparation obtained using recombinant DNA technology from the Chinese hamster ovary (CHO) cell line. Purified galsulfase (recombinant form of human N-acetylgalactosamine-4-sulfatase) is a glycoprotein with a molecular weight of about 56 kDa. The molecule of the galsulfase consists of 495 amino acid residues (after cleavage of the N-terminal fragment) and contains six asparagine-linked oligosaccharide chains, four of which have bis-mannose-6-phosphate in their composition,necessary for the recognition of the drug by the cellular receptor. After intravenous administration galsulfase quickly disappears from the bloodstream and is absorbed by cellular lysosomes. Penetration into the lysosomes is most likely accomplished by binding the oligosaccharide chain of mannose-6-phosphate-terminated galsulfase to specific mannose-6-phosphate receptors.

    Specific activity of the drug Naglazim is approximately 70 U / mg protein weight (one unit of activity is defined as the amount of enzyme required to convert 1 μmol 4-methylumbelliferyl sulfate to 4-methylumbelliferone and free sulfate anion per minute at 37 ° C).

    It was shown that the change in the excretion of GAG in the urine correlates with the change in the dose of the drug Naglazim. The relationship between the content of GAG in urine and other methods of assessing the clinical effectiveness of the drug is not established.

    Pharmacokinetics:

    Evaluation of the pharmacokinetic parameters of galsulfase was performed with the participation of 13 patients with type VI mucopolysaccharidosis, which received 1 mg / kg of galsulfase at a dose of 4 hours infusion once a week for 24 weeks.The pharmacokinetic parameters of the galsulfase after 1 week and 24 weeks of use are shown in Table 1.

    Table 1. Pharmacokinetic parameters (mean ± standard deviation)

    Pharmacokinetic parameter

    Week 1

    (single administration)

    Week 24

    (repeated administration)

    Maximum concentration (FROMmax);

    0.816 ± 0.216 μg / ml

    2.357 ± 1.560 μg / ml

    Area under the curve "Concentration - time" (AUCo-t)

    2.21 ± 0.604 ng * h / ml

    5,860 ± 4,184 ng * h / ml

    The volume of distribution, (Vz)

    118 ± 74.7 ml / kg

    316 ± 752 ml / kg

    Clearance (CL)

    7.2 ± 1.48 ml / min / kg

    7.9 ± 14.7 ml / min / kg

    The half-life (T1/2)

    11.1 ± 5.26 min

    22.8 ± 10.7 min

    a) The area under the pharmacokinetic curve (plasma concentration of gulsulfase - time) for the period from the onset of infusion to 60 minutes after infusion.

    The pharmacokinetic parameters of the galsulfase should be evaluated with caution due to the large variability of the measurement methods. It is suggested that the formation of antibodies to galsulfase may affect the pharmacokinetics of the drug, but the available data are not sufficient to assess this effect.

    An expected consequence of the metabolism of polypeptide drugs obtained using recombinant technology is degradation with the formation of small peptide fragments.Accordingly, the dysfunction of the liver does not appear to have a clinically significant effect on the pharmacokinetics of the galsulfase. It is believed that only a small part of the drug is excreted through the kidneys.

    Pre-clinical safety study results

    According to preclinical data (the results of standard pharmacological safety studies, single dose toxicity, multiple dose toxicity, general reproductive toxicity, or embryo-fetal development in rats and rabbits), the use of galsulfase does not pose any specific hazard to humans. The effect of the drug on prenatal and postnatal development has not been studied. Genotoxic and carcinogenic effects of the drug are unlikely.

    Indications:Naglazim is indicated for use in long-term enzyme replacement therapy in patients with confirmed diagnosis of "Mucopolysaccharidosis type VI" (MPS VI type, Maroto-Lamy syndrome). It is established that the drug Naglazim improves the ability of patients to walk and climb the stairs.
    Contraindications:Severe or life-threatening uncontrolled hypersensitivity reactions to the active substance or any of the excipients.
    Pregnancy and lactation:

    Pregnancy

    Adequate controlled studies of the drug Naglazim with the participation of pregnant women were not conducted. Studies of reproductive function were performed in rats with intravenous administration at doses up to 3 mg / kg / day (approximately 0.5 times the recommended dose of 1 mg / kg for humans in terms of body surface area) and on rabbits with intravenous doses up to 3 mg / kg / day (approximately 0.97 times the recommended dose of 1 mg / kg for humans in terms of body surface area). The resulting data did not show fetotoxicity of the Naglazim drug or its adverse effect on fertility.

    The drug Naglazim should not be used during pregnancy (except in cases of extreme necessity).

    Breastfeeding period

    It is not known whether galsulfase in human milk. During the use of the drug, Naglazim should stop breastfeeding.

    Influence on reproductive function

    The results of studies of reproductive function, which were performed on rats and rabbits with the introduction of intravenous galsulfase in doses up to 3 mg / kg / day,Not demonstrated a violation of fertility or danger of the drug Naglazim for the embryo or fetus.

    Dosing and Administration:

    The drug is administered intravenously.

    The administration of the drug Naglazim should be carried out in a medical institution equipped with all the necessary equipment for carrying out resuscitation in the event of emergence of emergency conditions.

    In order to reduce the risk of occurrence of reactions associated with infusion, it is recommended to premedicate with antihistamine drugs in combination with antipyretic drugs 30-60 minutes before the infusion of the drug Naglazimparacetamol) or without them

    The recommended dose of Naglazim is 1 mg / kg body weight and is administered intravenously for at least 4 hours 1 time per week.

    The contents of the required number of bottles of the drug Naglazim are diluted in 250 ml of 0.9% solution of sodium chloride (see the section "Instructions for preparation and administration of the drug"). After dilution, the drug is administered at a controlled rate with an infusion dispenser. The rate of administration of the drug Nahlazim is selected so that approximately 2.5% of the total volume of the solution is introduced during the first hour (injection rate no more than 6 ml / h).The remaining preparation (approximately 97.5% of the total volume) for 3 hours (the rate of administration can be increased to 80 ml / h).

    In patients who are sensitive to bulk fluid overload and in patients with a body weight of 20 kg or less, Naglazim is diluted in 100 ml of 0.9% sodium chloride solution. In this case, the infusion rate should be reduced so that the total duration of administration is at least 4 hours.

    Special patient groups

    Elderly and elderly people

    In clinical studies of the drug, Naglazim did not participate in patients older than 29 years. It is not known whether the efficacy and tolerability of Naglazim is different in older patients compared to younger patients.

    The safety and effectiveness of Naglazim in patients older than 65 years is not established, so an alternative dosing regimen can not be recommended for patients of these age groups.

    Children

    Special instructions when using the drug Naglazim in children does not exist. In clinical studies of the drug, Naglazim, 56 patients aged from 5 to 29 years, most of whom belonged to the children's age group, participated.An open-label study evaluated the use of the drug in four children aged 3 to 12.7 months. Data on the safety of use of the drug in young children are consistent with the results obtained in the treatment of patients aged 5-29 years.

    Renal and hepatic impairment

    The safety and effectiveness of Naglazim in patients with renal or hepatic insufficiency has not been studied, so an alternative dosing regimen can not be recommended for these patients.

    Instructions for preparation and administration of the drug:

    Each bottle of Naglazim is intended for single use only.

    Do not use the vial more than once!

    The concentrated solution of the drug Naglazim must be diluted with 0.9% solution of sodium chloride in accordance with the rules of asepsis. It is recommended to inject the solution of the drug Naglazim to patients using an infusion device (infusion doser) equipped with a built-in 0.2 μm filter.

    For the dilution and administration of Naglazim, plastic infusion containers and infusion systems with a low protein-binding capacity should be used.There is no information on the interaction of diluted Naglazim with glass containers.

    1. Determine the number of vials with a solution of the drug that must be diluted, taking into account the patient's body weight and the recommended dose of the drug Naglazim 1 mg / kg:

    Body weight of the patient (kg) x 1 ml / kg of the drug Naglazim® = total amount of the drug Naglazim®

    Total number of ml of the drug Naglazim / 5 ml in the vial = total number of vials.

    It should be rounded to the nearest whole number of bottles. Extract the required number of vials from the refrigerator at least 20 minutes before the injection, so that the solution of the drug Naglazim gradually warmed to room temperature. Do not leave bottles of Naglazim at room temperature for more than 24 hours before breeding. Do not heat bottles or expose them to microwave radiation.

    2. Before removing the Naglazim solution from the vial, each bottle should be inspected for mechanical inclusions or discoloration of the solution. Naglazim drug solution should be clear or slightly opalescent, colorless or pale yellow, and must not contain visible particles.Do not use the drug if the solution has changed color or if mechanical inclusions are found in the solution.

    3. From the infusion container containing 250 ml of 0.9% solution of sodium chloride for infusion, it is necessary to remove and remove the sodium chloride solution in a volume equal to the added volume of the solution of the drug Naglazim. In patients who are sensitive to volume overload, as well as in individuals with a body weight of 20 kg or less, it may be more preferable to dilute the drug in 100 ml of a 0.9% solution of sodium chloride. In this case, the rate of infusion should be reduced so that the total duration of the administration is at least 4 hours (see section "Method of administration and dose"). If an infusion container of 100 ml volume is used, the preliminary extraction of the sodium chloride solution is not necessary, and the necessary volume of the Naglazim drug can be injected directly into the infusion bag.

    4. Slowly and carefully extract the calculated volume of Naglazim from the appropriate number of vials, avoiding excessive shaking. To remove the drug, do not use a needle with a filter, as this may cause stirring of the solution. Shaking may lead to denaturation and inactivation of the drug Naglazim.

    5.Carefully rotate the infusion set in order to ensure a uniform distribution of the drug Naglazim in the resulting solution. Do not shake the resulting solution.

    6. Before administration, the bottle should be inspected for mechanical inclusions. Use only a clear and colorless solution that does not contain visible particles.

    7. Introduce the diluted solution of the drug Naglazim with an infusion system equipped with a built-in 0.2 μm filter for at least 4 hours (see section "Method of administration and dose").

    Due to the fact that the drug Naglazim does not contain preservatives, after dilution in a solution of sodium chloride for injection, the entire contents of the infusion package should be used immediately .. If immediate use of the solution is not possible, then the storage time of the finished solution of the drug Naglazim should not be more than 24 hours at a temperature of 2 - 8 ° C and 24 hours at a temperature of 23 - 27 ° C from the time of preparation until the completion of the injection. Unused medication and used containers / infusion systems should be stored and disposed of in accordance with local requirements.

    The drug Naglazim can not be administered together with other drugs through a single system for infusion. Compatibility in the solution of the drug Naglazim® with other drugs has not been studied.

    Side effects:

    Due to the small number of patients in clinical trials, the incidence of adverse events in all of the Naglazim studies was combined and presented as a single safety analysis.

    All 59 patients participating in five clinical trials had at least one adverse event. At 42 of 59 patients (71%), at least one undesirable drug reaction (NLP) developed. The most frequent adverse reactions were fever, rash, itching, urticaria, chills / shivering, nausea, headache, abdominal pain, vomiting and shortness of breath. Serious adverse events observed in clinical trials include laryngeal edema, apnea (temporary respiratory arrest), febrile fever, urticaria, respiratory distress syndrome, angioedema, bronchial asthma and anaphylactoid reactions.

    In 33 of 59 patients (56%) who participated in five clinical trials, there were reactions associated with infusion (i.e.undesirable drug reactions that occurred during infusion or during the day after its completion). Infusion-related reactions (RSI) were first developed both at the first administration and after 146 weeks of application of the Naglazim drug. RCIs were observed with repeated infusions of the drug, although they did not always occur with each of the successive weekly administrations. The most frequent RSI were fever, chills, skin rashes, hives and shortness of breath. Frequent RSIs were itching, vomiting, abdominal pain, nausea, hypertension, headache, chest pain, erythema, cough, arterial hypotension, angioedema, respiratory distress syndrome, tremor, conjunctivitis, malaise, bronchospasm, arthralgia. In clinical studies, one case of the development of the syndrome of obstructive sleep apnea was noted.

    Table 2 presents information on adverse events that have been observed with the use of Naglazim. To denote the frequency, WHO's NLR classification was used for the frequency of occurrence:

    Often: ≥1/10 (> 10 %)

    Often: from ≥1/100 to <1/10 (from ≥ 1% to <10%)

    Infrequently aboutt ≥1/1000 to <1/100 (from ≥ 0.1% to <1%)

    Rarely from ≥1/10 000 to <1/1000 (from ≥ 0.01% to <0.1%)

    Very rarely <1/10 000 (<0.01%)

    The frequency is not set.

    Undesirable reactions are classified according to the damage to organs and organ systems (in the terminology of the Medical Dictionary for Regulatory Activities MedDRA). Within each class, NLRs are listed in order of decreasing severity.

    Table 2. Undesirable reactions observed with the use of the drug Naked eyes

    Organ organs and systems (in terminology MedDRA)

    Unwanted reaction (in terminology MedDRA)

    Frequency

    Immune system disorders

    Anaphylaxis1, shock1

    Frequency not set

    Infectious and parasitic diseases

    Pharyngitis2, gastroenteritis2

    Often

    Violations of the blood and lymphatic system

    Thrombocytopenia1

    Frequency not set

    Disturbances from the nervous system

    Areflexia2, headache3

    Often

    Tremor3

    Often

    Paresthesia1

    Frequency not set

    Disturbances on the part of the organ of sight

    Conjunctivitis2, corneal opacity2

    Often

    Heart Disease

    Bradycardia1, tachycardia1, cyanosis1

    Frequency not set

    Hearing impairment and labyrinthine disorders

    Earache2, hearing impairment2

    Often

    Vascular disorders

    Arterial hypertension2

    Often

    Arterial hypotension3

    Often

    Pale skin1

    Frequency not set

    Disturbances from the respiratory system, chest and mediastinal organs

    Dyspnea2, nasal congestion2

    Often

    Apnea2, coughing3, respiratory distress syndrome3, bronchial asthma3, bronchospasm3

    Often

    Laryngeal edema1, hypoxia1, tachypnoe1

    Frequency not set

    Disorders from the gastrointestinal tract

    Abdominal pain2, umbilical hernia2, vomiting3, nausea3

    Often

    Disturbances from the skin and subcutaneous tissues

    Angioedema2, rash3, urticaria2, itching3

    Erythema3

    Often

    Often

    General disorders and disorders at the site of administration

    Pain2, chest pain2, malaise2, chills / shivering1, fever3

    Often

    Disturbances from musculoskeletal and connective tissue

    Arthralgia3

    Often

    Disorders from the kidneys and urinary tract

    Membranous nephropathy1

    Frequency not set

    1. NLRs, the incidence of which is not established, were registered in post-marketing application of the drug.

    2. These drug reactions in a placebo-controlled study were more likely to occur in active treatment groups than in placebo groups. The frequency of HLR was determined from the observation of 39 patients participating in a masked Phase III clinical trial.

    3. Other NLRs with a known incidence rate were recorded in 59 patients in all five clinical studies of the Naglazim drug.

    The NLR observed in 4 open trials (up to 261 weeks of treatment) did not differ in nature or severity from those observed in a placebo-controlled study. In clinical trials, none of the patients stopped treatment with Naglazim because of the development of adverse events.

    Aftermexperience in drug use

    In the post-marketing application of the drug, along with reports of reactions associated with infusion, information was obtained on such serious reactions as anaphylaxis, shock, hypotension (lowering blood pressure), bronchospasm and respiratory failure. Other reactions associated with infusion included fever, erythema, pallor of the skin, bradycardia, tachycardia, hypoxia, cyanosis, tachypnea and paresthesia.There have been reports of rare cases of thrombocytopenia and of a single case of development of membranous nephropathy, confirmed by biopsy of the kidney tissue (complexes of galsulfase and immunoglobulin were detected in the glomeruli). In all these cases, patients resumed and continued therapy with Naglazim.

    Immunogenicity

    In 54 of the 59 patients who participated in clinical trials, the antibody was tested IgG. 53 of 54 (98%) patients who received the drug Naglazim, noted the appearance of antibodies to the class Galsulfase IgG for 4-8 weeks of treatment. In 19 patients who received the Naglazim drug in a placebo-controlled study, antibodies to galsulfase were detected. However, the results of the analysis did not reveal a stable relationship between the total antibody titre, the neutralizing antibody titre or IgE class antibodies on the one hand, and the reactions associated with infusion, GAG content in the urine, or tolerability of treatment on the other. The study evaluated the ability of antibodies to inhibit the enzymatic activity of galsulfase, but did not evaluate their effect on the absorption of the drug by cells.The presented data reflect the number (in%) of patients who have antibodies to galsulfase with the help of specific methods of laboratory diagnosis. These data largely depend on the sensitivity and specificity of the methods of analysis used. In addition, the frequency of detection of antibodies can be influenced by other factors, such as sample transport, blood sampling time, concomitant therapy and the course of the underlying disease. For this reason, comparing the incidence of antibodies to galsulfase with the frequency of antibodies to other drugs may be unjustified and misleading.

    Overdose:

    There are reports of several cases of excess, approximately 2 times, the recommended rate of infusion of the drug Naglazim (without increasing the total dose of the drug), not accompanied by the development of adverse reactions.

    In case of an overdose, continuous monitoring of the patient and symptomatic therapy are recommended.

    Interaction:

    Studies of the interaction of the drug Naglazim with other drugs have not been conducted.

    The drug Naglazim can not be mixed with other medicines.

    The drug Naglazim is diluted only 0.9% solution of sodium chloride for injection (see "Method of application").

    Special instructions:

    It is very important, especially in case of severe forms of diseases, to begin treatment as early as possible, before the appearance of irreversible clinical manifestations of the disease.

    Treatment with Naglazim should be carried out under the supervision of a doctor who has experience in treating patients with type VI MPS or other congenital metabolic disorders.

    Reactions associated with infusion (RSI)

    Patients treated with Naglazim received reactions associated with infusion (ie, undesirable drug reactions that occurred during the infusion of the drug or within a day after its completion). Symptoms of RSI tend to decrease after a slowing or temporary cessation of infusion and the introduction of additional antihistamines, antipyretics and, in some cases, glucocorticosteroids. In clinical studies, arrest of the RCI was achieved by interrupting the infusion or decreasing the rate of administration of the drug Naglazim, and also by prescribing antihistamine and / or antipyretic (before the infusion or after the development of RSI)paracetamol) of medicines, which allowed continuing the ongoing treatment. Most patients managed to complete the infusion. Subsequent infusions of the drug Naglazim were conducted at a lower rate and were accompanied by an additional prophylactic use of antihistamines and, in the case of a heavier RSI, the intake of glucocorticosteroids.

    There were no factors that contributed to the emergence of infusion-related reactions in patients. The relationship between the severity of RSI and the titre of antibodies to galsulfase has not been established.

    Since there is very limited experience with the resumption of therapy with Naglazim after a prolonged break, special care should be taken in such cases in connection with the theoretically increased risk of developing hypersensitivity reactions.

    In order to reduce the likelihood of RSI occurrence, it is recommended to perform premedication (antihistamines in combination with antipyretic drugs or without them) approximately 30-60 minutes before the infusion of the drug Naglazim. In the case of an RSI of mild to moderate severity, it is recommended that an additional antihistamine be prescribed and paracetamol and / or halve the rate of infusion of the drug (compared to the rate of administration at which the RSI originated).

    In the case of a single occurrence of severe RSI should stop the infusion of the drug Naglazim until the disappearance of symptoms of RSI; an antihistamine supplement should also be prescribed and paracetamol. After discontinuation of the RCI, infusion can be resumed at a rate of 50% -25% lower than the rate of administration of the Naglazim drug, at which the RSI originated.

    In the case of recurrence of a moderate degree of RSI, or with the re-appointment of a drug after the development of a single severe infusion reaction, premedication should be performed (antihistamine, paracetamol and / or glucocorticosteroids), and also reduce the infusion rate by 50% -25% relative to

    the rate of administration of the drug Naglazim, in which the previous RSI originated.

    Anaphylactic and other allergic reactions

    As with the use of other protein-containing drugs, the infusion of the drug Naglazim may develop severe allergic reactions (hypersensitivity reactions).Anaphylactic and other severe allergic reactions were observed in patients during infusion and within 24 hours after the administration of the drug Naglazim. Some allergic reactions pose a threat to the lives of patients (anaphylaxis, shock, acute respiratory failure, increased dyspnoea, bronchospasm, laryngeal edema, arterial hypotension).

    In case of occurrence of the specified reactions it is necessary to stop application of Naglazim immediately and to start corresponding treatment. In the treatment of allergic reagents should be guided by the current standards of emergency medical care. Patients who have previously experienced allergic reactions during the infusion of the drug Naglazim, repeated administration of the drug should be carried out with extreme caution in connection with the risk of repeated development of hypersensitivity reactions. In such cases, the infusion of the drug should be carried out in a medical facility that has the necessary equipment for emergency resuscitation (including the introduction of epinephrine), and in the presence of properly trained personnel for the provision of qualified medical care.Severe and life-threatening hypersensitivity reactions, uncontrollable, are a contraindication to the further use of the drug Naglazim.

    Immuno-mediated reactions

    When using the drug Naglazim, (as well as with the use of other enzyme replacement drugs), allergic reactions of type III (including membranous glomerulonephritis) mediated by circulating immune complexes were noted. In case of occurrence of immuno-mediated type III reactions, the administration of Naglazim should be stopped and appropriate treatment initiated. After the onset of an immune-mediated response, the risk and possible benefits of re-administering Naglazim should be carefully assessed. To some patients, the drug was successfully re-introduced, and they later continued treatment with Naglazim under close supervision.

    Risk of acute cardiopulmonary insufficiency

    Drug Naglazim should be administered with caution to patients who are sensitive to bulk overload of the injected fluid (patients with a body weight of 20 kg or less, patients with concomitant acute respiratory disease,patients with impaired contractility of the heart and / or respiratory function) due to the high risk of developing acute heart failure. The introduction of the drug to such patients should be carried out in a specialized department with constant monitoring of vital functions. Some patients may require longer follow-up after completion of the infusion.

    Acute respiratory complications associated with the administration of the drug

    Patients with type VI MPS often develop obstructive sleep apnea syndrome. Premedication with antihistamines may increase the risk of apnea attacks. Before the start of treatment should assess the patency of the airways. If patients regularly receive inhalation of oxygen and / or use devices that create positive airway pressure during sleep (CPAP), then these treatments should be available during the infusion, and be immediately applied when an infusion-related reaction occurs or when excessive drowsiness caused by the use of antihistamines.

    Patients with acute febrile or respiratory illness are advised to delay the administration of Naglazim because of the increased risk of developing acute respiratory failure during infusion.

    Violation of airway patency

    Special care should be taken in the treatment of patients with impaired airway patency. In such patients it is recommended to limit the use of antihistamines and other sedative drugs. In some clinical situations, the use of devices that create positive airway pressure during sleep or the imposition of a tracheostomy may be justified. If the patient develops an intercurrent acute respiratory disease, it is necessary to postpone the planned infusion of the drug, and perform it later.

    Compression of the spinal cord or compression of the cervical spinal cord

    Compression of the spinal cord, incl. compression of the cervical spinal cord (CSM), leading to myelopathy, is a known and serious complication of MPS VI type. In the post-marketing application of the drug, Naglazim, there were reports of the appearance or weighting of symptoms of IBC, requiring an operative intervention for the purpose of decompression.In this regard, patients with type VI MPS need continuous monitoring in order to timely identify subjective and objective signs of developing compression of the spinal cord or

    compression of the cervical spinal cord (such as back pain, paralysis of the limbs below the level of compression, urinary incontinence and feces) and appropriate treatment.

    If it is necessary to limit the consumption of sodium salts

    This preparation contains 0.8 mmol (18.4 mg) sodium chloride in one bottle. This information should be taken into account for patients on a diet with limited use of sodium salts.

    Effect on the ability to drive transp. cf. and fur:Studies to study the effect of the drug on the ability to drive vehicles and work with mechanisms have not been carried out. However, with the use of Naglazim, severe allergic reactions, dizziness, a decrease or increase in blood pressure and other symptoms that may affect the ability to drive or use mechanisms can be observed. Patients should be warned that when these or any other symptoms appear, they can not drive the car or work withmechanisms.
    Form release / dosage:Concentrate for the preparation of a solution for infusions of 1 mg / ml in vials of 5 ml.
    Packaging:

    Each bottle contains 5 mg of galsulfase.

    Each bottle is packed in a cardboard box with a nested instruction for use.

    Bottle (type I glass) with a stopper (siliconized chlorobutyl rubber) and a lid (aluminum) with a flared cap (polypropylene).

    Packing size: 1 bottle.

    Storage conditions:

    Store in a dark place at a temperature of 2 to 8 ° C.

    DO NOT freeze and do not shake.

    Keep out of the reach of children.

    Shelf life:

    3 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-005730/09
    Date of registration:15.07.2009 / 01.10.2009
    Expiration Date:Unlimited
    The owner of the registration certificate:BioMarin Europe Ltd.BioMarin Europe Ltd. United Kingdom
    Manufacturer: & nbsp
    Representation: & nbspPharmInform Ltd.PharmInform Ltd.Russia
    Information update date: & nbsp30.05.2018
    Illustrated instructions
      Instructions
      Up