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

Active substance:
Proteins of human plasma, of which immunoglobulin G not less than 98%	100 mg
Excipients:
L-proline	28.8 mg
Water for injections	q.s. up to 1 ml

Description:Colorless or light yellow transparent or slightly opalescent liquid.

Pharmacotherapeutic group:MIBP - globulin

ATX: & nbsp

J.06.B.A.02 Immunoglobulin normal human for intravenous administration

Pharmacodynamics:

Characteristics of the preparation

Distribution by subclass of immunoglobulin G (mean values) in the preparation Privégen: IgG₁ 67,8%, IgG₂ 28,7%, IgG₃ 2,3%, IgG₄ 1,2%.

Maximum Content IgA is 0.025 mg / ml.

The ghost is an isotonic solution with an osmolality of 320 mOsmol / kg and a low sodium content ≤ 1 mmol / l.

The drug is produced from plasma obtained from no less than 1000 donors.

The process of production of the drug Privyzhen includes the following stages: precipitation with ethanol IgG plasma fractionation, further fractionation with octanoic acid and incubation at pH 4. Subsequent purification steps of the preparation include deep filtration, chromatography, and a filtration step to remove particles larger than 20 nm.

Prizvestzhen contains antibodies of a class IgG, present in a normal population.

Pharmacodynamics

Spiny is mainly composed of immunoglobulin G (IgG) with a wide range of functionally intact antibodies to infectious agents. Both functions Fc and Fab molecules IgG saved. Plots ability Fab To bind to antigens was demonstrated by biochemical and biological methods. Function Fc was tested by the activation of complement and mediated Fc-receptor activation of leukocytes. In Prividzhen, the inhibition of immune complex-induced complement activation ("purification", anti-inflammatory effect of immunoglobulin for intravenous administration) is retained. Spiny does not lead to nonspecific activation of the complement system or prekallikrein.

Distribution of subclasses IgG approximately corresponds to their distribution in normal human plasma. Optimal doses of Privégen can restore a low concentration IgG up to normal values.

The mechanism of action when applied according to the indications, with the exception of substitution therapy, is not fully explained, but includes the immunomodulating effect.The drug increases the nonspecific resistance of the body.

Pharmacokinetics:

Suction

After intravenous injection Prividzhen becomes immediately and completely bioavailable in the patient's blood circulation.

Distribution

The drug Privédzhen is distributed relatively quickly between plasma and extravascular fluid. The balance between the intravascular and extravascular parts is achieved in about 3-5 days.

Excretion

The pharmacokinetic parameters for the Privigene preparation were determined in both clinical trials of primary immunodeficiency therapy. Pharmacokinetic parameters were determined in 25 patients aged 13 to 69 years in the main study and in 13 patients aged 9 to 59 years in the extended study (see table below).

Pharmacokinetic parameters of the drug Privyzhen in patients with primary immunodeficiencies

Parameter	Basic research (n=25) Average concentration (range)	Extended research (n=13) Average concentration (range)
FROM_mOh (maximum concentration) in g / l	23,4(10,4-34,6)	26,3 (20,9-32,9)
C_min (minimum concentration) in g / l	10,2 (5,8-14,7)	9,75 (5,72-18,01)
T_1/2(half-life) in days	36,6 (20,6-96,6)	31,1 (14,6-43,6)

In the main study, the median half-life of Prividgen in patients with primary immunodeficiency was 36.6 days and 31.1 days in the extended study. The half-life may vary from patient to patient. IgG and complexes IgG are destroyed in the cells of the reticulo-endothelial system.

Indications:

Substitution therapy with:

- Primary immunodeficiencies (FID), such as:

Congenital agammaglobulinemia and hypogammaglobulinemia;
general variable immune deficiency;
severe combined immune deficiency;
Wiskott-Aldrich syndrome;

- Multiple myeloma with severe form of secondary hypogammaglobulinemia and recurrent bacterial infections with ineffective vaccination with pneumococcal vaccine;

- chronic lymphoid leukemia with severe form of secondary hypogammaglobulinemia and recurrent bacterial infections with ineffective prophylactic antibacterial therapy;

- congenital syndrome of acquired human immunodeficiency syndrome (AIDS) in children in the presence of recurrent infections;

- hypogammaglobulinemia in patients with allogeneic transplantation of hematopoietic stem cells.

As an immunomodulating agent for:

- idiopathic thrombocytopenic purpura (ITP) in children or adults with a high risk of bleeding or before surgery to correct the number of platelets;

- Guillain-Barre syndrome;

- Kawasaki disease;

- chronic inflammatory demyelinating polyneuropathies.

Contraindications:

- Hypersensitivity to the active substance or any other component included in the preparation;

- increased sensitivity to homologous immunoglobulins, especially in very rare cases of immunoglobulin deficiency A (IgA), when the patient has antibodies to IgA;

- hyperprolinaemia (a very rare disease that affects only a few families in the world).

Pregnancy and lactation:

The safety of Prividzhen during pregnancy and the period of breastfeeding in controlled clinical trials has not been established. Immunoglobulins penetrate the placenta, especially in the third trimester of pregnancy. Immunoglobulins are excreted in breast milk, while antibodies can have a protective effect in a newborn.Thus, Priovgen during pregnancy and the period of breastfeeding should be used with caution.

However, a great experience in the clinical use of immunoglobulins shows that the occurrence of a negative effect on the course of pregnancy, fetus or on the newborn is unlikely.

Auxiliary substance studies L-proline, conducted on animals, revealed the absence of direct or indirect toxic effects on the course of pregnancy, the development of an embryo or fetus.

Dosing and Administration:

The dose and dosage regimen depend on the indication for use. In the case of substitution therapy, the dose of the drug can be selected individually for each patient, depending on the pharmacokinetic parameters and the clinical response. As a guide, the following doses of the drug are recommended.

Substitution therapy for primary immunodeficiencies

It is recommended to choose a dosing regimen in which the concentration IgG increases a minimum of 5-6 g / l (definition of the content IgG spend before further infusion). Equilibrium concentrations are achieved 3-6 months after the start of treatment.The recommended starting dose is from 0.4 to 0.8 g / kg body weight, subsequent doses - not less than 0.2 g / kg body weight every 3-4 weeks.

Doses of the preparation necessary to achieve concentration IgG 5-6 g / l, are from 0.2 to 0.8 g / kg body weight per month. The interval between doses, when equilibrium concentrations are reached, varies from 3 to 4 weeks. Measure concentrations IgG to regulate the dose and the interval of administration.

Replacement therapy for multiple myeloma with severe form of secondary hypogammaglobulinemia and recurrent bacterial infections with ineffective vaccination with pneumococcal vaccine; chronic lymphoid leukemia with severe form of secondary hypogammaglobulinemia and relapsing bacterial infections at inefficiencies preventive antibacterial therapy; congenital AIDS in children in the presence of recurrent infections

A dosage regimen of 0.2 to 0.4 g / kg body weight is recommended every 3-4 weeks.

Hypogammaglobulinemia in patients with allogeneic transplantation of hematopoietic stem cells

Doses of the drug necessary to maintain concentration IgG at a level of more than 5 g / l, range from 0.2 to 0.4 g / kg body weight every 3-4 weeks.

Idiopathic thrombocytopenic purpura

In case of an exacerbation, appoint 0.8 to 1 g / kg of body weight on the first day (it is possible to repeat this dose again one more time in the next 3 days) or 0.4 g / kg of body weight daily for 2-5 days. In case of relapse, treatment can be repeated.

Guillain-Barre Syndrome

0.4 g / kg body weight for 5 days. There is limited experience in children.

Kawasaki disease

From 1.6 to 2 g / kg body weight in separate equal doses for 2-5 days or a single dose of 2 g / kg body weight once. Patients should be assigned acetylsalicylic acid as concomitant therapy.

Chronic inflammatory demyelinating polyneuropathies *

The starting dose is 2 g / kg body weight in separate equal doses for 2-5 consecutive days; subsequent doses in the calculation of 1 g / kg of body weight every 3 weeks for 1-2 consecutive days.

Recommendations for dosage regimens are given in the following table.

Indications	Doses	Interval between injections
Substitution therapy
Primary immunodeficiencies	Starting dose: 0.4-0.8 g / kg body weight further: 0.2-0.8 g / kg body weight	Once, every 3-4 weeks until concentration is reached IgG not less than 5-6 g / l.
Secondary immunodeficiencies	0.2-0.4 g / kg body weight	Once, every 3-4 weeks until concentration is reached IgG not less than 5-6 g / l.
Children with congenital AIDS in the presence of recurrent infections	0.2-0.4 g / kg body weight	Once, every 3-4 weeks.
Hypogammaglobulinemia (<4 g / l) in patients with allogeneic transplantation of hematopoietic stem cells	0.2-0.4 g / kg body weight	Once, every 3-4 weeks, to maintain concentration IgG more than 5 g / l.
Application as an immunomodulator
Idiopathic thrombocytopenic purpura	0.8-1 g / kg body weight	First day; it is possible to repeat a single administration in the next 3 days from the date of the first administration.
Idiopathic thrombocytopenic purpura	or 0.4 g / kg body weight	Daily for 2-5 days.
Guillain-Barre Syndrome	0.4 g / kg body weight	Daily for 5 days.
Kawasaki disease	1.6-2 g / kg body weight	Assign in equal doses for 2-5 days in combination with the appointment acetylsalicylic acid.
Kawasaki disease	or 2 g / kg body weight	Once in combination with the appointment acetylsalicylic acid.
Chronic inflammatory demyelinating polyneuropathy *	Starting dose: 2 g / kg body weight;	Assign in equal doses in within 2-5 days.
Chronic inflammatory demyelinating polyneuropathy *	maintenance dose: 1 g / kg body weight	Every 3 weeks for 1 2 consecutive days.

^*Treatment duration of more than 24 weeks should be considered by the doctor and be based on the observed response to the drug and the estimated efficacy in long-term treatment. The dosage regimen should be selected in accordance with the observed clinical picture of the course of the disease.

Mode of application

Spiny should be administered only in the form of intravenous infusions.

The ghost is a solution ready for use. In the case of storing the drug in the refrigerator before the introduction of the temperature of the solution should be brought to room temperature. For the introduction should use an infusion system with an air valve and built-in filter. The vial plug should always be pierced in the center in the marked area.

If dilution is necessary, use a 5% dextrose solution. To obtain an immunoglobulin solution of 50 mg / ml (5%), Prividin solution for infusions of 100 mg / ml (10%) should be diluted with an equal volume of 5% dextrose solution.The technique of working in aseptic conditions should be strictly observed during the breeding of Prividzhen. Pristavgen can not be mixed with 0.9% sodium chloride solution. The solution should be clear or slightly opalescent.

In case of turbidity of the solution or the presence of mechanical inclusions in the solution, the preparation is not to be used.

Unused product and consumables should be disposed of in a suitable way.

The rate of administration

The drug should be administered initially at a rate of 0.3 ml / kg body weight / hour (0.5 mg / kg body weight / minute, approximately 30 minutes). If the drug is well tolerated, the infusion rate can be gradually increased to 4.8 ml / kg body weight / h (8 mg / kg body weight / min). In patients with primary immunodeficiencies who tolerated Priwidgen replacement therapy well, the infusion rate may be gradually increased to a maximum of 7.2 mL / kg body weight / h (12 mg / kg body weight / minute).

Special patient groups

Children

In the baseline phase III study in patients with primary immunodeficiencies (n= 80) were attended by 19 patients aged 3 to 11 years and 15 patients aged 12 to 18 years.

In an expanded clinical study on patients with primary immunodeficiencies (n= 50) involved 13 patients aged 3 to 11 years and 11 patients aged 12 to 18 years.

In a clinical study involving 57 patients with chronic idiopathic thrombocytopenic purpura, 2 patients aged 15 and 16 took part.

None of the three studies required a dosage adjustment for children.

Side effects:

The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems (classification MedDRA) and frequency of occurrence. Frequency of occurrence is defined as follows: very often (≥1 / 10), often (≥1 / 100 and <1/10), infrequently (≥ 1/1 000 and <1/100), rarely (≥ 1/10 000 and <1/1 000), very rarely (<1/10 000, including individual cases). Frequency categories were formed on the basis of data obtained during clinical trials of the drug.

In connection with the intravenous route of the drug, adverse reactions such as chills, headache, fever, vomiting, allergic reactions, nausea, joint pain, lowering blood pressure, and moderate back pain were infrequent.

Rarely, hypersensitivity reactions with a sharp decrease in blood pressure and, in some cases, anaphylactic shock, even when the patient has not previously revealed hypersensitivity reactions with the use of the drug.

Cases of reversible aseptic meningitis and, in rare cases, temporary skin reactions were observed in patients after using human immunoglobulin. Hemolytic reactions were observed in patients with blood groups A (II), B (III) and AB (IV). Hemolytic anemia requiring blood transfusion can rarely occur after treatment with high doses of human immunoglobulin preparations for intravenous administration (see section "Special instructions").

There have been cases of increased serum creatinine concentration and / or acute renal failure.

Very rarely there were thromboembolic complications, such as myocardial infarction, stroke, pulmonary embolism and deep vein thrombosis.

Four clinical studies have been conducted with Privigene, two in patients with primary immunodeficiency (FID), one involving patients with idiopathicthrombocytopenic purpura (ITP) and one involving patients with chronic inflammatory demyelinating polyneuropathies. In the main clinical study of PID, 80 patients were treated with Prividgen. Of these, 72 patients received treatment within 12 months. 55 patients were enrolled in the expanded clinical study of Priwidgen PID therapy. A clinical study of ITP was performed with the participation of 57 patients. A clinical study of chronic inflammatory demyelinating polyneuropathies was performed with the participation of 28 patients. Most of the adverse reactions observed in four clinical trials were mild or moderate.

The following summary table contains information on the side effects of Privigene, identified in four clinical trials. Within the frequency of occurrence in each group, adverse reactions are listed in descending order of severity.

Classification of undesirable reactions in compliance with organ and organ damage (MedDRA)	Clinical manifestations	Category frequencies occurrence
Infectious and parasitic diseases	Infections of ENT organs (otitis media, nasopharyngitis), influenza	Infrequently
Violations of the blood and lymphatic system	Anemia, anisocytosis, leukopenia, hemolysis	Infrequently
Disturbances from the nervous system	Headache	Often
Disturbances from the nervous system	Dizziness, discomfort in the head, drowsiness, tremor, sinus headache, migraine, dysaesthesia	Infrequently
Heart Disease	Rapid palpitations (palpitation)	Infrequently
Vascular disorders	Arterial hypertension	Often
Vascular disorders	Arterial hypotension, hot flashes, peripheral vascular disorders	Infrequently
Disturbances from the respiratory system, chest and mediastinal organs	Difficulty breathing, the formation of bubble cells on the mucous membrane of the mouth and throat, pain in breathing, a feeling of restraint in the throat	Infrequently
Disorders from the gastrointestinal tract	Vomiting, nausea	Often
Disorders from the gastrointestinal tract	Diarrhea, epigastric pain	Infrequently
Disturbances from the liver and bile ducts	Hyperbilirubinemia	Infrequently
Disturbances from the skin and subcutaneous tissues	Hives, rashes	Often
Disturbances from the skin and subcutaneous tissues	Itching, skin lesions, night sweats	Infrequently
Disturbances from musculoskeletal and connective tissue	Backache	Often
Disturbances from musculoskeletal and connective tissue	Pain in the neck, pain in the limbs, stiff muscles, muscle spasms, muscle and bone pain, myalgia, muscle weakness	Infrequently
Infringements from kidneys and urinary tract	Proteinuria	Infrequently
General disorders and disorders at the site of administration	Chills, fatigue, fever, asthenia, flu-like condition	Often
	Chest pain, general malaise, fever, pain, pain at the injection site	Infrequently
Laboratory and instrumental data	An increase in the concentration of bound and unbound bilirubin in the blood, a positive direct Coombs test, a positive indirect Coombs test, an increase in lactate dehydrogenase activity in the blood, a decrease in hematocrit, an increase in activity of alanine aminotransferase, an increase in activity of aspartate aminotransferase, an increase in the concentration of creatinine, a decrease in blood pressure, body temperature, decreased hemoglobin	Infrequently

Overdose:

Overdose can lead to hypervolemia and increased blood viscosity, especially in patients who are at risk, including elderly patients and patients with impaired renal function.

Treatment: symptomatic.

Interaction:

Live attenuated viral vaccines

After immunoglobulin therapy, the effectiveness of live measles, mumps, rubella and varicella vaccines can be reduced for at least 6 weeks and up to 3 months. An interval of 3 months between the appointment of Privigene and the vaccination with live attenuated vaccines should be observed. In the case of measles vaccination, a decrease in vaccine efficacy may last up to 1 year. Thus, in patients vaccinated with the measles vaccine, it is necessary to control the level of antibodies.

Special instructions:

Incompatibility

Prividzhen should not be mixed with other drugs and with 0.9% sodium chloride solution. However, dilution with 5% dextrose solution is permitted. The established severe adverse reactions may be associated with the rate of administration of the drug.It is necessary to carefully observe the speed of administration of the drug, indicated in the section "Method of administration and dose". It is necessary to carefully monitor patients and monitor for any symptoms during the infusion period.

Some unwanted reactions can be observed more often:

- in the case of a high rate of administration;

- in patients with hypogammaglobulinemia or agammaglobulinemia with insufficiency IgA or without insufficiency IgA;

- in patients who receive normal human immunoglobulin therapy for the first time, or in rare cases when a normal human immunoglobulin preparation is substituted for Privigene, or with a long break after a previous infusion.

Possible complications can be avoided by making sure that:

- the patient does not show a hypersensitivity to the human immunoglobulin normal with slow administration of the drug (0.3 ml / kg body weight / h);

- During and after the infusion period, all symptoms that occur in patients are carefully monitored. In particular, patients who have not received normal human immunoglobulin therapy before,and also transferred from treatment with another preparation of immunoglobulin for intravenous administration, or with a long interval after the previous infusion, it is necessary to monitor during the first infusion and within the first hour after the first infusion to identify potential adverse events. All other patients should be monitored for at least 20 minutes after use.

In case of development of an undesirable phenomenon it is necessary to reduce the rate of administration or to stop the administration of the drug. The required treatment depends on the nature and severity of the undesirable phenomenon.

In the case of development of shock, it is necessary to use standard treatment of shock conditions.

All patients before the initiation of human immunoglobulin for intravenous administration require appropriate hydration.

Hypersensitivity

True hypersensitivity reactions are rare. They can occur in very rare cases with a deficit IgA with antibodies to IgA.

Rarely normal human immunoglobulin may be the cause of a decrease in blood pressure with the development of an anaphylactoid reaction, even in patients who previously tolerated normal human immunoglobulin therapy.

Chronic inflammatory demyelinating polyneuropathies

There is limited experience in the use of intravenous immunoglobulins in children with chronic inflammatory demyelinating polyneuropathies.

Hemolytic anemia

Human immunoglobulin preparations for intravenous administration may contain antibodies against blood group antigens that can act as hemolysins and bind in vivo with erythrocytes, which can cause a positive direct antiglobulin test (Coombs test) and, rarely, hemolysis. Hemolytic anemia can develop after therapy with human immunoglobulin preparations for intravenous administration resulting from increased erythrocyte sequestration. Individual cases of renal and / or renal failure or disseminated intravascular coagulation disorder associated with hemolysis have been reported.

The development of hemolysis is associated with the following risk factors: high doses, regardless of the administration in the form of a single dose or individual doses for several days; as well as blood groups A (II), B (III) and AB (IV) in conjunction with the concomitant presence of the inflammatory process.When treating patients with blood groups A (II), B (III) or AB (IV) with high doses of the drug according to indications other than PID, it is advisable to take extra care. There are separate reports of hemolysis cases in patients with PID receiving substitution treatment.

It is necessary to monitor the clinical signs and symptoms of hemolysis in patients receiving therapy with human immunoglobulin preparations for intravenous administration. If there are signs and / or symptoms of hemolysis during or after infusion of the immunoglobulin for intravenous administration, the attending physician should consider canceling further treatment (see also the "Side effect" section).

Syndrome of aseptic meningitis (CAM)

When treating immunoglobulin preparations for intravenous administration, cases of the development of aseptic meningitis syndrome were recorded. After the abolition of the immunoglobulin for intravenous administration, the remission of CAM occurred within a few days without any consequences. Typically, this syndrome begins in the period from a few hours to 2 days after treatment with an immunoglobulin for intravenous administration.When analyzing the cerebrospinal fluid, pleocytosis is often observed up to several thousand cells per mm³, usually due to granulocyte-numbered cells, as well as an increased protein concentration, up to several hundred mg / dL.

CAM can develop more often when using immunoglobulin for intravenous administration in high doses (2 g / kg).

Thromboembolic complications

There are clinical data on the relationship between the use of human immunoglobulin for intravenous administration and the occurrence of thromboembolic complications, such as myocardial infarction, acute cerebrovascular accident (including stroke), pulmonary thromboembolism and deep vein thrombosis, which are presumably associated with a relative increase in blood viscosity at administration of a large number of immunoglobulins. Caution should be exercised when administering and administering immunoglobulin infusions for intravenous administration to obese patients and patients with previously established risk factors for thrombotic complications such as advanced age, hypertension, diabetes mellitus,thromboembolism or cardiovascular disease in history, cases of hereditary or acquired thrombophilia, prolonged period of mobility impairment, patients with severe hypovolemia and patients with diseases in which an increase in blood viscosity is observed.

Acute kidney failure

There were cases of development of acute renal failure in patients who received human immunoglobulin therapy for intravenous administration. In most cases, risk factors such as previous presence of renal failure, diabetes mellitus, hypovolemia, excess weight, concomitant treatment with nephrotoxic drugs or age over 65 years have been identified.

In the case of the development of renal failure, therapy with human immunoglobulin for intravenous administration should be discontinued. It should be noted that among the reports on cases of development of renal dysfunction or kidney failure developing against the background of the use of registered preparations of human immunoglobulins, the share of preparations containing sucrose as a stabilizer was disproportionately high.Thus, for patients who are at risk, use of intravenous immunoglobulin preparations that do not contain sucrose is recommended. The ghost does not contain sucrose or other sugars in its composition.

Patients at risk of developing acute renal failure or thromboembolic complications should be given immunoglobulin preparations for intravenous administration with a minimum infusion rate and at the lowest possible dose.

Effect on diagnostic tests

After the introduction of immunoglobulins in the patient's blood, the number of different passively transmitted antibodies is temporarily increased, which can lead to a false positive result in serological tests.

Passive transfer of antibodies to erythrocyte antigens, for example, A, B and D, can lead to an incorrect result in some serological tests to determine antibodies to erythrocytes (for example, Coombs test), in determining the amount of reticulocytes and in the haptoglobin test.

Safety information for infectious agents

Ghost is produced from human plasma.

Standard measures to prevent the transmission of infections resulting from the use of drugs derived from human blood or plasma include selection of donors, screening of individual donations and plasma pools for the presence of specific infection markers and the inclusion of effective production steps aimed at inactivating and / or removing viruses . Despite this, with the use of drugs made from human blood or plasma, the possibility of transmitting infectious agents can not be completely ruled out. This provision also applies to unknown or new viruses and other infectious agents.

Measures taken to ensure antiviral safety are considered effective for enveloped viruses such as HIV, hepatitis B and C viruses, and for non-enveloped viruses such as hepatitis A virus and paravovirus B19. An encouraging clinical experience has been obtained indicating that there is no transmission of hepatitis A virus and parvovirus B19 to human immunoglobulin preparations, and it is also believed that the presence of antibodies contributes significantly to viral safety.It is recommended that every name of the drug Prividzhen be registered with the name and serial number of the drug, which is administered to the patient, to maintain communication between the patient and the drug series.

Prizvenhen can not be used after the expiry date indicated on the cardboard pack and label of the vial.

Spotted is designed for single use. After opening the vial, the consumer is responsible for the storage time and storage conditions. The solution does not contain preservatives. Thus, after opening, the contents of the vial should be used within 24 hours.

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

Some of the undesirable reactions associated with the effect of Privigene may affect the ability to drive a vehicle or moving machinery. For patients who have experienced adverse reactions with the introduction of Privigene, vehicle management or moving mechanisms is only possible after the symptoms of unwanted reactions have disappeared.

Form release / dosage:

Solution for infusion, 100 mg / ml.

Packaging:

For 25 ml (2.5 g of active ingredient), 50 ml (5 g of active ingredient) or 100 ml (10 g of active ingredient) in a vial of clear, colorless glass (type I (FF or FSC)), sealed rubber stopper and rinsed aluminum cap with a plastic disc.

For 1 bottle with instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 25 ° C in a dark place. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002452

Date of registration:06.05.2014

Date of cancellation:2019-05-06

The owner of the registration certificate:CESEL Behring AGCESEL Behring AG Switzerland

Manufacturer: & nbsp

CSL BEHRING, AG Switzerland

Representation: & nbspGlaxoSmithKline group of companies GlaxoSmithKline group of companies Unknown

Information update date: & nbsp13.10.2015

Illustrated instructions

Instructions

Privived (Privigen)