Phlebogamma 5% - instructions for use, doses, side effects, contraindications

Proteins of human plasma, of which:	0.5 g
immunoglobulin G (IgG)	not less than 97%
immunoglobulin A (IgA)	less than 0.00005 g
immunoglobulin M (IgM)	less than 0.00003 g
Distribution of immunoglobulin subclasses G (IgG):	IgG₁ - about 70.3%;
	IgG₂ - about 24.7%;
	IgG₃- about 3.1%;
	IgG₄ - about 1.9%
Excipients:
D-sorbitol	0.5 g
water for injections	up to 1 ml

Description:

Transparent or slightly opalescent, colorless or light yellow solution.

Pharmacotherapeutic group:MIBP - globulin

ATX: & nbsp

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

Pharmacodynamics:

Phlebogamma® 5% contains mainly immunoglobulin G with a broad spectrum of antibodies against infectious agents. The drug has all the properties of immunoglobulin G (IgG), which occurs in a healthy population.

Typically, the preparation of Flebogamma® 5% is prepared from a pool of plasma of not less than 1000 donors. Ratio of subclasses of immunoglobulin G in the preparation corresponds to that in normal human plasma. Adequate doses of the drug can restore pathologically low levels of immunoglobulin G plasma to normal values.

Pharmacokinetics:

Bioavailability of Phlebogamma® 5% with infusion is 100%.It is distributed between plasma and extravascular fluid quickly enough, and in 3-5 days an equilibrium state between intravascular and extravascular space is reached.

The half-life (T₁_/₂) of the drug is 46 (33-65) days. T₁_/₂may differ in different patients, especially in the case of primary immunodeficiencies. Immunoglobulin G and its complexes are utilized by the cells of the reticuloendothelial system.

Indications:

1. For replacement therapy:

- Primary immunodeficiency syndromes, such as

Congenital agammaglobulinemia and hypogammaglobulinemia;
unclassifiable variable immunodeficiency;
severe combined immunodeficiencies;
Wiskott-Aldrich syndrome.

- Secondary hypogammaglobulinemia in patients with chronic lymphocytic leukemia and myeloma, accompanied by recurrent infections.

- Recurrent infections in children with congenital HIV infection.

2. For use as an immunomodulator:

- Idiopathic thrombocytopenic purpura in adults and children with a high risk of bleeding or before surgery to correct the number of platelets.

- Guillain-Barre Syndrome.

- Kawasaki's disease.

3. Allogeneic bone marrow transplantation.

Contraindications:

Hypersensitivity to the drug components (for details, see "Precautions").

Intolerance to human immunoglobulin preparations, immunoglobulin A deficiency in individuals who have antibodies to immunoglobulin A.

Congenital intolerance to fructose.

Pregnancy and lactation:

Safety of the use of phlebogamma 5% during pregnancy in controlled clinical trials have not been evaluated, so during pregnancy and lactation it should be used after a thorough assessment of the risk / benefit ratio. Clinical experience of medical use of immunoglobulins does not allow expecting any harmful effect on the course of pregnancy, as well as on the fetus and on the newborn.

Application during lactation: the administered immunoglobulins are excreted in the mother's milk and can facilitate the transfer of protective antibodies to the newborn.

Dosing and Administration:

The drug is used in the form of infusions.

Doses and duration of therapy are determined by indications for use.With replacement therapy, the dose is selected individually, taking into account the pharmacokinetics (T₁_/₂) and clinical response of the patient.

Substitution therapy for primary immunodeficiencies: the goal is maintenance of IgG level in plasma not less than 4-6 g / l (the determination should be made before each subsequent infusion), which is achieved within 3-6 months from the beginning of treatment. The initial dose is 0.4-0.8 g / kg, then the drug is administered every 3 weeks at a dose of 0.2 g / kg. The required dose to maintain the IgG titer in the plasma at a level of 6 g / l is 0.2-0.8 g / kg per month. After reaching the equilibrium concentration, the drug is administered at intervals of 2-4 weeks. To determine the optimal dose and the interval between administrations, the level of IgG in the plasma should be monitored.

Substitution therapy for chronic lymphocytic leukemia or myeloma with severe secondary hypogammaglobulinemia and recurrent bacterial infections; Replacement therapy for relapsing infections in children with congenital HIV infection: the recommended dose is 0.2-0.4 g / kg every 3-4 weeks.

Idiopathic thrombocytopenic purpura: when treating acute episodes at the first administrationthe drug is prescribed in a dose of 0.8-1 g / kg and, if necessary, repeat on the third day or 0.4 g / kg daily for 2-5 days. In case of insufficient effectiveness, therapy can be repeated.

Heine-Barre Syndrome: 0.4 g / kg daily for 3-7 days. Experience with children is limited.

Kawasaki disease: cumulative dose of 1.6-2 g / kg, administered for several infusions for 2-5 days (possibly daily) or at a dose of 2 g / kg once, in combination with acetylsalicylic acid therapy.

Allogeneic bone marrow transplantation: Phlebogamma® 5% therapy can be administered as part of the preparations for and after transplantation. To treat infection and prevent the "graft versus host" reaction, the dosage should be selected individually. The recommended initial dose is 0.5 g / kg and administered once 7 days before transplantation. Introduction continues weekly for three months after transplantation. With persistent immunodeficiency, infusion is recommended once a month at a dose of 0.5 g / kg until the level of antibodies normalizes.

Recommendations for dosage are summarized in the table:

Indication	Dose	Intervals between infusions
Substitution therapy:
With primary immunodeficiencies	Initial dose - 0.4-0.8 g / kg,
	then 0.2-0.8 g / kg	Every 2-4 weeks to achieve plasma IgG levels minimum 4-6 g / l
With secondary immunodeficiencies	0.2-0.4 g / kg	Every 3-4 weeks to achieve IgG levels in plasma minimum 4-6 g / l
HIV infection in children	0.2-0.4 g / kg	Every 3-4 weeks
Immunomodulation:
Idiopathic corymbromatocytopenic purpura	0.8-1 g / kg	In a single dose, if necessary - repeatedly in the same dose on the third day
	or 0.4 g / kg / day	For 2-5 days in a row
Guillain-Barre Syndrome	0.4 g / kg / day	For 3-7 days in a row
Kawasaki disease	1.6-2 g / kg	Several injections for 2-5 days (in combination with acetylsalicylic acid therapy)
	or 2 g / kg	In a single dose (in combination with therapy with acetylsalicylic acid)
Allogeneic bone marrow transplantation:
- infection therapy and prophylaxis of the "graft versus host" reaction	0.5 g / kg	Weekly, initiation of therapy - 7 days before transplantation; ending - 3 months after it
- persistent immunodeficiency	0.5 g / kg	Monthly before the normalization of the level of antibodies

Rules for administering the solution

The preparation Flebogamma® 5%, unseparated, is administered with an initial infusion rate of 0.6-1.2 ml / kg / h for the first 30 min. With good portability the rate of administration can be gradually increased to 2.4 ml / kg / h (maximum). Infusion should be carried out only through a separate system. Before administration, the preparation should be heated at least to room temperature or to the temperature of the human body. It is inadmissible to use a turbid solution or solution with a precipitate. Due to the risk of bacterial contamination, any amount of unused solution should be destroyed.

Pharmaceutical incompatibility

Do not mix Phlebogamma ® 5% with other medicines or infusion solutions. The drug should be administered only through a separate infusion system.

Side effects:

Possible side effects such as chills, headache, fever, nausea, vomiting, allergic reactions, aching joints and mild back pain.

In rare cases, as a result of the introduction of normal human immunoglobulin, a sudden drop in blood pressure may be possible, and in some cases, the development of symptoms of anaphylactic shock, even if the patient did not show increased sensitivity to it during the previous administration of the drug.

In connection with the introduction of human immunoglobulin, there were rare cases of the appearance of signs of aseptic meningitis and in some patients - hemolytic anemia / hemolysis, as well as transient skin reaction (rash or hyperemia), which completely disappeared after discontinuation of therapy.

In rare cases, there was an increase in serum creatinine and / or acute renal failure.

Individual patients developed thromboembolic reactions, such as myocardial infarction, pulmonary embolism, deep vein thrombosis of the lower extremities.

The patient should be warned that if he has noted any side effects not described in this manual, he should inform his or her treating physician about it.

Overdose:

Overdosing of the drug may lead to the development of hypervolemia and increased blood viscosity, most often in patients at risk, including the elderly and patients with impaired renal function.

Interaction:

The introduction of immunoglobulins can adversely affect for 6 weeks and up to 3 months on the effectiveness of live vaccines against such viral diseases as measles, rubella, mumps and chicken pox.

Vaccination with an appropriate live vaccine should be given no earlier than 3 months after the administration of Phlebogamma 5%. In the case of measles vaccination, this effect of immunoglobulin can last up to 1 year, in patients vaccinated against measles and during the same year receiving immunoglobulin therapy, the level of the corresponding antibodies in the blood should be monitored.

After the introduction of an immunoglobulin, a temporary increase in the titer of various passively introduced antibodies is possible, which can lead to false-positive analysis results in a serological study.

Passively introduced antibodies against erythrocyte antigens (eg A, B, D) can affect serological parameters such as the level of alloantibodies to erythrocytes (eg, Coombs reaction) and the number of reticulocytes, a test for haptoglobin.

Special instructions:

Precautionary measures

Certain severe side effects may develop during the infusion of the drug and may be associated with the rate of its administration. Recommendations for dosage and rate of administration are described in detail in the section "Method of administration and dose" and must be strictly observed.During the infusion of the drug should closely monitor the patient's condition.

Certain side effects can occur more often:

- with a high infusion rate;

- in patients with hypogammaglobulinemia or agammaglobulinemia in the presence or absence IgA-deficiency;

- in patients receiving normal human immunoglobulin for the first time or in rare cases when switching to another immunoglobulin preparation, or if treatment with immunoglobulins was carried out a very long time ago.

True hypersensitivity reactions are extremely rare, with an immunoglobulin deficiency in the blood A (IgA) and the presence of antibodies to IgA.

In extremely rare cases with the infusion of immunoglobulin preparations may develop hypotension and anaphylactic reaction, even if previously the patient was well tolerated infusion of the drug.

In most cases, possible complications can be avoided if:

- make sure that the patient does not have an increased sensitivity to normal human immunoglobulin, injecting the drug at the beginning of the infusion very slowly (0.6-1.2 mg / kg / h);

- carefully monitor the patient all the time infusion of the drug and monitor the appearance of signs of undesirable effects.Especially carefully, in order to control the possible occurrence of symptoms of hypersensitivity, it is necessary to observe throughout the infusion and at least 1 hour after its completion for patients who have never received normal human immunoglobulin, or previously received other immunoglobulin preparations, or if immunoglobulins have been administered for a long time. All other patients should be monitored for at least 20 minutes after the end of the injection.

There are suspicions about the relationship between the infusion use of immunoglobulins and thromboembolism such as myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis of the lower limbs, which are thought to be associated with a relative increase in blood viscosity due to a significant increase in the level of immunoglobulins in patients at risk of thrombotic complications. It is advisable to prescribe and administer immunoglobulins to patients with obesity and patients at risk of developing thrombotic complications (for example: senile, suffering from arterial hypertension, diabetes mellitus,vascular disease and history of thrombosis, hereditary or acquired thrombophilic disorders, patients who have been immobile for a long time, with severe hypovolemia, as well as patients with diseases that increase the viscosity of the blood).

In patients with the introduction of immunoglobulins, very rarely there may be signs of acute renal failure. In most cases, this side effect has occurred in patients who have additional risk factors: already existing disorders of kidney function, diabetes mellitus, hypovolemia, overweight, patients taking drugs that have a nephrotoxic effect, and also age over 65 years.

In the case of a violation of the kidneys should decide whether to abolish therapy with immunoglobulins.

Cases of development of renal dysfunction were noted during the infusion of many registered normal human immunoglobulin preparations containing sucrose as a stabilizer in a disproportionately high concentration. Phlebogamma 5% sucrose does not contain. In patients at risk of developing acute renal failure (ARF), the use of normal human immunoglobulin preparations that do not contain sucrose is justified.

Patients with a high risk of acute arterial hypertension or thrombotic complications should receive the normal human immunoglobulin preparation at recommended doses with a minimum infusion rate.

When carrying out immunoglobulin therapy for all patients, it is necessary:

- the intake of sufficient amounts of fluid before the infusion of the immunoglobulin;

- monitoring diuresis;

- control serum creatinine (indicator of kidney function);

- exclusion of simultaneous intake of diuretics.

With prolonged use of the drug should monitor the functional state of the kidneys of patients.

In the case of the appearance of hypersensitivity or intolerance to the drug, it is necessary to reduce the rate of administration or stop its infusion. The choice of appropriate treatment depends on the type and severity of the side effect.

In the event of a shock, it is necessary to follow the current recommendations for antishock therapy.

Special warning: Phlebogamma® 5% contains an excipient D-sorbitol in an amount of 5 g per 100 ml. With congenital intolerance to fructose, the drug should not be prescribed.

Special safety information

In the production of drugs from human blood or plasma, including Phlebogamma 5%, certain measures are being taken to prevent the transmission of infections to patients. These measures include the careful selection of blood and plasma donors to eliminate the risk of transmission of infections, as well as testing of each individual portion and pool of plasma for the detection of virus / infectious agents. Producers include in the process of manufacturing drugs and processing blood or plasma all the necessary steps to ensure inactivation or removal of viruses. Despite these measures, it is impossible to exclude completely the possibility of transmission of infections when using drugs from human blood or plasma. This also applies to any unknown viruses or other types of infectious agents.

The measures taken have been shown to be effective for envelope viruses, such as the human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, as well as for the non-enveloped hepatitis A virus.

Measures may have limited effect on non-enveloped viruses, such as parvovirus B19.

Immunoglobulins are usually not associated with infections caused by the hepatitis A virus or parvovirus B19,that they contain antibodies against these infectious agents, creating additional safety.

Each time a 5% dose of Phlebogamma is administered, the name and serial number of the drug should be recorded to account for the series used.

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

There is no indication that immunoglobulins can affect the ability to drive or serve machinery.

Form release / dosage:Solution for infusions, 50 mg / ml.

Packaging:

For 10 ml, 50 ml, 100 ml and 200 ml of the drug in glass bottles, class II (EF), sealed with a plug of chlorobutyl rubber with an aluminum cap, closed with a plastic lid.

One bottle with instructions for use is placed in a cardboard box.

Storage conditions:

At a temperature of 2 to 30 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

The expiration date is indicated on the label.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000293/10

Date of registration:25.01.2010

The owner of the registration certificate:Institute Grifols S.A.Institute Grifols S.A. Spain

Manufacturer: & nbsp

Instituto GRIFOLS, S.A. Spain

Representation: & nbspINSTITUTE GRIFOLZ SA.INSTITUTE GRIFOLZ SA.Russia

Information update date: & nbsp14.10.2015

Illustrated instructions

Instructions

Phlebogamma 5% (Flebogamma 5%)