GENTASEPT

INSTRUCTIONS for medical use of the medicinal product TETANUS GAMMA

Composition:

Active substance: human antitetanus immunoglobulin;

Distribution of IgG subclasses:

IgG1 65.1 %

IgG2 30.3 %

IgG3 3.2 %

IgG4 1.4 %

Maximum content of immunoglobulin A (IgA) – 300 μg/ml;

Excipients: glycine, sodium chloride, water for injections.

Excipients with known effect

This medicinal product contains no more than 10 mg and 20 mg of sodium in a pre-filled syringe containing 1 ml or 2 ml, respectively.

Pharmaceutical form.

Solution for injection for intramuscular administration.

Main physical and chemical properties:

Colorless or pale yellow or light brown liquid.

Pharmacotherapeutic group.

Immune sera and immunoglobulins. Specific immunoglobulins. Antitetanus immunoglobulin. ATC code J06B B02.

Pharmacological properties.

Pharmacodynamics.

Human antitetanus immunoglobulin contains mainly immunoglobulin G (IgG) with a high content of antibodies specific to the toxin produced by Clostridium tetani bacteria.

Pharmacokinetics.

Absorption

Human antitetanus immunoglobulin for intramuscular administration is bioavailable in the patient's bloodstream within 2-3 days after administration.

Elimination

The half-life of human antitetanus immunoglobulin is 3-4 weeks. The half-life may vary in different patients.

IgG and IgG complexes are broken down in the cells of the reticuloendothelial system.

Non-clinical data on safety

Immunoglobulins are natural components of the human body.

Studies of toxicity after single administration of high doses to animals are not meaningful, as high doses cause hypervolemia. Studies of toxicity after repeated administration and studies of embryonic/fetal toxicity are not possible due to the induction and synthesis of antibodies. The effect of immunoglobulins on the immune system of newborns has not been studied.

Since clinical experience with immunoglobulins has not confirmed their carcinogenic and mutagenic effects, conducting experimental studies, including those involving heterological species, is not considered necessary.

Clinical characteristics.

Indications.

1. Prevention of infected wounds

For emergency prevention of tetanus in cases of wounds that may be infected, in patients who have not been properly vaccinated or whose vaccination status is not reliably known, and in patients with severe antibody synthesis deficiency.

2. Treatment of clinically manifest tetanus

Administration of antitetanus immunoglobulin is performed simultaneously with active vaccination against tetanus, except in cases of contraindications or confirmation of proper vaccination.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients listed in the "Composition" section.

Hypersensitivity to human immunoglobulins.

To avoid shock, the medicinal product TETANUS GAMMA should not be administered into the patient's blood vessel (see "Special warnings and precautions for use").

TETANUS GAMMA should not be used in patients who have antibodies to immunoglobulin A (IgA). The presence of antibodies to IgA is rarely observed in patients who lack immunoglobulin A (see "Special warnings and precautions for use").

Special warnings and precautions.

TETANUS GAMMA, solution for injection in a pre-filled syringe

Before injection, screw the plunger rod.

Before administration, the medicinal product should be brought to room temperature or body temperature.

The color of the solution may vary from colorless to slightly yellow or light brown. Do not use the solution if it is significantly cloudy or contains sediment.

Unused medicinal product and/or residues that remain after its use should be disposed of in accordance with local requirements.

Interaction with other medicinal products and other forms of interaction.

Live attenuated viral vaccines

Administration of immunoglobulin may interfere with the formation of an immune response to live attenuated viral vaccines, including those against measles, mumps, and rubella, for up to 3 months. Vaccination with live attenuated viral vaccines should be performed no earlier than 3 months after administration of this medicinal product. In the case of vaccination against measles, the period of influence of immunoglobulin on the formation of an immune response may last up to 5 months.

Influence on the results of serological studies

After administration of immunoglobulins, a temporary increase in the level of various antibodies that have been passively transferred to the patient's blood may lead to false-positive results of serological studies.

Passive transfer of antibodies to erythrocyte antigens, such as A, B, D, may negatively affect the results of some serological tests for erythrocyte antibodies, such as the antiglobulin test (Coombs test).

Special precautions.

To avoid shock when using the medicinal product TETANUS GAMMA, it should be ensured that the medicinal product is not administered into the patient's blood vessel (see "Contraindications").

Monitoring

To improve the traceability of biological medicinal products, the name and batch number of the medicinal product should be recorded every time it is administered to the patient.

True hypersensitivity reactions are rare.

The medicinal product TETANUS GAMMA contains a small amount of immunoglobulin A (IgA). In patients with immunoglobulin A deficiency, there is a risk of developing anaphylactic reactions after administration of blood components that contain IgA, due to possible formation of antibodies to IgA. Therefore, the doctor should weigh the benefits of treatment with TETANUS GAMMA against the potential risk of developing possible hypersensitivity reactions (see "Contraindications").

Rarely, human antitetanus immunoglobulin may cause a decrease in blood pressure with the development of an anaphylactic reaction, even in patients who have previously tolerated human immunoglobulin well.

In case of suspected allergic or anaphylactic reactions, administration of the medicinal product should be stopped immediately. In case of shock, standard anti-shock measures should be taken.

Viral safety

Standard measures to prevent infections caused by the use of medicinal products manufactured from human blood or plasma include donor selection, screening of individual plasma donations and plasma pools for specific infection markers, and the use of effective measures for virus inactivation/removal during production.

Despite this, when administering medicinal products manufactured from human blood or plasma, it is not possible to completely exclude the risk of transmission of infectious agents. This also applies to unknown or new viruses and other pathogens.

The measures taken are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), as well as against non-enveloped viruses, such as hepatitis A virus (HAV).

The measures taken may have limited effectiveness against non-enveloped viruses, such as parvovirus B19.

There is encouraging clinical experience regarding the absence of transmission of hepatitis A virus or parvovirus B19 with immunoglobulins. It is also assumed that the presence of antibodies is an important factor in antiviral protection.

It is strongly recommended to record the name and batch number of the medicinal product every time it is administered to the patient to maintain a link between the patient's condition and the batch of the medicinal product.

Children

Specific data on children are not available. The above special precautions and precautions for use of the medicinal product also apply to children (from 0 to 18 years old).

Important information about the excipients of TETANUS GAMMA

This medicinal product contains no more than 10 mg and 20 mg of sodium in a pre-filled syringe containing 1 ml or 2 ml, respectively, and is therefore essentially sodium-free.

Use during pregnancy or breastfeeding.

Pregnancy and breastfeeding

The safety of using this medicinal product in pregnant women has not been established in controlled clinical trials, so it should be used with caution in women during pregnancy and breastfeeding.

Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, lactation, fetus, and newborn are expected.

Fertility

The effect of using the medicinal product TETANUS GAMMA on fertility has not been evaluated in controlled clinical trials. Clinical experience with immunoglobulins suggests that no harmful effects on fertility are expected.

Ability to influence the reaction rate when driving vehicles or using other mechanisms.

TETANUS GAMMA does not affect or has a negligible effect on the ability to drive vehicles or use other mechanisms.

Method of administration and dosage.

Dosage

Prevention of infected wounds

- 250 IU in case of moderate risk;

- the dose can be increased to 500 IU in case of:

impossibility of providing proper surgical treatment within 24 hours after infection;

deep or contaminated wounds with tissue damage and limited oxygen access, as well as traumatic injuries with foreign bodies (bites, punctures, or gunshot wounds).

Treatment of clinically manifest tetanus

For the treatment of clinically manifest tetanus, several studies have determined a single dose of 3,000 to 6,000 IU of human antitetanus immunoglobulin in combination with other relevant clinical procedures.

Method of administration

Human antitetanus immunoglobulin should be administered intramuscularly.

If it is necessary to administer a large volume (> 2 ml in children or > 5 ml in adults), it is recommended to divide it into smaller doses and administer it at different sites.

If vaccination is to be performed simultaneously, the immunoglobulin and vaccine should be administered at two different sites.

For the purpose of prevention, in cases where intramuscular administration is contraindicated (in cases of hemorrhagic disorders), the medicinal product can be administered subcutaneously. However, it should be noted that there are no clinical efficacy data on the use of the medicinal product that would support subcutaneous administration.

For the purpose of emergency treatment, in cases where intramuscular administration of the solution is not clinically feasible, an alternative medicinal product for intravenous administration may be used.

Children

The recommended dose for children (from 0 to 18 years old) does not differ from the dose for adults.

Overdose.

The consequences of overdose are unknown.

Adverse reactions.

Clinically significant adverse reactions to medicinal products containing human antitetanus immunoglobulin for intramuscular administration may include hypersensitivity reactions and anaphylactic shock.

Among other adverse reactions that may occur when using medicinal products containing human antitetanus immunoglobulin, the following are noted: tachycardia, hypotension, headache, nausea, vomiting, skin reactions, erythema, itching, arthralgia, fever, malaise, and chills.

At the injection site, the following adverse reactions may develop: swelling, pain, erythema, induration, sensation of heat, itching, and rash.

Information on the safety of transmissible agents can be found in the "Special precautions" section.

Adverse reactions in the form of a table

During a clinical study of the medicinal product TETANUS GAMMA involving 30 patients, none of the adverse reactions observed in patients were related to the use of this medicinal product.

Children

Specific data on children are not available.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after authorization of the medicinal product is important, as it allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national reporting system.

Shelf life.

3 years.

Storage conditions.

Store in a refrigerator (at a temperature of 2 to 8 °C).

Do not freeze.

Store in the original packaging to protect from light.

Incompatibility.

Due to the lack of compatibility studies, this medicinal product should not be mixed with other medicinal products.

Packaging.

Pre-filled syringe with solution for injection, 250 IU and 500 IU

Carton box containing one pre-filled syringe made of neutral glass, which contains 250 IU or 500 IU of human antitetanus immunoglobulin.

Authorization status.

Prescription only.

Manufacturer.

KEDRION S.P.A.

Manufacturer's location and address.

SS. 7 Bis Km. 19.5 – 80029 SANT'ANTIMO (NA), ITALY

Marketing authorization holder.

Kedrion S.p.A.

Marketing authorization holder's location.

Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca) Italy.