Tetanus gamma

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT TETANUS GAMMA

Composition:

active substance: human tetanus immunoglobulin;

Distribution of IgG subclasses:

IgG1 65.1%
IgG2 30.3%
IgG3 3.2%
IgG4 1.4%

Maximum immunoglobulin A (IgA) content – 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 the pre-filled syringe containing 1 mL or 2 mL, respectively.

Pharmaceutical form. Solution for injection for intramuscular administration.

Main physicochemical properties: colorless or pale yellow or light brown liquid.

Pharmacotherapeutic group. Immune sera and immunoglobulins. Specific immunoglobulins. Antirabies immunoglobulin. ATC code J06BB02.

Pharmacological properties.

Pharmacodynamics.

Human tetanus immunoglobulin contains predominantly immunoglobulin G (IgG) with a high content of antibodies specific against the toxin produced by Clostridium tetani bacteria.

Pharmacokinetics.

Absorption

Human tetanus immunoglobulin administered intramuscularly becomes bioavailable in the patient's systemic circulation within 2–3 days after administration.

Elimination

The elimination half-life of human tetanus immunoglobulin is 3–4 weeks. The half-life may vary among individual patients.

IgG and IgG complexes are degraded in the cells of the reticuloendothelial system.

Preclinical safety data

Immunoglobulins are natural components of the human body.

Single-dose toxicity studies with high doses in animals are not considered relevant because high doses cause hypervolemia. Repeated-dose toxicity studies and embryotoxic/foetotoxic studies are not feasible due to induction and synthesis of antibodies. The impact of immunoglobulins on the immune system of newborns has not been investigated.

Since clinical experience with immunoglobulins has not demonstrated any carcinogenic or mutagenic effects, experimental studies, particularly those involving heterologous species, are not considered necessary.

Clinical characteristics.

Indications.

1. Prevention of infected wounds

For emergency prophylaxis of tetanus in case of wounds that may be infected, in patients who have not received appropriate vaccination or whose immunization status is unknown, and in patients with severe antibody synthesis deficiency.

2. Treatment of clinically manifest tetanus

Administration of tetanus immunoglobulin is carried out simultaneously with active tetanus vaccination, except in cases of contraindications or confirmed appropriate vaccination.

Contraindications.

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

Hypersensitivity to human immunoglobulins.

To avoid shock, the medicinal product TETANUS GAMMA must not be administered intravascularly (see section "Special precautions").

TETANUS GAMMA must not be administered to patients who have antibodies to immunoglobulin A (IgA). The presence of antibodies to IgA is rarely observed in patients who lack immunoglobulin A in their blood (see section "Special precautions").

Special safety measures.

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

Before injection, fully advance the plunger rod.

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

The solution may vary in color from colorless to pale yellow or light brown. Do not use the solution if it is markedly turbid or contains a precipitate.

Any unused medicinal product and/or waste material resulting from its use should be destroyed 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 development of immune response to live attenuated viral vaccines, particularly against rubella virus, mumps virus, and varicella virus, for a period 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 case of measles vaccine administration, the period of immunoglobulin influence on immune response formation may last up to 5 months.

Effect on serological test results

Following administration of immunoglobulins, transient elevation of various passively transferred antibodies into the patient's bloodstream may lead to false-positive results in serological tests.

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

Special precautions for use.

To avoid shock when administering TETANUS GAMMA, ensure that the medicinal product is not injected intravascularly (see section "Contraindications").

Traceability

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

True hypersensitivity reactions are rare.

TETANUS GAMMA contains a small amount of immunoglobulin A (IgA). In patients with immunoglobulin A (IgA) deficiency, there is a risk of developing anaphylactic reactions following administration of blood components containing IgA, due to the possible formation of anti-IgA antibodies. Therefore, the physician must weigh the benefits of treatment with TETANUS GAMMA against the potential risk of possible hypersensitivity reactions (see section "Contraindications").

Rarely, human tetanus immunoglobulin may cause a decrease in blood pressure leading to anaphylactic reaction, even in patients who previously tolerated immunoglobulin treatment well.

If an allergic or anaphylactic reaction is suspected, administration of the medicinal product should be stopped immediately. In case of shock, standard medical anti-shock measures should be implemented.

Viral safety

Standard measures to prevent infections from medicinal products derived from human blood or plasma include donor selection, screening of individual plasma donations and plasma pools for specific infectious markers, and the use of effective manufacturing steps for virus inactivation/removal.

Nevertheless, when administering medicinal products derived from human blood or plasma, the possibility of transmitting infectious agents cannot be completely ruled out, including unknown or emerging 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 reassuring clinical experience regarding the absence of transmission of hepatitis A virus or parvovirus B19 with immunoglobulins. It is also considered 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 product each time TETANUS GAMMA is administered to a patient, in order to maintain a link between the patient and the product batch.

Children

Specific data in children are lacking. The special precautions and warnings described above apply also to children (aged 0 to 18 years).

Important information on excipients of TETANUS GAMMA

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

Use during pregnancy or breastfeeding.

Pregnancy and breastfeeding

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

Clinical experience with immunoglobulins indicates that harmful effects on pregnancy, lactation, fetus, or newborn are not expected.

Fertility

The effect of TETANUS GAMMA on fertility has not been evaluated in controlled clinical trials. Clinical experience with immunoglobulins indicates that harmful effects on fertility are not expected.

Ability to influence the speed of reaction when driving or operating machinery.

TETANUS GAMMA has no effect or has a negligible effect on the ability to drive or operate machinery.

Administration and Dosage

Dosage

Prophylaxis of infected wounds

• 250 IU in cases of moderate risk;

• the dose may be increased to 500 IU in cases of:

  • inability to provide appropriate surgical treatment within 24 hours after an infected wound;

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

Treatment of clinically manifest tetanus

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

Route of administration

Human tetanus immunoglobulin should be administered intramuscularly.

If a large volume needs to be administered (> 2 mL in children or > 5 mL in adults), it is recommended to divide the dose into smaller volumes and inject at different sites.

If vaccination is required simultaneously, the immunoglobulin and the vaccine should be administered at two separate sites.

For prophylaxis in patients in whom intramuscular administration is contraindicated (e.g., in cases of hemorrhagic disorders), the product may be administered subcutaneously. However, it should be noted that clinical efficacy data supporting the subcutaneous route of administration are lacking.

For emergency treatment in cases where intramuscular administration is not clinically appropriate, an alternative medicinal product suitable for intravenous administration may be used, if available.

Children

The recommended dose for children (aged 0 to 18 years) 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 anti-tetanus immunoglobulin for intramuscular administration may include hypersensitivity reactions and anaphylactic shock.

Other adverse reactions that may occur during the use of medicinal products containing human anti-tetanus immunoglobulin include tachycardia, hypotension, headache, nausea, vomiting, skin reactions, erythema, pruritus, arthralgia (joint pain), fever, malaise, and chills.

Local adverse reactions at the injection site may include swelling, pain, erythema, induration (hardening), warmth, pruritus, and rash.

For safety information regarding transmissible agents, see section "Special precautions for use".

Adverse reactions in tabular form

Adverse reactions that may occur during the use of medicinal products containing human anti-tetanus immunoglobulin for intramuscular administration are presented in the table below, classified according to MedDRA system organ classes and preferred terms.

The frequency is defined according to the following conventional categories: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated from the available data).

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

Children

Specific data in children are lacking.

Reporting of suspected adverse reactions

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

Shelf life.

3 years.

Storage conditions.

Store in a refrigerator (at 2 to 8 ºC).

Do not freeze.

Keep in the original packaging to protect from light.

Incompatibilities.

Due to the lack of compatibility studies, this medicinal product must 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 transparent glass, containing 250 IU or 500 IU of human tetanus immunoglobulin.

Prescription status.

Prescription only.

Manufacturer.

KEDRION S.P.A.

Manufacturer’s name and address.

S.S.7 Bis Km 19.5 – 80029 Sant’Antimo (NA), ITALY

Marketing Authorization Holder.

Kedrion S.p.A.

Address of the Marketing Authorization Holder.

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