Rebinolin immunoglobulin antirabies human
UkraineTable of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT REBINOLIN HUMAN ANTI-RABIES IMMUNOGLOBULIN
Composition:
Active substance: human anti-rabies immunoglobulin;
1 ml of solution contains 150 IU/ml of human anti-rabies immunoglobulin;
Excipients: glycine, water for injections, sodium hydroxide.
Pharmaceutical form. Solution for injection.
Main physicochemical properties: transparent, slightly opalescent, colorless or pale yellow solution; slight sediment formation is permissible, which disappears upon shaking.
Pharmacotherapeutic group. ATC code. Immunoglobulins. Specific immunoglobulins. Anti-rabies immunoglobulin.
ATC code J06B B05
Pharmacological Properties
Pharmacodynamics
Rabies is a zoonotic disease caused by RNA viruses of the genus Lyssavirus in the family Rhabdoviridae. The virus is usually present in the saliva of rabid mammals and is primarily transmitted through bites.
REBINOLIN RABIES IMMUNOGLOBULIN HUMAN is a buffered isotonic solution of specific human anti-rabies immunoglobulin obtained from the plasma of donors immunized with inactivated rabies vaccine (prepared from a strain grown on human diploid cell culture) and contains a high concentration of specific antibodies against the rabies virus. Immediate administration following exposure provides passive immunity to the rabies virus, prolongs the incubation period, and thereby supports effective vaccination as part of comprehensive rabies immunoprophylaxis.
Maximum antibody concentration is reached within 2–3 days after intramuscular administration of anti-rabies immunoglobulin. The elimination half-life (T½) of antibodies ranges from 3 to 4 weeks. Immunoglobulin G and immunoglobulin G-complexes are degraded in the cells of the reticuloendothelial system. A protective threshold for rabies virus neutralizing activity (RVNA) has never been definitively established. However, the WHO generally defines a rabies virus neutralizing activity of at least 0.5 IU/mL measured 14 days after initiation of post-exposure prophylaxis as protective.
Pharmacokinetics
Not applicable.
Clinical characteristics.
Indications.
For therapeutic and prophylactic immunization against rabies following any skin injury (bites, wounds, scratches), inflicted by wild or domestic animals, confirmed or suspected of having rabies, whether under veterinary supervision or not, as well as upon exposure of mucous membranes or damaged skin to saliva from infected animals. The medicinal product should be administered simultaneously with a full course of rabies vaccine.
Contraindications.
There are no contraindications (100% fatality rate of rabies overrides any contraindications).
Use with caution in patients with documented hypersensitivity to any component of the product.
Special safety measures.
Repeated administration of the product should not be performed after initiation of a rabies vaccination regimen, as such actions may reduce the development of maximal immunity.
Hypersensitivity reactions, including anaphylaxis, may occur with intravenous administration of the medicinal product. Prior to injection, ensure that the needle has not entered a blood vessel. A history of systemic allergic reactions to human immunoglobulin products increases the risk of hypersensitivity reactions. Epinephrine must be readily available to treat acute allergic symptoms. Patients with isolated immunoglobulin A (IgA) deficiency may develop severe hypersensitivity reactions to REBINOLIN HUMAN ANTIRABIES IMMUNOGLOBULIN or subsequently to blood products containing IgA. Allergic reactions to human-derived antirabies immunoglobulins following intramuscular administration are rare. In the event of shock, standard therapy should be initiated. In patients with a history of hypersensitivity to blood products, antihistamines should be administered (with careful monitoring of the patient).
Surgical and antiseptic wound management (including thorough washing with soap and water and disinfection) should be performed as soon as possible after the bite, regardless of the time elapsed since exposure. After administration of the product, the patient should remain under medical supervision for at least 20 minutes. Following immunoglobulin administration, transient elevation of antibody levels may lead to false-positive results in serological tests. Passive transfer of antibodies against erythrocyte antigens, such as A, B, and D, may interfere with serological testing for erythrocyte antibodies, including the antiglobulin test (Coombs test).
Administration of the medicinal product may interfere with the development of immune response to vaccines containing live attenuated viruses. If possible, vaccination against measles should be delayed for 4 months and vaccination with other live attenuated viral vaccines for 3 months after administration of REBINOLIN HUMAN ANTIRABIES IMMUNOGLOBULIN.
The medicinal product is manufactured from human plasma and may carry a risk of transmission of infectious agents, such as viruses, agents of the type causing Creutzfeldt-Jakob disease, and theoretically, the agent of Creutzfeldt-Jakob disease.
The physician or other healthcare provider must inform the manufacturer of any infection that may have been transmitted by this medicinal product.
Interaction with other medicinal products and other forms of interaction.
This medicinal product enhances the effect of rabies vaccination and is used in combination with other medicinal products. Combination with inactivated rabies vaccine prepared on human diploid cell culture is particularly recommended, as it has high immunogenicity and induces active antiviral immunity.
REBINOLIN HUMAN ANTIRABIES IMMUNOGLOBULIN may affect the immune response to rabies vaccine. Therefore, the recommended dose of the medicinal product should not be exceeded, and additional (repeat) doses should not be administered after initiation of rabies vaccination.
REBINOLIN HUMAN ANTIRABIES IMMUNOGLOBULIN may inactivate the rabies vaccine. Therefore, the medicinal product REBINOLIN HUMAN ANTIRABIES IMMUNOGLOBULIN should not be administered in the same syringe as the rabies vaccine or at an anatomical site close to the site of rabies vaccine administration.
Patients who can document prior complete rabies prophylaxis before potential virus exposure or complete post-exposure prophylaxis should receive only a booster dose of rabies vaccine without administration of REBINOLIN HUMAN ANTIRABIES IMMUNOGLOBULIN, as the medicinal product may interfere with the anamnestic response to the vaccine.
Administration of immunoglobulins may negatively affect the efficacy of vaccines containing live attenuated viruses such as measles, rubella, mumps, poliomyelitis, or varicella. Therefore, an interval of 3 months should be maintained between administration of REBINOLIN HUMAN ANTIRABIES IMMUNOGLOBULIN and live attenuated vaccines, and 4 months in the case of measles vaccine. This medicinal product is compatible with antitetanus serum and antibiotics.
Special precautions for use.
Use in elderly patients
Clinical studies of the medicinal product did not include a sufficient number of patients aged 65 years and older to determine whether they respond differently compared to younger patients. Clinical experience with human rabies immunoglobulin has not revealed any differences in efficacy between elderly and younger patients.
Use during pregnancy or breastfeeding
The use of the medicinal product during pregnancy has not been studied in controlled clinical trials; therefore, the drug should be administered during pregnancy and lactation only if the expected benefit to the woman outweighs the potential risk to the fetus or infant.
Long-term medical experience with immunoglobulins suggests no harmful effects on the course of pregnancy or on the fetus and newborn. It should be noted that immunoglobulins are excreted in breast milk, which may contribute to the transfer of protective antibodies to the infant (passive immunity).
Ability to influence reaction speed when driving vehicles or operating machinery
REBINOLIN HUMAN ANTIRABIES IMMUNOGLOBULIN has no effect or has a negligible effect on the ability to drive vehicles or operate other machinery.
Method of Administration and Dosage
Route of Administration
Administer intramuscularly to adults and children at a single dose of 20 IU/kg (0.133 mL/kg). The dose should not be exceeded under any circumstances, as administration of immunoglobulin may partially suppress the production of endogenous antibodies. If anatomically feasible, the maximum possible portion of the dose should be infiltrated around the wound, and the remainder administered intramuscularly (into the upper outer quadrant of the gluteus). The central part of the gluteal region should be avoided due to the risk of sciatic nerve injury.
Simultaneously, the first dose of rabies vaccine (see Table 1) (produced on human diploid cell culture) should be administered at a different injection site, preferably as far as possible from the site of anti-rabies immunoglobulin administration (preferably into the deltoid muscle area).
If therapy has been delayed for any reason, the immunoglobulin should be administered no later than the eighth day after the first vaccine dose, regardless of the time interval between virus exposure and initiation of therapy.
Table 1
Post-Exposure Rabies Prophylaxis Schedule
| Vaccination status |
Intervention |
Regimen 1 |
| Previously unvaccinated |
Wound cleansing |
|
| REBINOLIN HUMAN RABIES IMMUNOGLOBULIN 20 IU/kg body weight |
|
|
| Rabies vaccine |
|
|
| Previously vaccinated3 |
Wound cleansing |
|
| REBINOLIN HUMAN RABIES IMMUNOGLOBULIN |
|
|
| Rabies vaccine |
|
|
| Other factors to consider |
Tetanus prophylaxis and/or antibiotic therapy |
|
| 1 The stated regimens apply to all age groups, including children. 2 Day 0 is the day the first vaccine dose is administered. Refer to vaccine manufacturer instructions or recommendations from the Advisory Committee on Immunization Practices for the appropriate vaccine formulation, schedule, and dosage. 3 Any individual with a history of rabies vaccination and documented immune response to prior vaccination. |
||
If the bite site is unknown or cannot be determined, or if infiltration at the bite site is difficult (e.g., lips, fingers, knee), administer the full dose of the medicinal product by intramuscular injection at a site distant from the rabies vaccine administration site.
The product must not be administered using the same syringe or in the same anatomical area of the body as the rabies vaccine.
To ensure adequate infiltration of affected tissue areas in children (especially those with multiple wounds), the dose of the product may be diluted 2–3 times in 0.9% sodium chloride solution. If a large intramuscular volume is required (> 2 ml for children or > 5 ml for adults), the total dose should be administered as separate injections at different sites.
Anti-rabies immunoglobulin should be administered exclusively in combination with rabies vaccine. The only exception is individuals who have previously been vaccinated with rabies vaccine and in whom the presence of rabies virus antibodies has been confirmed. These individuals should receive only the vaccine.
Treatment should be discontinued if the animal remains healthy during the 10-day observation period or if the virus is not detected in the euthanized animal after appropriate laboratory testing. Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. Do not use if either condition is present, and contact the manufacturer. Unused portions of the medicinal product should be discarded in the vial. Do not discard the vial. REBINOLIN HUMAN ANTI-RABIES IMMUNOGLOBULIN is supplied in single-dose vials containing 2 ml or 10 ml of ready-to-use solution with a nominal potency of 150 IU/ml (note that more than one vial may be required to treat a single patient).
- The 2 ml vial contains a total of 300 IU, sufficient for a child weighing 15 kg.
- The 10 ml vial contains a total of 1500 IU, sufficient for an adult weighing 75 kg.
Children.
The product is indicated for use in children from birth.
Overdose.
Not observed.
Side effects.
Local reactions: pain, soreness, and discomfort at the injection site.
Systemic reactions: hyperthermia, allergic reactions (skin reactions, anaphylactic shock, angioneurotic edema), headache, muscle pain, joint pain, limb pain, fatigue, dizziness, vomiting, bruising, decreased blood pressure, tachycardia.
Shelf life.
2.5 years.
Incompatibility.
There are no data on incompatibility; therefore, the medicinal product REBINOLIN HUMAN RABIES IMMUNOGLOBULIN must be administered separately and should not be mixed with other medicinal products.
Storage conditions.
Store at a temperature of 2 °C to 8 °C, in the original light-protective packaging.
Packaging.
Solution for intramuscular injection 150 IU/mL. 2 mL or 10 mL of the product in vials made of colorless hydrolytic glass (USP) type I, hermetically sealed with rubber stoppers and crimped with aluminum caps with a plastic flip-off cap. One vial per cardboard box.
Prescription status.
Prescription only.
Manufacturer.
KAMADA LTD.
Manufacturer's address.
KIBBUTZ BEIT KAMA, M.P. NEGEV 8532500, ISRAEL.
Marketing Authorization Holder.
NEO PROBIO KEAR INC., Canada.
Address of the Marketing Authorization Holder.
599 Sandcherry Drive, Burlington, Ontario L7T 4L7, Canada.