SUMMARY OF PRODUCT CHARACTERISTICS

Transcription

1 SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF MEDICINAL PRODUCT Botulinum Antitoxin ABE, 500 IU IU IU/ml, solution for injections 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One vial (10 ml) contains: Botulinum antitoxin type A: Botulinum antitoxin type B: Botulinum antitoxin type E: 1 ml of the solution contains: Botulinum antitoxin type A: Botulinum antitoxin type B: Botulinum antitoxin type E: 5000 IU 5000 IU 1000 IU 500 IU 500 IU 100 IU Detailed list of exipients, see item PHARMACEUTICAL FORM Solution for injections. Clear solution, light-straw colour. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications The preparation is used for neutralisation of botulinum toxin or toxins types A, B and E ( in botulism). 4.2 Posology and method of administration Application of Botulinum Antitoxin ABE is ordered by a doctor. Before administration of the preparation history data concerning patient s allergic condition and previous administration of equine antitoxin should be taken. Perform allergic test for equine antitoxin (equine protein). In case of positive or doubtful results of the allergic tests with the simultaneous indication to apply the preparation, Botulinum Antitoxin ABE can be administered with the use of desensitization method. Before performance of allergic tests and administration of an animal antitoxin one should always have a whole set of ready-to-use shock-controlling agents prepared. Preventively/prophylactically: Way of administration: intramuscularly Dose: 10 ml to 20 ml (one to two vials)

2 Therapeutically: Way of administration: intramuscularly; in life-saving situation: intravenously. Dose: 50 ml to 100 ml (five to ten vials) Note: Before intravenous administration the preparation should be warmed up to 37ºC. Allergic test: according to A. Gałązka, J. Januszkiewicz. Inject intradermally: 0,1 ml of the preparation diluted with aseptic, physiological sodium chloride solution 1:10, or 0,2 1:100, or more if the allergic reactions of the patient are known. The method applied more often is administration of: 0,2 ml of the preparation diluted with physiological sodium chloride solution 1:1000. If after 30 minutes, in one of the intradermal tests occurs no local or general allergic reaction, 0,2 ml of undiluted antitoxinone should be injected intradermally. If after 30 minutes occurs no allergic reaction, the antitoxin can be administered both intramuscularly and intravenously. If within minutes during the allergic tests the place of injection becomes red and there appears a blister, it indicates that the patient is allergic to equine protein. If the result is not certain, and there is indication to apply botulinum antitoxin, it should be administered with the use of the desensitization method. Allergic test according to B. Dębiec and W. Magdzik Inject intradermally 0,1 ml of the antitoxin diluted 1:10 with 0,9% sodium chloride solution. If within minutes the place of injection becomes red and there appears a blister, it indicates that the patient is allergic to the specific type of antitoxin protein. Desensitization method of administration of Equine Botulinum Antitoxin Method one: (acc. to A. Gałązka) Start with intradermal injection of the lowest dose tolerated in intradermal test. If within 30 minutes occurs no reaction, increase the intradermal dose every 30 minutes until it is injected 0,2 ml of undiluted antitoxin. Then administer the remaining part of the planned dose intramuscularly. According to J. Januszkiewicz, a planned desensization consists in injections of small volumes of the preparation (from 0,1 ml to 0,5 ml) intradermally, in minutes intervals. Often, it is necessary to repeat the same doses as the allergic reactions are doubtful or obvious. Method two: (according to B. Dębiec) Inject intradermally antitoxin diluted with 0,9% sodium chloride, in 30 minutes to 1 hour intervals, in quantities 0,1 ml to 0,5 ml, then inject undiluted Botulinum Antitoxin ABE, 0,2 ml and 0,5 ml. (In the allergic test there was given information on dilution 1:10, here the dilution is not given). The remaining part of the planned dose should be administered intramuscularly. 4.3 Contraindications Hypersensitivity to the active substances (equine protein) or to any of the excipients.

3 However, in cases of severe intoxication and the necessity to apply botulinum antitoxin, it can be administered with the use of desensitization method or after application of shockcontrolling agents. 4.4 Special warnings and special precautions for use Application of the preparation is ordered by a doctor. Before making a decision on administration of the preparation patient s allergic states and previous administration of equine antitoxin should be checked in anamnesis. Intradermal tests or injections of the preparation should not be performed without ready-touse shock-controlling set. Antitoxin obtained from horse serum must not be administered to persons: with allergy to equine protein, who are known from the anamnesis to be allergic, who were previously administered equine antitoxin. 4.5 Interactions with other medicinal products and other forms of interaction There were no trials made concerning interactions of Botulinum Antitoxin ABE with other medicaments. 4.6 Pregnancy and lactation No sufficient data concerning application of Botulinum Antitoxin ABE in pregnant and lactating women. Precautious should be taken while prescribing the medicament to pregnant and lactating women. 4.7 Effects on ability to drive and use machines Botulinum Antitoxin ABE is unlikely to produce an effect on the ability to drive and use machines. 4.8 Undesirable effects No sufficient data obtained during clinical trials concerning frequency of occurrence of undesirable effects. Based on the literature the following undesirable effects were reported: Similarly as after applying other animal antitoxins, there are observed rare but severe general responses of allergic origin, i.e. anaphylactic shock and/or serum sickness. Serum sickness begins between 7 th and 20 th day following administration of the preparation and results in oedema in the place of injection, enlarged lymph nodes, increased body temperature, oedema of joints, urticaria, or in acute cases kidneys damage. In the result of the surplus quantity of the antigen (heterologous protein) developing IgG antibodies form complexes with them. Also IgE antibodies, responsible for the general urticaria occurring in this system, develop in humans. The complexes are gradually picked up

4 by the macrophages system and part of them is deposited in vessels endothelium, in basement membrane of renal glomerule, joints and muscles. Neurological complications in the form of brachial plexus, cranial nerve and peripheral nerve neuritis (i.e. encephalopathy) or Guillan-Barre syndrome (acute inflammatory demyelinating polyneuropathy) occur seldom. Symptoms abate after withdrawal of the antigen from the body. In rare cases inflammatory condition, i.e. oedema and pain may occur in the place of injection. 4.9 Overdose Administration of higher doses than required should be omitted. Higher dose may cause sharpening of undesired effects. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotheraupeutic group: medicaments used in infections; immune serums and immunoglobulins; immune serums; botulinum antitoxin, ATC code: J 06 AA 04. The preparation contains a mixture of three equine botulinum antitoxins neutralising respective toxin types (A, B and E) produced by Clostridium botulinum. Each of those antitoxins obtained from serum of immunized horses contains specific immunoglobulin of G class. Each immunoglobulin G obtained for one type of toxin is purified by digestion method through proteolysis of proteins with pepsin at 4.0 ph, precipitation of labile proteins by thermocoagulation and selective precipitation with ammonium sulphate. Botulinum Antitoxin ABE neutralizes the effect of botulinum toxins type A, B and E by peculiar relation of the antigen (toxin)- antibody (antitoxin) type. Half-life of specific IgGs is approx. 3 days. 5.2 Pharmacokinetic properties The preparation has been manufactured in Poland for over 30 years. Clinical trials are retrospective and limited in number. Following the progress of sanitary education and production technology of food products the number of botulism cases has decreased. In 1980s the number of such intoxications in Poland decreased to approx cases annually. After intramuscular administration of the preparation the maximum concentration of the antitoxin in blood serum is obtained within 1-2 days. Absorption of the medicament from the place of injection occurs in the result of simple diffusion from the environment of a tissue into plasma. The antigen (toxin)- antibody (antitoxin) complex undergoes phagocytosis. Half-life is 2-3 days. Absorption After intramuscular injection of Botulinum Antitoxin ABE maximum concentration of the antitoxin in serum is obtained within 1 to 2 days. After intravenous administration of the preparation the maximum concentration of the antitoxin in serum is obtained immediately after infusion.

5 Distribution Absorption from the place of intramuscular injection occurs in the result of simple diffusion from the environment of a tissue into plasma. At intravenous infusion the preparation is transferred with the blood circulation. Metabolism The antigen (toxin)- antibody (antitoxin) complex undergoes phagocytosis. Half-life is 2-3 days, complete elimination takes place within 8-12 days. Elimination/excretion Complete elimination takes place within 8-12 days. The mechanism has not been discovered yet. 5.3 Preclinical safety data Non-clinical data obtained on the basis of pharmacological surveys concerning safety of application, toxicity after multiple administration, genotoxicity, potential cancer-productivity and toxic effect on reproduction, show no particular threat to humans. 6. PHARMACEUTICAL PARTICULARS 6.1 List of Excipients Phenol, Sodium chloride, Water for injections, Sodium hydroxide and hydrochloric acid- in small quantities to determine ph 6.2 Incompatibilities Not applicable 6.3 Shelf Life 3 years After first opening- 48 hours 6.4 Special precautions for storage Store in refrigerator (2ºC - 8ºC). Do not freeze! Keep in the original package to protect from light. 6.5 Nature and contents of the container Glass vial (type I glass) with a bromobutyl rubber cap containing 10 ml of the solution- pack of 1 or pack of Instructions for use and handling Before administering the preparation intravenously it should be warmed up to 37ºC.

6 All residues of unused product or its wastes should be disposed according to the applicable local regulations. 7. MARKETING AUTHORISATION HOLDER Wytwórnia Surowic i Szczepionek BIOMED Sp. z o.o. ul. Chełmska 30/ Warszawa (Warsaw) Tel MARKETING AUTHORISATION NUMBERS No. 824/S R/ DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION DATE OF REVISION OF THE TEXT