1. Trade name of the medicinal product. TetaQuin. 2. Qualitative and quantitative composition. 2.1 Active ingredient

Transcription

1 1. Trade name of the medicinal product TetaQuin. 2. Qualitative and quantitative composition 2.1 Active ingredient TetaQuin consists of a protein fraction prepared from human plasma with a high tetanus antibody titre. The product contains g of protein per litre. The protein fraction consists of at least 90% immunoglobulin G (IgG), small quantities of immunoglobulin A (IgA) and immunoglobulin M (IgM), and traces of other plasma proteins. The tetanus antibody content is at least 100 IU/ml. TetaQuin is supplied in vials à 250 IU. The product is supplied sterile and pyrogen-free. 2.2 Viral safety TetaQuin is prepared from venous plasma by means of ethanol fractionation. The plasma has to be derived from voluntary, non-remunerated donors who satisfy the requirements of the Blood Transfusion Council of the Netherlands Red Cross. This means, among other things, that each individual donation has tested negative for hepatitis B surface antigen (HBsAg), for antibodies against the human immunodeficiency virus 1 and 2 (HIV-1 and HIV-2, the inducers of AIDS), and for antibodies against the hepatitis C virus. The manufacturing by means of the ethanol fractionation and the treatment at ph 4 ensure that the risk of transmission of viral diseases, especially AIDS, hepatitis B and hepatitis non-a, non-b (including hepatitis C), is extremely small. 3. Pharmaceutical form Solution for injection for intramuscular administration. 4. Clinical particulars 4.1 Therapeutic indications A. Prophylaxis of tetanus TetaQuin is administered prophylactically as a passive immunisation in the case of wounds in which there is a chance of infection with Clostridium tetani. This risk is especially great in the case of bites, stab and bullet wounds, wounds contaminated with soil, street dirt and animal faeces, and necrotising wounds. Simultaneously with the administration of TetaQuin, a start must be made on active immunisation against tetanus using tetanus toxoid. Whether active or passive immunisation is used depends on the vaccination status of the patient concerned, as shown in the table below:

2 Vaccination status of active immunisation (tetanus toxoid) in the case of wounds, prophylaxis with: tetanus toxoid TetaQuin Unknown yes yes 1 or 2 doses yes yes 3 or more doses, with the last having been administered: - < 1 year ago years ago - > 10 years ago no yes yes no no yes B. Therapeutic treatment of clinically manifest tetanus. 4.2 Posology and method of administration Posology Children and adults should be given the same dosage. Passive immunisation in the case of wounds: 1 dose of TetaQuin (1 vial, 250 IU). The dosage should be doubled in the case of necrotising or infected wounds or if injury occurred more than 24 hours beforehand. Doubling of the dosage (i.e. to 500 IU) is also indicated in adults with a body weight greater than the normal value. If the product is administered to patients with wounds more than 3-4 days old, it will no longer have much effect. Clinically manifest tetanus: as soon as diagnosis has been made, 12 doses of TetaQuin (12 vials) must be administered. The next day, the administration of the 3000 IU dosage should be repeated. Method of administration The product should be injected slowly and deeply intramuscularly. In the case of clinically manifest tetanus, the 12 doses of TetaQuin should be administered at different sites. It is recommended that the product be warmed to body temperature before administration. For tetanus prophylaxis in the case of wounds, besides debridement and the administration of TetaQuin, a start should also be made on active immunisation against tetanus using tetanus toxoid. To achieve this, 0.5 ml of tetanus toxoid should be administered intramuscularly on the contralateral side of the body using a separate hypodermic. The second dose should be administered four weeks later. Immunisation is not complete unless a booster injection (0.5 ml) is administered at least six months after the second injection. 4.3 Contra-indications Hypersensitivity to the ingredients of the product; see also 'Special warnings and special precautions for use'. 4.4 Special warnings and special precautions for use The product is not suitable for intravenous administration.

3 In order to be sure that the tip of the needle is not in a blood vessel, the plunger of the hypodermic should be retracted a little before administration. In patients with a haemorrhagic diathesis, subcutaneous administration of the product can be considered. It should be noted that no research has been done to confirm whether a minimally effective titre of tetanus-antibodies is reached by this administration route. Patients with a haemorrhagic diathesis will need to be individually assessed in order to decide which is the greater risk: the risk of tetanus or the risk of haemorrhages associated with intramuscular administration. In patients with a selective IgA deficiency in whom anti-iga-antibodies have been detected - a very rare disorder - an anaphylactic reaction can occur. In such patients, administration of immunoglobulin is, in principle, contra-indicated. In this case, however, the risks of a manifest tetanus infection or an anaphylactic reaction should be considered carefully. If a decision is made to administer TetaQuin, this should be done under strict clinical supervision. In the case of patients who displayed an atypical reaction to an earlier use of blood or blood products, an anaphylactic reaction can occur. Such patients should preferably not be treated with the product - nor should other blood products be administered to them. If, for some urgent reason, this rule must be departed from, administration should take place under strict clinical supervision. Allergic reactions to TetaQuin administered intramuscularly in the prescribed way are rare. Mild reactions, such as urticaria, should they arise, can be treated with antihistamines and corticosteroids. In the case of serious reactions (e.g. anaphylactic shock), the reaction should be treated with intravenously- (not intramuscularly-) administered corticosteroids and adrenaline. The patient should be observed for at least 20 minutes after administration. Although precautions have been taken to eliminate blood-borne infectious agents both from the starting material - plasma - and from the final product, the risk of infection with blood-borne infectious agents cannot be entirely excluded. Children who are participating in the National Vaccination Programme should never be given tetanus toxoid separately, but should always receive the next vaccination (DKTP or DTP vaccine) that they would be due to receive in the National Vaccination Programme. In the case of clinically manifest tetanus, in addition to the administration of TetaQuin at a dosage of 3000 IU, an extensive symptomatic treatment is essential. This treatment should preferably take place at a centre that specialises in such treatment. Because a patient who has had tetanus does not acquire immunity to the disease as a result, every patient must be actively vaccinated against tetanus after they have fully recovered from the disease. During the storage period, a slight turbidity or a small amount of precipitation can occur. This is not an impediment to clinical use. 4.5 Interaction with other medicinal products and other forms of interaction 1. Live attenuated vaccines The immune response to certain live attenuated vaccines -especially measles, mumps, chicken pox and rubella vaccine - can be impaired by immunoglobulin. After administration of such a vaccine, TetaQuin should not be administered for three to four weeks; if administration is unavoidable, revaccination must take place three months after the administration of TetaQuin. After administration of TetaQuin, vaccination with live attenuated vaccine should be postponed for at least three months. N.B.: tetanus toxoid and TetaQuin can be administered simultaneously without any problems: TetaQuin provides immunity during the period in which the active immunity is still being built up. 2. Interference with serological tests After an injection with immunoglobulins, the transitory rise of the various passivelytransferred antibodies in the patient's blood can lead to misleading positive results in serological tests.

4 4.6 Pregnancy and lactation The safety of using TetaQuin during pregnancy has not been established in controlled clinical trials, and care must therefore be exercised in the administration of this product to pregnant and breast-feeding women. Long-term clinical experience with immunoglobulins has revealed that no harmful effects on the course of the pregnancy, on the foetus and on the neonate are to be expected. Immunoglobulins are secreted in the maternal milk and contribute to the transfer of protective antibodies to the neonate. 4.7 Effects on ability to drive and use machines There are no indications that immunoglobulins can affect the ability to drive and use machines. 4.8 Undesirable effects Pain and sensitivity at the injection site can be experienced; this can be reduced by distributing the larger dosages over several injection sites. Occasionally, fever and/or exanthema occur. In rare cases, nausea, vomiting, hypotension, tachycardia and hypersensitivity reactions or anaphylactic reactions, including shock, have been reported. If medicinal products prepared from human blood or plasma are administered, infectious diseases resulting from the transfer of pathogens cannot be entirely excluded. This also applies to pathogens, the nature of which is as yet unknown. 4.9 Overdose With respect to the occurrence and symptoms of possible overdose, no data is yet available. 5. Pharmacological properties 5.1 Pharmacodynamic properties The action of TetaQuin rests, in the case of wounds and clinically manifest tetanus, on passive immunisation. It is generally accepted that a serum antibody titre > 0.01 IU/ml offers protection against tetanus. Administration of TetaQuin after wounding provides immediate prophylactic protection, both against tetanus toxin introduced directly into the wound and against the toxin produced in the wound by Clostridium tetani bacteria. The tetanus antibodies administered to the patient will neutralise the toxin, after which further elimination by the immune system can take place. In the case of clinically manifest tetanus, the tetanus toxin has already reached the central nervous system and the plate nerve endings and is thus beyond the reach of the administered antibodies. However, by administering 3000 IU of tetanus immunoglobuline, any freely-circulating and newly-formed tetanus toxin will be neutralised. The prognosis for the patient will improve as a result. The protection offered by passive immunisation lasts only a short time. More protracted immunity can only be obtained through active immunisation with tetanus toxoid. 5.2 Pharmacokinetic properties Absorption: after intramuscular administration, the immunoglobulin administered to the patient is gradually released from the intramuscular depot into the circulation. The maximum level is achieved after two to four days.

5 Metabolism/elimination: the half-life of IgG is approximately 21 days. IgG itself or IgG in complexes breaks down in the cells of the reticuloendothelial system. 5.3 Preclinical safety data Immunoglobulins are normal constituents of the human body. Animal research into their toxicity in once-only administration is not relevant, given that overdosing occurs at higher dosages. Research into their toxicity in repeated administration and their toxicity for the embryo/foetus is not feasible due to their induction of and disturbance by antibodies. No research has been done into the effects of the product on the immune system of the neonate. Given that clinical trials have not shown any evidence of oncogenic and mutagenic effects on the part of immunoglobulins, experimental research, especially into heterologous species, is not considered necessary. 6. Pharmaceutical particulars 6.1 List of excipients The product contains g of protein per litre. The protein fraction consists of at least 90% IgG, small quantities of IgA and IgM, and traces of other plasma proteins. The tetanus antibody content is at least 100 IU/ml. Tetanus Immunoglobulin 250 IE is supplied in vials of 250 IU. In addition, the product contains 0.3 mol/l of glycine as stabiliser. The product is supplied sterile and pyrogen-free. 6.2 Incompatibilities No medication may be added to TetaQuin because of the possibility of incompatibilities. 6.3 Shelf life The shelf life of TetaQuin is 4 years. The shelf life of the product, if it is stored according to the instructions, extends until the date shown on the packaging. The product should not be used after this date. After the vial has been pierced, the product must be used immediately. Any remainder should be destroyed. 6.4 Special precautions for storage TetaQuin should be stored at 2-8 C protected from light. 6.5 Nature and content of container TetaQuin is supplied in colourless glass vials (glass type I) with a bromobutyl rubber stopper sealed with an aluminium cap. TetaQuin is supplied in a single-administration container and in boxes of 10 and 50 vials. 6.6 Instructions for use/handling It is recommended that the product be warmed to body temperature before administration. 7. Holder of the marketing authorisation Sanquin Amsterdam, the Netherlands, tel.:

6 8. Marketing authorisation number Registered in the Netherlands under RVG Date of first authorisation/renewal of the authorisation 5 September Date (of revision) of the text February 2003 Latest partial revision: 2 September 2003, concerning 1, 7