Summary of Product Characteristics
Contents
1. Powder and Solvent for Sealant Freeze dried constituents are hygroscopic white or pale yellow powders or friable solids liquid constituents are clear colourless solutions 4 CLINICAL PARTICULARS 4 1 Therapeutic Indications As a coagulant producer for use as a tissue sealant and haemostatic for surgical incisions plastic surgical repairs orthopaedic traumatic and dental surgery 4 2 Posology and method of administration The use of TISSEEL Lyo is restricted to experienced surgeons who have been trained in the use of TISSEEL Lyo Posology The amount of TISSEEL Lyo to be applied and the frequency of application should always be oriented towards the underlying clinical needs of the patient The dose to be applied is governed by variables including but not limited to the type of surgical intervention the size of the area and the mode of intended application and the number of applications Application of the product must be individualized by the treating physician In clinical trials the individual dosages have typically ranged from 4 to 20 ml For some procedures e g liver traumata or the sealing of large burned surfaces larger volumes may be required The initial amount of the product to be applied at a chosen anatomic site or target surface area should be sufficient to entirely cover the intended application area The application can be repeated if necessary However avoid reapplication of TISSEEL Lyo to a pre existing po2. Apply TISSEEL Lyo as a thin layer Excessive clot thickness may negatively interfere with the product s efficacy and the wound healing process Life threatening fatal air or gas embolism has occurred with the use of spray devices employing a pressure regulator to administer fibrin sealants This event appears to be related to the use of the spray device at higher than recommended pressures and or in close proximity to the tissue surface The risk appears to be higher when fibrin sealants are sprayed with air as compared to CO and therefore cannot be excluded with TISSEEL Lyo when sprayed in open wound surgery Date Printed 27 03 2014 CRN 2134788 page number 4 Irish Medicines Board When applying TISSEEL Lyo using a spray device be sure to use a pressure within the pressure range recommended by the spray device manufacturer see table in section 6 6 for pressures and distances TISSEEL Lyo spray application should only be used if it is possible to accurately judge the spray distance as recommended by the manufacturer Do not spray closer than the recommended distances When spraying TISSEEL Lyo changes in blood pressure pulse oxygen saturation and end tidal CO should be monitored because of the possibility of occurrence of air or gas embolism also see section 4 2 TISSEEL must not be used with the EasySpray Spray set in enclosed body areas As with any protein containing product allergic type hypersensitivity reactions are possi
3. containing the Sealer Protein Concentrate Lyophilized using one needle and the blue scaled syringe provided in the single sterile kit for reconstitution Return the Sealer Protein vial to the water bath at 33 37 C for one minute Swirl briefly but avoid excessive frothing Then return the vial to the water bath and check periodically for complete dissolution Reconstitution is complete as soon as no particles are visible when holding the vial against the light If particles are present keep the vial at 33 37 C for a few more minutes and agitate the solution until complete dissolution Keep the Sealer Protein Solution at 33 37 C or at room temperature up to 25 C if not used immediately Before use the solution should be warmed to 33 37 C To ensure homogeneity swirl briefly before drawing up the Sealer Protein Solution into the blue scaled syringe provided in the double sterile kit for application Withdraw the reconstituted Sealer Protein Solution from the vial under sterile conditions Note When using a water bath for reconstitution instead of the FIBRINOTHERM device special precautions must be taken against submersing the vial particularly the septum to avoid possible contamination II Preparation of Component 2 Thrombin Solution The Thrombin Lyophilized is dissolved with the Calcium Chloride Solution to form the Thrombin Solution Transfer the contents of the Calcium Chloride Solution vial into the Thrombi
4. taken into account In the event of anaphylactic or severe hypersensitivity reactions administration is to be discontinued and state of the art emergency measures are to be taken In case of shock standard medical treatment for shock should be implemented Sealer Protein Concentrate and Thrombin are made from human plasma The risk of transmitting an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses by testing for the presence of certain current viral infections and by inactivating and or removing viruses Despite this when medicinal products prepared from human blood or plasma are administered the possibility of transmitting infective agents cannot be totally excluded This also applies to unknown or emerging viruses or other pathogens The measures taken are considered effective for enveloped viruses such as HIV HBV and HCV and for the non enveloped virus HAV The measures taken may be of limited value against small non enveloped viruses such as parvovirus B19 Parvovirus B19 infection may be serious for pregnant women fetal infection and for individuals with immunodeficiency or increased red blood cell turnover e g hemolytic anemia It is strongly recommended that every time a patient receives a dose of TISSEEL Lyo the name and batch number of the product are recorded in order to maintain a record of the batches used Oxidized cellulose containing preparations should not be
5. used regulatorto distance from LE pressure be used target tissue Tisseel Spray Set 1 5 2 0 bar Open wound Tisseel 10 15cm 21 5 28 5 as Set n a EasySpray psu Duplospray MIS Regulator Duplospray MIS Regulator NIST B11 Duplospray MIS Regulator Duplospray MIS Applicator 20cm Duplospray MIS Laparoscopic Duplospray minimally in ae oe MIS 2 5cm 1 2 1 5 bar invasive oe Regulator 18 22 psi procedures NIST B11 Duplospray MIS Regulator Duplospray MIS Duplospray MIS Applicator 40cm Regulator NIST B11 Duplospray MIS Date Printed 27 03 2014 CRN 2134788 page number 13 Irish Medicines Board Regulator Duplospray MIS Regulator NIST B11 Replaceable tip When spraying the TISSEEL Lyo changes in blood pressure pulse oxygen saturation and end tidal CO should be monitored because of the possibility of occurrence of air or gas embolism see sections 4 2 and 4 4 Disposal Any unused product or waste material should be disposed of in accordance with local requirements 7 MARKETING AUTHORISATION HOLDER Baxter Healthcare Caxton Way Thetford Norfolk IP24 3SE UK 8 MARKETING AUTHORISATION NUMBER PA 167 129 6 9 DATE OF FIRST AUTHORISATION RENEW AL OF THE AUTHORISATION Date of first authorisation 21st January 2011 10 DATE OF REVISION OF THE TEXT March 2014 Date Printed 27 03 2014 CRN 2134788 page number 14
6. Irish Medicines Board Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT TISSEEL Lyo Powder and Solvent for Sealant 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Component 1 Sealer Protein Solution Sealer Protein Concentrate Lyophilized reconstituted with Aprotinin Solution Human Fibrinogen as clottable Protein 9 mg ml Human Factor XIII 0 6 5 IU ml Aprotinin 3000 KIU ml Component 2 Thrombin Solution Thrombin Lyophilized reconstituted with Calcium Chloride Solution Human Thrombin 500 IU ml Calcium Chloride 40 micromoles ml ml 2ml and 5 ml Sealer Protein Solution and 1 ml 2ml and 5 ml Thrombin Solution respectively result in 2 ml 4 ml and 10 ml final product ready for use Component 1 Sealer protein solution Human Fibrinogen 45 5 mg 91 mg 182 mg 455 mg as clottable protein Aprotinin 1 500 KIU 3 000 KIU 6 000 KIU 15 000 KIU Component 2 Thrombin solution Human Thrombin 250 IU 500 IU 1 000 IU 2 500 IU Calcium Chloride 20 40 80 200 micromoles micromoles micromoles micromoles For full list of excipients see section 6 1 Contained in a total protein concentration of 110 5 mg ml 2 1 EPU European Pharmacopoeia Unit corresponds to 1800 KIU Kallidinogenase Inactivator Unit 3 Thrombin activity is calculated using the current WHO International Standard for Thrombin Date Printed 27 03 2014 CRN 2134788 page number 1 Irish Medicines Board 3PHARMACEUTICAL FORM
7. ans and tissues no preclinical safety data are available for Fibrin Sealant VH S D on subacute and chronic toxicity carcinogenicity reproductive and developmental toxicity or immune stimulation Single dose toxicity studies in rats and rabbits indicated no acute toxicity of Fibrin Sealant VH S D frozen presentation Furthermore no evidence for mutagenicity could be seen in appropriate in vitro tests Fibrin Sealant VH S D frozen presentation proved well tolerated in wound healing models in rats and rabbits The Sealer Protein Solutions of Fibrin Sealant VH S D frozen and lyophilized presentations were also well tolerated by in vitro human fibroblast cultures demonstrating excellent cellular compatibility and non cytotoxicity Based on a detailed literature review any negative influence or toxicity of the residual solvent detergent reagents see 6 1 on Fibrin Sealant VH S D can be essentially excluded 6 PHARMACEUTICAL PARTICULARS 6 1 List of excipients Component 1 Sealer Protein Solution Human Albumin Solution Histidine Nicotinic Acid Polysorbate 80 Tween 80 Sodium Citrate Water for Injections Component 2 Thrombin Solution Human Albumin Solution Sodium Chloride Water for Injections 6 2 Incompatibilities This medicinal product must not be mixed with medicinal products other than appropriate solvents mentioned in 6 6 6 3 Shelf life 2 years 6 4 Special precautions for storage Keep out of the reach and sight of chi
8. ble Signs of hypersensitivity reactions may include hives generalized urticaria tightness of the chest wheezing hypotension and anaphylaxis If these symptoms occur the administration must be discontinued immediately Intravascular application might increase the likelihood and severity of acute hypersensitivity reactions in susceptible patients Manifestations of hypersensitivity reactions to TISSEEL Lyo observed include bradycardia tachycardia hypotension flushing bronchospasm wheezing dyspnea nausea urticaria angioedema pruritus erythema paresthesia Fatal anaphylactic reactions including anaphylactic shock have also been reported with TISSEEL Lyo see section 4 8 At the first sign or symptom of a hypersensitivity reaction TISSEEL Lyo application must be stopped and medical care initiated Remaining product must be removed from the site of application TISSEEL Lyo contains bovine protein aprotinin a polypeptide known to be associated with anaphylactic reactions Even in case of strict local application there is a risk of anaphylactic reaction linked to the presence of bovine aprotinin The risk seems to be higher in cases where there was previous exposure even if it was well tolerated Therefore any use of aprotinin or aprotinin containing products should be recorded in the patients records If fibrin sealants are applied in confined spaces e g the brain or the spinal cord the risk of compressive complication should be
9. e chest tingling vomiting wheezing may occur in rare cases in patients treated with fibrin sealants hemostatics In isolated cases these reactions have progressed to severe anaphylaxis Such reactions may especially be seen if the preparation is applied repeatedly or administered to patients known to be hypersensitive to aprotinin see section 4 4 or any other constituents of the product Even if a second treatment with TISSEEL Lyo was well tolerated a subsequent administration of TISSEEL Lyo or systemic administration of aprotinin may result in severe anaphylactic reactions Antibodies against components of fibrin sealant hemostatic may rarely occur VASCULAR DISORDERS Embolism arterial including cerebral artery embolism cerebral infarction SKIN AND SUBCUTANEOUS TISSUE DISORDERS Impaired healing as a result of intravascular application into the superior petrosal sinus For safety with respect to transmissible agents see section 4 4 The adverse reactions presented in this section were reported from clinical trials investigating the safety and efficacy of TISSEEL and from post marketing experience with Baxter Fibrin Sealants In these trials TISSEEL was administered for adjunct hemostasis in cardiac vascular and total hip replacement surgeries and in liver and spleen surgeries Other clinical trials included the sealing of lymphatic vessels in patients undergoing axillary lymph node dissection sealing of colonic anastomosis and
10. ided in the single sterile kit for reconstitution Place the Sealer Protein vial into the stirring well of the FIBRINOTHERM device use the adaptor if necessary and stir until complete dissolution Reconstitution is complete as soon as no particles are visible anymore when holding the vial against the light If particles are present keep on stirring the solution at 37 C for a few more minutes until complete dissolution Turn off the magnetic stirrer when dissolution is complete Note Excessive stirring might compromise product quality Date Printed 27 03 2014 CRN 2134788 page number 10 Irish Medicines Board Keep the Sealer Protein Solution at 37 C or at room temperature up to 25 C without stirring if it is not used immediately Before use the solution should be warmed to 37 C To ensure homogeneity stir or swirl briefly before drawing up the Sealer Protein Solution into the blue scaled syringe provided in the double sterile kit for application Withdraw the reconstituted Sealer Protein Solution from the vial under sterile conditions For further instructions please refer to the instructions for use of the FIBRINOTHERM device Reconstitution using a water bath Preheat the vials containing the Sealer Protein Concentrate Lyophilized and the Aprotinin Solution for approximately 3 minutes in a water bath at a temperature of 33 37 C Heating beyond 37 C must be avoided Transfer the Aprotinin Solution into the vial
11. in durasealing in the posterior fossa In these studies a total of 1146 patients were administered Baxter Fibrin Sealant Date Printed 27 03 2014 CRN 2134788 page number 6 Irish Medicines Board Very common 2 1 10 Common 2 1 100 to 1 10 Uncommon 2 1 1 000 to 1 100 Rare 2 1 10 000 to 1 1 000 Very rare 1 10 000 Not known cannot be estimated from the available data SOC infestations EX L u E system disorders RENE ee products increased disorders Anaphylacicreacions t Not known Anaphylacticshock dL Not known aresthesia Notknwn Ee pd Bronchospasm Notknwn Wheezing j Notknwn E rts Not known po Erythema Not known E Nervous system Sensory disturbance Common disorders po Tachycardia Not known Ee po ypotension Rare po Haemaoma NOS Not known E Embolismarterial Notknown Cerebral artery embolism Not known 1 Cerebralinfarction Not known and mediastinal disorders disorders Intesindobstrucion Notknown tissue disorders Urticata Not known IHmpaiedheding O Z 1 1 Notknown Musculoskeletal and Pain in an extremity Common connective tissue disorders General disorders and Procedural pain Uncommon administration site conditions pai Common pi Increased body temperature Common po Pushing Not known OE po edema Not known E Date Pri
12. in the cannula Replace the application cannula with a new one only immediately before application is resumed If the apertures of the joining piece are clogged use the spare joining piece provided in the package Date Printed 27 03 2014 CRN 2134788 page number 12 Irish Medicines Board Note After blending of the sealant components the fibrin sealant starts to set within seconds on account of the high Thrombin concentration 500 IU ml Application is also possible with other accessories supplied by BAXTER that are particularly suited for e g endoscopic use minimally invasive surgery application to large or difficult to access areas When using these application devices strictly follow the Instructions for Use of the devices After the two components have been applied approximate the wound areas Fix or hold the glued parts with continuous gentle pressure in the desired position for about 3 5 minutes to ensure that the setting fibrin sealant adheres firmly to the surrounding tissue In certain applications biocompatible material such as collagen fleece is used as a carrier substance or for reinforcement Spray application When applying TISSEEL Lyo using a spray device be sure to use a pressure and a distance from tissue within the ranges recommended by the manufacturer as follows Recommended pressure distance and devices for spray application of TISSEEL Lyo Pressure Recommended Spray set Applicator LE tips to be
13. ldren Store TISSEEL Lyo below 25 C Do not freeze Keep TISSEEL Lyo in the outer carton to protect from light Use the reconstituted sterile solutions within 4 hours of preparation Keep the reconstituted sterile solutions at 37 C or at room temperature up to 25 C without stirring if not used immediately Date Printed 27 03 2014 CRN 2134788 page number 9 Irish Medicines Board Reconstituted solutions must not be refrigerated or frozen 6 5 Nature and contents of container All components of TISSEEL Lyo are filled into glass containers Sealer Protein Concentrate Lyophilized type I glass 1 ml 2 ml and type II glass 5ml all other vials type I glass conforming to Ph Eur requirements The vial containing Sealer Protein Concentrate Lyophilized is equipped with a magnetic stirrer TISSEEL Lyo is available in the following pack sizes 1 x 2 ml 1 ml 1 ml 1 x 4 ml 2 ml 2 ml and 1 x 10 ml 5 ml 4 5 ml The Kit for Reconstitution and Application DUPLOJECT System is for single use only Do not resterilize Not all pack sizes may be marketed Other accessories for application of the product can be obtained from BAXTER 6 6 Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product General Before administration of TISSEEL Lyo care has to be taken that parts of the body outside the desired application area are sufficien
14. lymerized TISSEEL Lyo layer as TISSEEL Lyo will not adhere to a polymerized layer As a guideline for the gluing of surfaces 1 pack of TISSEEL Lyo 2 ml i e 1 ml Sealer Protein Solution plus 1 ml Thrombin Solution will be sufficient for an area of at least 10 cm When TISSEEL Lyo is applied by spray application the same quantity will be sufficient to coat considerably larger areas depending on the specific indication and the individual case Caution must be used when applying fibrin sealant using pressurized gas The user must follow the instructions and precautions in the device user manual for example regarding the need to limit the gas pressure in accordance with the instructions and is cautioned against the spray application of TISSEEL Lyo with devices produced by other manufacturers see also section 4 4 The only device designed for the application of TISSEEL Lyo in enclosed thoracic and abdominal spaces is the DuploSpray MIS applicator and regulator system However all the other instructions and warnings listed in the previous paragraph and in section 4 4 still apply To avoid the formation of excess granulation tissue and to ensure gradual absorption of the solidified fibrin sealant as thin a layer as possible of the mixed Sealer Protein Thrombin Solutions or of the individual components should be applied Date Printed 27 03 2014 CRN 2134788 page number 2 Irish Medicines Board Excessive thickness of the fibrin laye
15. mber 5 Irish Medicines Board It is strongly recommended that every time TISSEEL Lyo is applied to a patient the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product 4 3 Contraindications TISSEEL Lyo alone is not indicated for the treatment of massive and brisk arterial or venous bleeding TISSEEL Lyo must not be applied intravascularly Intravascular application of TISSEEL Lyo may result in life threatening thromboembolic events TISSEEL Lyo must not be used to replace skin sutures intended to close surgical wounds Known hypersensitivity to any constituents of the product including aprotinin see also section 4 4 Warnings 4 4 Special warnings and precautions for use Caution must be used when applying fibrin sealant using pressurized air or gas See section 4 2 and section 4 8 TISSEEL Lyo alone is not indicated for the treatment of severe or brisk arterial or venous bleeding which is not controlled by conventional surgical techniques For epilesional use only Do not apply intravascularly Soft tissue injection of TISSEEL Lyo carries the risk of local tissue damage Intravascular application can lead to intravascular coagulation and may result in life threatening thromboembolic events and might increase the likelihood and severity of acute hypersensitivity reactions in susceptible patients TISSEEL Lyo must be applied with caution to minimize any risk of i
16. n Lyophilized vial Use the second needle and the black scaled syringe provided in the single sterile kit for reconstitution Swirl briefly to dissolve the lyophilized material To warm the Thrombin Solution either the FIBRINOTHERM device or a water bath can be used Keep the Thrombin Solution at 33 37 C or at room temperature up to 25 C if not used immediately Before use the solution should be warmed to 33 37 C Prior to use draw up the Thrombin Solution from the vial using the second needle and the black scaled syringe provided in the double sterile kit for application Note Syringes and needles used for the reconstitution of one component must not be re used for the reconstitution of the other component as this would lead to solidification of that component in the vial or syringe III Use of reconstituted TISSEEL Lyo Components Both fibrin sealant components must be used within 4 hours after reconstitution Reconstituted solutions must not be refrigerated or frozen Date Printed 27 03 2014 CRN 2134788 page number 11 Irish Medicines Board Administration The Sealer Protein and the Thrombin Solutions should be clear or slightly opalescent Do not use solutions that are cloudy or have deposits Reconstituted products should be inspected visually for particulate matter and discoloration prior to administration For application the two single use syringes with the reconstituted Sealer Protein Solution and Thrombin Solution
17. nted 27 03 2014 CRN 2134788 page number 7 Irish Medicines Board Injury poisoning and Seroma Very common procedural complications 1 Angiedem Z j Notknown E anaphylactic reactions and anaphylactic shock have included fatal outcomes as a result of intravascular application into the superior petrosal sinus Class Reactions Other adverse reactions associated with the fibrin sealant hemostatic class include Air or gas embolism when using devices with pressurized air or gas this event appears to be related to the use of the spray device at higher than recommended pressures and in close proximity to the tissue surface Manifestations of hypersensitivity include application site irritation chest discomfort chills headache lethargy restlessness and vomiting Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important It allows continued monitoring of the benefit risk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via IMB Pharmacovigilance Earlsfort Terrace IRL Dublin 2 Tel 353 1 6764971 Fax 353 1 6762517 Website http www imb ie e mail imbpharmacovigilance imb ie 4 9 Overdose No case of overdose has been reported 5 PHARMACOLOGICAL PROPERTIES 5 1 Pharmacodynamic properties Pharmacotherapeutic group local hemostatics ATC code BO2BC tissue adhesives ATC c
18. ntravascular application for example in coronary bypass surgery Because of the risk of intravascular injection the product also must not be injected into highly vascularized tissue such as nasal mucosa In surgical applications that require the use of minimal volumes of fibrin sealant e g pterygium surgery the first few drops should be expelled and discarded before application to ensure adequate mixing of the sealer protein and thrombin solutions Use of the first few drops in these procedures could result in the product being ineffective In two retrospective non randomized studies in Coronary Artery Bypass Graft CABG surgery patients that received fibrin sealant showed a statistically significant increased risk of mortality While these studies could not provide a determination of a causal relationship the increased risk associated with the use of TISSEEL Lyo in these patients cannot be excluded Therefore additional care should be taken to avoid inadvertent intravascular administration of this product Life threatening thromboembolic complications may occur if the preparation is unintentionally applied intravascularly Injection into the nasal mucosa must be avoided as thromboembolic complications may occur in the ophthalmic arterial region Any application of pressurized air or gas is associated with a potential risk of air or gas embolism tissue rupture or gas entrapment with compression which may be life threatening or fatal
19. ode V03A K The fibrin adhesion system imitates the last phase of physiological blood coagulation Conversion of fibrinogen into fibrin occurs by the splitting of fibrinogen into fibrin monomers and fibrinopeptides The fibrin monomers aggregate and form a fibrin clot Factor XIIIa which is generated from Factor XIII by the concerted action of thrombin and calcium ions stabilizes the clot by the cross linking of fibrin fibres As wound healing progresses increased fibrinolytic activity is induced by plasmin and decomposition of fibrin to fibrin degradation products is initiated Proteolytic degradation of fibrin is inhibited by anti fibrinolytics Aprotinin is present in TISSEEL Lyo as an antifibrinolytic to prevent premature degradation of the clot Fibrin Sealant VH S D frozen presentation was evaluated in a prospective parallel design randomized 1 1 double blind multicenter clinical study against a previous single virus inactivated formulation of the product TISSEEL Kit VH lyophilized presentation in 317 subjects undergoing cardiac surgery requiring cardiopulmonary bypass CPB and median sternotomy Patients were treated with Fibrin Sealant VH S D or the control product only when hemostasis was not achieved by conventional surgical methods For the endpoint hemostasis achieved at the primary treatment site within 5 minutes of treatment and maintained until closure of the surgical wound Fibrin Sealant VH S D was non inferior to the ea
20. r may negatively interfere with the product s efficacy and the wound healing process If used for tissue adherence it is recommended that the initial application cover the entire intended application area Paediatric population Safety and efficacy of the product in paediatric patients have not been established Method and route of administration For topical i e epilesional use only do not inject Prepare the solutions as described at 6 6 In order to ensure optimal safe use of TISSEEL Lyo by spray application the following recommendations should be followed In open wound surgery a pressure regulator device that delivers a maximum pressure of no more than 2 0 bar 28 5 psi should be used In minimally invasive laparoscopic procedures a pressure regulator device that delivers a maximum pressure of no more than 1 5 bar 22 psi and uses carbon dioxide gas only should be used Prior to applying TISSEEL Lyo the surface area of the wound needs to be dried by standard techniques e g intermittent application of compresses swabs use of suction devices TISSEEL Lyo should only be reconstituted and administered according to the instructions and with the devices recommended for this product see section 6 6 For spray application see sections 4 4 and 6 6 for specific recommendations on the required pressure and distance from tissue per surgical procedure and length of applicator tips Prior to application TISSEEL Lyo must be
21. rlier formulation of the product using a one sided 97 5 confidence interval on the difference in the proportion of subjects successfully treated Hemostasis within 5 minutes and maintained until surgical closure FIBRIN SEALANT VH S D FIBRIN SEALANT VH Intent to Treat Analysis 127 144 88 2 129 144 89 6 Per Protocol Analysis 108 123 87 8 122 135 90 496 No difference to control groups not receiving Fibrin Sealant VH S D frozen presentation was observed in an exploratory study in hip joint replacement for postoperative blood loss and in a study in axillary lymph node dissection for duration of axillary drainage Date Printed 27 03 2014 CRN 2134788 page number 6 Irish Medicines Board 5 2 Pharmacokinetic properties Intravascular administration is contraindicated As a consequence intravascular pharmacokinetic studies were not performed in man Fibrin sealants hemostatics are metabolized in the same way as endogenous fibrin by fibrinolysis and phagocytosis 5 3 Preclinical safety data For efficacy in vivo studies in four animal models closely imitating the situation in patients were used Fibrin Sealant VH S D demonstrated efficacy regarding primary secondary and sustained hemostasis and sealing Due to its nature as well as its method of application and mechanism of action usually single only in exceptional cases repeated application of small volumes local efficacy without systemic exposure or distribution to other org
22. should be clipped into the DUPLOJECT Two Syringe Clip and this assembly should be connected to a joining piece and an application cannula All necessary devices are provided in the double sterile kit for application The common plunger of the DUPLOJECT Two Syringe Clip ensures that equal volumes are fed through the joining piece before being mixed in the application cannula and ejected Operating Instructions Syringe Application Canula m DUPLOJECT s Two Syringe Clip Joining piece Place the two syringes filled with Sealer Protein Solution and with Thrombin Solution into the clip Both syringes should be filled with equal volumes Connect the nozzles of the two syringes to the joining piece ensuring that they are firmly fixed Secure the joining piece by fastening the tether strap to the DUPLOJECT Two Syringe Clip Should the pull strap tear use the spare joining piece If none is available further use is still possible but tightness of the connection needs to be ensured to prevent any risk of leaking Fitan application cannula onto the joining piece Do not expel the air remaining inside the joining piece or application cannula until you start actual application as the aperture of the cannula may clog otherwise Apply the mixed Sealer Protein Thrombin Solution onto the recipient surface or surfaces of the parts to be sealed If application of the fibrin sealant components is interrupted clogging occurs immediately
23. tly covered to prevent tissue adhesion at undesired sites To prevent TISSEEL Lyo from adhering to gloves and instruments wet these with sodium chloride solution before contact Preparation and reconstitution Prior to reconstitution of the fibrin sealant components the rubber stoppers of all vials should be cleansed Direct contact between disinfectant and product must be avoided see section 4 5 I Preparation of Component 1 Sealer Protein Solution The Sealer Protein Concentrate Lyophilized is dissolved with the Aprotinin Solution to form the Sealer Protein Solution Sealer Protein Concentrate Lyophilized is reconstituted using the FIBRINOTHERM warming and stirring device recommended method Alternatively a sterile water bath at a temperature of 33 37 C can be used Reconstitution using the FIBRINOTHERM device The FIBRINOTHERM device maintains a constant temperature of 37 C It also shortens the dissolution time of the Sealer Protein Concentrate Lyophilized by rotating the magnetic stirrer contained in each Sealer Protein Concentrate Lyophilized vial Place the vials containing Sealer Protein Concentrate Lyophilized and Aprotinin Solution into the appropriate openings of the preheated FIBRINOTHERM device and heat the vials for approximately 3 minutes Transfer the Aprotinin Solution into the vial containing the Sealer Protein Concentrate Lyophilized using one needle and the blue scaled syringe prov
24. used with TISSEEL Lyo See section 6 2 Incompatibilities Safety and effectiveness of the product in pediatric patients has not been established as limited clinical study data are available Date Printed 27 03 2014 CRN 2134788 page number 5 Irish Medicines Board 4 5 Interaction with other medicinal products and other forms of interaction No formal interaction studies have been performed Similar to comparable products or thrombin solutions the product may be denatured after exposure to solutions containing alcohol iodine or heavy metals e g antiseptic solutions Such substances should be removed to the greatest possible extent before applying the product 4 6 Fertility pregnancy and lactation There are no adequate data from the use of TISSEEL Lyo in pregnant or lactating women Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing TISSEEL Lyo See section 4 4 for information on Parvovirus B19 infection The effects of TISSEEL Lyo on fertility have not been established 4 7 Effects on ability to drive and use machines Not relevant 4 8 Undesirable effects Hypersensitivity or allergic reactions which may include but are not limited to angioedema burning and stinging at the application site bradycardia bronchospasm chills dyspnea flushing generalized urticaria headache hives hypotension lethargy nausea pruritus restlessness tachycardia tightness of th
25. warmed to 33 37 C Tisseel must not be exposed to temperatures above 37 C and must not be microwaved Separate sequential application of the two components of TISSEEL Lyo must be avoided Application beyond the intended area should be avoided If application is interrupted clogging occurs immediately in the cannula Replace the application cannula with a new one only immediately before application is resumed If the aperture of the joining piece Y connector facing the cannula is clogged use the spare joining piece provided in the package In cases where very small volumes 1 to 2 drops of TISSEEL Lyo are administered expel and discard the first several drops from the application cannula immediately before application to ensure use of adequatemixed product see Section 4 4 The sealer protein and thrombin solutions are denatured by alcohol iodine or heavy metal ions If any of these substances have been used to clean the wound area the area must be thoroughly rinsed before application of TISSEEL Lyo Oxidised cellulose containing preparations may reduce the efficacy of TISSEEL Lyo and should not be used as carrier materials see section 6 2 After TISSEEL Lyo has been applied the area should not be disturbed for 3 to 5 minutes to allow the product to polymerize for adherence Depending on type of use the sealed parts may have to be fixed or held in the desired position for this time Date Printed 27 03 2014 CRN 2134788 page nu
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