Product Information
Registration Status: ActiveSIN14707P
TISSEEL FIBRIN SEALANT VH S/D (FROZEN) is approved to be sold in Singapore with effective from 2014-12-22. It is marketed by BAXTER HEALTHCARE (ASIA) PTE LTD, with the registration number of SIN14707P.
This product contains Aprotinin 2250-3750 KIU/ml,Calcium Chloride 36-44 umol/ml,Fibrinogen 72-110mg/ml, and Thrombin 400-625 IU/ml in the form of SOLUTION. It is approved for TOPICAL use.
This product is manufactured by BAXTER AG (Site: Industriestrasse 72)
BAXTER AG (Site: Lange Allee 24B)
BAXTER AG (Site: Lange Allee 24A) (Primary in AUSTRIA.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}Description
Aprotinin, also known as bovine pancreatic trypsin inhibitor, BPTI (Trasylol, Bayer) is a protein, that is used as medication administered by injection to reduce bleeding during complex surgery, such as heart and liver surgery. Its main effect is the slowing down of fibrinolysis, the process that leads to the breakdown of blood clots. The aim in its use is to decrease the need for blood transfusions during surgery, as well as end-organ damage due to hypotension (low blood pressure) as a result of marked blood loss. The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death; after this was confirmed by follow-up studies, Trasylol was entirely and permanently withdrawn in May 2008, except - at least for the time being - for very restricted research use.
Indication
For prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery who are at an increased risk for blood loss and blood transfusion.
Mechanism of Action
Aprotinin inhibits several serine proteases, specifically trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/ml, and kallikrein at 300,000 IU/ml. Its action on kallikrein leads to the inhibition of the formation of factor XIIa. As a result, both the intrinsic pathway of coagulation and fibrinolysis are inhibited. Its action on plasmin independently slows fibrinolysis.
Pharmacokinetics
- Absorption
- 100% (IV)
- Distribution
- Metabolism
- Aprotinin is slowly degraded by lysosomal enzymes.
- Elimination
Active Ingredient/Synonyms
Aprotinin (bovine) | Aprotinin Biosynthetic | Aprotinin Bovine | Aprotinin Concentrated Solution | Bovine Aprotinin | Bovine Pancreatic Trypsin Inhibitor | BPTI | Fibrinolysis Inhibitor | Trypsin Inhibitor, Pancreatic Basic | Aprotinin |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
Calcium chloride is an ionic compound of calcium and chlorine. It is highly soluble in water and it is deliquescent. It is a salt that is solid at room temperature, and it behaves as a typical ionic halide. It has several common applications such as brine for refrigeration plants, ice and dust control on roads, and in cement. It can be produced directly from limestone, but large amounts are also produced as a by-product of the Solvay process. Because of its hygroscopic nature, it must be kept in tightly-sealed containers.
Indication
For the treatment of hypocalcemia in those conditions requiring a prompt increase in blood plasma calcium levels, for the treatment of magnesium intoxication due to overdosage of magnesium sulfate, and used to combat the deleterious effects of hyperkalemia as measured by electrocardiographic (ECG), pending correction of the increased potassium level in the extracellular fluid.
Mechanism of Action
Calcium chloride in water dissociates to provide calcium (Ca2+) and chloride (Cl-) ions. They are normal constituents of the body fluids and are dependent on various physiological mechanisms for maintenance of balance between intake and output. For hyperkalemia, the influx of calcium helps restore the normal gradient between threshold potential and resting membrane potential.
Toxicity
Too rapid injection may produce lowering of blood pressure and cardiac syncope. Persistent hypercalcemia from overdosage of calcium is unlikely because of rapid excretion.
Active Ingredient/Synonyms
Calcium chloride anhydrous | Calcium chloride, anhydrous | calcium(2+) chloride | Calcium Chloride |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
Fibrinogen concentrate (human) is a hematological agent. It works by replacing a certain protein in the blood that helps with blood clotting. Fibrinogen (factor I) is a soluble plasma glycoprotein with a molecular weight of about 340 kDa. It is a physiological substrate for three enzymes: plasmin, factor XIIIa and thrombin. it is indicated for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia.
Indication
For the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia.
Mechanism of Action
Fibrinogen (factor I) is a soluble plasma glycoprotein with a molecular weight of about 340 kDa. The native molecule is a dimer and consists of three pairs of polypeptide chains (Aα, Bβ and γ). Fibrinogen is a physiological substrate of three enzymes: thrombin, factor XIIIa, and plasmin. During the coagulation process, thrombin cleaves the Aα and Bβ chains releasing fibrinopeptides A and B (FPA and FPB, respectively). FPA is separated rapidly and the remaining molecule is a soluble fibrin monomer (fibrin I). The slower removal of FPB results in formation of fibrin II that is capable of polymerization that occurs by aggregation of fibrin monomers. The resulting fibrin is stabilized in the presence of calcium ions and by activated factor XIII, which acts as a transglutaminase. Factor XIIIa-induced cross-linking of fibrin polymers renders the fibrin clot more elastic and more resistant to fibrinolysis. Cross-linked fibrin is the end result of the coagulation cascade, and provides tensile strength to a primary hemostatic platelet plug and structure to the vessel wall.
Pharmacokinetics
- Absorption
- Cmax is 140 mg/dL
- Distribution
- Mean volume of distribution is 52.7 mL/kg.
- Metabolism
- Elimination
Clearance
0.59 mL/h/kg
Active Ingredient/Synonyms
Coagulation Factor I | Factor I (fibrinogen) | Factor I human | Fibrinogen | Fibrinogen (human) | Fibrinogen Concentrate (Human) | Fibrinogen concentrate human | Fibrinogen human | Fibrinogen human plasma-derived | Fibrinogen, human | Human fibrinogen | Fibrinogen Human |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
Also known as coagulation factor II, thrombin is a serine protease that plays a physiological role in regulating hemostasis and maintaining blood coagulation. Once converted from prothrombin, thrombin converts fibrinogen to fibrin, which, in combination with platelets from the blood, forms a clot. Medical thrombin is a protein substance produced through a conversion reaction in which prothrombin of bovine origin is activated by tissue thromboplastin in the presence of calcium chloride. Thrombin requires no intermediate physiological agent for its action. It clots the fibrinogen of the blood directly. Failure to clot blood occurs in the rare case where the primary clotting defect is the absence of fibrinogen itself. Bovine thrombin however, is capable of causing fatal severe bleeding or thrombosis [FDA Label]. This thrombosis may result from the development of antibodies against bovine thrombin [FDA Label]. Bleeding may result from the development of antibodies against bovine factor V [FDA Label]. These antibodies may subsequently cross-react with endogenous human factor V and lead to its deficiency [FDA Label]. Patients who are know or suspected to have antibodies to bovine thrombin and/or bovine factor V should not be re-exposed to the product [FDA Label]. Patients who are administered bovine thrombin should be monitored for abnormal coagulation laboratory values, bleeding, or indeed, thrombosis [FDA Label]. A variety of human thrombin and recombinant thrombin (ie. thrombin alfa) products are available as alternatives to using bovine thrombin.
Indication
Bovine thrombin is a topical thrombin indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (like suture, ligature, or cautery) is ineffective or impractical [FDA Label]. Additionally, topical bovine thrombin can also be used in combination with an absorbable gelatin sponge, USP [FDA Label].
Mechanism of Action
Bovine thrombin requires no intermediate physiological agent for its action [FDA Label]. It activates platelets and catalyzes the conversion of fibrinogen to fibrin, which are essential steps for clot formation [FDA Label]. Failure to clot blood occurs in the case where the primary clotting defect is the absence of fibrinogen itself [FDA Label]. The speed with which the bovine thrombin clots blood is dependent upon the concentration of both the bovine thrombin and the fibrinogen present [FDA Label].
Pharmacokinetics
- Absorption
- Little has been reported about the systemic pharmacokinetics of bovine thrombin preparations [T155], but owing to its topical mode of administration, it is expected that any kind of systemic absorption would be minimal.
- Distribution
- Little has been reported about the systemic pharmacokinetics of bovine thrombin preparations [T155], but owing to its topical mode of application, systemic exposure or distribution to other organs and tissues is not expected.
- Metabolism
- Although little has been reported about the systemic pharmacokinetics of bovine thrombin preparations [T155], such products are expected to be metabolized in the same way as endogenous thrombin is. Endogenous thrombin does not circulate in the blood as a free, active molecule for very long [L2079]. After performing its function it is rapidly inactivated after formation of complexes with various circulating endogenous plasma inhibitors (like antithrombin III) [L2079]. This rapid inactivation prevents the active agent from diffusing into the general circulation. The complexes formed are then generally cleared and eliminated by the liver [L2079].
- Elimination
Clearance
Although little has been reported about the systemic pharmacokinetics of bovine thrombin preparations [T155], it is expected that they are generally rapidly neutralized by naturally circulating plasma inhibitors limiting its duration of action and preventing the active form from diffusing into the general circulation [L2079].
Toxicity
With regards to bovine thrombin, no cases of overdose have been reported so far [T155]. Bovine thrombin however, is capable of causing fatal severe bleeding or thrombosis [FDA Label]. This thrombosis may result from the development of antibodies against bovine thrombin [FDA Label]. Bleeding may result from the development of antibodies against bovine factor V [FDA Label]. These antibodies may subsequently cross-react with endogenous human factor V and lead to its deficiency [FDA Label]. Patients who are know or suspected to have antibodies to bovine thrombin and/or bovine factor V should not be re-exposed to the product [FDA Label]. Patients who are administered bovine thrombin should be monitored for abnormal coagulation laboratory values, bleeding, or indeed, thrombosis [FDA Label]. LD50 values are available for rat and mouse models where rat subcutaneous LD50 > 40mg/kg, rat IP LD50 > 40mg/kg, and mouse subcutaneous LD50 > 50 mg/kg (in which the greater than symbol indicates that the toxicity endpoint being tested was not achievable at the highest dose used in the test) [MSDS]. Regardless, the most common adverse reactions following administration of bovine thrombin include hypersensitivity, bleeding, anemia, post-operative wound infection, thromboembolic events, hypotension, pyrexia, tachycardia, and/or thrombocytopenia [FDA Label].
Active Ingredient/Synonyms
coagulation factor II | Thrombin bovine | Thrombin, Topical (Bovine) | Thrombin |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.