Fibrinogen human and Human thrombin

TachoSil is a fibrin sealant patch indicated for use with manual compression in adult and pediatric patients as an adjunct to hemostasis in cardiovascular and hepatic surgery when control of bleeding by standard surgical techniques (such as suture, ligature or cautery) is ineffective or impractical. Limitations for Use TachoSil cannot safely or effectively be used in place of sutures or other form of mechanical ligation for the treatment of major arterial or venous bleeding. Not for use in children under one month of age. Limitations for Use Not for use in place of sutures or other forms of mechanical ligation in treatment of major arterial or venous bleeding.

The mechanism of action of TachoSil is based on the interaction between the active biological substances (human fibrinogen and human thrombin) and the physiology of the fibrin clot formation (Fig. 3A). Upon contact with a bleeding wound surface, the active substances coated onto the equine collagen patch become dissolved and partly diffuse into the wound surface. The subsequent fibrinogen-thrombin reaction initiates the last step in the cascade of biochemical reactions-conversion of fibrinogen into fibrin monomers that further polymerize to form the fibrin clot. Hemostasis is achieved when the formed fibrin clot adheres the collagen patch to the wound surface, thus providing a physical barrier to bleeding (Fig 3B). TachoSil exhibits flexibility to accommodate for the physiological movements of tissues and organs and can withstand pressures up to 61.4 hPa (46.1 mmHg).

For topical use on cardiovascular or hepatic tissue only Determine the number of patches to be applied by the size of the bleeding area. Apply the yellow, active side of the patch to the bleeding area. When applying TachoSil, do not exceed the maximum number of patches shown in Table 1. Table 1. Amount of Fibrinogen and Thrombin per Total Patch Size and Maximum Number of TachoSil Patches to be Applied TachoSil Patch Size Human Fibrinogen (mg) Human Thrombin (Units) Maximum Number of Patches to be Applied 3.7 inch x 1.9 inch (9.5 cm x 4.8 cm) 337.4 123.1 10 1.9 inch x 1.9 inch (4.8 cm x 4.8 cm) 170.5 62.2 14 Apply on the surface of cardiovascular or hepatic tissue only. • Determine the number of TachoSil patches to be applied by the size of the bleeding area. • Apply the yellow, active side of the patch to the bleeding surface.

Do not use TachoSil for: • Intravascular application. Bleeding from large defects in visible arteries or veins where the injured vascular wall requires repair and maintenance of vessel patency or where there would be persistent exposure of TachoSil to blood flow during absorption of the product. This can result in life-threatening thromboembolic events. • Individuals known to have anaphylactic or severe systemic reaction to human blood products or horse proteins. Do not apply TachoSil intravascularly. Intravascular application of TachoSil may result in life-threatening thromboembolic events.

• Thrombosis can occur if TachoSil is applied intravascularly. Ensure that TachoSil is applied to the surface of cardiac, vascular or hepatic tissue only. • Can cause hypersensitivity or allergic/anaphylactoid reactions with first time or repetitive application. • Avoid use in contaminated areas of the body or in the presence of an active infection. • TachoSil contains collagen, which may adhere to bleeding surfaces. May carry a risk of gastrointestinal obstruction in abdominal surgery due to tissue adhesions. To prevent the development of tissue adhesions at undesired sites, ensure tissue areas outside the application area are adequately cleansed before administration of TachoSil. • Avoid packing in cavities or closed spaces, because this may cause compression of underlying tissue. • Use the least number of patches required to cover the entire bleeding area. Do not pack.

The adverse reactions reported in more than one percent of patients during clinical trials were anemia, nausea and vomiting, fever, abdominal pain, increased white blood cell count, ascites, itching, atrial fibrillation, pleural effusion, gastrointestinal hemorrhage, wound infection, hypophosphatemia, urinary tract infection, and post-procedural bile leakage in hepatic surgery. The most common adverse reactions reported in >1% of patients during clinical trials were anemia, nausea and vomiting, fever, abdominal pain, increased white blood cell count, ascites, itching, atrial fibrillation, pleural effusion, gastrointestinal hemorrhage, wound infection, hypophosphatemia, urinary tract infection and post-procedural bile leakage in hepatic surgery.

Store unopened packages of TachoSil between 2ºC and 25ºC. TachoSil does not require refrigeration. Do not freeze.