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Thrombin Human And Fibrinogen

FDA Drug Information • Also known as: Tachosil

Brand Names
Tachosil
Drug Class
Human Blood Coagulation Factor [EPC]
Route
TOPICAL
Dosage Form
PATCH
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION TachoSil Fibrin Sealant Patch is a sterile, bioabsorbable combination product comprised of two active substances (human plasma-derived fibrinogen and human plasma-derived thrombin) coated onto a collagen sponge of equine origin. The collagen sponge serves as a flexible and mechanically stable carrier for the active substances to facilitate application of the human fibrinogen and thrombin to the wound surface. The active side of the patch is yellow in color due to the presence of a colorant riboflavin (E101); and the non-active side is off-white in color. Each square inch of the patch contains approximately 35.5 mg of human fibrinogen and 12.9 units of human thrombin. Other inactive ingredients include equine collagen, human albumin, sodium chloride, sodium citrate, and L‑arginine hydrochloride. TachoSil is sterilized by gamma irradiation after completion of inner and outer packaging, resulting in a sterile product in a sterile inner package. Viral Clearance The active biological substances of TachoSil (human fibrinogen and human thrombin) are manufactured from pooled human plasma collected in facilities in the United States. Human plasma is tested by a Nucleic Acid Test (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus-1 (HIV-1). NAT testing for hepatitis A virus (HAV) and parvovirus B19 is also performed. Human plasma is also tested for the presence of hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency viruses types 1 and 2 (anti-HIV 1/2). The manufacturing procedure for each TachoSil component and final product include processing steps designed to reduce the risk of viral transmission. In particular, the virus clearance steps in the manufacture of human fibrinogen and thrombin include pasteurization, precipitation and adsorption. The virus clearance step in the manufacture of the collagen sponge is the pH treatment. The virus clearance capacity of...

What Is Thrombin Human And Fibrinogen Used For?

1 INDICATIONS AND USAGE 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. 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. ( 1 ) Limitations for Use Not for use in place of sutures or other forms of mechanical ligation in treatment of major arterial or venous bleeding. ( 1 ) Not for use in children under one month of age. ( 8.4 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION 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 [see Warnings and Precautions (5.6) ] . 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. ( 2 )
  • Apply the yellow, active side of the patch to the bleeding surface. ( 2 ) 2.1 Preparation for Application TachoSil comes ready to use in sterile packages and must be handled using sterile technique in aseptic conditions. Discard damaged packages as resterilization is not possible. When in the operating room, the outer aluminum foil pouch may be opened in a non-sterile environment (Fig. 1A) . The inner sterile blister must be opened in a sterile environment (Fig. 1B) . Remove the TachoSil patch from the blister (Fig. 1C) , which can be used as a container for pre-moistening of the patch, if needed. Determine the size of patch(es) to be applied to the bleeding surface. Select the appropriate TachoSil patch so that it extends 1 to 2 cm beyond the margins of the wound. The patch can be cut to the correct size and shape if desired (Fig. 1D) . If more than one patch is used, overlap patches by at least 1 cm. Prior to application, cleanse the area to be treated to remove disinfectants and other fluids. The fibrinogen and thrombin proteins can be denatured by alcohol, iodine or heavy metal ions. If any of these substances have been used to clean the wound area, thoroughly irrigate the area before the application of TachoSil. Apply TachoSil directly to the bleeding area either wet or dry. If applied wet, pre-moisten TachoSil in 0.9% saline solution and then apply immediately. In the case of a wet tissue surface (e.g., oozing bleeding) TachoSil may be applied without pre-moistening. Figure 1: Pictures illustrating steps for preparation for application of TachoSil A B C D 21a 21b 21c 21d 2.2 Method of Application To ensure TachoSil adheres effectively, follow the recommended handling, preparation, and application procedures. Incorrect handling may result in non-adherence and reduced efficacy of TachoSil. Cleanse surgical instruments, gloves and adjacent tissues with saline solution to reduce the adherence to the TachoSil patch. The white, inactive side of TachoSil may also adhere to surgical instruments (e.g., forceps), gloves or adjacent tissues covered with blood due to the affinity of collagen to blood. It is important to...

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Corza Medical GmbH at 1-800-997-1067 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Cardiovascular Surgery In the cardiovascular trial, the most frequently reported adverse reactions were atrial fibrillation and pleural effusion. Seventy-four percent (74%) of patients treated with TachoSil and 75% of comparator treated patients experienced one or more clinically relevant adverse reactions (see Table 2) . Table 2. Most Frequent Adverse Reactions (Cardiovascular Trial) Adverse Reaction TachoSil Comparator Comparator: Hemostatic fleece material without additional active coagulation stimulating compounds. N = 62 As treated population (safety data set). n (%) N = 57 n (%) Atrial fibrillation 18 (29%) 14 (25%) Pleural effusion 14 (23%) 11 (19%) Pyrexia 4 (6%) 3 (5%) Hepatic Surgery In the hepatic surgery trial, the most frequently reported adverse reactions were nausea and anemia (see Table 3). Ninety-four percent (94%) of patients treated with TachoSil and 94% of comparator treated patients experienced one or more clinically relevant adverse reactions. Table 3. Most Frequent Adverse Reactions (Hepatic Resection Trial) Adverse Reaction TachoSil Comparator Comparator: Hemostatic fleece material without additional active coagulation stimulating compounds. N = 114 As treated population (safety data set). n (%) N = 109 n (%) Nausea 34 (30%) 29 (27%) Anemia 26 (23%) 23 (21%) Post-operative bile leakage was observed in 8 (7%) of patients after treatment with TachoSil and 13 (12%) after treatment with comparator. Immunogenicity Antibodies against components of fibrin sealant/hemostatic products may occur. However in a clinical trial with human fibrinogen/human thrombin sponge (patch) in hepatic surgery, in which patients were investigated for the development of antibodies, 26% of the 96 patients tested and treated with human fibrinogen/human thrombin sponge (patch) developed antibodies to equine collagen. The equine collagen antibodies that developed in some patients after human fibrinogen/human thrombin sponge (patch) use were not reactive with human collagen. One patient developed antibodies to human fibrinogen. There were no adverse events attributable to the development of human fibrinogen or equine collagen antibodies. There is very limited clinical data available regarding re-exposure of the human fibrinogen/human thrombin sponge (patch). Two subjects have been re-exposed in a clinical trial and have not reported any immune-mediated adverse events, however, their antibody status to collagen or fibrinogen is unknown. Pediatric Clinical Trial Experience In pediatric patients, the most frequently reported adverse reactions were diarrhea, hypertension and increased transaminases (see Table 4). Ninety-four percent (94%) of patients treated with TachoSil and 100% of comparator treated patients experienced one or more clinically...

    Contraindications

    4 CONTRAINDICATIONS 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 [see Warnings and Precautions (5.1) ] .
  • Individuals known to have anaphylactic or severe systemic reaction to human blood products or horse proteins [see Warnings and Precautions (5.2) ] . Do not apply TachoSil intravascularly. Intravascular application of TachoSil may result in life-threatening thromboembolic events. ( 4 ) Do not use TachoSil in individuals with known hypersensitivity to human blood products or horse proteins. ( 4 )

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary A review of available data suggests that major birth defects occur in 2-4% of the U.S. general population and that miscarriage occurs in 15-20% of clinically recognized pregnancies, regardless of drug exposure. Animal reproduction studies have not been conducted with TachoSil. There are no adequate and well-controlled studies in pregnant women. It is also not known whether TachoSil can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. TachoSil should be administered to pregnant women only if clearly needed.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING Each TachoSil patch is packaged individually in a tray with lidding. This is placed in an outer pouch with a desiccant bag and packaged into a folding carton. TachoSil is supplied in the following pack sizes: Package with 1 patch of 3.7 inch x 1.9 inch (9.5 cm x 4.8 cm) (NDC 83078-701-01) Package with 2 patches of 1.9 inch x 1.9 inch (4.8 cm x 4.8 cm) (NDC 83078-702-02) Storage Use TachoSil before expiration date indicated on the package. Store unopened packages of TachoSil between 2ºC and 25ºC. TachoSil does not require refrigeration. Do not freeze. Do not use if package is opened or damaged.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.