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FIBRIN SEALANT (Human) HIGHLIGHTS OF PRESCRIBING INFORMATION ------------------------------CONTRAINDICATIONS------------------------------ These highlights do not include all the information needed to use FIBRIN • Do not inject directly into the circulatory system. (4) SEALANT (Human) safely and effectively. See full prescribing information • Do not use for the treatment of severe or brisk arterial bleeding. for FIBRIN SEALANT (Human). • Do not use in patients with history of anaphylaxis or severe systemic reactions to human blood products. (4) FIBRIN SEALANT (Human) • Do not use FIBRIN SEALANT (Human) for spraying unless the minimum Frozen solutions of fibrinogen and thrombin recommended distance from the applicator tip to the bleeding site can be For Topical Use Only achieved. (2.3, 4) Initial U.S. Approval: Month/YYYY ------------------------WARNINGS AND PRECAUTIONS ------------------------ ----------------------------INDICATIONS AND USAGE--------------------------- • Thromboembolic events may occur if FIBRIN SEALANT (Human) is FIBRIN SEALANT (Human) is indicated as an adjunct to hemostasis for mild to administered intravascularly. (5.1) moderate bleeding in adults undergoing surgery when control of bleeding by • Life-threatening air or gas embolism may occur when using air- or gas- standard surgical techniques (such as suture, ligature, and cautery) is ineffective pressurized sprayers to administer fibrin sealants. Use the spray device at or impractical. FIBRIN SEALANT (Human) is effective in heparinized patients. the recommended pressure and distance. When spraying FIBRIN (1) SEALANT (Human), monitor blood pressure, pulse, oxygen saturation and -----------------------DOSAGE AND ADMINISTRATION----------------------- end tidal CO2. (5.2, 5.4) For Topical Use Only. • Do not spray in confined spaces. (5.2) • After thawing, use FIBRIN SEALANT (Human) within 48 hours if stored at • Hypersensitivity reactions can occur. (5.3) 2 ºC – 8 ºC [36 ºF - 46 ºF], or within 24 hours if stored at room temperature • May carry a risk of transmitting infectious agents, e.g., viruses, the variant (20 °C – 25 °C [68 ºF - 77 ºF]), if it remains sealed in the original Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt- packaging. (2.2, 16) Jakob disease (CJD) agent. (5.5) • Prior to applying FIBRIN SEALANT (Human), use standard techniques (e.g., intermittent application of compresses, swabs, use of suction devices) -------------------------------ADVERSE REACTIONS----------------------------- to dry the surface area of the target bleeding site. (2.3) The most common adverse reactions (reported in >1% of clinical trial subjects) • Apply FIBRIN SEALANT (Human) by dripping or spraying. When were nausea and procedural pain. (6) applying FIBRIN SEALANT (Human) using a spray device, ensure that the pressure and the distance from the tissue are within the recommended To report SUSPECTED ADVERSE REACTIONS, contact Grifols ranges. (2.3) Therapeutics Inc. at 1-800-520-2807 or FDA at 1-800-FDA-1088 or • Apply a sufficient volume of FIBRIN SEALANT (Human) to entirely cover www.fda.gov/medwatch. the intended application area with a thin layer. (2.1) ----------------------DOSAGE FORMS AND STRENGTHS--------------------- FIBRIN SEALANT (Human) is supplied as a kit consisting of two separate See 17 for PATIENT COUNSELING INFORMATION. packages: Revised: MM/YYYY • A package containing one syringe each of human fibrinogen 80 mg/mL (component 1) and human thrombin 500 IU/mL (component 2) sterile frozen solutions which are assembled on a syringe holder. • A package containing an application cannula. FIBRIN SEALANT (Human) is available in the following package sizes: Package size Human Human (Total volume) fibrinogen thrombin 2 mL 1 mL 1 mL 4 mL 2 mL 2 mL 6 mL 3 mL 3 mL 10 mL 5 mL 5 mL FULL PRESCRIBING INFORMATION: CONTENTS* 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 1 INDICATIONS AND USAGE 8.2 Lactation 2 DOSAGE AND ADMINISTRATION 8.4 Pediatric Use 2.1 Dosage 8.5 Geriatric Use 2.2 Preparation and Handling 11 DESCRIPTION 2.3 Administration 12 CLINICAL PHARMACOLOGY 3 DOSAGE FORMS AND STRENGTHS 12.1 Mechanism of Action 4 CONTRAINDICATIONS 12.2 Pharmacodynamics 5 WARNINGS AND PRECAUTIONS 12.3 Pharmacokinetics 5.1 Thrombosis 13 NONCLINICAL TOXICOLOGY 5.2 Gas or air embolism 13.1 Carcinogenicity, Mutagenesis, Impairment of Fertility 5.3 Hypersensitivity 14 CLINICAL STUDIES 5.4 Application precautions 16 HOW SUPPLIED/STORAGE AND HANDLING 5.5 Transmissible Infectious Agents 17 PATIENT COUNSELING INFORMATION 6 ADVERSE REACTIONS * Sections or subsections omitted from the full prescribing information are not 6.1 Clinical Trials Experience listed 1 FULL PRESCRIBING INFORMATION 2 1 INDICATIONS AND USAGE 3 FIBRIN SEALANT (Human) is indicated as an adjunct to hemostasis for mild to moderate 4 bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques DCM\Fibrin Sealant\USA\Dossier\Module 1\1.14 labeling\labeltext-fs-version October 25 2017_clean 5 (such as suture, ligature, and cautery) is ineffective or impractical. FIBRIN SEALANT 6 (Human) is effective in heparinized patients. 7 2 DOSAGE AND ADMINISTRATION 8 For topical use only. 9 2.1 Dosage 10 11 Individualize application of the fibrin sealant. Individual doses typically ranged from 0.3 to 18.0 mL 12 in the clinical studies. Larger volumes may be required for surgical procedures other than those 13 included in the clinical studies. 14 15 The approximate surface area coverage for each FIBRIN SEALANT (Human) package size is 16 provided in Table 1. 17 Table 1. Surface Area Coverage Surface area coverage (cm2) FIBRIN SEALANT Application by dripping or spray (Human) package size (1 mm thick layer) 2 mL 14-20 4 mL 28-40 6 mL 42-60 10 mL 70-100 18 19 Dose depends on variables including, but not limited to, the type of surgical intervention, the 20 size of the area, the intended application method, and the number of applications. 21 22 Apply a sufficient volume of FIBRIN SEALANT (Human) to entirely cover the intended 23 application area with a thin layer. Repeat the application if necessary. 24 25 2.2 Preparation and Handling 26 Prepare and administer the product only according to the instructions and with the 27 recommended devices. 28 Thawing 29 Room temperature 30 Thaw FIBRIN SEALANT (Human) at room temperature using the following steps: 31 1. Open the cardboard case and take out the inner contents. 32 2. Place the package with pre-filled syringes on a surface at room temperature 33 (20 ºC - 25 ºC, [68 – 77 ºF]) 34 for approximately 80 minutes for the 2 mL and the 4 mL package sizes 35 for approximately 120 minutes for the 6 mL and the 10 mL package sizes 36 After thawing, it is not necessary to warm the product for its use. DCM\Fibrin Sealant\USA\Dossier\Module 1\1.14 labeling\labeltext-fs-version October 25 2017_clean 37 Water bath 38 Thaw FIBRIN SEALANT (Human) in a thermostatic water bath at a temperature not higher 39 than 37 ºC [99 ºF] using the following steps: 40 1. Open the cardboard case and take out the inner contents. 41 2. Place the package with pre-filled syringes into water bath. At 37 ºC, the times needed 42 are 43 approximately 20 minutes for the 2 mL and the 4 mL package sizes 44 approximately 30 minutes for the 6 mL and the 10 mL package sizes 45 3. Ensure the package remains submerged throughout thawing. 46 The temperature must not exceed 37 ºC. 47 Preparation 48 After thawing, FIBRIN SEALANT (Human) can be stored before use for not more than 49 48 hours in the refrigerator at 2-8 ºC [36 - 46 ºF] or 24 hours at room temperature (20 °C - 50 25 °C [68 - 77 ºF]) if it remains sealed in the original packaging. 51 52 After thawing, the solutions must be clear to slightly opalescent and colorless to pale 53 yellow. Do not use solutions that are cloudy or have deposits. 54 55 Transferring instructions: 56 1. Remove the package from the surface at room temperature, from the refrigerator at 2 - 57 8 °C or from the water bath (and dry the outer pouch) after thawing. 58 2. Open the outer pouch and remove the sterile inner blister. See Figure 1. 59 Figure 1 60 61 3. Open the inner blister and make the FIBRIN SEALANT (Human) syringe holder 62 available to a second person for transfer to the sterile field. The outside of the blister 63 package should not come in contact with the sterile field. See Figure 2. 64 Figure 2 65 66 Connection instructions: 67 1. Hold the FIBRIN SEALANT (Human) syringe holder slightly inclined upwards. 68 2. Unscrew and remove the tip cap of both fibrinogen and thrombin syringes. See 69 Figure 3. DCM\Fibrin Sealant\USA\Dossier\Module 1\1.14 labeling\labeltext-fs-version October 25 2017_clean 70 Figure 3 71 72 3. To remove air bubbles from syringes, strike gently the side of the syringes one or 73 two times while keeping the syringe holder in an upright position and eject air. See 74 Figure 4. 75 Figure 4 76 77 4. To attach the applicator tip, place it in the luer connector of the syringes and screw 78 both syringe bodies counterclockwise consecutively, making a quarter (90 degree) 79 turn each time. See Figure 5 for drip applicator. See Figure 6 for spray applicator. 80 Figure 5 Figure 6 81 82 2.3 Administration 83 Apply FIBRIN SEALANT (Human) using the syringe holder and plunger link supplied. 84 85 Before administration of FIBRIN SEALANT (Human): DCM\Fibrin Sealant\USA\Dossier\Module 1\1.14 labeling\labeltext-fs-version October 25 2017_clean 86 - To prevent tissue adhesion at undesired sites, protect (cover) parts of the body outside 87 the intended application area. [see Warnings and Precautions (5.4)] 88 - Use standard techniques (e.g., intermittent application of compresses, swabs, use of 89 suction devices) to dry the surface area of the target bleeding site.
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