Fibrin Sealant

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit:

Artiss: Solution, topical: Fibrinogen 67-106 mg/mL and thrombin 2.5-6.5 units/mL (2 mL, 4 mL, 10 mL) [contains albumin (human), aprotinin, polysorbate 80; prefilled syringe]

Tisseel: Powder for solution, topical: Fibrinogen 67-106 mg/mL and thrombin 400-625 units/mL (2 mL, 4 mL, 10 mL) [contains albumin (human), aprotinin, polysorbate 80; packaged with reconstituting solutions]

Tisseel: Solution, topical: Fibrinogen 67-106 mg/mL and thrombin 400-625 units/mL (2 mL, 4 mL, 10 mL) [contains albumin (human), aprotinin, polysorbate 80; prefilled syringe]

Kit [preservative free]:

Evicel: Solution, topical: Fibrinogen 55-85 mg/mL and thrombin 800-1200 units/mL (2 mL, 4 mL [DSC], 10 mL [DSC]) [contains albumin (human)]

Patch, topical:

Evarrest: Fibrinogen 8.6 mg/cm² and thrombin 37.5 units/cm² (1s) [contains albumin (human); 10.2 cm x 10.2 cm]

Evarrest: Fibrinogen 8.6 mg/cm² and thrombin 37.5 units/cm² (2s) [contains albumin (human); 5.1 cm x 10.2 cm]

TachoSil: Fibrinogen 3.6-7.4 mg/cm² and thrombin 1.3-2.7 units/cm² (1s) [contains albumin (human), collagen (equine); 9.5 cm x 4.8 cm]

TachoSil: Fibrinogen 3.6-7.4 mg/cm² and thrombin 1.3-2.7 units/cm² (2s) [contains albumin (human), collagen (equine); 4.8 cm x 4.8 cm]

Powder, topical [preservative free]:

Raplixa: Fibrinogen 79 mg/g and thrombin 699 units/g (1 g) [contains albumin (human)] [DSC]

Pharmacology

Mechanism of Action

Formation of a biodegradable adhesive is done by duplicating the last step of the coagulation cascade, the formation of fibrin from fibrinogen. Fibrinogen is the main component of the sealant solution. The solution also contains thrombin, which transforms fibrinogen from the sealer protein solution into fibrin, and fibrinolysis inhibitor (aprotinin), which prevents the premature degradation of fibrin. When mixed as directed, a viscous solution forms that sets into an elastic coagulum. Patches contain fibrinogen and thrombin that, in contact with bleeding surfaces, hydrate, form active fibrin, then produce a fibrin clot.

Pharmacokinetics/Pharmacodynamics

Onset of Action

Artiss: Full adherence achieved: ~2 hours

Time to hemostasis: Evarrest: 4 minutes; Evicel: 4 to 10 minutes; Raplixa: 5 minutes; TachoSil: 3 to 6 minutes; Tisseel: 5 minutes

Use: Labeled Indications

Colonic anastomosis sealing (Tisseel only): As an adjunct to standard surgical techniques (such as suture and ligature) to prevent leakage from colonic anastomoses following the reversal of temporary colostomies

Facial rhytidectomy (Artiss only): To adhere tissue flaps during facial rhytidectomy surgery (face lift)

Hemostasis, adjunct:

Artiss: Not indicated as an adjunct to hemostasis

Evarrest, Evicel: As an adjunct to hemostasis for use in patients undergoing surgery when control of bleeding by conventional surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical

Raplixa: As an adjunct to hemostasis for mild to moderate bleeding in adults undergoing surgery when control of bleeding by standard surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical

TachoSil: As an adjunct to hemostasis for use with manual compression in adults and pediatric patients ≥1 month in cardiovascular and hepatic surgery when control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical

Tisseel: As an adjunct to hemostasis in adult and pediatric patients (≥1 month) undergoing surgery when control of bleeding by conventional surgical techniques, including suture, ligature, and cautery, is ineffective or impractical. Tisseel is effective in heparinized patients.

Skin graft adhesion (Artiss only): To adhere autologous skin grafts to surgically prepared wound beds resulting from burns in adults and pediatric patients ≥1 year

Contraindications

Artiss: Hypersensitivity to aprotinin or any component of the formulation (including proteins such as fibrinogen, thrombin, and human albumin); injection directly into the circulatory system or into highly vascularized tissue; use where the minimum recommended distance from the applicator tip to the target site cannot be assured.

Evarrest: Anaphylactic or severe systemic reaction to human blood products; intravascular application; treatment of bleeding from large defects in visible arteries or veins

Evicel: Anaphylactic or severe systemic reaction to human blood products; severe or brisk arterial bleeding; direct intravascular injection; for spraying in endoscopic or laparoscopic procedures where the minimum recommended distance from the applicator tip to the target site cannot be assured

Raplixa: Anaphylactic or severe systemic reaction to human blood products; intravascular application; treatment of severe or brisk arterial bleeding

TachoSil: Anaphylactic or severe systemic reaction to human blood products or horse protein; intravascular application

Tisseel: Hypersensitivity to aprotinin or any component of the formulation; direct intravascular injection; severe or brisk arterial or venous bleeding; application where the minimum recommended distance from the applicator tip to the target site cannot be assured.

Dosage and Administration

Dosing: Adult

Colonic anastomosis: Tisseel: Package size to be used is determined by the size of the surface to be covered. Apply in a thin layer by dripping or spraying to completely cover the application area.

Maximum area to be sealed: 8 cm² (cannula application) or 100 cm² (spray application)

Required package size of Tisseel: 2 mL

Maximum area to be sealed: 16 cm² (cannula application) or 200 cm² (spray application)

Required package size of Tisseel: 4 mL

Maximum area to be sealed: 40 cm² (cannula application) or 500 cm² (spray application)

Required package size of Tisseel: 10 mL

Hemostasis, adjunct: Apply topically in an even, thin layer (do not inject intravascularly); actual dose is based on size of surface to be covered:

Evarrest: Apply appropriate number of patches as determined by location and surface area; do not use more than four 10.2 cm x 10.2 cm (4 inch x 4 inch) patches or eight 5.1 cm x 10.2 cm (2 inch x 4 inch) patches. If hemostatic effect is not complete due to insufficient area coverage, apply more patches with edges overlapping 1 to 2 cm (0.5 to 1 inch) with the existing patch. If hemostatic effect is not complete due to incomplete adherence to the tissue, remove patch and use a new one.

Evicel: Spray or drop onto surface of bleeding tissue in short bursts (0.1 to 0.2 mL); if hemostatic effect is not complete, apply a second layer. See product labeling for additional administration details. To cover a layer of 1 mm thickness:

Maximum area to be sealed: 20 cm²

Required size of Evicel: 2 mL

Maximum area to be sealed: 40 cm²

Required size of Evicel: 4 mL

Maximum area to be sealed: 100 cm²

Required size of Evicel: 10 mL

Raplixa: Adults: Maximum total dose per surgery: 3 g. Note: Used with concomitant absorbable gelatin sponge

Direct application:

Maximum surface area 25 cm²: Required package size of Raplixa: 0.5 g

Maximum surface area 50 cm²: Required package size of Raplixa: 1 g

Maximum surface area 100 cm²: Required package size of Raplixa: 2 g

RaplixaSpray device application:

Maximum surface area 50 cm²: Required package size of Raplixa: 0.5 g

Maximum surface area 100 cm²: Required package size of Raplixa: 1 g

Maximum surface area 200 cm²: Required package size of Raplixa: 2 g

TachoSil: Apply patch to surface of cardiovascular or hepatic tissue only. The number of patches applied is determined by the size of the bleeding area. Do not exceed the following maximums:

Patch size: 9.5 cm x 4.8 cm; maximum patches to be applied: 10

Patch size: 4.8 cm x 4.8 cm; maximum patches to be applied: 14

Patch size: 3 cm x 2.5 cm; maximum patches to be applied: 42

Tisseel: Package size to be used is determined by the size of the surface to be covered. Apply in thin layer by dripping or spraying to completely cover the application area.

Maximum area to be sealed: 8 cm² (cannula application) or 100 cm² (spray application)

Required package size of Tisseel: 2 mL

Maximum area to be sealed: 16 cm² (cannula application) or 200 cm² (spray application)

Required package size of Tisseel: 4 mL

Maximum area to be sealed: 40 cm² (cannula application) or 500 cm² (spray application)

Required package size of Tisseel: 10 mL

Skin graft adherence: Artiss: Apply by spraying topically in an even, thin layer over the wound bed immediately prior to applying graft (do not inject intravascularly); actual dose is based on size of surface to be covered:

Approximate graft fixation area: 100 cm²

Required size of Artiss: 2 mL

Approximate graft fixation area: 200 cm²

Required size of Artiss: 4 mL

Approximate graft fixation area: 500 cm²

Required size of Artiss: 10 mL

Facial rhytidectomy (facelift) surgery: Artiss: Adults: Apply by spraying topically in an even, thin layer over the wound bed immediately prior to attaching the skin flap (do not inject intravascularly); actual dose is based on size of surface to be covered:

Approximate graft fixation area: 100 cm²

Required size of Artiss: 2 mL

Approximate graft fixation area: 200 cm²

Required size of Artiss: 4 mL

Approximate graft fixation area: 500 cm²

Required size of Artiss: 10 mL

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hemostasis, adjunct: Topical: Apply topically in an even, thin layer (do not inject intravascularly); actual dose is based on size of surface to be covered:

Evicel: Infants >6 months, Children, and Adolescents: Spray or drop onto surface of bleeding tissue in short bursts (0.1 to 0.2 mL); if hemostatic effect is not complete, apply a second layer. Amount required depends on method of administration as well as surface area to be covered. Area of coverage for specific Evicel package size:

Evicel Package Size: 2 mL; BAC2 (fibrinogen) vial size: 1 mL; Thrombin vial size: 1 mL; Area of Coverage with 1 mm thickness: 20 cm²

Evicel Package Size: 4 mL; BAC2 (fibrinogen) vial size: 2 mL; Thrombin vial size: 2 mL; Area of Coverage with 1 mm thickness: 40 cm²

Evicel Package Size: 10 mL; BAC2 (fibrinogen) vial size: 5 mL; Thrombin vial size: 5 mL; Area of Coverage with 1 mm thickness: 100 cm²

TachoSil: Infants ≥1 month, Children, and Adolescents: Apply patch to surface of cardiovascular or hepatic bleeding tissue only. The number of patches applied is determined by the size of the bleeding area. Do not exceed the following maximums:

Patch size: 9.5 cm x 4.8 cm; maximum patches to be applied: 10

Patch size: 4.8 cm x 4.8 cm; maximum patches to be applied: 14

Patch size: 3 cm x 2.5 cm; maximum patches to be applied: 42

Tisseel: Infants > 1 month, Children, and Adolescents: Package size to be used is determined by the size of the surface to be covered. Apply in thin layer by dripping or spraying with an approved spray set to completely cover the application area.

Size of Tisseel Package: 2 mL; Maximum Surface Area With Spray: 100 cm²; Maximum Surface Area With Cannula: 8 cm²

Size of Tisseel Package: 4 mL; Maximum Surface Area With Spray: 200 cm²; Maximum Surface Area With Cannula: 16 cm²

Size of Tisseel Package: 10 mL; Maximum Surface Area With Spray: 500 cm²; Maximum Surface Area With Cannula: 40 cm²

Skin graft adherence: Topical:

Artiss: Children ≥1 year and Adolescents: Apply by spraying topically in an even, thin layer over the wound bed immediately prior to applying graft (do not inject intravascularly); actual dose is based on size of surface to be covered:

Approximate graft fixation area: 100 cm²

Required size of Artiss: 2 mL

Approximate graft fixation area: 200 cm²

Required size of Artiss: 4 mL

Approximate graft fixation area: 500 cm²

Required size of Artiss: 10 mL

Reconstitution

Evicel: Thaws within 1 day under refrigeration at 2°C to 8°C (35°F to 46°F); within 1 hour at room temperature (20°C to 25°C [68°F to 77°F]) or within 10 minutes at 37°C (98.6°F) (do not exceed 37°C [98.6°F]; do not exceed 10 minutes at 37°C [98.6°F]). Draw up equal volumes of each vial into application device.

Raplixa: RaplixaSpray device (refer to absorbable gelatin sponge and RaplixaSpray device manufacturer's labeling for detailed instructions): To attach the vial to the RaplixaSpray device, invert the device and place the upright vial into the gray rubber ring on the device then turn the device upright. Activate air or gas (CO₂) flow. Do not push spray device operating button until ready for administration. Pressure should be 1.5 bar (22 psi) and vial should be kept within 45º of vertical. Spray nozzle should be a minimum of 5 cm (or 2 inches) from the bleeding site.

Tisseel kit, powder for solution: Store at 2°C to 25°C (35°F to 77°F); do not freeze. Prior to reconstitution, all 4 vials (sealer protein concentrate, fibrinolysis inhibitor solution, thrombin, calcium chloride solution) from the kit should be placed into the prewarmed wells of Baxter's Fibrinotherm heating and stirring device and allowed to warm for up to 5 minutes. Do not expose to temperatures >37°C (>98.6°F) during preparation. When disinfecting the rubber stoppers of vials during reconstitution, do NOT use a germicidal solution that contains iodine or heavy metals (eg, Betadine). Allow alcohol-based disinfectants to evaporate before puncturing the stopper.

To reconstitute the sealer protein: Transfer the fibrinolysis inhibitor solution into the vial of the freeze dried sealer protein concentrate. Use the appropriate adapter to insert the vial into the largest opening of the Fibrinotherm. Turn on the stirring switch of the Fibrinotherm and stir contents until all sealer protein concentrate has dissolved. If total dissolution has not occurred within 20 minutes, discard and prepare a fresh kit. If not used promptly, keep the solution at 37°C (98.6°F) without stirring. Stir again shortly before drawing up solution.

To reconstitute the thrombin: Add the calcium chloride to the thrombin vial. Swirl briefly. Allow complete dissolution of thrombin concentrate. Place vial into the adapted opening of the Fibrinotherm device. Keep the prepared solution at 37°C (98.6°F) until use.

Preparation of the final solution: Prior to application, the sealer protein solution and the thrombin solution should be transferred to a sterile field. To do this, the scrub nurse should withdraw the solution into the provided syringes, while the circulating nurse holds the vials. Withdraw solutions slowly to reduce the possible formation of large air bubbles. The two resulting solutions are then placed into the Duploject Preparation and Application syringe system (provided in the kit) or an equivalent device. Tisseel application must be completed within 4 hours of preparing the solution.

Artiss prefilled syringe, Tisseel prefilled syringe: Prior to use, product should be completely thawed and warmed to 33°C to 37°C (91°F to 98.6°F). Product may be thawed per manufacturer's guidelines using either room temperature thawing or a quick thawing method (water bath or incubator); do not microwave. Do not remove protective syringe cap until fully thawed and warmed. Tisseel application must be completed within 4 hours of opening the package. Artiss must be used within 12 hours after warming or removal from pouch. Do not refrigerate or refreeze after thawing.

Administration

Artiss: Prior to use, dry application site using standard techniques (eg, intermittent application of compresses, swabs, use of suction devices); do not use pressurized air or gas for drying the site. Apply only to application sites that are visible using a painting motion from side to side in a thin layer to dry wound surface using EasySpray and Spray set or an equivalent device cleared by FDA (areas covered with fibrin sealant will appear to “glisten”); do not use EasySpray and Spray set system in enclosed body cavities. Immediately after spraying fibrin sealant, attach flap or skin graft; approximate time available for manipulation/positioning is 60 seconds. Hold graft in position with gentle compression for at least 3 minutes; full adherence is achieved in ~2 hours. To prevent sealant from adhering to gloves, wet them with saline prior to contact. The cannulas included with the application system may be used for small wounds or for edges of a skin graft that did not adhere to the wound bed. Immediately before application, expel and discard the first several drops from the application cannula to ensure adequate mixing of the sealer protein and thrombin solutions. Cannulas may become clogged if application is interrupted; replace cannula immediately prior to resuming application; if Y connector is clogged, use provided spare piece.

Evarrest: For topical use only; apply to surface of bleeding site only. Prior to applying, remove excess blood or fluid from the site of application to improve visibility. The anatomic location and surface area of the bleeding should be used to determine how many patches should be applied. Patches can be cut to shape and size; ensure an overlap of about 0.5 to 1 inch. The active, powdery side of the patch should be applied to the tissue or prosthetic graft. Immediate, continuous manual compression using dry or moist laparotomy pads or surgical gauze should be applied evenly to the entire surface of the patch and continuous contact pressure should be held for 3 minutes.

Evicel: For topical use only; apply to surface of bleeding tissue only; do not inject directly into the circulatory system or into tissues. Prior to applying, dry surface areas of wound and remove excess blood from site of application by standard techniques (eg, intermittent application of compresses, swabs, use of suction devices).

Application by 4 cm control tip by drip method: Bend tip to desired position (tip will retain shape); keep tip of applicator as close as possible to the tissue surface without touching during application. Apply solution to surface area to be treated; as soon as solution is applied, pull back tip from treated area surface immediately. Control coverage area by varying applied force on plunger and tip distance from tissue.

Application by 6 cm, 35 cm, and 45 cm tips by spray or drip methods: Solution should be sprayed or dripped in short bursts (0.1 to 0.2 mL) on the tissue to produce an even, thin layer. Application with provided device allows for the simultaneous application of both solutions. Apply spray with provided air tube; distance between nozzle and tissue surface should be 10 to 15 cm for open surgery or 4 to 10 cm for laparoscopic surgery. Apply drops keeping applicator close to, but not touching tissue surface.

Application by airless spray accessory: Once airless spray accessory (no connection to an external CO₂ source) is firmly attached, do not press plungers to prime device until intended use because the two biologic components will premix in spray tip forming a fibrin clot that prevents dispensing. Position tip at least 2 cm away from the target tissue; increase distance accordingly to achieve desired coverage of target area. Replace spray tip if any pause in expression; do not try and clear fibrin clot within tip by depressing plunger.

Raplixa: For topical use only.

Direct application (refer to absorbable gelatin sponge labeling for detailed instructions): Remove vial stopper and sprinkle a thin layer of powder onto the bleeding site OR sprinkle a thin layer of powder onto a pre-wetted gelatin sponge and place onto the bleeding site; apply gentle pressure with gelatin sponge using sterile gauze.

RaplixaSpray device (refer to absorbable gelatin sponge and RaplixaSpray device manufacturer's labeling for detailed instructions): To attach the vial to the RaplixaSpray device, invert the device and place the upright vial into the gray rubber ring on the device then turn the device upright. Activate air or gas flow. Do not push spray device operating button until ready for administration. Pressure should be 1.5 bar (22 psi) and vial should be kept within 45º of vertical. Spray nozzle should be a minimum of 5 cm (or 2 inches) from the bleeding site. Apply within 10 to 60 seconds; powder should cover bleeding surface as a thin layer. Place a gelatin sponge (trimmed to appropriate size) on top of the powder immediately after application; sponge may be dry or moistened with sterile saline (moistened sponge molds better to contoured bleeding areas); apply manual pressure to gelatin sponge with sterile gauze. After application, remove empty vial by holding the device upside down. No more than 2 vials may be used with a single RaplixaSpray device; to use a third vial, open a new RaplixaSpray delivery device.

TachoSil: The outer aluminum foil pouch may be opened in a nonsterile environment; the inner sterile blister must be opened in a sterile environment. Adequately cleanse tissue areas outside the desired application area to prevent tissue adhesions at undesired sites. Apply the yellow, active side directly to the bleeding tissue (extending 1 to 2 cm beyond margins of wound) either wet or dry. If applied wet, premoisten patch in NS for ≤1 minute, then apply immediately. After applying, hold in place with gentle compression through moistened gloves or moistened pad for at least 3 minutes. To prevent inactive side of patch from adhering to pad or gloves, place a clean surgical instrument at one end of the patch prior to relieving pressure; area may also be moistened with saline solution. Once patch adheres, leave in place. Handle unattached patches with care and replace with new patches. The application procedure may be repeated if bleeding continues during or after the compression period, but do not remove applied patches. Document product batch number(s) in patient record.

Tisseel: Apply in thin layers (by dripping or spraying using a cannula or spray set) to avoid excess formation of granulation tissue and slow absorption of the sealant. When using a spray device, use the ranges of gas, pressure, and distance from tissue recommended in the manufacturer's labeling. Following application, hold the sealed parts in the desired position for 3 to 5 minutes. If repeat application is necessary, dry the site as much as possible before reapplying. To prevent sealant from adhering to gloves or surgical instruments, wet them with saline prior to contact. In cases where very small volumes (1 to 2 drops) are required, expel and discard the first several drops from the application cannula to ensure adequate mixing of the sealer protein and thrombin solutions. Cannulas may become clogged if application is interrupted; replace cannula immediately prior to resuming application; if Y connector is clogged, use provided spare piece.

Storage

Evarrest Store unopened packages at 2°C to 25°C (35°F to 77°F); do not refrigerate; do not freeze. Once opened in the sterile field, keep the patches dry to prevent premature activation of the components. Discard any damaged packages because they cannot be resterilized.

Evicel: Store vials in an upright position; store frozen at or below -18°C for ≤2 years; unopened vials may also be stored at 2°C to 8°C (35°F to 46°F) for up to 30 days or up to 24 hours at room temperature. Vials should be thawed prior to use; do not refreeze; if thawed at room temperature, do not re-refrigerate; do not exceed 10 minutes at 37°C (98.6°F). Vials are for single use only; discard any unused product after 24 hours at room temperature.

Raplixa: Store intact vials at 2°C to 25°C (35°F to 77°F). Refrigeration is not required. Do not freeze. Use within 1 hour of opening the vial.

Tisseel kit, powder for solution: Store intact vials at 2°C to 25°C (35°F to 77°F); do not freeze; do not microwave. Do not refrigerate or freeze after reconstitution.

Artiss prefilled syringe, Tisseel prefilled syringe: Store frozen at or below -20°C. Unopened pouches (which have been thawed at room temperature) may be stored for up to 48 hours (Tisseel) or 14 days (Artiss) at room temperature (15°C to 25°C). If Artiss is removed from original pouch or warmed to 33°C to 37°C (91°F to 98.6°F), use within 12 hours. Do not expose product to temperatures >37°C (>98.6°F). Do not microwave. Do not refrigerate or refreeze. For single use only; discard any unused product. Refer to Artiss manufacturer's labeling for additional thawing instructions.

TachoSil patch: Store at 2°C to 25°C (35°F to 77°F); refrigeration not required; do not freeze. The outer aluminum foil pouch may be opened in a nonsterile environment; the inner sterile blister must be opened in a sterile environment. Discard any damaged packages since they cannot be resterilized.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Frequency may vary by product and patient age.

>10%:

Cardiovascular: Atrial fibrillation (29%), hypertension (children: 17%)

Gastrointestinal: Nausea (30%), diarrhea (children: 17%)

Hematologic & oncologic: Anemia (23%)

Hepatic: Increased serum transaminases (children: 11%)

Immunologic: Antibody development (equine collagen: 26% human thrombin: 2%, human fibrinogen: 1%)

Respiratory: Pleural effusion (23%)

1% to 10%:

Cardiovascular: Bradycardia (≥5%), peripheral edema (≥5%), thromboembolism (≤3%), deep vein thrombosis (≤1%)

Dermatologic: Pruritus (1%)

Immunologic: Graft complications (skin graft failure in burn patients: 3%)

Infection: Localized infection (grafts: ≥5%)

Miscellaneous: Postoperative complication (bile leakage after hepatic surgery; 7%), fever (6% to 7%), procedural complications (seroma; ≤4%)

Frequency not defined:

Hematologic & oncologic: Decreased hemoglobin, hematoma

Infection: Abscess (abdomen), staphylococcal infection

Local: Incision site hemorrhage

<1%, postmarketing, and/or case reports: Abdominal distension, anaphylactic shock, anaphylactoid reaction, anaphylaxis, angioedema, ascites, bile leakage (postprocedural), bronchospasm, catheter complication, cerebral embolism, cerebral infarction, chest discomfort, chills, dyspnea, edema, eosinophilia, erythema, flushing, gastrointestinal hemorrhage, granuloma, hemorrhage (internal, postprocedural), hemothorax, hepatitis C, hypersensitivity reaction, hypotension, inflammation, ischemic bowel disease, laryngeal edema, local hemorrhage (spleen), multiorgan failure, mydriasis, nerve compression, paralysis, parathyroid disease, paresthesia, procedural complications (thoracic cavity drainage), pulmonary embolism, renal artery thrombosis, renal failure, respiratory distress, tachycardia, thrombosis, urticaria, wheezing

Warnings/Precautions

Concerns related to adverse effects:

• Human plasma: Components of fibrin sealant products are made from human plasma and theoretically may potentially transmit disease; viral infections, variant Creutzfeldt-Jakob disease (vCJD) and Creutzfeldt-Jakob disease (CJD) are potential risks. Any infection suspected of being transmitted by a product should be reported to the manufacturer.
• Hypersensitivity: Cases of hypersensitivity or allergic/anaphylactoid reactions which may progress to severe anaphylaxis have been reported (rarely) with use; risk may increase with repetitive use use or with prior systemic aprotinin administration. Discontinue use if symptoms (bradycardia, bronchospasm, dyspnea, erythema, flushing, hypotension, nausea, paresthesia, pruritus, tachycardia, urticaria, wheezing) occur.

Dosage form specific issues:

• Artiss: May contain aprotinin (synthetic source). Not indicated and should not be used for hemostasis.
• Evarrest patch: May cause thrombosis if systemically absorbed. The fewest number of patches should be applied to cover entire bleeding area, portions of excess patch material can become dislodged and migrate to other areas of the body. Do not use in place of sutures or other forms of mechanical ligation in treatment of major arterial or venous bleeding. Do not apply to active infections or contaminated areas (risk for infection). Not for use in, around, or in proximity to foramina in bone or areas of bony confine where swelling may cause nerve or blood vessel compression. Use may result in inadvertent adhesion. Not for use in laparoscopic and other minimally invasive surgeries where manual compression would be difficult to achieve. Do not use to treat bleeding from defects in large arteries or veins where the injured vascular wall requires conventional surgical repair for maintenance of vessel patency or where there would be persistent exposure of fibrin sealant to blood flow and/or pressure during absorption of the product.
• TachoSil patch: May contain collagen, which may adhere to bleeding surfaces. Adhesion to GI tissues leading to GI obstruction have been reported with use during abdominal surgery. Do not apply or leave product in an infected or contaminated space due to potential for infection exacerbation. Do not over-pack when applying product in closed spaces or cavities; may compress underlying tissue. Do not use in place of sutures or other forms of mechanical ligation in treatment of major arterial or venous bleeding. Adequately cleanse tissue areas outside the desired application area to prevent tissue adhesions at undesired sites. Use the minimum amount of patches necessary; excess patch material may (theoretically) become dislodged and migrate to other areas of the body. Thrombosis can occur if applied intravascularly; apply only to surface of vascular, cardiac, or hepatic tissue.
• Tisseel: May contain aprotinin (synthetic source). Do not use with oxycellulose-containing preparations; may decrease efficacy. Safety and efficacy in neurologic procedures (or other procedures within a confined space) have not been established.

Other warnings/precautions:

• Administration: For topical use only; do not inject or apply intravascularly; inadvertent intravascular administration may result in serious or life-threatening thromboembolic or allergic/anaphylactoid reaction. Use only the minimum amount necessary; excessive use may decrease efficacy and interfere with wound healing. Air or gas embolism, tissue rupture, or gas entrapment with compression (may be life threatening) has occurred when using spray devices with pressure regulators to apply fibrin sealants; risk of embolism appears to be related to using higher than recommended pressures, administering closer than the recommended distance from tissue surface, or when fibrin sealants are sprayed with air, as compared with CO₂. Use only with product-recommended regulators, pressure ranges, and applicator positions. Patches are not for use as substitutes for sutures or any mechanical ligation in major vessel bleeding. Do not use Evarrest or TachoSil patches in children <1 month of age (application is limited due to size).
• Alcohol, iodine, or heavy-metal ions: Exposure to any of these solutions may denature fibrinogen and thrombin proteins; if any were used, thoroughly rinse area before applying fibrin sealant.

Monitoring Parameters

Monitor changes in blood pressure, pulse, oxygen saturation and end-tidal CO₂ when spraying (due to the possibility of gas embolism); hypersensitivity reactions.

Pregnancy

Pregnancy Risk Factor

C (manufacturer dependent)

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.