fibrinogen human, aprotinin (synthetic);human thrombin, calcium chloride

Local Hemostatics
Needles, Syringes and Injection Supplies

When applying fibrin sealant using a spray device, use pressure within the pressure range and spray from a distance specified by the manufacturer. If specific recommendations are not available, avoid using pressure above 20 to 25 psi and spraying closer than 5 to 15 cm from the surface of the tissue. Monitor for changes in blood pressure, pulse, oxygen saturation, and end-tidal carbon dioxide when spraying fibrin sealant.[41169] [41170] [41172] [61539]
Artiss
Do not expose to temperatures above 37 degrees C during preparation.
The sealer protein and thrombin solutions of Artiss can be denatured by alcohol, iodine, or heavy metal ions found in antiseptics. If these substances have been used to clean the wound area, thoroughly rinse and dry prior to application of fibrin sealant.[41169]
Preparation (freeze-dried kit)
Place all 4 vials from the kit into pre-warmed wells of the Fibrinotherm, and allow the vials to warm for up to 5 minutes; room temperature product may take less time.
To prevent premature clotting, use separate syringes for reconstitution of the sealer protein and thrombin solutions and for application to the wound.
Remove the flip-off caps from the vials containing sealer protein concentrate and the fibrinolysis inhibitor solution. Disinfect the rubber stoppers with a germicidal solution and allow drying.
Using Duploject or an equivalent FDA-approved device, transfer the fibrinolysis inhibitor solution into the vial containing the sealer protein concentrate. Gently swirl the vial to ensure the freeze-dried material is completely soaked.
Place the vial into the largest opening of the Fibrinotherm, and allow the vial contents to stir until all sealer protein concentrate is dissolved. Reconstitution is complete once no undissolved particles are visible and the solution appears homogeneous. If the particles do not dissolve within 20 minutes, discard the vial and use a new kit. If not used promptly, keep the solution at 37 degrees C without stirring. To ensure homogeneity, switch on the Fibrinotherm stirrer shortly before drawing up the solution.
Remove the flip-off caps from the vials containing thrombin and calcium chloride solutions. Disinfect the rubber stoppers with a germicidal solution and allow drying.
Using Duploject or an equivalent FDA-approved device, transfer the calcium chloride solution into the vial containing thrombin and gently swirl.
Place the vial into the Fibrinotherm. Reconstitution is complete once all the concentrate is dissolved. Keep the solution at 37 degrees C until used.
When transferring the sealer protein solution and the thrombin solution to the sterile field, the circulating nurse should hold the non-sterile vials while the scrub nurse withdraws the solutions slowly by firm constant aspiration to reduce the risk of large air bubbles.
Storage: After reconstitution, the product must be used within 4 hours. Do not refrigerate or freeze after reconstitution.[41169]
Preparation (pre-filled frozen syringe)
Do not use unless it is completely thawed and warmed to a liquid consistency. Do not remove the protective syringe cap until thawing is complete and the application tip is ready to be attached.
Room temperature thawing: Approximate thawing times by package size (pouch) are 60 minutes for 2 mL, 110 minutes for 4 mL, and 160 minutes for 10 mL. Once at room temperature, unopened pouches may be stored for up to 14 days at 15 to 25 degrees C. Prior to use, the product should be warmed to 33 to 37 degrees C in an incubator (15 minutes for 2 mL pouch, 25 minutes for 4 mL pouch, and 35 minutes for 10 mL pouch).
Quick thawing on the sterile field using a water bath: Transfer the inner pouch to the sterile field. Using a sterile water bath heated to a temperature of 33 to 37 degrees C, remove the prefilled syringe from the inner pouch, and place directly into the sterile bath ensuring that the entire contents of the prefilled syringe are completely underwater. Approximate thawing times with pouches removed by pack size are 5 minutes for 2 mL and 4 mL and 12 minutes for 10 mL.
Quick thawing off the sterile field using a water bath: Using a non-sterile water bath heated to a temperature of 33 to 37 degrees C, immerse the prefilled syringe in both pouches into the water ensuring that the entire contents of the prefilled syringe are completely underwater. Approximate thawing times in pouches by pack size are 30 minutes for 2 mL, 40 minutes for 4 mL, and 80 minutes for 10 mL. Once thawed, remove the pouches from the water bath; dry the external pouch, and transfer the inner pouch with the prefilled syringe onto the sterile field.
Quick thawing off the sterile field using an incubator: Using an incubator heated to a temperature of 33 to 37 degrees C, place the prefilled syringe in both pouches into the incubator. Approximate thawing times in pouches by pack size are 40 minutes for 2 mL, 85 minutes for 4 mL, and 105 minutes for 10 mL. Once thawed, remove from the incubator and transfer the inner pouch containing the prefilled syringe onto the sterile field.
Storage: Once warmed to 33 to 37 degrees C or if removed from the original pouch, the product must be used within 12 hours. Do not microwave, refrigerate, or refreeze.[41169]
Application
Apply Artiss using the Easyspray and Spray Set or an equivalent FDA-approved device.
To prevent adherence, wet gloves with normal saline before product contact.
Using a painting motion from side to side, apply a thin layer topically to dry wound surface.
The wound bed will glisten in the area where the fibrin sealant has been applied; any areas not covered by fibrin sealant will be readily visible.
Attach the skin graft immediately after the fibrin sealant has been sprayed. The surgeon has approximately 60 seconds to manipulate the graft before polymerization.
Hold the graft in the desired position with gentle compression for at least 3 minutes.
Use cannulas included with the Duploject Preparation and Administration System or Duo Set for small wounds or edges of a skin graft that did not adhere. Immediately before application, expel and discard the first several drops from the cannula.
For freeze-dried product, refer to Duploject Preparation and Administration System instructions.
For frozen product, use Duo Set. Insert plunger into syringe barrel. Connect the 2 syringe nozzles to the joining piece and secure by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. If application is interrupted, replace cannula immediately before resuming application.[41169]
 
Evicel
Evicel, the application device, and accessory tips should only be used by persons trained in laparoscopic, laparoscopic-assisted, endoscopic, or open surgical procedures.[41170]
Preparation
Thaw the 2 components (BAC2 and thrombin). Vials thaw within 1 day using temperatures of 2 to 8 degrees C (refrigerator); within 1 hour using temperatures of 20 to 25 degrees C (room temperature); or within 10 minutes using a temperature of 37 degrees C (warm water bath). Do not expose vials to 37 degrees C for more than 10 minutes, and do not exceed 37 degrees C.
While maintaining a sterile surgical field, draw the BAC2 and thrombin into the application device provided. Fill both syringes with equal volumes. The solutions should not contain air bubbles.
Carefully remove the vial assembly by rotating in the direction indicated by the arrows.
Storage: Once thawed, use within 30 days if refrigerated or within 24 hours if stored at room temperature. Do not refreeze after thawing, and do not refrigerate after storage at room temperature.[41170]
Application
Use standard surgical techniques for hemorrhage control, and dry surface areas of wounds before applying fibrin sealant.
Apply a thin film topically to the surface of bleeding tissue. If hemostatic effect is not complete, apply a second layer.
4 cm Control Tip by Drip Method with the Evicel Application Device: Bend tip to desired position. Keep the applicator tip as close as possible to tissue surface without touching the surface during application. Apply product to surface area to be treated, and pull back tip immediately after application. Control the coverage area by varying applied force on the plunger and tip distance from the tissue. If tip becomes clogged, wipe off or remove any visible clot using sterile gauze; do not trim the tip.
6 cm, 35 cm, and 45 cm Tips by Drip Method with the Evicel Application Device: Keep the applicator tip as close as possible to tissue surface without touching the surface during application. Apply individual drops to the surface area to be treated. Allow the drops to separate from each other and from the applicator tip. If tip becomes clogged, wipe off or remove any visible clot using sterile gauze or may cut it back in 0.5 cm increments for the 6 cm or 45 cm tips; do not trim the 35 cm tip.
6 cm, 35 cm, and 45 cm Tips by Spray Method with the Evicel Application Device: Use only with carbon dioxide as the gas. Connect the application device short gas tube to the Luer-lock end of the long gas hose. Connect the Luer-lock of the long gas hose with the 0.2-micron filter to a pressure regulator. For 6 cm, 35 cm, and 45 cm tips for spray use for open surgery, ensure 10 to 15 cm (4 to 6 inch) distance from target tissue and 20 to 25 psi (1.4 to 1.7 bar) spray pressure. For 35 cm and 45 cm tips for spray use for laparoscopic surgery, ensure 4 to 10 cm (1.6 to 4 inch) distance from target tissue and 15 to 20 psi (1 to 1.4 bar) and 20 to 25 psi (1.4 to 1.7 bar) spray pressure, respectively. Carefully monitor insufflation pressure in all laparoscopic/endoscopic procedures. Apply in short bursts (0.1 to 0.2 mL) onto the tissue to produce an even layer.
Airless Spray Accessory: No connection to external carbon dioxide source is possible. Once the spray accessory is firmly attached, do not depress plungers to prime device until intended use. Position the tip at least 2 cm away from the target tissue, and apply firm even pressure to the plunger to spray the fibrin sealant. Increase distance accordingly to achieve desired coverage of target area. After any pause in expression, replace the spray tip. Do not try and clear fibrin clot within the tip by depressing the plunger; the application device may become unusable.
Specific bleeding points may be visible through the fibrin sealant transparent layer, and these bleeding points may be sutured or electrocauterized through the fibrin sealant layer.[41170]
 
TachoSil
Preparation
When in the operating room, the outer aluminum foil pouch may be opened in a non-sterile environment. The inner sterile blister must be opened in a sterile environment.
Remove the patch from the blister. If needed, the blister can be used as a container for pre-moistening of the patch.
Determine the size of patch(es) to be applied to the bleeding surface. Select the appropriate 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.
Cleanse the area to be treated prior to application to remove disinfectants and other fluids. The sealer protein and thrombin solutions of TachoSil can be denatured by alcohol, iodine, or heavy metal ions found in antiseptics. If these substances have been used to clean the wound area, thoroughly rinse and dry prior to application of fibrin sealant.
Cleanse surgical instruments, gloves, and adjacent tissues with saline solution to reduce adherence to the fibrin sealant patch. The white, inactive side of the patch may also adhere to surgical instruments, gloves, and adjacent tissues covered with blood. Failure to adequately clean adjacent tissues may cause adhesions.
Application
Apply the yellow, active side of the fibrin sealant patch directly to the bleeding area either wet or dry. If applied wet, pre-moisten the patch in 0.9% Sodium Chloride Injection for no more than 1 minute and then apply immediately. In the case of a wet tissue surface, such as oozing bleeding, the patch may be applied without pre-moistening.
Hold patch in place with gentle pressure applied through moistened gloves or a moist pad for at least 3 minutes.
To avoid pulling the patch loose, place a pre-moistened surgical instrument at 1 end of the patch before relieving pressure. Alternatively, gentle irrigation may also be used to remove the pre-moistened pad or gloved hand without removing the patch from the bleeding area.
Leave the patch in place once it adheres to organ tissue. If not satisfied with patch placement, or if bleeding still occurs after the specified duration of compression, repeat application procedure; do not remove already applied fibrin sealant patch.
If more than 1 patch is needed, overlap patches by at least 1 cm.
Remove unattached patches (or part of) and replace with new.
For record-keeping purposes, the patient name and batch number should be recorded with every administration.
Storage: Once removed from inner patch, TachoSil cannot be resterilized; discard unused, opened packages.
 
Tisseel
Do not expose to temperatures above 37 degrees C during preparation.
The safety and effectiveness of the combined use of Tisseel with other biocompatible materials have not been evaluated.
The sealer protein and thrombin solutions of Tisseel are denatured by alcohol, iodine, or heavy metal ions found in antiseptics. Do not use iodine or heavy metal containing preparations (e.g., Betadine) for disinfection of vial stoppers; allow alcohol-based disinfectants to evaporate before puncturing the stopper. If these substances have been used to clean the wound area, thoroughly rinse and dry prior to application of fibrin sealant.[41172]
Preparation (freeze-dried kit)
Place all 4 vials from the kit into pre-warmed wells of the Fibrinotherm, and allow the vials to warm for up to 5 minutes; room temperature product may take less time.
Use separate syringes for reconstituting the sealer protein and thrombin solutions and for application to prevent premature clotting.
Remove the caps from the sealer protein concentrate and the fibrinolysis inhibitor solution vials.
Using Duploject or an equivalent FDA-approved device, transfer the fibrinolysis inhibitor solution into the vial containing the sealer protein concentrate. Gently swirl the vial to ensure the freeze-dried material is completely soaked.
Place the vial into the largest opening of the Fibrinotherm, and allow the vial contents to stir until all sealer protein concentrate is dissolved. Reconstitution is complete once no undissolved particles are visible and the solution appears homogeneous. If the particles do not dissolve within 20 minutes, discard the vial and use a new kit. If not used promptly, keep the solution at 37 degrees C without stirring. To ensure homogeneity, switch on the Fibrinotherm stirrer shortly before drawing up the solution.
Remove the caps from the vials containing thrombin and calcium chloride solutions.
Using Duploject or an equivalent FDA-approved device, transfer the calcium chloride solution into the thrombin vial and gently swirl.
Place the vial into the Fibrinotherm. Reconstitution is complete once all the concentrate is dissolved. Keep the solution at 37 degrees C until used.
When transferring the sealer protein solution and the thrombin solution to the sterile field, the circulating nurse should hold the non-sterile vials while the scrub nurse withdraws the solutions slowly by firm constant aspiration to reduce the risk of large air bubbles.
Storage: After reconstitution, the product must be used within 4 hours. Do not microwave, refrigerate, or refreeze.[41172]
Preparation (prefilled-frozen syringes)
Do not use unless it is completely thawed and warmed to a liquid consistency. Do not remove the protective syringe cap until use.
Room temperature thawing: Unopened pouches may be stored for up to 48 hours at room temperature (15 to 25 degrees C). Approximate thawing times in pouches by pack size are 80 and 60 minutes for 2 mL, 90 and 110 minutes for 4 mL, and 160 and 160 minutes for 10 mL, in the PRIMA and AST syringe, respectively. When product is thawed, warm to 33 to 37 degrees C prior to use, and use immediately. Total thawing and warming time cannot exceed 48 hours.
Quick thawing on the sterile field using a water bath: Transfer the inner pouch to the sterile field. Using a sterile water bath heated to a temperature of 33 to 37 degrees C, remove the prefilled syringe from the inner pouch, and place directly into the sterile bath ensuring that the entire contents of the prefilled syringe are completely under water. Approximate thawing times with pouches removed by pack size are 5 minutes for 2 mL and 4 mL and 10 to 12 minutes for 10 mL.
Quick thawing off the sterile field using a water bath: Using a non-sterile water bath heated to a temperature of 33 to 37 degrees C, immerse the prefilled syringe in both pouches into the water ensuring that the entire contents of the prefilled syringe are completely underwater. Approximate thawing times in pouches by pack size are 15 and 30 minutes for 2 mL, 20 and 40 minutes for 4 mL, and 35 and 80 minutes for 10 mL, in the PRIMA and AST syringe, respectively. Once thawed, remove the pouches from the water bath; dry the external pouch, and transfer the inner pouch with the prefilled syringe onto the sterile field.
Quick thawing off the sterile field using an incubator: Using an incubator heated to a temperature of 33 to 37 degrees C, place the prefilled syringe in both pouches into the incubator. Approximate thawing times in pouches by pack size are 40 and 40 minutes for 2 mL, 50 and 85 minutes for 4 mL, and 90 and 105 minutes for 10 mL, in the PRIMA and AST syringe, respectively. Once thawed, remove from the incubator and transfer the inner pouch containing the prefilled syringe onto the sterile field.
Storage: Once warmed to 33 to 37 degrees C or if removed from the original pouch, the product must be used within 4 hours. Do not microwave, refrigerate, or refreeze.[41172]
Application
Spray only onto application sites that are visible.
Dry wound surface using standard techniques (e.g., intermittent compress, swabs, use of suction devices) prior to application; do not use pressurized air or gas to dry the site.
If small volumes (1 to 2 drops) are required, expel and discard the first several drops from the application cannula immediately prior to application to ensure administration of adequately mixed fibrin sealant.
Apply a thin layer sufficient to entirely cover the intended application area. Allow at least 2 minutes after application to achieve sufficient polymerization. Avoid application beyond the intended area. If repeat application is required, dry the site as much as possible before reapplying. Reapply after removing residues from the prior application or before polymerization takes place since fibrin sealant may not adhere to polymerized layer.
For freeze-dried product, use the Duploject Preparation and Application System or an equivalent FDA-approved delivery device to apply Tisseel. Refer to delivery device instructions.
For frozen product, use DUO Set (AST syringe) or Duploject Combi (PRIMA syringe) to apply Tisseel.
For the DUO Set, insert plunger into syringe barrel and remove all air from the double chamber syringe. Connect the 2 syringe nozzles to the joining piece and secure by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.
For the Duploject Combi, the plunger is already attached to the syringe. Remove all air from the double chamber syringe. Connect the 2 syringe nozzles to the joining piece and secure by fastening the tether strap to the syringe. Fit an application cannula to the joining piece. Apply by depressing plunger.
If application is interrupted in either device, replace cannula immediately before resuming application.[41172]
 
Raplixa
Do not reconstitute.
Storage: Use within 1 hour of opening.[61539]
Preparation
Remove vial from pouch following standard sterile technique to ensure that the vial and surgical field remain sterile.
Ensure powder is at the bottom of the vial.
Remove flip-off top, leaving stopper in place until immediately before use.
Prepare sterile gelatin sponge by trimming to appropriate size for bleeding site.[61539]
Application (direct) with absorbable gelatin sponge
Remove stopper and sprinkle a uniform coating gently onto bleeding site and apply gentle pressure with gelatin sponge using sterile gauze. Alternately, sprinkle thin layer onto a pre-moistened gelatin sponge and place onto the bleeding site with gentle pressure using the sterile gauze.[61539]
Application using the RaplixaSpray device with absorbable gelatin sponge
Prepare the pressure regulator according to manufacturer's instructions for use.
To attach the vial to the RaplixaSpray device, invert the device and place the upright vial into the gray rubber ring on the device. Turn the device upright and return the device to the sterile field for use.
Activate air or gas flow. Check that the pressure is 22 psi (1.5 bar). Do not push button until ready for use.
Ensure the vial is kept within 45 degrees of vertical at all times.
Hold nozzle at a minimum distance of 5 cm from the bleeding site.
Start application by gently pressing the operating button. Powder should cover the bleeding surface as a uniform thin coating. Apply within 10 to 60 seconds.
Immediately after application, place a gelatin sponge on top of the powder. The gelatin sponge may be used dry or moistened with sterile saline. A moistened sponge molds more easily to irregularly-shaped and contoured bleeding areas. Hold the gelatin sponge in place with manual pressure using sterile gauze.
Hold the device upside down and carefully remove the empty vial. If needed, attach the second vial.
Use no more than 2 vials with the RaplixaSpray device. If a third vial is needed, use a new RaplixaSpray device.[61539]
Vistaseal
Preparation
Remove carton from freezer and take out the 2 blisters.
Room temperature thawing (preferred)
Place the blister containing the syringe holder with pre-filled syringes on a surface at room temperature:
For the 2 mL and 4mL package sizes, thaw for approximately 70 minutes
For the 6 mL and 10 mL package sizes, thaw for approximately 90 minutes
Storage: After thawing, store for no more than 24 hours at room temperature (20 to 25 degrees C [68 to 77 degrees F]) or 48 hours in the refrigerator (2 to 8 degrees C [36 to 46 degrees F]). Use immediately once blisters are opened. Discard any unused contents. Do not re-freeze after thawing.
To transfer to a sterile field, open the blister and make the syringe holder with pre-filled syringes available to a second person in the sterile field. The outside of the blister should not come into contact with the sterile field.
Sterile water bath (quick thawing)
Open the blister and make the syringe holder with pre-filled syringes available to a second person in the sterile field. The outside of the blister should not come into contact with the sterile field.
Place the syringe holder wither with pre-filled syringes directly into a sterile thermostatic water bath at a temperature no higher than 37 degrees C (99 degrees F). Ensure it is fully immersed in the water.
For the 2, 4, 6, and 10 mL package sizes, thaw time is approximately 5 minutes.
Do not leave in the water bath for more than 10 minutes.
Use a sterile surgical gauze to dry the syringe holder with pre-filled syringes.
Storage: Use immediately. Discard any unused contents.
Connect inside the sterile field, hold the syringe holder with syringe luer caps pointed upward.
Unscrew and discard luer caps on both the fibrinogen and thrombin syringes.
Gently strike the side of the syringe holder 1 to 2 times to remove air bubbles. Lightly depress the plunger to eject air.
Attach the dual applicator. Do not depress the plunger during attachment or prior to intended use. If this occurs, a fibrin clot will form and prevent dispensing.
Tighten luer locks and ensure applicator is firmly attached.
Application
Apply with the Dual Applicator provided. Applicator tips cleared by the FDA for specific use with Vistaseal may also be used.
Cover and protect parts of the body outside the intended application area to prevent tissue adhesion at unintended sites.
Use standard techniques to dry the surface area of the target bleeding site.
Spray application
Grasp and bend the Dual Applicator to the desired position. The tip will retain its shape.
Position the tip at least 2 cm away from the target tissue.
Apply firm even pressure to the plunger.
Increase distance as needed to achieve desired coverage of the target area.
If expression is stopped for any reason, change the Airless Spray Tip.
Remove device from the patient and unscrew the used tip.
Wipe the end of the applicator using dry or moist sterile surgical gauze.
Connect a new Airless Spray Tip and ensure firm connection. The red indicator will not be visible if it is properly connected.
Do not continue to push the plunger to clear a fibrin clot within the tip.
Do not trim the Dual Applicator to avoid exposing internal wire.
Drip application
Remove the Airless Spray Tip and drip tip by unscrewing the Airless Spray Tip.
Grasp and bend the drip tip to the desired position. The tip will retain its shape.
Keep the end of the drip tip as close to the tissue surface as possible without touching the tissue during application.
Apply individual drops to the surface area to be treated. Allow the drops to separate from each other and from the end of the drip tip to prevent uncontrolled clotting.
Do not reconnect a used drip tip after it has been removed from the adapter.

pulmonary embolism / Delayed / 1.0-1.0
thrombosis / Delayed / 1.0-1.0
ileus / Delayed / 1.0-1.0
cardiac arrest / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
bradycardia / Rapid / Incidence not known
pleural effusion / Delayed / Incidence not known
laryngeal edema / Rapid / Incidence not known
GI obstruction / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
air embolism / Rapid / Incidence not known

constipation / Delayed / 15.0-24.0
anemia / Delayed / 0.5-23.0
elevated hepatic enzymes / Delayed / 1.0-11.0
hypotension / Rapid / 2.0-8.0
hypertension / Early / 1.0-5.0
hyponatremia / Delayed / 1.0-1.0
hypocalcemia / Delayed / 1.0-1.0
hypokalemia / Delayed / 1.0-1.0
urinary retention / Early / 1.0-1.0
peripheral edema / Delayed / 0.5-0.5
ascites / Delayed / 1.0
hypophosphatemia / Delayed / 1.0
sinus tachycardia / Rapid / Incidence not known
edema / Delayed / Incidence not known
erythema / Early / Incidence not known
eosinophilia / Delayed / Incidence not known
wheezing / Rapid / Incidence not known
dyspnea / Early / Incidence not known
bleeding / Early / Incidence not known

nausea / Early / 1.0-30.0
diarrhea / Early / 17.0-17.0
vomiting / Early / 5.0-13.0
fever / Early / 1.0-8.0
pruritus / Rapid / 2.0-2.0
headache / Early / 1.0-1.0
insomnia / Early / 1.0-1.0
abdominal pain / Early / 1.0
leukocytosis / Delayed / 1.0
infection / Delayed / 1.0
lethargy / Early / Incidence not known
urticaria / Rapid / Incidence not known
chills / Rapid / Incidence not known
paresthesias / Delayed / Incidence not known
skin irritation / Early / Incidence not known
restlessness / Early / Incidence not known
flushing / Rapid / Incidence not known
mydriasis / Early / Incidence not known

ARTISS, TachoSil Absorbable Fibrin Sealant, TISSEEL

Rx

Human plasma-derived, fibrinogen and thrombin sealant
Used to promote the adherence of autologous skin grafts to burn wounds, for hemostasis of surgical bleeding, and for colonic anastomoses leakage prophylaxis
For topical use only

Apply a thin layer topically to the dry, surgically prepared wound surface. Approximate surface areas covered by each package size are 100 cm2 for the 2 mL package, 200 cm2 for the 4 mL package, and 500 cm2 for the 10 mL package. Immediately position the skin graft after application of the sealant.

Apply a thin layer topically to the surface of the bleeding tissue. If hemostatic effect is not complete, apply a second layer. Approximate surface areas covered by each package size are 20 cm2 for 2 mL package, 40 cm2 for 4 mL package, and 100 cm2 for 10 mL package.

Apply a thin layer topically to the surface of the bleeding tissue. If hemostatic effect is not complete, apply a second layer. Approximate surface areas covered by each package size are 20 cm2 for 2 mL package, 40 cm2 for 4 mL package, and 100 cm2 for 10 mL package.

Apply a thin layer topically to the surface of the bleeding tissue. Approximate surface areas covered by each package size for vial and spray device, respectively, are 25 cm2 and 50 cm2 for 0.5 g package, 50 cm2 and 100 cm2 for 1 g package, and 100 cm2 and 200 cm2 for 2 g package. In clinical trials, 0.5 to 1 g was used for smaller bleeding sites covering an area of less than 10 cm2, and 1 to 2 g were used for larger bleeding sites covering an area of 10 to 100 cm2. The maximum total dose per surgery is 3 g.

Apply the yellow, active site of the patch to the bleeding area. Determine the number of patches to be applied by the size of the bleeding area. Select the appropriate patch so that it extends 1 to 2 cm beyond the margins of the wound. Use the minimum number of patches necessary to achieve hemostasis. The maximum numbers of patches to be applied by patch size are 10 patches for 3.7 inch by 1.9 inch, 14 patches for 1.9 inch by 1.9 inch, and 42 patches for 1.2 inch by 1 inch. TachoSil is specifically FDA-approved for use with manual compression in cardiovascular or hepatic surgery.

Apply the yellow, active site of the patch to the bleeding area. Determine the number of patches to be applied by the size of the bleeding area. Select the appropriate patch so that it extends 1 to 2 cm beyond the margins of the wound. Use the minimum number of patches necessary to achieve hemostasis. The maximum numbers of patches to be applied by patch size are 10 patches for 3.7 inch by 1.9 inch, 14 patches for 1.9 inch by 1.9 inch, and 42 patches for 1.2 inch by 1 inch. TachoSil is specifically FDA-approved for use with manual compression in cardiovascular or hepatic surgery.

Apply a thin layer topically to the wound surface. Approximate surface areas covered by each package size for cannula and compressed gas, respectively, are 8 cm2 and 100 cm2 for 2 mL package, 16 cm2 and 200 cm2 for 4 mL package, and 40 cm2 and 500 cm2 for 10 mL package. The application can be repeated, if needed.[41172]

Apply a thin layer topically to the wound surface. Approximate surface areas covered by each package size for cannula and compressed gas, respectively, are 8 cm2 and 100 cm2 for 2 mL package, 16 cm2 and 200 cm2 for 4 mL package, and 40 cm2 and 500 cm2 for 10 mL package. The application can be repeated, if needed.[41172]

Apply a thin layer topically to the wound surface. Approximate surface areas covered by each package size, respectively, are 16 to 22 cm2 for the 2 mL package, 32 to 44 cm2 for the 4 mL package, 48 to 66 cm2 for the 6 mL package, and 80 to 110 cm2 for the 10 mL package. The application can be repeated, if needed.

Apply a thin layer topically to the surface of the wound surface. Approximate surface areas covered by each package size for cannula and compressed gas, respectively, are 8 cm2 and 100 cm2 for 2 mL, 16 cm2 and 200 cm2 for 4 mL, and 40 cm2 and 500 cm2 for 10 mL. The application can be repeated, if needed.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Povidone-Iodine: (Moderate) If povidone-iodine has been used to clean the wound area, thoroughly rinse and dry prior to application of fibrin sealant. The sealer protein and thrombin solutions of Artiss, TachoSil, and Tisseel can be denatured by povidone-iodine.

ARTISS/TISSEEL Topical Sol: 1mL, 3000-40-90-500IU, 90-4U, 90-500-3000-40umole, 90-500-3000-40mMole
Raplixa Topical Pwd: 1g, 79-699IU
TachoSil Absorbable Fibrin Sealant Transdermal Film: 35.5-12.9U
TISSEEL Topical Pwd F/Recon: 1mL, 3000-40-90-500IU

Artiss, Evicel, Tisseel, and Vistaseal: Maximum dosage not specified.
Raplixa: 3 g.
TachoSil: 10 patches for 3.7 inch by 1.9 inch, 14 patches for 1.9 inch by 1.9 inch, and 42 patches for 1.2 inch by 1 inch.

Artiss, Evicel, Tisseel, and Vistaseal: Maximum dosage not specified.
Raplixa: 3 g.
TachoSil: 10 patches for 3.7 inch by 1.9 inch, 14 patches for 1.9 inch by 1.9 inch, and 42 patches for 1.2 inch by 1 inch.

Artiss, Raplixa, and Vistaseal: Safety and efficacy have not been established.
Evicel and Tisseel: Maximum dosage not specified.
TachoSil: 10 patches for 3.7 inch by 1.9 inch, 14 patches for 1.9 inch by 1.9 inch, and 42 patches for 1.2 inch by 1 inch.

Artiss, Raplixa, and Vistaseal: Safety and efficacy have not been established.
Evicel and Tisseel: Maximum dosage not specified.
TachoSil: 10 patches for 3.7 inch by 1.9 inch, 14 patches for 1.9 inch by 1.9 inch, and 42 patches for 1.2 inch by 1 inch.

Artiss, Raplixa, and Vistaseal: Safety and efficacy have not been established.
Evicel: Maximum dosage not specified for infants older than 6 months. Safety and efficacy have not been established for infants 6 months and younger.
TachoSil: 10 patches for 3.7 inch by 1.9 inch, 14 patches for 1.9 inch by 1.9 inch, and 42 patches for 1.2 inch by 1 inch.
Tisseel: Maximum dosage not specified.

Safety and efficacy have not been established.

The fibrin sealant system initiates the last phase of physiological blood coagulation. Thrombin activates the conversion of fibrinogen into fibrin, which occurs by splitting fibrinogen into fibrinogen monomers and fibrinopeptides. The fibrinogen monomers polymerize and form a fibrin clot. Factor XIIIa, which is activated from Factor XIII by thrombin, crosslinks fibrin. Hemostasis or sealing of tissues is achieved when the formed fibrin clot adheres to the wound surface. Artiss and Tisseel also contain aprotinin, which has been shown to increase resistance of the fibrin sealant clot to degradation in a fibrinolytic environment.

Fibrin sealant, human is applied topically. In general, systemic exposure or distribution to other organs or tissues is not expected. Fibrin sealant is metabolized by fibrinolysis and phagocytosis. With wound healing, increased fibrinolytic activity is induced by plasmin and fibrin decompensation to fibrin degradation products occurs.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

In rabbit studies of thrombin applied to the cut surface of the liver, slow absorption of biologically inactive peptides resulting from the breakdown of thrombin occurred. Cmax was reached in 6 to 8 hours, and at the Cmax, the plasma concentration represented only 1% to 2% of the applied dose. The systemic exposure to thrombin when it is applied directly to a hepatic wound was estimated to be approximately equivalent to that generated by minor bleeding.

There are no data with fibrin sealant, human in pregnant women to inform a drug-associated risk. It is not known if fibrin sealant, human can cause fetal harm when administered during pregnancy or can affect reproductive capacity. Animal reproduction studies have not been conducted with fibrin sealant, human. Because fibrin sealant, human is made from human plasma, it may carry a risk of transmitting infectious agents (e.g., viruses). Some viruses, such as parvovirus B19, are difficult to remove or inactivate. Parvovirus B19 seriously affects pregnant woman (fetal infection). Fibrin sealant, human should only be used during pregnancy if clearly needed.

There is no information regarding the presence of fibrin sealant, human in human milk, the effect on the breast-fed infant, or the effects on milk production. Because many drugs are excreted in human milk, use caution when administering fibrin sealant, human to a breast-feeding woman. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for fibrin sealant, human and any potential adverse effects on the breast-fed infant from fibrin sealant, human or the underlying maternal condition.