ARTISS Solutions for sealant Ref.[4781] Active ingredients: Aprotinin Calcium chloride Human fibrinogen Thrombin

ARTISS is intended for hospital use only. The use of ARTISS is restricted to experienced surgeons who have been trained in the use of ARTISS.

Posology

The amount of ARTISS to be applied and the frequency of application should always be oriented towards the underlying clinical needs of the patient.

The dose to be applied is governed by variables including, but not limited to, the type of surgical intervention, the size of the area and the mode of intended application, and the number of applications.

Application of the product must be individualized by the treating physician. In clinical trials, the individual dosages have typically ranged from 0.2-12 ml. For some procedures (e.g. the sealing of large burned surfaces), larger volumes may be required.

The initial amount of the product to be applied at a chosen anatomic site or target surface area should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary, to any small areas that may have not been previously treated. However, avoid reapplication of ARTISS to a pre-existing polymerized ARTISS layer as ARTISS will not adhere to a polymerized layer.

It is recommended that the initial application covers the entire intended application area.

As a guideline for the gluing of surfaces, 1 pack of ARTISS 2 ml (i.e., 1 ml Sealer Protein Solution plus 1 ml Thrombin Solution) will be sufficient for an area of at least 10 cm².

The skin graft should be attached to the wound bed immediately after ARTISS has been applied. The surgeon has up to 60 seconds to manipulate and position the graft prior to polymerization. After the flap or graft has been positioned, hold in the desired position by gentle compression for at least 3 minutes to ensure ARTISS sets properly and the graft or flap adheres firmly to the underlying tissue.

To avoid the formation of excess granulation tissue and to ensure gradual absorption of the solidified fibrin sealant, only a thin layer of the mixed Sealer Protein – Thrombin Solution should be applied.

ARTISS has not been administered to patients > 65 years old in clinical trials.

Paediatric Population

Currently available data are described in section 5.1 but no recommendation on a posology can be made.

Method of administration

For epilesional (topical) use. Do not inject.

For subcutaneous use only. ARTISS is not recommended for laparoscopic surgery.

In order to ensure optimal safe use of ARTISS it should be sprayed using a pressure regulator device that delivers a maximum pressure of up to 2.0 bar (28.5 psi).

Prior to applying ARTISS the surface area of the wound needs to be dried by standard techniques (e.g. intermittent application of compresses, swabs, use of suction devices).

ARTISS should only be reconstituted and administered according to the instructions and with the devices recommended for this product (see section 6.6).

For spray application, see sections 4.4 and 6.6 for specific recommendations on the required pressure and distance from tissue per surgical procedure and length of applicator tips.

No case of overdose has been reported.

Shelf life: 2 years.

Store and transport frozen (at ≤ -20°C).

Keep the syringe in the outer carton in order to protect from light.

Unopened pouches, thawed at room temperature, may be stored for up to 14 days at controlled room temperature (not exceeding +25°C). Do not refreeze or refrigerate after thawing.

1 ml, 2 ml, or 5 ml of sealer protein solution and 1, 2 or 5 ml of Thrombin Solution in a single-use double-chamber syringe (polypropylene) with a tip-cap in a bag, and one device set with one double syringe plunger, 2 joining pieces and 4 application cannulae.

Pack size of 1 (1 × 1 ml + 1 ml, 1 × 2 ml + 2 ml, 1 × 5 ml + 5 ml)

Both Sealer Protein Solution and Thrombin Solution are contained in a single-use double-chamber syringe made of polypropylene.

Not all pack sizes may be marketed.

Other accessories for application of the product can be obtained from BAXTER.

General

To prevent ARTISS from adhering to gloves and instruments, wet these with sodium chloride solution before contact.

As a guideline for the gluing of surfaces, 1 pack of ARTISS 2 ml (i.e., 1 ml Sealer Protein Solution plus 1 ml Thrombin Solution) will be sufficient for an area of at least 10 cm².

The required dose of ARTISS depends on the size of the surface to be covered.

Handling and Preparation

The inner bag and its contents are sterile unless the integrity of the outside package is compromised.

It is recommended to thaw and warm the two sealant components using a sterile water bath at a temperature of 33 – 37°C. The water bath must not exceed a temperature of 37°C. (In order to control the specified temperature range, the water temperature should be monitored using a thermometer and the water should be changed as necessary. When using a sterile water bath for thawing and warming, the pre-filled double chamber syringe assembly should be removed from the aluminum-coated plastic bags.)

The protective syringe cap should not be removed until thawing is complete and the joining piece is ready to be attached. Do not use ARTISS unless it is completely thawed and warmed (liquid consistency).

Thaw pre-filled syringes using one of the following options:

1. Room Temperature Thawing (not exceeding +25°C):

The product can be thawed at room temperature. Times given in Table 1 are minimum times for thawing at room temperature. The maximum time the product can be kept (in both aluminum-coated plastic bags) at room temperature is 14 days.

When thawing at room temperature, the product must be additionally warmed to 33°C – 37°C in an incubator just before use. Respective warming times in the incubator are also given in Table 1.

Table 1: Thawing times at Room Temperature (= RT) followed by additional warming, prior to use, in an Incubator at 33°C to a maximum of 37°C

Once ARTISS has been warmed up to 33 – 37°C the product may be stored for up to 4 hours.

2. Quick Thawing:

Table 2: Thawing and Warming Times with Sterile Water Bath at 33°C to a maximum of 37°C

Transfer plunger and the inner pouch to the sterile field, remove prefilled syringe from inner pouch and place directly into sterile water bath. Ensure the contents of the prefilled syringe are completely immersed in water.

A third alternative is to thaw the product off the sterile field using a non-sterile water bath.

Maintain the prefilled syringe in both pouches and place into a water bath off the sterile field for an appropriate time (see Table 3). Ensure the pouches remain submerged throughout thawing. Remove from the water bath after thawing, dry external pouch and transfer inner pouch with prefilled syringe and plunger to the sterile field.

Table 3: Thawing and Warming times off the Sterile Field with Non-Sterile Water Bath at 33°C to a maximum of 37°C

Alternatively, the sealant components may be thawed and warmed in an incubator between 33°C and 37°C. The thawing and warming times in the incubator are indicated in Table 4 below. The times refer to product in the aluminum-coated plastic bags.

Table 4: Thawing and Warming Times in Incubator at 33°C to a maximum of 37°C

Note:

Do not thaw by holding product in your hands.

Do not microwave.

After thawing do not refrigerate or refreeze.

After Quick Thawing (i.e. thawing at a temperature of 33 – 37°C) ARTISS may be stored at 33 – 37°C for a maximum of 4 hours.

To facilitate optimal blending of the two solutions, the two sealant components must be warmed to 33 – 37°C immediately before use. (The temperature of 37°C must, however, not be exceeded!)

The Sealer Protein and the Thrombin Solutions should be clear or slightly opalescent. Do not use solutions that are cloudy or have deposits. Thawed products should be inspected visually for particulate matter and discoloration prior to administration or any variation in physical appearance. In the event of either being observed, discard the solution.

The thawed Sealer Protein Solution should be a slightly viscous liquid. If the solution has the consistency of a solidified gel, it must be assumed to have become denatured (e.g., due to an interruption of the cold storage chain or by overheating during warming). In this case, ARTISS must not be used.

Unopened pouches, thawed at room temperature, may be stored for up to 14 days at controlled room temperature (not exceeding +25°C). If not used within 14 days after thawing, ARTISS has to be discarded.

The protective syringe cap should not be removed until thawing is complete and the joining piece is ready to be attached. Do not use ARTISS unless it is completely thawed and warmed (liquid consistency).

For further preparation instructions please refer to the responsible nurse or medical doctor.

ADMINISTRATION

For application, the double-chamber syringe with the Sealer Protein Solution and the Thrombin Solution has to be connected to a joining piece and an application cannula as provided in the accompanying set of devices. The common plunger of the double-chamber syringe ensures that equal volumes are fed through the joining piece before being mixed in the application cannula and ejected.

Operating Instructions

• Connect the nozzles of the double-chamber syringe to the joining piece ensuring that they are firmly fixed. Secure the joining piece by fastening the tether strap to the double-chamber syringe. If the tether strap tears, use the spare joining piece. If none is available, further use is still possible but tightness of the connection needs to be ensured to prevent any risk of leaking.
• Fit an application cannula onto the joining piece.
• Do not expel the air remaining inside the joining piece or application cannula until you start actual application as the aperture of the cannula may clog otherwise.
• Immediately before application expel and discard the first several drops from the application cannula to ensure adequately mixed product
• Apply the mixed Sealer Protein – Thrombin Solution onto the recipient surface or surfaces of the parts to be sealed.

If application of the fibrin sealant components is interrupted, clogging may occur in the cannula. Replace the application cannula with a new one only immediately before application is resumed. If the apertures of the joining piece are clogged, use the spare joining piece provided in the package.

Application is also possible with other accessories supplied by BAXTER that are particularly suited for, e.g. minimally invasive surgery, application to large or difficult-to-access areas. When using these application devices, strictly follow the Instructions for Use of the devices.

Spray application

When applying ARTISS using a spray device be sure to use a pressure and a distance from tissue within the ranges recommended by the manufacturer as follows:

When spraying the ARTISS, changes in blood pressure, pulse, oxygen saturation and end tidal CO2 should be monitored because of the possibility of occurrence of air or gas embolism (see sections 4.2 and 4.4).

Disposal

Any unused product or waste material should be disposed of in accordance with local requirements.