Data from FDA - Curated by Toby Galbraith - Last updated 18 April 2017

Licensing authority

FDA (Food and Drug Administration, USA)

Indication(s)

1 INDICATIONS AND USAGE ARTISS is indicated to adhere autologous skin grafts to surgically prepared wound beds resulting from burns in adult and pediatric populations greater than or equal to 1 year of age.

ARTISS is not indicated for hemostasis.

ARTISS is indicated to adhere autologous skin grafts to surgically prepared wound beds resulting from burns in adult and pediatric populations greater than or equal to 1 year of age (1) ARTISS is not indicated for hemostasis (1)

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Transplantation

See information on best practice in solid organ transplantation, and expert discussions on related hot topics.

Visit Transplantation

Fluid Management

Are you up-to-date with the latest evidence of effective procedures for fluid management?

Visit Fluid Management

Related Content

Advisory information

contraindications

4 CONTRAINDICATIONS Do not inject directly into the circulatory system (4.1) Do not use in individuals with a known hypersensitivity to aprotinin (4.2, 5.1, 6.1) 4.1 Intravascular Application Do not inject ARTISS directly into blood vessels.

Intravascular application of ARTISS may result in life-threatening thromboembolic events.

4.2 Aprotinin Hypersensitivity Do not use ARTISS in individuals with a known hypersensitivity to aprotinin and/or hypersensitivity to any of the active substances or excipients (see WARNINGS/PRECAUTIONS, Hypersensitivity/Allergic/Anaphylactic Reactions (5.1) and ADVERSE REACTIONS, Overall Adverse Reactions (6.1)).

Adverse reactions

6 ADVERSE REACTIONS Adverse reactions occurring in greater than 1 % of patients treated with ARTISS were skin graft failure and pruritus (6.1, 6.2) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare Corporation at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Overall Adverse Reactions Adverse reactions occurring in greater than 1 % of patients treated with ARTISS were skin graft failure and pruritus.

Hypersensitivity/Allergic/Anaphylactic Reactions: Hypersensitivity or allergic/anaphylactoid reactions may occur (see WARNINGS/PRECAUTIONS, Hypersensitivity/Allergic/Anaphylactic Reactions (5.1)).

No adverse events of this type were reported during clinical trials.

6.2 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug can not be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse reactions have been reported from a clinical trial where ARTISS was used to affix split thickness sheet skin grafts to excised burn wounds (see CLINICAL STUDIES (14)).

A total of 8 non-serious adverse reactions were deemed related to the use of ARTISS by the investigator.

Of the 8 related non-serious adverse reactions, 5 were incidences of skin graft failure: 4 were graft detachment/non-adherence and 1 was graft necrosis.

The graft detachment in 2 patients may have been related to the maximum thawing temperature (40°C) being exceeded during study product preparation.

The 3 other non-serious adverse reactions considered related to ARTISS were 2 incidences of pruritus and 1 incidence of dermal cyst.

The graft necrosis and the 2 cases of pruritus considered related to ARTISS each had an equivalent adverse reaction with the exact start date and severity reported at a control wound where skin grafts were affixed with staples.

Therefore, these events are most likely not related to ARTISS, but instead are expected outcomes for any grafted wound regardless of the method of attachment.

Overall, the data collected and analyzed during this study demonstrated that ARTISS is safe for the attachment of sheet skin grafts in subjects with deep partial thickness or full thickness burn wounds.

The adverse reactions and their frequencies are summarized in Table 2: Table 2.

Adverse reactions (Preferred Term) Number of events/Number of patients treated Dermal cyst 1/138 Pruritus 2/138 Skin graft failure 5/138 6.3 Post Marketing The following adverse reactions reflect what has been reported in post marketing experience with Baxter 's fibrin sealant that could reasonably be expected to occur with ARTISS: Immune system disorders: anaphylactic responses, hypersensitivity Cardiac disorders: bradycardia, tachycardia Respiratory, thoracic and mediastinal disorders: dyspnea Gastrointestinal disorders: nausea Skin and subcutaneous tissue disorders: urticaria

General disorders and administration site conditions: flushing, impaired healing, edema, pyrexia Injury, poisoning and procedural complication: seroma Air embolism associated with misapplication of fibrin sealant using the spray device, Class Effect: A postmarketing fatality was reported in association with the use of another fibrin sealant when applied using a spray device.

The case involved an attempt to stop active bleeding by applying the fibrin sealant using a spray device attached to a wall unit at a higher than recommended pressure for the spray device.

In addition, the spray head was placed at a distance from the bleeding site that was closer than the recommended distance guidelines for the application of the sealant.

The patient suffered a fatal air embolism.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Usage information

Dosing and administration

2 DOSAGE AND ADMINISTRATION FOR TOPICAL USE ONLY - DO NOT INJECT.

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

The approximate surface areas covered by each package size of ARTISS are: Table 1.

Approximate area requiring skin graft fixation Required package size of ARTISS 100 cm2 2 mL 200 cm2 4 mL 500 cm2 10 mL It is recommended that every time a patient receives a dose of ARTISS the name and lot number (batch number) of the product are documented in order to maintain a record of the batches used.

For Topical Use Only.

Do Not Inject (2).

Apply on surface of prepared wound beds only (2.3) ARTISS Kit (Freeze-Dried) requires reconstitution prior to use (2.1) ARTISS Pre-filled Syringe (Frozen) requires thawing prior to use (2.2) Apply as a thin layer using the Easyspray and Spray Set (2.3, 5.2) Dosage: 2 mL will cover approximately 100 cm2 surface area (2) Vials and pre-filled syringes are for single use only.

Discard unused contents (2.3) 2.1 Preparation of ARTISS Kit (Freeze-Dried) During preparation of ARTISS Kit: DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C DO NOT REFRIGERATE OR FREEZE AFTER RECONSTITUTION Do not use iodine or heavy metal containing preparations such as betadine for disinfection of vial stoppers.

Allow alcohol-based disinfectants to evaporate before puncturing stopper.

After reconstitution, the product must be used within 4 hours.

Use separate syringes for reconstituting Sealer Protein and Thrombin solutions and for application to prevent premature clotting.

ARTISS Kit contains the following substances in four separate vials: -Sealer Protein Concentrate (Human) -Fibrinolysis Inhibitor Solution (Synthetic) -Thrombin (Human) -Calcium Chloride Solution Freeze-dried Sealer Protein Concentrate and Thrombin are reconstituted in Fibrinolysis Inhibitor Solution and Calcium Chloride Solution, respectively.

The Sealer Protein Solution and Thrombin Solution are then combined using the DUPLOJECT Preparation and

Application System, or an equivalent delivery device cleared by FDA for use with ARTISS to form the Fibrin Sealant.

Prewarming ARTISS Kit with FIBRINOTHERM If a FIBRINOTHERM device is not available, contact Baxter (1-800-423-2090) for assistance.

See FIBRINOTHERM manual for complete operating instructions.

Plug the FIBRINOTHERM Heating and Stirring Device into an electrical socket and activate the warmer (amber switch).

Ensure that the stirring mechanism of the FIBRINOTHERM device is initially switched off (green switch).

Place all four vials from the ARTISS Kit into the prewarmed wells of the FIBRINOTHERM, using the appropriately sized adapter rings, and allow the vials to warm for up to 5 minutes (room temperature product may take less time).

Preparation of Sealer Protein Solution with FIBRINOTHERM Remove the flip-off caps from the vial containing the Sealer Protein Concentrate and the vial containing the Fibrinolysis Inhibitor Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry.

Transfer the Fibrinolysis Inhibitor Solution into the vial containing the freeze-dried Sealer Protein Concentrate using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions).

Gently swirl the vial to ensure that the freeze-dried material is completely soaked.

Place the vial into the largest opening of the FIBRINOTHERM device with the appropriate adaptor.

Switch on the stirrer (green switch) and allow the vial contents to stir until all Sealer Protein Concentrate is dissolved.

Reconstitution of the freeze-dried Sealer Protein Concentrate is complete as soon as no undissolved particles are visible.

Otherwise, return the vial to the FIBRINOTHERM device and agitate for a few more minutes until the solution appears homogeneous.

Notes: Do not use the Sealer

Protein

Concentrate until it has fully dissolved.

If the Sealer Protein Concentrate has not dissolved within 20 minutes using the FIBRINOTHERM device, discard the vial and prepare a fresh kit.

Excessive stirring (20 minutes or more) may compromise product quality.

If not used promptly, keep the Sealer Protein Solution at 37°C without stirring.

To ensure homogeneity, switch on the stirrer of the FIBRINOTHERM device shortly before drawing up the solution.

Preparation of Thrombin Solution with FIBRINOTHERM Remove the flip-off caps from the vial containing Thrombin and the vial containing Calcium Chloride Solution, disinfect the rubber stoppers of both vials with a germicidal solution and allow to dry.

Transfer the contents of the vial with Calcium Chloride Solution into the vial containing the freeze-dried Thrombin using the sterile reconstitution components provided with the DUPLOJECT Preparation and Application System, or an equivalent device cleared by FDA for use with ARTISS (see directions provided with the device system for specific reconstitution instructions).

Swirl briefly.

Place the vial into the adapted opening of the FIBRINOTHERM device.

Reconstitution of Thrombin is complete when all of the Thrombin concentrate is dissolved.

Keep the Thrombin Solution at 37°C until used.

Transferring to the Sterile Field For transfer of the Sealer Protein Solution and the Thrombin Solution to the sterile field, the scrub nurse should withdraw the solutions while the circulating nurse holds the non-sterile vials.

The solutions should be withdrawn slowly by firm constant aspiration to reduce the risk of large air bubbles.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.2 Preparation of ARTISS Pre-filled Syringe (Frozen) During preparation of ARTISS (frozen): DO NOT EXPOSE TO TEMPERATURES ABOVE 37°C DO NOT MICROWAVE DO NOT REFRIGERATE OR RE-FREEZE AFTER THAWING Do not use ARTISS (frozen) unless it is completely thawed and warmed (liquid consistency).

Do not remove the protective syringe cap until thawing is complete and the application tip is ready to be attached.

ARTISS (frozen) can be prepared (thawed) using one of two options: Room Temperature Thawing Approximate thawing times when using this method are: Pack Size Room Temperature (In Pouches) 2 mL 60 minutes 4 mL 110 minutes 10 mL 160 minutes Unopened pouches, thawed at room temperature, may be stored for up to 14 days at 15-25°C.

Prior to use, the product should be warmed to 33-37°C: Pack Size 33°C to 37°C Incubator (In Pouches) 2 mL 15 minutes 4 mL 25 minutes 10 mL 35 minutes Quick Thawing Thawing on the sterile field using a water bath 33°C to 37°C sterile water bath - transfer the inner pouch to the sterile field, remove pre-filled syringe from inner pouch and place directly into sterile water bath.

Ensure the contents of the pre-filled syringe are completely immersed under the water.

Approximate thawing times when using this method are: Pack Size 33°C to 37°C Sterile

Water Bath (Pouches

Removed) 2 mL 5 minutes 4 mL 5 minutes 10 mL 12 minutes Thawing off the sterile field using a water bath 33°C to 37°C non-sterile water bath in two pouches - maintain the pre-filled syringe in both pouches and place into a water bath off the sterile field for appropriate time.

Ensure the pouches remain submerged throughout thawing.

Remove from the water bath after thawing, dry external pouch and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are: Pack Size 33°C to 37°C Non-Sterile Water Bath (In Pouches) 2 mL 30 minutes 4 mL 40 minutes 10 mL 80 minutes Thawing off the sterile field using an incubator 33°C to 37°C incubator in pouches - maintain the pre-filled syringe in both pouches and place into an incubator for appropriate time.

Remove from incubator after thawing and transfer inner pouch with pre-filled syringe onto the sterile field.

Approximate thawing times when using this method are: Pack Size 33°C to 37°C

Incubator (In Pouches) 2 mL 40 minutes 4 mL 85 minutes 10 mL 105 minutes Maintain the product at 33-37°C until use.

If product is removed from original pouch or warmed to 33-37°C it must be used within 12 hours.

See DOSAGE AND ADMINISTRATION, Method of Application (2.3).

2.3 Method of Application Apply ARTISS using the Easyspray and Spray Set, or an equivalent device cleared by FDA for application of ARTISS. See additional instructions for use provided with the spray set.

The wound surface should be as dry as possible before application.

Apply ARTISS as a thin layer to avoid the formation of excess granulation tissue and to ensure gradual absorption of the polymerized fibrin sealant.

The aerosolized sealant should be applied to the wound in a painting motion from side to side to achieve a single thin application.

The wound bed will glisten in the area to which fibrin sealant has been applied.

Any areas not covered by fibrin sealant will be clearly visible.

The skin graft should be attached to the wound bed immediately after ARTISS has been sprayed.

The surgeon has approximately 60 seconds to manipulate and position the graft prior to polymerization.

To prevent adherence, wet gloves with normal saline before product contact.

After the graft has been applied, hold in the desired position by gentle compression for at least 3 minutes to ensure ARTISS sets properly and adheres firmly to the surrounding tissue.

The solidified fibrin sealant reaches its final strength in approximately 2 hours after application.

The cannulas included with the DUPLOJECT Preparation and Application System or DUO Set may be used for small wounds or for edges of a skin graft that did not adhere to the wound bed (see WARNINGS/PRECAUTIONS Application Precautions (5.2)).

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.

Freeze-Dried: Refer to instructions for use provided with the DUPLOJECT Preparation and Application System.

Frozen: DUO Set Instructions (see Figure 1 below): Insert plunger into syringe barrel.

Firmly connect the two syringe nozzles to the joining piece and secure it by fastening the tether strap to the syringe.

Fit an application cannula to the joining piece.

If application of ARTISS is interrupted, replace the cannula immediately before application is resumed.

Figure 1 DUO SET A Vials and pre-filled syringes are for single use only.

Discard unused contents.

DUO set indicating syringe barrel, 2 syringe nozzles with joining piece and application cannula

Use in special populations

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with ARTISS.

It is also not known whether ARTISS can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Some viruses, such as parvovirus B19, are particularly difficult to remove or inactivate at this time.

Parvovirus B19 most seriously affects pregnant women (fetal infection).

ARTISS should be given to a pregnant woman only if deemed medically necessary.

8.3 Nursing Mothers It is not known whether this drug is excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when ARTISS is administered to a lactating woman.

8.4 Pediatric Use Thirty six pediatric subjects aged 1-16 years old were included in the prospective, randomized, controlled, evaluator-blinded, multicenter burn clinical study.

There was no exclusion criterion for age.

Overall, the efficacy of ARTISS was demonstrated in subjects less than or equal to 18 years old (Nineteen (13.8 %) subjects were less than or equal to 6 years old, 21 (15.2 %) subjects were 7 to 18 years old, and 98 (71.0 %) were greater than 18 years old) [ITT] (see CLINICAL STUDIES (14)).

8.5 Geriatric Use Clinical studies of ARTISS did not include any subjects aged 65 and over.

Pregnancy and lactation
8.3 Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ARTISS is administered to a lactating woman.

Interactions

7 DRUG INTERACTIONS No interaction studies have been performed.

More information

Category Value
Authorisation number BLA125266
Agency product number 6K15ABL77G
Orphan designation No
Product NDC 0944-8503,0944-4351
Date Last Revised 23-12-2010
Type HUMAN PRESCRIPTION DRUG
RXCUI 1305890
Storage and handling

Storage Store ARTISS in original carton to protect from light.

ARTISS Kit (Freeze-Dried) Store at 2°C to 25°C. Avoid freezing.

After reconstitution, the product must be used within 4 hours.

Reconstituted solutions must not be refrigerated or frozen.

ARTISS Pre-filled Syringe (Frozen) Long term: Store at?

- 20°C. Short term: Room Temperature Thawing: Unopened pouches, thawed at room temperature, may be stored for up to 14 days at room temperature (15-25°C) after removal from the freezer.

Quick Thawing: Maintain the product at 33-37°C until use.

If the product is removed from original pouch or warmed to 33-37°C it must be used within 12 hours.

Do not refrigerate or re-freeze after thawing.

Do not microwave.

Do not use after the expiration date.

Discard if packaging of any components is damaged.

Marketing authorisation holder Baxter Healthcare Corporation