Artiss

Name: Artiss

Artiss Overview

Artiss is a brand name medication included in a group of medications called Blood coagulation factors. For more information about Artiss see its generic Fibrin Sealant, Human

Artiss Drug Class

Artiss is part of the drug class:

  • Blood coagulation factors

What should I avoid after being treated with fibrin sealant topical?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Proper Use of fibrinogen/aprotinin and thrombin/calcium chloride

This section provides information on the proper use of a number of products that contain fibrinogen/aprotinin and thrombin/calcium chloride. It may not be specific to Artiss. Please read with care.

A doctor or other trained health professional will give you this medicine. This medicine is applied only to your skin or incision during surgery. It may be used with a spray applicator.

This medicine should not be given as an injection.

Indications and Usage for Artiss

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 Description

Artiss [Fibrin Sealant], Vapor Heated, Solvent Detergent Treated, (Artiss) is a two-component fibrin sealant made from pooled human plasma. When combined, the two components, Sealer Protein (Human) and Thrombin (Human), mimic the final stage of the blood coagulation cascade.

Sealer Protein (Human)

Sealer Protein (Human) is a sterile, non-pyrogenic, vapor-heated and solvent/detergent treated preparation made from pooled human plasma. Sealer Protein (Human) is provided either as a freeze-dried powder [Sealer Protein Concentrate (Human)] for reconstitution with Fibrinolysis Inhibitor Solution (Synthetic) or as a frozen liquid solution pre-filled into one side of a dual-chambered syringe (1). The active ingredient in Sealer Protein (Human) is fibrinogen. A Fibrinolysis Inhibitor, Aprotinin (Synthetic) is included in the Sealer Protein (Human) component to delay fibrinolysis. Aprotinin (Synthetic) is manufactured by solid phase synthesis from materials completely of non-human/non-animal origin.

To obtain Sealer Protein (Human), cryoprecipitate derived from the plasma is dissolved in buffer solution, solvent/detergent treated, vapor heat treated, sterile filtered and either freeze-dried in vials or frozen in pre-filled syringes.

Thrombin (Human)

Thrombin (Human) is a sterile, non-pyrogenic, vapor-heated and solvent/detergent treated preparation made from pooled human plasma. Thrombin (Human) is also provided either as a freeze-dried powder for reconstitution with Calcium Chloride Solution or as a frozen liquid solution pre-filled into one side of a dual-chambered syringe (2).

Thrombin is prepared from plasma through a series of separation and filtration steps followed by incubation of the solution with calcium chloride to activate prothrombin to thrombin. The solution subsequently undergoes ultra/diafiltration, vapor heat treatment, solvent/detergent treatment, sterile filtration and either freeze-drying in vials or frozen in pre-filled syringes.

Sealer Protein (Human) and Thrombin (Human) are made from pooled human plasma collected at US licensed collection centers. The vapor heat and solvent/detergent treatment steps used in the manufacturing process have been shown to be capable of significant viral reduction. No procedure, however, has been shown to be completely effective in removing viral infectivity from derivatives of human plasma (see CLINICAL PHARMACOLOGY, Other Clinical Pharmacology Information (12.4) and WARNINGS/PRECAUTIONS, Infection Risk from Human Plasma (5.3).

See DOSAGE FORMS AND STRENGTHS (3).

Artiss - Clinical Pharmacology

Mechanism of Action

Upon mixing Sealer Protein (Human) and Thrombin (Human), soluble fibrinogen is transformed into fibrin that adheres to the wound surface and to the skin graft to be affixed. Due to the low thrombin concentration, polymerization of Artiss will take approximately 60 seconds.

Pharmacodynamics

Thrombin is a highly specific protease that transforms the fibrinogen contained in Sealer Protein (Human) into fibrin (see Pharmacokinetics (12.3)). Fibrinolysis Inhibitor, Aprotinin (Synthetic), is a polyvalent protease inhibitor that prevents premature degradation of fibrin. Free Aprotinin and its metabolites have a half-life of 30 to 60 minutes and are eliminated by the kidney. Preclinical studies with different fibrin sealant preparations simulating the fibrinolytic activity generated by extracorporeal circulation in patients during cardiovascular surgery have shown that incorporation of aprotinin in the product formulation increases resistance of the fibrin sealant clot to degradation in a fibrinolytic environment.

Pharmacokinetics

Pharmacokinetic studies were not conducted. Because Artiss is applied only topically, systemic exposure or distribution to other organs or tissues is not expected.

Other Clinical Pharmacology Information

Viral Clearance

The manufacturing procedure for Artiss includes processing steps designed to further reduce the risk of viral transmission. In particular, vapor heating and solvent/detergent treatment processes are included in the manufacturing of Sealer Protein Concentrate and Thrombin. Validation studies were conducted using samples drawn from manufacturing intermediates for each of the two human plasma derived components. These samples were spiked with stock virus suspensions of known titers followed by further processing under conditions equivalent to those in the respective manufacturing steps. The stock virus suspensions represent HIV, HBV, HCV, HAV and Human Parvovirus B19.

The virus reduction factors (expressed as log10) of independent manufacturing steps are shown in Table 3 for each of the viruses tested:

Table 3.
n.d. = not determined
HIV-1: Human immunodeficiency virus 1; HAV: Hepatitis A virus; BVDV: Bovine viral diarrhea virus, a model for Hepatitis C virus; PRV: Pseudorabies virus, a model for enveloped DNA viruses, among those Hepatitis B virus; MMV: Mice minute virus, a model for B19V.
Reduction Factors for Virus Removal and/or Inactivation
Sealer Protein Component
Mean Reduction Factors [log10] of Virus Tested
Manufacturing Step HIV-1 HAV BVDV PRV MMV
Early Manufacturing Steps n.d. n.d. n.d. n.d. 2.7
Solvent/Detergent Treatment >5.3 n.d. >5.7 >5.9 n.d.
Vapor Heat Treatment >5.5 >5.6 >5.7 >6.7 1.2
Overall Reduction Factor (ORF) >10.8 >5.6 >11.4 >12.6 3.9
Reduction Factors for Virus Removal and/or Inactivation
Thrombin Component
Mean Reduction Factors [log10] of Virus Tested
Manufacturing Step HIV-1 HAV BVDV PRV MMV
Thrombin precursor mass capture 3.2 1.5 1.8 2.5 1.2
Vapor Heat Treatment >5.5 >4.9 >5.3 >6.7 1.0
Solvent/Detergent Treatment >5.3 n.d. >5.5 >6.4 n.d.
Ion Exchange Chromatography n.d. n.d. n.d. n.d. 3.6
Overall Reduction Factor (ORF) >14.0 >6.4 >12.6 >15.6 5.8

In addition, Human Parvovirus B19 was used to investigate the upstream Thrombin precursor mass capture step, the Sealer Protein early manufacturing steps and the Thrombin and Sealer Protein vapor heating steps. Using quantitative PCR assays, the estimated log reduction factors obtained were 1.7 and 3.4 for the Thrombin precursor mass capture step and Sealer Protein early manufacturing steps and >4 / 1.0 for the Thrombin / Sealer Protein vapor heating steps, respectively.

What happens if I miss a dose?

Because you will receive Artiss in a clinical setting, you are not likely to miss a dose.

Fibrin sealant topical Pregnancy Warnings

Fibrin sealant topical has been assigned to pregnancy category C by the FDA. Animal reproduction studies have not been conducted with fibrin sealant topical. There are no controlled data in human pregnancy. Fibrin sealant topical should be given during pregnancy when need has been clearly established.

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

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