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

For epilesional use only. Do not apply intravascularly. Life threatening thromboembolic complications may occur if the preparation is applied intravascularly. Soft tissue injection of ARTISS carries the risk of local tissue damage.

Caution must be used when applying fibrin sealant using pressurized air or gas.

• Any application of pressurized air or gas is associated with a potential risk of air or gas embolism, tissue rupture, or gas entrapment with compression, which may be life-threatening or fatal.
• Apply ARTISS as a thin layer. Excessive clot thickness may negatively interfere with the product’s efficacy and the wound healing process.
• Life-threatening air or gas embolism has occurred with the use of spray devices employing a pressure regulator to administer fibrin sealants. This event appears to be related to the use of the spray device at higher than recommended pressures and/or in close proximity to the tissue surface. The risk appears to be higher when fibrin sealants are sprayed with air, as compared to CO2 and therefore cannot be excluded with ARTISS.
• When applying ARTISS using a spray device, be sure to use a pressure within the pressure range recommended by the spray device manufacturer (see table in section 6.6 for pressures and distances).
• ARTISS spray application should only be used if it is possible to accurately judge the spray distance as recommended by the manufacturer. Do not spray closer than the recommended distances.
• When spraying 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 (also see section 4.2).
• ARTISS must not be used with the Easy Spray / Spray Set system in enclosed body areas.
• Only use application devices CE marked for the administration of ARTISS.

ARTISS is not indicated for hemostasis and sealing in situations where a fast clotting of the sealant is required. Especially in cardiovascular procedures in which sealing of vascular anastomoses is intended ARTISS should not be used.

ARTISS is not indicated for use in neurosurgery and as a suture support for gastrointestinal anastomoses or vascular anastomoses as no data are available to support these indications.

Before administration of ARTISS care is to be taken that parts of the body outside the designated application area are sufficiently protected/covered to prevent tissue adhesion at undesired sites.

Oxycellulose-containing preparations may reduce the efficacy of ARTISS and should not be used as carrier materials (see Section 6.2).

As with any protein-containing product, allergic type hypersensitivity reactions are possible. Signs of hypersensitivity reactions may include hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. If these symptoms occur, the administration must be discontinued immediately.

ARTISS contains aprotinin. Even in case of strict local application, there is a risk of anaphylactic reaction linked to the presence of aprotinin. The risk seems to be higher in cases where there was previous exposure, even if it was well tolerated. Therefore any use of aprotinin or aprotinin containing products should be recorded in the patients' records.

As synthetic aprotinin is structurally identical to bovine aprotinin the use of ARTISS in patients with allergies to bovine proteins should be carefully evaluated.

In the event of anaphylactic/anaphylactoid or severe hypersensitivity reactions, administration is to be discontinued. If possible, remove any applied, polymerized product from the surgical site. Adequate medical treatment and provisions should be available for immediate use in the event of an anaphylactic reaction. State-of-the-art emergency measures are to be taken. In case of shock, standard medical treatment for shock should be implemented.

Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses or other pathogens.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), and for the non-enveloped hepatitis A virus (HAV).

The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g., hemolytic anemia).

It is strongly recommended that every time that ARTISS is administered to the patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.

No formal interaction studies have been performed.

Similar to comparable products or thrombin solutions, the product is denatured after exposure to solutions containing alcohol, iodine or heavy metals (e.g. antiseptic solutions). Such substances should be removed to the greatest possible extent before applying the product.

See section 4.4 or 6.2 for substances that can interfere with the product’s performance.

The safety of fibrin sealants/haemostatics for use in human pregnancy or breastfeeding has not been established in controlled clinical trials. Animal studies have also not been performed.

Therefore, the product should be administered to pregnant and lactating women only if clearly needed.

See section 4.4 for information on Parvovirus B19 infection.

The effects of ARTISS on fertility have not been established.

Not relevant.

Intravascular injection could lead to thromboembolic events and DIC and there is also a risk of anaphylactic reactions (see 4.4).

Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the application site, bradycardia, bronchospasm, chills, dyspnoea, flushing, generalized urticaria, headache, hives, hypotension, lethargy, nausea, pruritus, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) may occur in rare cases in patients treated with fibrin sealants/hemostatics.

In isolated cases, these reactions have progressed to severe anaphylaxis. Such reactions may especially be seen if the preparation is applied repeatedly, or administered to patients known to be hypersensitive to aprotinin (see section 4.4) or any other constituents of the product.

Even if a first treatment with ARTISS was well tolerated, a subsequent administration of ARTISS or systemic administration of aprotinin may result in severe anaphylactic reactions.

Antibodies against components of fibrin sealant may rarely occur.

For safety with respect to transmissible agents, see section 4.4.

Adverse reactions reported from clinical studies are summarized in the following. Known frequencies of these adverse reactions are based on a controlled clinical study in 138 patients where skin grafts were fixed to excised burn wounds using ARTISS. None of the events were classified as serious.

The ADRs and their frequencies are summarized below:

Common (≥1/100 to <1/10)
Uncommon (≥1/1000 to <1/100)

Table 1 – Clinical Trial Adverse Reactions:

Class Reactions

Other adverse reactions associated with products of the fibrin sealant/hemostatic class include: Air or gas embolism when using devices with pressurized air or gas; this event appears to be related to the use of the spray device at higher than recommended pressures and in close proximity to the tissue surface. Manifestations of hypersensitivity include application site irritation, chest discomfort, chills, headache, lethargy, restlessness and vomiting.

Further class reactions are: Anaphylactic reaction, bradycardia, tachycardia, hypotension, haematoma, dyspnoea, nausea, urticaria, flushing, impaired healing, oedema, pyrexia and seroma.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. Oxycellulose-containing preparations may reduce the efficacy of ARTISS and should not be used as carrier materials.