ATENATIV Powder and solvent for solution for infusion Ref.[4776] Active ingredients: Antithrombin III

Antithrombin should be administered restrictively in connection with acquired antithrombin deficiency and in consultation with a coagulation specialist (also see section 5.1).

As with any intravenous protein product, allergic type hypersensitivity reactions are possible.

Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis.

If allergic or anaphylactic reactions occur, the injection/infusion should be stopped immediately.

The applicable guidelines for shock treatment should be followed.

When medical products prepared from human blood or plasma are administered, infectious diseases due to the transmission of infective agents cannot be totally excluded. This also applies to pathogens of unknown nature. The risk of transmission of infective agents is however reduced by:

• selection of donors by medical interview and screening of donations and plasma pools for HBsAg and antibodies to HIV and HCV.
• testing of plasma pools for HCV genomic material.
• inactivation/removal procedures included in the production process that have been validated using model viruses. These procedures are considered effective for HIV, HCV, HBV and HAV.

The viral inactivation/removal procedures may be of limited value against certain non-enveloped viruses such as parvovirus B19.

Appropriate vaccination (hepatitis A and B) for patients with congenital deficiency in regular receipt of plasma derived antithrombin concentrates should be considered.

In the interest of patients, it is recommended that, whenever possible, every time Atenativ is administered to them, the name and batch number of the product is recorded.

Clinical and Biological surveillance when antithrombin is used together with heparin:

• in order to adjust heparin dosage and to avoid excessive hypocoagulability, controls of the extent of anticoagulation (aPPT, and where appropriate anti-FXa activity) should be performed regularly, at close intervals and in particular in the first minutes/hours following the start of antithrombin use.
• daily measure of antithrombin levels, in order to adjust the individual dose, because of the risk of diminution of antithrombin levels by prolonged treatment with non fractionated heparin.

Heparin: antithrombin replacement during administration of heparin in therapeutic dosage increases the risk of bleeding. The effect of antithrombin is greatly enhanced by heparin. The half-life of antithrombin may be considerably decreased with concomitant heparin treatment due to accelerated antithrombin turnover. Therefore, the concurrent administration of heparin and antithrombin to a patient with an increased risk of bleeding must be monitored clinically and biologically and considered very carefully. If it is decided to use heparin, only standard heparin in low doses should be given.

Experience as to the safety of human antithrombin products for use in human pregnancy is limited.

Atenativ should be administered to pregnant and lactating antithrombin deficient women only if clearly indicated, taking into consideration that pregnancy confers an increased risk of thromboembolic events in these patients.

No effects on ability to drive and use machines have been observed.

Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed infrequently, and may in some cases progress to severe anaphylaxis (including shock). On rare occasions, fever has been observed.

For information on viral safety see 4.4.

Atenativ should not be mixed with other medicinal products.