Transfusion medicine handbook

5. Fractionated Products

5.2.1 KYBERNIN P

Powder and solvent for solution for injection or infusion

• Vial containing powder (white lyophilisate): 500 IU antithrombin III
• Vial containing solvent: 10 mL water for injections

Kybernin P does not have full New Zealand registration and so consultation with an NZBS Transfusion Medicine Specialist/ Medical Officer is required prior to product release. It is supplied by NZBS under Section 29, a provision in the Medicines Act 1981, whereby a medical practitioner can prescribe a medicine that is not registered with Medsafe.

Indications for Use

Kybernin P is indicated as substitution therapy in patients with congenital antithrombin III deficiency for:

• Prevention of thrombosis in situations where the administration of oral anticoagulants or heparin is contraindicated, particularly during surgery and during pregnancy.
• Treatment of thrombosis in case of extensive thrombosis combined with heparin as well as in case of disseminated intravascular coagulation.

In congenital deficiency, the dosage should be individualised for each patient. Here, the family history with regard to thromboembolic events, the actual clinical risk factors and the laboratory assessment should be taken into account.

Normal dosage

The dosage and duration of the substitution therapy in acquired deficiency depend on the plasma antithrombin level, the presence of signs for increased turnover, the underlying disorder and the severity of the clinical symptoms. The amount to be administered and the frequency of administration should always be based on the clinical efficacy and laboratory assessment in each individual case.

The number of units of antithrombin administered is expressed in international units (IU), which are related to the current WHO standard for antithrombin products. Antithrombin activity in plasma is expressed either as a percentage (relative to normal human plasma) or in international units (relative to the international standard for antithrombin in plasma).

One international unit (IU) of antithrombin activity is equivalent to the quantity of antithrombin contained in 1 ml of normal human plasma.

The calculation of the required dosage is based on the empirical finding that 1 IU of antithrombin/kg body weight raises the plasma antithrombin activity by approximately 1.5%.

The initial dose is determined using the following formula:

            Units required = body weight [kg] x (100 - actual antithrombin activity [%]) x 2/3.

The initial target antithrombin activity depends on the clinical situation. For antithrombin substitution, the dosage should be selected so as to achieve the target antithrombin level and to maintain it. This should be monitored on the basis of laboratory measurements of the antithrombin activity. These antithrombin measurements should be performed at least twice a day until the patient is stabilised, thereafter once a day and, in particular, immediately before the next administration.

For dosage adjustment, both laboratory results with possible evidence of increased antithrombin turnover as well as clinical parameters should be taken into account. The antithrombin activity should be maintained above 80% for the duration of the treatment, unless the clinical situation indicates a different effective level.

The usual starting dose in congenital deficiency is 30 – 50 IU/kg.

Thereafter, dosage and frequency as well as duration of treatment should be adjusted to the biological data and clinical situation.

Paediatric population

40 - 60 IU antithrombin/kg body weight/day, depending on coagulation status. If required by the clinical condition, higher dosages may be necessary in individual cases. The antithrombin activity must then be monitored more frequently and should not exceed 120%.