CEPROTIN Powder and solvent for solution for injection Ref.[8817] Active ingredients: Protein C

Treatment with CEPROTIN should be initiated under the supervision of a physician experienced in substitution therapy with coagulation factors/inhibitors where monitoring of protein C activity is feasible.

The dose should be adjusted on the basis of laboratory assessment for each individual case.

A protein C activity of 100% should be achieved initially and the activity should be maintained above 25% for the duration of the treatment.

An initial dose of 60 to 80 IU/kg for determination of recovery and half-life is advised. The measurement of protein C activity using chromogenic substrates is recommended for the determination of the patient’s plasma level for protein C before and during treatment with CEPROTIN.

The dosage should be determined on the basis of laboratory measurements of the protein C activity. In the case of an acute thrombotic event these should be performed every 6 hours until the patient is stabilised, thereafter twice a day and always immediately before the next injection. It should be kept in mind that the half-life of protein C may be severely shortened in certain clinical conditions such as acute thrombosis with purpura fulminans and skin necrosis.

Patients treated during the acute phase of their disease may display much lower increases in protein C activity. The wide variation in individual responses implies that the effects of CEPROTIN on coagulation parameters should be checked regularly.

Patients with renal and/or hepatic impairment should be monitored more closely. (see section 4.4)

Based on the limited clinical experience in children from reports and studies covering 83 patients, dosing guidelines for adult subjects are considered valid for neonatal and paediatric patient population (see section 5.1).

In rare and exceptional cases, subcutaneous infusion of 250-350 IU/kg was able to produce therapeutic protein C plasma levels in patients with no intravenous access.

If the patient is switched to permanent prophylaxis with oral anticoagulants, protein C replacement is to be discontinued only when stable anticoagulation is obtained (see section 4.5). Furthermore, during the initiation of oral anticoagulant therapy it is advisable to start with a low dose and adjust this incrementally, rather than use a standard loading dose.

In patients receiving prophylactic administration of protein C, higher trough levels may be warranted in situations of an increased risk of thrombosis (such as infection, trauma, or surgical intervention).

In patients with combined severe congenital protein C deficiency and with APC resistance, there are limited clinical data to support the safety and efficacy of CEPROTIN.

CEPROTIN is administered by intravenous injection after reconstitution of the powder for solution for injection with Sterilised Water for Injections.

CEPROTIN should be administered at a maximum injection rate of 2 ml per minute except for children with a body weight of <10 kg, where the injection rate should not exceed a rate of 0.2 ml/kg/min.

As with any intravenous protein product, allergic type hypersensitivity reactions are possible. For the events that allergic symptoms arise which are of an acute and life-threatening nature, administration should be made within reach of life-supporting facilities.

For instructions on reconstitution of the medicinal product before administration, see section.6.6.

No symptoms of overdose with CEPROTIN have been reported.

3 years.

The reconstituted solution should be used immediately.

Store in a refrigerator (2°C-8°C). Do not freeze. Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

500 IU and 1000 IU: CEPROTIN powder comes in vials of neutral glass of either hydrolytic type I (500 IU) or hydrolytic type II (1000 IU). The solvent comes in vials of neutral glass of hydrolytic type I. The product and the solvent vials are closed with butyl rubber stoppers.

Each pack also contains:

• one transfer needle
• one filter needle

Not all pack sizes may be marketed.

Reconstitute lyophilised CEPROTIN powder for solution for injection, with the supplied solvent (Sterilised Water for Injections) using the sterile transfer needle. Gently rotate the vial until all powder is dissolved. After reconstitution the solution is colourless to slightly yellowish and clear to slightly opalescent and essentially free from visible particles.

The solution is drawn through the sterile filter needle into a sterile disposable syringe. A separate unused filter needle must be used to withdraw each vial of reconstituted CEPROTIN. The solution should be discarded if particulate matter is visible.

The reconstituted solution should be administered immediately by intravenous injection.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.