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

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity

As the risk of an allergic type hypersensitivity reaction cannot be excluded, patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. If these symptoms occur, they should inform the physician. Immediate discontinuation of product use is advised.

In case of shock, the current medical standards for shock treatment are to be observed.

Inhibitors

If the preparation is used in patients with severe congenital protein C deficiency, antibodies inhibiting protein C may develop.

Transmissible agents

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 and other pathogens.

The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV and for the non-enveloped 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 (foetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia).

Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived Protein C products.

Heparin induced thrombocytopenia (HIT)

CEPROTIN may contain trace amounts of heparin. Heparin induced allergic reactions, which can be associated with a rapid decrease of the number of thrombocytes, may be observed (HIT). In patients with HIT, symptoms such as arterial and venous thrombosis, disseminated intravascular coagulation (DIC), purpura, petechiae and gastrointestinal bleeding (melena), may occur. If HIT is suspected, the number of thrombocytes should be determined immediately and if necessary, therapy with CEPROTIN should be stopped. Identifying HIT is complicated by the fact that these symptoms may already be present in acute phase patients with severe congenital protein C deficiency. Patients with HIT should avoid the use of heparin containing drugs in the future.

Concurrent anticoagulant medication

In the context of clinical experience several bleeding episodes have been observed. Concurrent anticoagulant medication (such as heparin) may have been responsible for these bleeding episodes. However, it cannot be completely ruled out that the administration of CEPROTIN further contributed to these bleeding events.

Sodium

This medicinal product contains 22.5 mg sodium per vial, equivalent to 1.1% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

No interactions with other medicinal products are currently known.

Interaction with Vitamin K antagonists

In patients starting treatment with oral anticoagulants belonging to the class of vitamin K antagonists (e.g. warfarin), a transient hypercoagulable state may arise before the desired anticoagulant effect becomes apparent. This transient effect may be explained by the fact that protein C, itself a vitamin K dependent plasma protein, has a shorter half-life than most of the vitamin K dependent proteins (i.e. II, IX and X). Subsequently, in the initial phase of treatment, the activity of protein C is more rapidly suppressed than that of the procoagulant factors. For this reason, if the patient is switched to oral anticoagulants, protein C replacement must be continued until stable anticoagulation is obtained. Although Warfarin-induced skin necrosis can occur in any patient during the initiation of oral anticoagulant therapy, individuals with congenital protein C deficiency are particularly at risk. (See section 4.2).

Although CEPROTIN has been used safely in the treatment of pregnant protein C-deficient women, its safety for use in human pregnancy has not been established in controlled clinical trials. Furthermore, no information on excretion of protein C in the milk is available. Therefore, the benefit of using CEPROTIN during pregnancy or lactation must be judged against the risk for the mother and baby and should be used only if clearly needed.

For information on parvovirus B19 infection, see section 4.4.

CEPROTIN has no influence or negligible influence on the ability to drive and use machines.

Summary of the safety profile

As with any intravenous product allergic type hypersensitivity reactions are possible. Patients should be informed of the early signs of hypersensitivity reactions, which may include angioedema, burning and stinging at the injection site, chills, flushing, rash, pruritus, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, and wheezing. Patients should be advised to immediately contact their physician if these symptoms occur (see section 4.4).

Tabulated list of adverse reactions

During clinical studies with CEPROTIN, a total of 3 non-serious adverse drug reactions (ADRs) were reported in 1 of 67 patients enrolled (rash and pruritus (grouped as hypersensitivity), and dizziness). In total 6375 administrations of CEPROTIN have been given.

Frequencies have been evaluated according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000); not known (cannot be estimated from the available data).

The distribution of the related ADRs is as follows:

Post-marketing experience

The following ADRs have been reported in the post-marketing experience and the frequency of these ADRs is not known:

Psychiatric disorders: restlessness

Skin and subcutaneous tissue disorders: hyperhidrosis

General disorders and administration site conditions: injection site reaction

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 national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.