Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
CEPROTIN 500 IU powder and solvent for solution for injection
⚠ This medicine appears to have been discontinued
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Protein c may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
What it is and what it is used for
for
CEPROTIN belongs to a class of medicines called antithrombotics. This medicine contains Protein C, a natural protein that is made in the liver and is present in your blood. Protein C plays a major role in prevention of excessive clot formation thus, prevent and/or treat intravascular thrombosis. CEPROTIN is used in the treatment and prevention of thrombotic and haemorrhagic skin lesions (named purpura fulminans) in patients with severe congenital protein C deficiency. CEPROTIN may be used to treat a rare complication of a blood thinner medicine (anticoagulant medicine named coumarin) which may result in severe skin lesion (necrosis). Additionally, CEPROTIN may be used in the treatment of blood clot (venous thrombotic) events. 2.
What you need to know before you take it
e CEPROTIN
Do not use CEPROTIN –
if you are allergic to human protein C or any of the other ingredients of this medicine (listed in section 6) including mouse protein or heparin.
However, in the case of life-threatening thrombotic complications your doctor may still decide to continue treatment with CEPROTIN. Warnings and precautions Talk to your doctor or pharmacist before using CEPROTIN. Take special care with CEPROTIN if symptoms of allergy occur. Symptoms of allergy include rash, hives, breathing difficulties, low blood pressure, tightness of chest, and shock. If such symptoms occur during the administration of CEPROTIN, injection should be stopped. Such symptoms may constitute an allergic reaction to any of the components, to mouse protein or heparin. The preparation may contain traces of heparin and/or mouse protein as a result of the manufacturing process. If such a reaction occurs, your doctor will decide on the most appropriate treatment. 1
If the preparation is used in patients with severe congenital protein C deficiency, antibodies inhibiting protein C may develop that can inhibit protein C and therefore diminish the effect of the preparation. However, this has not been observed in the clinical studies to date. When medicines are made from human blood or plasma, certain measures are put in place to prevent infections being passed on to patients. These include careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded, and the testing of each donation and pools of plasma for signs of virus/infections. Manufacturers of these products also include steps in the processing of the blood or plasma that can inactivate or remove viruses. Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging viruses or other types of infections. The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, and for the non-enveloped hepatitis A virus. The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B 19 infection may be serious for pregnant women (foetal infection) and for individuals whose immune system is depressed or who have some types of anaemia (e.g. sickle cell disease or haemolytic anaemia). Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly/repeatedly receive human plasma-derived Protein C products. Other medicines and CEPROTIN No interactions with other medicinal products are currently known. Nevertheless, please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. If you change to treatment with oral anticoagulants, treatment with CEPROTIN must continue until the blood level of the oral anticoagulation is adequate and stable. CEPROTIN with food and drink Not applicable. Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your doctor will decide if CEPROTIN may be used during pregnancy and lactation. Driving and using machines CEPROTIN has no influence on your ability to drive or to operate machines. CEPROTIN contains Sodium This medicine contains 22.5 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 1.1% of the recommended maximum daily dietary intake of sodium for an adult. 3.
How to take it
CEPROTIN
CEPROTIN is intended for intravenous administration (infusion into a vein). It is given to you under close supervision of your doctor who is experienced in substitution therapy of coagulation
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factors/inhibitors and where monitoring of protein C activity is possible. Dosage will vary depending on your condition and your body weight. Dosage The dose, administration frequency and duration of treatment depend on the severity of the protein C deficiency as well as on your clinical condition and on your plasma level of protein C. They should be adjusted accordingly on the basis of clinical effectiveness and laboratory assessment. Treatment of acute episodes and short-term prophylaxis A protein C activity of 100 % (1 IU/ml) 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 should be administered. Your physician will take several blood drawings over time to determine how long protein C is remaining in your body. The measurement of protein C activity using chromogenic substrates is recommended for the determination of your 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 your condition 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. If the response to CEPROTIN injection is satisfactory, dosing may be gradually reduced to 12 hourly dosing ensuring trough protein C activity >25%. If you receive 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). Long-term prophylaxis For the long-term prophylactic treatment, a dose of 45 to 60 IU/kg every 12 hours is recommended. Measurement of the protein C activity should be performed to ensure trough levels of 25% or more. In rare cases, subcutaneous infusion of 250 – 350 IU/kg has produced therapeutic plasma protein C levels in patients with no intravenous access. If you have kidney and/or liver disease, please inform your doctor, because he may have to adjust your treatment accordingly. Combination treatment If you are switched to permanent prophylaxis with oral anticoagulants, protein C replacement is to be discontinued only when stable anticoagulation is obtained (see "Important information about some of the ingredients of CEPROTIN"). At start of a combination treatment of anticoagulants (especially Vitamin K antagonists) with Protein C, stable activity levels of Protein C above 0.25 IU/ml should be maintained before starting the anticoagulation. Careful monitoring of the international normalized ratio (INR) is recommended. In the combination of Protein C Concentrate and anticoagulants, a Protein C trough level of about 10% or more is recommended to be maintained. If you have APC resistance which is a thromboembolic risk factor present in up to 5 % of the population in Europe your doctor may need to adjust your treatment accordingly.
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Administration CEPROTIN will be administered to you by intravenous injection after reconstitution of the powder for solution for injection with Sterilised Water for Injections. It is strongly recommended that every time you receive a dose of CEPROTIN the name and batch number of the product are recorded in order to maintain a record of the batches used. 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 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. CEPROTIN should be administered at a maximum injection rate of 2 ml per minute. In children with a body weight of less than 10 kg, the injection rate should not exceed a rate of 0.2 ml/kg/min. All unused solution, empty vials and used needles and syringes must be discarded appropriately. Frequency and duration of treatment depend on the severity of your protein C deficiency, on the results of determination of protein C levels in your plasma as well as on the location and extent of thrombosis. In case of acute thrombosis CEPROTIN may be administered to you every 6 hours. As the tendency for thrombus formation decreases, the frequency may be reduced. If you use more CEPROTIN than you should It is recommended that you adhere to the dose level and frequency of administration as recommended by your doctor. In case you administered more CEPROTIN than recommended, please inform your doctor as soon as possible. If you forget to use CEPROTIN Not applicable. If you stop using CEPROTIN Do not stop using CEPROTIN without consulting your doctor. If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 4.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. You may notice any of the following side effects after administration of CEPROTIN: •
As with any product administered by infusion into a vein allergic reactions including severe and potentially life-threatening reactions (anaphylaxis) are possible. You should be aware of the early signs of allergic reactions such as burning and stinging at the injection site, chills, flushing, rash, hives, breathing difficulty, nausea, headache, lethargy, low blood pressure, and tightness of the chest.
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• •
The following side effects were rarely observed during clinical studies (less than 1 case in 1,000 administrations given to patients): itching (pruritus), rash and dizziness. In the postmarketing experience there have been reports of restlessness, excessive sweating, and pain and redness at the injection site.
Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine. 5.
How to store it
CEPROTIN
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month. Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the vial in the outer carton in order to protect from light. The reconstituted solution should be used immediately. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. 6.
Contents of the pack and other information
What CEPROTIN contains Powder: The active substance is human protein C The other ingredients are human albumin, trisodium citrate dihydrate and sodium chloride. As solvent sterilised water for injections is used. What CEPROTIN looks like and contents of the pack CEPROTIN is presented as powder and solvent for solution for injection and is a white or cream coloured powder or friable solid. After reconstitution the solution is colourless to slightly yellowish and clear to slightly opalescent and essentially free from visible particles. Each pack also contains one transfer needle and one filter needle. Marketing Authorisation Holder and Manufacturer: Takeda Manufacturing Austria AG Industriestrasse 67 1221 Vienna Austria Tel.: + 44 (0)3333 000181 E-mail: [email protected] This leaflet was last approved in January 2023.
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Frequently asked questions about CEPROTIN 500 IU powder and solvent for solution for injection
How do I take CEPROTIN 500 IU powder and solvent for solution for injection?
CEPROTIN 500 IU powder and solvent for solution for injection comes as injection containing 500iu. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
What is the active substance in CEPROTIN 500 IU powder and solvent for solution for injection?
The active substance in CEPROTIN 500 IU powder and solvent for solution for injection is protein c.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for CEPROTIN 500 IU powder and solvent for solution for injection, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Can I get CEPROTIN 500 IU powder and solvent for solution for injection without a prescription?
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
About this leaflet
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
- Source: electronic medicines compendium (emc), Datapharm
- Active substance: protein c
- Official document: view the original leaflet on emc →
⚕For healthcare professionals — Summary of Product Characteristics (SmPC)Full SmPC: dosage, interactions, contraindications, warnings+
4.1. Therapeutic indications
CEPROTIN is indicated for prophylaxis and treatment of purpura fulminans, coumarin-induced skin necrosis and venous thrombotic events in patients with severe congenital protein C deficiency.
4.2. Posology and method of administration
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.
Posology
The dose should be adjusted on the basis of laboratory assessment for each individual case.
Treatment of acute episodes and short-term prophylaxis (including invasive procedures)
A protein C activity of 100 % (1 IU/ml) 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.
If the response to CEPROTIN injection is satisfactory (measured by chromogenic assays), dosing may be gradually reduced to 12 hourly dosing ensuring trough protein C activity >25% (>0.25 IU/ml).
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.
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).
Long-term prophylaxis
For the long-term prophylactic treatment, a dose of 45 to 60 IU/kg every 12 hours is recommended. Measurement of the protein C activity should be performed to ensure trough levels of 25% or more. Dose or frequency of infusions should be adjusted accordingly.
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.
Combination treatment
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.
At start of a combination treatment of anticoagulants (especially Vitamin K antagonists) with Protein C, stable activity levels of Protein C above 0.25 IU/ml (chromogenic) should be maintained before starting the anticoagulation. Careful monitoring of the international normalized ratio (INR) is recommended. In the combination of Protein C Concentrate and -anticoagulants, a protein C trough level of about 10% or more is recommended to be maintained.
Special populations
Paediatric population
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).
Activated Protein C (APC) resistance
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.
Renal and/or hepatic impairment
Safety and efficacy of CEPROTIN in patients with renal and/or hepatic impairment have not been established. Patients with any of these conditions should be monitored more closely.
Method of administration
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.
4.3. Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to mouse protein or heparin, except for control of life-threatening thrombotic complications.
4.4. Special warnings and precautions for use
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.
Renal and/or hepatic impairment
No experience in the treatment of patients with renal and/or hepatic impairment is available and therefore it is recommended that such patients be monitored more closely.
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.
4.5. Interaction with other medicinal products and other forms of interaction
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).
4.6. Fertility, pregnancy and lactation
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.
4.7. Effects on ability to drive and use machines
CEPROTIN has no influence or negligible influence on the ability to drive and use machines.
4.8. Undesirable effects
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 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. The distribution of the related ADRs is as follows:
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).
System Organ Class
Adverse Reaction
Preferred Term
Frequency Category by infusions
Immune System Disorders
Hypersensitivity
Rash
Rare
Pruritus
Rare
Nervous System Disorders
Dizziness
Dizziness
Rare
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 Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9. Overdose
No symptoms of overdose with CEPROTIN have been reported.
🇷🇴 Known in Romania as
Medicines sold in Romania with the same active substance: Cunoscut în România ca
- CEPROTIN 1000 UI prescriptionPROTEINA C · injection / infusion
- CEPROTIN 500 UI prescriptionPROTEINA C · injection / infusion
Same active substance. The strength, the form and whether you need a prescription can differ. Always ask a pharmacist before you switch. Romanian medicines in the UK →
🇵🇱 Known in Poland as
Medicines sold in Poland with the same active substance: W Polsce znany jako
⚠ Not the same combination. This medicine contains Protein c. The products below do not contain exactly the same set of active substances — they are not direct substitutes.
- Ceprotin partial — not the same combinationProteinum humanum C · injection / infusion
- Improvac partial — not the same combinationSyntetyczny peptydowy analog GnRF skoniugowany z proteiną nośnikową · injection / infusion
Some of these do not contain exactly the same active substances — check each one. The strength, the form and whether you need a prescription can differ. Always ask a pharmacist before you switch. Polish medicines in the UK →
💬 Ask about this leaflet
Ask anything about CEPROTIN 500 IU powder and solvent for solution for injection. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.