Consumer medicine information

Ceprotin

Protein C

BRAND INFORMATION

Brand name

Ceprotin

Active ingredient

Protein C

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ceprotin.

SUMMARY CMI

Ceprotin®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using CEPROTIN?

CEPROTIN is used in the treatment of purpura fulminans (blood spots, bruising and discolouring to the skin because of the clotting of small blood vessels in the skin) in patients born with severe protein C deficiency. Additionally, CEPROTIN may be used to treat a rare complication of a blood thinner medication (anticoagulant medication named coumarin) which may result in severe skin lesions (necrosis).

For more information, see Section 1. Why am I using CEPROTIN? in the full CMI.

2. What should I know before I use CEPROTIN?

Do not use if you have ever had an allergic reaction to CEPROTIN or any of the ingredients listed at the end of the CMI including mouse protein or heparin, except for control of life-threatening thrombotic complications.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use CEPROTIN? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with CEPROTIN and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use CEPROTIN?

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. CEPROTIN is given by injection into a vein. Your doctor will administer it to you.

More instructions can be found in Section 4. How do I use CEPROTIN? in the full CMI.

5. What should I know while using CEPROTIN?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using CEPROTIN.
  • Discuss with your doctor the progress you have experienced after the treatment.
Things you should not do
  • Do not stop using this medicine without consulting your doctor.
Driving or using machines
  • This medicine is not expected to affect your ability to drive a car or operate machinery.
Drinking alcohol
  • Be careful when drinking alcohol while taking this medicine.
Looking after your medicine
  • Store between 2°C and 8°C. Refrigerate; do not freeze.
  • Protect from light.

For more information, see Section 5. What should I know while using CEPROTIN? in the full CMI.

6. Are there any side effects?

As with any product administered by infusion into a vein, allergic reactions including severe and potentially life-threatening reactions (anaphylaxis) are possible but have not been seen with CEPROTIN.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Ceprotin®

Active ingredient(s): [Protein C, human]

Consumer Medicine Information (CMI)

This leaflet provides important information about using Ceprotin. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using CEPROTIN.

Where to find information in this leaflet:

1. Why am I using CEPROTIN?
2. What should I know before I use CEPROTIN?
3. What if I am taking other medicines?
4. How do I use CEPROTIN?
5. What should I know while using CEPROTIN?
6. Are there any side effects?
7. Product details

1. Why am I using CEPROTIN?

CEPROTIN contains the active ingredient Protein C, a natural protein that is made in the liver and is present in your blood. Protein C is part of human plasma that regulates the blood clotting (coagulation) system and prevents abnormal clot formation (thrombosis). Plasma is the liquid part of human blood.

CEPROTIN is used in the treatment of:

  • purpura fulminans (blood spots, bruising and discolouring to the skin because of the clotting of small blood vessels in the skin) in patients born with severe protein C deficiency
  • a rare complication of a blood thinner medication (anticoagulant medication named coumarin) which may result in severe skin lesions (necrosis).

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

2. What should I know before I use CEPROTIN?

Warnings

Do not use CEPROTIN if you are allergic to human Protein C, or any of the ingredients listed at the end of this leaflet including mouse protein or heparin.

However, in the case of life-threatening thrombotic complications, your doctor may still decide to continue treatment with CEPROTIN.

Always check the ingredients to make sure you can use this medicine.

Some of the symptoms of an allergic reaction may include the following:

  • tightness of chest
  • wheezing or difficulty breathing
  • low blood pressure
  • shock
  • rash, itching or hives on the skin.

If such symptoms occur during the administration of CEPROTIN, injection should be stopped, and your doctor will decide on the most appropriate treatment.

About blood products

When medicines are made from human blood or plasma, certain measures are put in place to prevent infections being passed from the blood/plasma donor to the person receiving the medicine. These processes include careful selection of the people who donate blood and plasma to make sure that those who might be carrying infections are excluded. In addition, each donation and pools of donations are tested for indications of virus or virus infection(s).

Manufacturers of these medicines also include steps in the processing of blood or plasma that inactivate or remove viruses. Despite the stringent measures, which have been put in place during the manufacturing processes, the risk of contamination by viral and other unknown agents 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 immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and for the non-enveloped hepatitis A 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 whose immune system is depressed or who have some types of anaemia (e.g.: 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.

Check with your doctor if you have:

  • hypersensitivity/allergic reaction to mouse protein and/or to heparin
  • heparin induced thrombocytopenia
  • internal bleeding or have had internal bleeding over the last few months
  • on a controlled sodium diet.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant or are breast-feeding. Your doctor will decide if CEPROTIN may be used during pregnancy and/or breast feeding. Your doctor can discuss with you the risks and benefits involved.

CEPROTIN contains sodium.

CEPROTIN 500 IU 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.

CEPROTIN 1000 IU contains 44.9 mg sodium per vial, equivalent to 2.2% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

As the quantity of sodium (main component of cooking/table salt) in the maximum daily dose may exceed 200 mg, this should be taken into consideration by patients on a controlled sodium diet.

3. What if I am taking other medicines?

No interactions with other medicinal products are currently known. Nevertheless, tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

If you change to treatment with oral anticoagulants (e.g. warfarin), treatment with CEPROTIN must continue until stable anticoagulation is achieved as assessed by your doctor.

Some medicines may interfere with CEPROTIN and affect how it works.

You may need different amounts of your medicines, or you may need to take different medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect CEPROTIN.

4. How do I use CEPROTIN?

CEPROTIN is given by injection into a vein after reconstitution of the powder for injection with the provided solvent (Water for Injections).

Your doctor will administer it to you.

For healthcare professionals, details are described in the Product Information.

It is strongly recommended that every time you receive a dose of CEPROTIN the name and batch number of the product are recorded to maintain a record of the batches used.

How much to use

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 based on clinical effectiveness and laboratory assessment.

Your doctor will decide how much CEPROTIN will be given to you, which depends on your need and condition.

5. What should I know while using CEPROTIN?

Things you should do

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box/bottle, ask your doctor or pharmacist for help.

  • Discuss with your doctor the progress you have experienced after the treatment, especially during the first few days. As CEPROTIN is given in a hospital, your healthcare professional will keep records of your progress and any unexpected reactions that may occur.
  • Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Things you should not do

Do not stop using this medicine without consulting your doctor.

Driving or using machines

This medicine is not expected to affect your ability to drive a car or operate machinery.

If you experience dizziness, light-headedness, tiredness or drowsiness, do not drive, operate machinery or do anything that could be dangerous.

Looking after your medicine

  • CEPROTIN is a protein preparation; therefore, it should be stored between 2°C and 8°C in a refrigerator.
  • Do not freeze.
  • Store in the outer carton to protect from light.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

This medicine helps most people with severe protein C deficiency, but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
In clinical trials:
  • with patients born with severe protein C deficiency, mild allergic reactions were reported
  • rarely observed adverse effects: fever, wheals (urticaria), itching (pruritus), rash and dizziness
If you were born with severe protein C deficiency: your body may develop antibodies that may decrease the effectiveness of this medicine
Post marketing experience:
  • restlessness,
  • bleeding,
  • excessive sweating,
  • fever,
  • arrhythmia
  • thrombosis
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • Anaphylaxis
As with any product administered by infusion into a vein, acute allergic reactions including severe and potentially life-threatening reactions are possible.
Your doctor is aware of this potential adverse effect, as, CEPROTIN contains a protein as an active ingredient.
  • Hypersensitivity or allergic reactions - which may include hives, generalized rash, tightness of chest, wheezing and low blood pressure
  • Burning and stinging at injection sites
  • Fever, chills, flushing, headaches, tiredness, nausea, vomiting, dizziness and excessive sweating.
Administration should be performed within reach of life-supporting facilities.
Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

Once you have consulted with a healthcare professional regarding any side effects that you have experienced, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What CEPROTIN contains

CEPROTIN comes in two strengths: 500 IU (AUST R 104537) and 1000 IU (AUST R 104538). The active component of CEPROTIN is protein C, which is isolated from the blood of healthy donors.

It also contains human albumin, which acts as a stabilizer.

Active ingredientHuman protein C
Other ingredientsHuman albumin
Sodium chloride
Sodium citrate dihydrate
Water for injections

Do not take this medicine if you are allergic to any of these ingredients.

What CEPROTIN looks like

It is presented as a white to cream coloured powder in a single dose glass vial accompanied by water for injections in a glass vial to be used for reconstitution.

After reconstitution, the solution is colourless to slightly yellowish and should be clear to slightly opalescent.

It should be essentially free from visible particles.

Who distributes CEPROTIN

Takeda Pharmaceuticals Australia Pty Ltd
Level 39, 225 George Street
Sydney, NSW 2000
Australia
Telephone: 1800 012 612

This leaflet was prepared in August 2024.

CEPROTIN is a registered trademark of Baxalta Incorporated. TAKEDA and the TAKEDA logo are registered trademarks of Takeda Pharmaceutical Company Limited.

Published by MIMS October 2024

BRAND INFORMATION

Brand name

Ceprotin

Active ingredient

Protein C

Schedule

Unscheduled

 

1 Name of Medicine

Protein C, human.

2 Qualitative and Quantitative Composition

Ceprotin is a freeze-dried, sterile high-purity protein C preparation, intended for intravenous application.
Ceprotin is available in the following strengths: 500 IU and 1000 IU.

Ceprotin 500 IU powder for injection with diluent vial.

Each vial of powder contains nominally 500 International Units (IU) of protein C. After reconstitution with the provided 5 mL diluent, Ceprotin contains 100 IU/mL protein C.

Ceprotin 1000 IU powder for injection with diluent vial.

Each vial of powder contains nominally 1000 International Units (IU) of protein C. After reconstitution with the provided 10 mL diluent, Ceprotin contains 100 IU/mL protein C.
One International Unit (IU) of protein C corresponds to the amidolytically measured activity of protein C in 1 mL of human plasma. The active ingredient, human plasma derived protein C, is purified by column chromatography packed with monoclonal antibody against protein C.
The lyophilised 500 and 1000 IU preparations contains 42.5 and 85.0 mg of protein respectively, of which the bulk is human albumin (approximately 94%, added as stabiliser), sodium chloride and sodium citrate dihydrate to assure isotonicity and stability of the reconstituted preparation.

Excipients with known effect.

Sodium chloride, sodium citrate dihydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Protein C, powder for injection vial with diluent vial.
Ceprotin is presented as a white to cream colour lyophilised powder in a single dose vial of neutral glass of either hydrolytic type I (500 IU) or hydrolytic type II (1000 IU).

4 Clinical Particulars

4.1 Therapeutic Indications

Ceprotin is indicated in purpura fulminans and coumarin-induced skin necrosis in patients with severe congenital protein C deficiency.
Since safety and efficacy data are not available in conditions other than severe congenital deficiency, use should be limited to these conditions.

4.2 Dose and Method of Administration

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

Dosage.

The dosage should be adjusted on the basis of laboratory assessment for each individual case.
Initially the activity of protein C at a level of 100% should be achieved 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 recommended. The determination of protein C activity using protein C specific chromogenic substrates is recommended for the assay of the patient's protein C plasma level before and during the treatment with Ceprotin.
The dosage should be determined on the basis of laboratory determination of the protein C activity. This 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 regularly checked.
If the patient is switched to permanent prophylaxis with oral anticoagulants, protein C replacement is to be discontinued only when stable anticoagulation has been achieved. 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.

Renal impairment.

No experience in the treatment of patients with renal impairment is available and therefore it is recommended that such patients be monitored more closely.

Hepatic impairment.

No experience in the treatment of patients with hepatic impairment is available and therefore it is recommended that such patients be monitored more closely.

Activated protein C (APC) resistance.

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

Method of administration.

Ceprotin is administered by intravenous injection after the lyophilised powder form is reconstituted with water for injections.
Ceprotin should be administered at a maximum injection rate of 2 mL/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/minute.
As with any intravenous protein product, allergic type hypersensitivity reactions may occur. The administration should be made within reach of life-supporting facilities, as the events of allergic symptoms may show up which are of an acute and life-threatening nature.

Instructions for use, handling and disposal.

Reconstitute the lyophilised Ceprotin powder with the supplied water for injections using sterile needle. Gently rotate the vial until all the powder has been dissolved. After reconstitution, the solution is drawn through the sterile filter needle into a sterile disposable syringe. A separate sterile filter needle must be used to withdraw the reconstituted Ceprotin from each vial. The solution should be discarded if particulate matter is visible.
The reconstituted solution should be administered immediately by intravenous route injection.
All unused solution, empty vials and used needles and syringes must be discarded appropriately.

4.3 Contraindications

Hypersensitivity to any of the components, to mouse protein or to heparin, except for control of life-threatening thrombotic complications.

4.4 Special Warnings and Precautions for Use

General.

Administration of Ceprotin may result in allergic reaction in some patients. 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 should be considered. Adequate medical treatment and provisions should be available for immediate use in the rare event of an anaphylactic reaction.

Transmission of infectious agents.

When medicinal products prepared from human blood or plasma is administered, infectious diseases due to transmission of infective agents cannot be totally excluded. This applies also to pathogens of hitherto unknown nature. The risk of transmission of infective agents is however reduced by:
selection of donors by a medical interview and screening of donations for the three major pathogenic viruses, HIV, HCV, HBV;
testing plasma pools for the absence of HCV genomic material;
removal/inactivation procedures included in the production process that have been validated using model viruses and are effective for HIV, HCV, HAV, and HBV.
The viral removal/inactivation procedure is of limited value against parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (foetal infection) and for individuals with immunodeficiency or increased red cell production (e.g. haemolytic anaemia).
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular and/or repeated receipt of human-plasma derived Protein C.
It is strongly recommended that every time that Ceprotin is administered to a patient, the name and batch number of the product are recorded to maintain a link between the patient and the batch of the product.

Sodium content.

A quantity of sodium in the maximum daily dose may exceed 200 mg. This should be taken into consideration by patients on a controlled sodium diet. Ceprotin 500 IU 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. Ceprotin 1000 IU contains 44.9 mg sodium per vial, equivalent to 2.2% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Heparin induced thrombocytopenia.

Ceprotin may contain trace amounts of heparin. Heparin induced allergic reactions which can be associated with a rapid decrease in the number of platelets can occur (Heparin-induced thrombocytopenia, HIT). In patients with HIT, symptoms such as arterial and venous thrombosis, disseminated intravascular coagulation (DIC), purpura, petechia, and gut bleeding (melena), can occur. If HIT is suspected, the platelet count 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.

Bleeding episodes.

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 administration of Ceprotin further contributed to these bleeding episodes.

Hypersensitivity/allergic reactions.

Ceprotin may contain traces of mouse protein and/or heparin as a result of the manufacturing process. Allergic reactions to mouse protein and/or heparin cannot be ruled out. If symptoms of hypersensitivity/allergic reaction occur, discontinue the injection/infusion. Adequate medical treatment and provisions should be available for immediate use in the event of an anaphylactic reaction.

Use in the elderly.

No data available.

Paediatric use.

See Section 4.2 Dose and Method of Administration for information on paediatric population.

Effects on laboratory tests.

See Section 4.2 Dose and Method of Administration for information on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interactions with other medicinal products are currently known. In patients starting treatment with oral anticoagulants of the vitamin K antagonists class (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 is a vitamin K dependent plasma protein having a shorter half-life than most of the vitamin K dependent proteins (factors II, IX, X). Subsequently, in the initial phase of treatment, the activity of protein C is suppressed more rapidly than that of procoagulant factors. For this reason, if the patient is switched to oral anticoagulants, protein C replacement must be continued until stable anticoagulation is achieved. 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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effect of protein C on fertility has not been investigated in animal studies.
(Category B2)
The safety of protein C during pregnancy has not been established. Ceprotin should not be used during pregnancy unless the benefit outweighs the risk to the foetus.
See Section 4.4 Special Warnings and Precautions for Use for information on Parvovirus B19 infection.
 The safety of Ceprotin in lactation has not been established.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Only few data are available. No prospective safety studies have been performed. Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the injection sites, chills, flushing, rash, generalized urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed infrequently.
In the clinical trials performed, two mild allergic adverse experiences occurred. The occurrence of fever, arrhythmia, bleedings and thrombosis in the course of the treatment has been reported. Some of these adverse reactions, experienced during the retrospective data collection are shown in Table 1.
If the preparation is used in patients with severe congenital protein C deficiency, antibodies inhibiting protein C may develop.

Adverse reactions from clinical trials.

Based on clinical studies involving patients with severe congenital and acquired protein C deficiency who received treatment with Ceprotin, only 3 adverse reactions, occurring in one subject, were considered to be related to Ceprotin. These were itching, rash and light-headedness. See Table 2.

Postmarketing adverse reactions.

The following adverse reactions have been reported in the postmarketing experience, listed by MedDRA System Organ Class (SOC), then by Preferred Term in order of severity, where feasible.

Psychiatric disorders.

Restlessness.

Skin and subcutaneous tissue disorders.

Hyperhidrosis.

General disorders and administration site conditions.

Injection site reaction.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre telephone: 131126 (Australia).
No symptoms of overdose with Ceprotin have been reported.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Circulating protein C is converted by thrombin-thrombomodulin complex on the endothelial surface to activated protein C which is a serine protease with anticoagulant activity, especially in the presence of cofactor protein S. Activated protein C exerts its effect by inhibition of the activated forms of factors V and VIII which results in a decrease in thrombin formation. It has also been shown to have profibrinolytic activity.

Clinical trials.

Congenital protein C deficiency syndrome is a very rare disease (1 per 160,000 to 300,000 births). Due to the rarity of the disease, prospective controlled clinical trials to assess the efficacy and safety of Ceprotin could not be conducted.
Efficacy and the safety were assessed through data collected retrospectively from patients treated over a ten year period (1989-1999). A total of 79 subjects with protein C deficiency were treated under two clinical trial protocols (n = 34 and n = 4) or under compassionate provisions (n = 41). Patients were treated in the USA, Canada and Europe.
Ten patients with severe congenital protein C deficiency were treated for a total 16 episodes of purpura fulminans and another four patients were treated for 6 episodes of coumarin induced skin necrosis. Clinical efficacy was assessed by the investigator in terms of improvement in skin lesions at the end of each treatment course. In all 22 episodes the outcome of treatment was assessed as "markedly improved or healed".

5.2 Pharmacokinetic Properties

Thirteen asymptomatic subjects with homozygous or double heterozygous protein C deficiency were evaluated for pharmacokinetic data. The protein C plasma activity was measured by chromogenic assay. The individual half-lives varied from 4.4 to 15.8 hours using a compartmental model and from 4.9 to 14.7 hours using the non-compartmental method. The individual in vivo recovery ranged from 20.4 to 83.2%. The patients differed significantly in age, body weight and plasma volume. In patients with acute thrombosis, both the increase in protein C plasma levels as well as half-life may be considerably reduced.

5.3 Preclinical Safety Data

Genotoxicity.

Protein C, was not mutagenic in an in vitro test for reverse mutation in S. typhimurium (Ames test).

Carcinogenicity.

Long-term carcinogenicity studies with protein C have not been conducted.

6 Pharmaceutical Particulars

6.1 List of Excipients

Albumin (human), sodium chloride, sodium citrate dihydrate, water for injections (diluent).
No preservative is added to the formulation.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the ARTG. The expiry date can be found on the packaging.
Contains no antibacterial agent. Product is for single use in one patient only. Discard any residue.

6.4 Special Precautions for Storage

Ceprotin should be stored at 2°C to 8°C (in a refrigerator). Do not freeze. Protect from light.

6.5 Nature and Contents of Container

Ceprotin is presented as a white to cream colour lyophilised powder in a single dose vial of neutral glass of either hydrolytic type I (500 IU) or hydrolytic type II (1000 IU). It is accompanied by water for injections (WFI) in vials of neutral glass of hydrolytic type I (5 mL and 10 mL), used as diluent for 500 IU and 1000 IU, respectively. The product and the diluent vials are closed with butyl rubber stoppers.
Each pack also contains: one transfer needle; one filter needle.

Pack size.

1 vial of powder for injection and 1 vial of WFI (diluent).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical name.

Blood coagulation factor XIV (MI).

Chemical structure.

Protein C is synthesized in the liver as a vitamin K dependent plasma protein. It is a two chain molecule consisting of a heavy and a light chain linked by a disulfide bridge. The apparent molecular weight of protein C is 62,000, which includes four N-linked carbohydrate side chains. The molecule contains several distinct domains of structural and functional significance. The 155-amino acid light chain consists of the N-terminal gamma-carboxyglutamic acid domain (with 9 gamma-carboxyglutamic acid residues) followed by two domains with homology to epidermal growth factor. The 252-amino acid heavy chain contains the 12-amino acids activation peptide and the serine protease domain. Upon activation of protein C by thrombin-thrombomodulin complex, the 12-amino acids activation peptides are cleaved off, yielding activated protein C.

CAS number.

60202-16-6.

7 Medicine Schedule (Poisons Standard)

Not scheduled.

Summary Table of Changes