Beriplex p/n 1000
Poland
Table of Contents
- 1. What Beriplex P/N 1000 is and what it is used for
- 2. Important information before using Beriplex P/N 1000
- 3. How to use Beriplex P/N 1000
- 4. Possible adverse reactions
- 5. How to store Beriplex P/N 1000
- 6. Contents of the pack and other information
- Information intended exclusively for medical professionals
Beriplex P/N 1000
Powder and solvent for solution for injection
Human prothrombin complex concentrate
Please read the entire leaflet before using the medicine, as it contains
important information for the patient.
- Keep this leaflet for future reference
- Consult your doctor or pharmacist if you have any further questions
- This medicine has been prescribed for a specific individual. Do not give it to others.
- The medicine may harm another person, even if their symptoms are the same.
- If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.
Leaflet contents:
- What Beriplex P/N 1000 is and what it is used for
- Important information before using Beriplex P/N 1000
- How to use Beriplex P/N 1000
- Possible side effects
- How to store Beriplex P/N 1000
- Contents of the pack and other information
1. What Beriplex P/N 1000 is and what it is used for
What is Beriplex P/N 1000?
Beriplex P/N 1000 is available as a powder with a solvent provided. It is a white or slightly coloured powder or a brittle, solid mass. The reconstituted solution is intended for intravenous injection.
Beriplex P/N 1000 is manufactured from human plasma (the liquid part of blood) and contains human clotting factors II, VII, IX, and X. Concentrates containing these clotting factors are known as prothrombin complex products. Vitamin K-dependent clotting factors II, VII, IX, and X play an important role in the blood coagulation process. Deficiency of any of these clotting factors results in blood not clotting as quickly as it should, increasing the risk of bleeding. Replenishing clotting factors II, VII, IX, and X by administration of Beriplex P/N 1000 restores the normal blood clotting mechanism.
What is Beriplex P/N 1000 used for?
Beriplex P/N 1000 is used to prevent (during surgical procedures) and treat bleeding caused by acquired or congenital deficiency of vitamin K-dependent clotting factors II, VII, IX, and X in blood, when a medicine containing purified, specific clotting factor is not available.
2. Important information before using Beriplex P/N 1000
The following section contains information that both the patient and physician should review before
using Beriplex P/N 1000.
When NOT to use Beriplex P/N 1000:
if the patient is allergic to the active substances or any of the other ingredients
of this medicine (listed in section 6).
The patient should inform the doctor about any allergies to medicines or food.
if there is an increased risk of blood clots (patients in risk groups for disseminated
intravascular coagulation).
in case of allergic reaction to heparin causing low platelet count (heparin-induced thrombocytopenia type II, HIT type II).
The patient should inform the doctor or pharmacist if such a condition exists.
Warnings and precautions
Before starting treatment with Beriplex, discuss this with your doctor or pharmacist.
- In acquired deficiency of vitamin K-dependent coagulation factors, which may result from taking vitamin K antagonist drugs. Beriplex P/N 1000 may be used only when rapid correction of prothrombin complex factor levels is required, e.g., in cases of severe bleeding or emergency surgery.
- In congenital deficiency of any vitamin K-dependent coagulation factor, a product containing the specific factor should be used whenever possible.
- If an allergic or anaphylactic reaction (serious allergic reaction causing severe breathing problems or dizziness) occurs: Administration of Beriplex P/N 1000 must be stopped immediately (e.g., discontinue injection).
- If there is a risk of increased blood clot formation in blood vessels (thrombosis), particularly in the following cases:
- in patients after heart attack (with diagnosed coronary artery disease or myocardial infarction)
- in patients with liver disease
- in patients immediately before and after surgical procedures
- in newborns
- in patients with increased risk of thrombosis (patients at risk of thromboembolic disease or disseminated intravascular coagulation, or with spontaneous deficiency of coagulation inhibitors)
- If there is an increased risk of coagulation disorders caused by increased consumption of platelets or coagulation factors. Treatment with Beriplex P/N 1000 may be initiated only after treatment of the underlying disease has been completed.
- Heparin-induced reduction in platelet production (heparin-induced thrombocytopenia, HIT type II). Heparin, a protein whose action results in clot dissolution, is a component of Beriplex. A significant decrease in platelet count may be associated with:
- formation of blood clots in the veins of the lower limbs,
- increased tendency to form clots,
- in some cases, skin rash at the injection site,
- petechiae, and
- presence of tarry stools. In such cases, heparin action may be impaired (heparin tolerance). If these symptoms occur, administration of the medicine must be stopped immediately and the doctor should be contacted. Heparin-containing medicines should not be used in the future.
- A specific form of kidney inflammation has been reported after treatment of patients with hemophilia B who have inhibitors to factor IX. These patients had a history of allergic reactions.
The physician should weigh the benefits of Beriplex P/N 1000 therapy against the risk of the
complications listed above.
Viral safety
When medicines are derived from human blood or human plasma, various methods are used to
prevent transmission of infectious agents to patients. These include:
- careful selection of blood and plasma donors to exclude the possibility of transmission of infectious agents,
- testing individual donors and plasma pools for the presence of viruses and other infections,
- inclusion of steps during manufacturing intended to inactivate or remove viruses.
Despite these safeguards, when using medicines derived from human blood or
plasma, it cannot be completely ruled out that infectious diseases may occur due to the potential
transmission of infectious agents. This also applies to pathogens not yet known
and other types of infections.
The methods used are considered effective against enveloped viruses such as human
immunodeficiency virus (HIV, the virus causing AIDS), hepatitis B virus, hepatitis
C virus (viral hepatitis), and the non-enveloped hepatitis A virus (viral hepatitis) and parvovirus B19.
The physician may recommend appropriate vaccination against hepatitis A and B
if medicines derived from human plasma are administered regularly or repeatedly.
It is strongly recommended that each time Beriplex P/N 1000 is administered,
the name and batch number of the medicine be recorded in the medical records to document the batches used.
Other medicines and Beriplex P/N 1000
- Inform your doctor or pharmacist about all medicines currently taken or recently taken, as well as any medicines the patient plans to take.
- Beriplex P/N 1000 may inhibit the action of vitamin K antagonists. Interactions with other medicines are not known.
- Beriplex P/N 1000 must not be mixed with other medicines, except those mentioned in section 6.
Pregnancy, breastfeeding, and fertility
- During pregnancy, breastfeeding, or if pregnancy is suspected, or when planning pregnancy, consult a doctor or pharmacist before using this medicine.
- In women who are pregnant or breastfeeding, Beriplex P/N 1000 should be used only when clearly indicated.
- There are no available data on the effect on fertility.
Driving and operating machinery
There are no adequate studies documenting the effect of this medicine on driving
and operating machinery.
Beriplex P/N 1000 contains sodium
Beriplex P/N 1000 contains up to 343 mg of sodium (approximately 15 mmol) per 100 ml. This amount should be taken into account in patients on a controlled sodium diet.
3. How to use Beriplex P/N 1000
Treatment should be initiated under the supervision of a physician experienced in the therapy of this type of disorder.
Dosage
The recommended dose of factors II, VII, IX and X, as well as the duration of treatment, depends on several factors, such as body weight, severity and course of the disease, location and intensity of bleeding, and the need to prevent bleeding during surgery or diagnostic procedures (see section “Information intended exclusively for healthcare professionals”).
If you have any doubts regarding the use of this medicine, please consult your doctor or pharmacist.
Overdose
During treatment, the physician should regularly monitor coagulation parameters.
Administration of high doses of prothrombin complex concentrate has been associated with myocardial infarction, development of disseminated intravascular coagulation, and formation of thrombi in blood vessels in patients at increased risk of these disorders.
4. Possible adverse reactions
Like all medicines, this medicine can cause adverse reactions, although not everybody will experience them.
The following adverse reactions have been observed frequently (in less than 1 in 10 patients):
- Risk of increased thrombosis (see section 2)
- Headache
- Increase in body temperature
The following adverse reactions have been observed uncommonly (in less than 1 in 100 patients):
- Hypersensitivity or allergic reactions (see section 2)
The frequency of the following adverse reactions is unknown (cannot be estimated from the available data):
- Severe bleeding due to excessive coagulation
- Anaphylactic reactions including shock (see section 2)
- Formation of circulating antibodies inhibiting one or more coagulation factors
Children and adolescents
There is no data available on the use of Beriplex in children and adolescents.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.
5. How to store Beriplex P/N 1000
- Keep the medicine out of the sight and reach of children.
- Do not use Beriplex P/N 1000 after the expiry date stated on the label and carton.
- Do not store above 25°C.
- Do not freeze.
- Store the vial in the outer packaging to protect from light.
- Beriplex P/N 1000 does not contain preservatives; the reconstituted product should be used immediately.
6. Contents of the pack and other information
What Beriplex P/N 1000 contains
Beriplex P/N 1000 contains 800–1240 IU of human coagulation factor IX per vial.
The active substance is:
Concentrate of human coagulation factors II, VII, IX and X, protein C and S.
Other components are:
Human antithrombin III, heparin, human albumin, sodium chloride, sodium citrate, HCl or NaOH
(in small amounts, for pH adjustment).
Solvent: Water for injections.
What Beriplex P/N 1000 looks like and contents of the pack
Beriplex P/N 1000 is a white or slightly coloured powder supplied with water for injections as solvent.
The powder should be dissolved in 40 ml of water for injections.
The resulting solution should be clear or slightly opalescent (may shimmer when viewed under light), and must not contain any particulate matter.
Available pack sizes
The 1000 IU pack of Beriplex P/N 1000 contains:
- 1 vial of powder
- 1 vial of 40 ml water for injections
- 1 transfer system 20/20 with filter
Name and address of the marketing authorisation holder and manufacturer:
CSL Behring GmbH
Emil-von-Behring-Str. 76
35041 Marburg
Germany
This medicinal product is authorised in the European Economic Area countries under the following names:
Austria Beriplex P/N 1000 I.E. Pulver und Lösungsmittel zur Herstellung einer Injektionslösung
Belgium Confidex 1000 I.E., poeder en oplosmiddel voor oplossing voor injectie
Bulgaria Beriplex P/N 1000, 1000 IU, Powder and solvent for solution for injection
Croatia Beriplex P/N 1000 IU prašak i otapalo za otopinu za injekciju
Czech Republic Beriplex 1000 IU
Denmark Confidex
Finland Confidex 1000 IU injektiokuiva-aine ja liuotin, liuosta varten
France Confidex 1000 UI, poudre et solvant pour solution injectable
Germany Beriplex P/N 1000
Greece Beriplex P/N
Κόνις και διαλύτης για ενέσιμο διάλυμα 1000IU/vial
Hungary Beriplex P/N 1000 por és oldószer oldatos injekcióhoz
Ireland Beriplex P/N 1000 IU, powder and solvent for solution for injection
Italy Confidex 1000
Luxembourg Confidex 1000 UI poudre et solvant pour solution injectable
Malta Beriplex P/N 1000, powder and solvent for solution for injection
Netherlands Beriplex P/N 1000 IE, poeder en oplosmiddel voor oplossing voor injectie
Norway Confidex 1000 IU pulver og væske til injeksjonsvæske, oppløsning
Poland Beriplex P/N 1000
Portugal Beriplex 1000 UI pó e solvente para solução injectável
Romania Beriplex P/N 1000 UI pulbere și solvent pentru soluție injectabilă
Slovakia Beriplex 1000 IU
Slovenia Beriplex P/N 1000 i.e. prašek in vehikel za raztopino za injiciranje
Spain Beriplex 1000 UI polvo y disolvente para solución inyectable
Sweden Confidex 1000 IE, pulver och vätska till injektionsvätska, lösning
United Kingdom Beriplex P/N 1000 IU, powder and solvent for solution for injection
Date of preparation of the leaflet:
Information intended exclusively for medical professionals
Qualitative and quantitative composition
Beriplex P/N 1000 nominally contains the following international units (IU) of human clotting factors, as stated
in the table below:
| Active ingredient name | Content after reconstitution (IU/ml) | Content per vial Beriplex P/N 1000 (IU) |
| Active substances | ||
| Human blood coagulation factor II | 20 – 48 | 800 – 1920 |
| Human blood coagulation factor VII | 10 – 25 | 400 – 1000 |
| Human blood coagulation factor IX | 20 – 31 | 800 – 1240 |
| Human blood coagulation factor X | 22 – 60 | 880 – 2400 |
| Other active substances | ||
| Protein C | 15 – 45 | 600 – 1800 |
| Protein S | 12 – 38 | 480 – 1520 |
The total protein content after reconstitution is 6 - 14 mg/ml in solution.
The specific activity of factor IX is 2.5 IU per mg of total protein.
The activity of all coagulation factors, as well as protein C and S (antigens), has been tested according to current WHO international standards.
Dosage and administration
Dosage
The following are only general dosage guidelines.
The dose and frequency of administration should be individually calculated for each patient. The intervals between doses should be adjusted according to the half-life of the individual coagulation factors belonging to the prothrombin complex. The individual dose is determined based on regular measurements of the plasma activity of individual coagulation factors, or on the basis of laboratory tests generally assessing the function of the prothrombin complex (INR, Quick's index), and through continuous monitoring of the patient's clinical condition.
In the case of major surgical procedures, precise monitoring of substitution therapy is required (tests for individual coagulation factors as well as general tests for prothrombin complex factors).
- Bleeding and perioperative bleeding prophylaxis in treatment with vitamin K antagonists:
The dose of the medicinal product depends on the INR value measured before starting treatment and on the target INR value to be achieved in the patient. The pre-treatment INR should be measured as close as possible to the time of administration to allow accurate calculation of the appropriate dose of Beriplex. The table below specifies the doses (ml/kg body weight of reconstituted product and IU of factor IX/kg body weight) required to achieve normalization of the INR (i.e., INR ≤ 1.3) from various initial INR values.
| INR value before treatment | 2.0 – 3.9 | 4.0 – 6.0 | >6.0 |
| Approximate dose in ml/kg body weight | 1 | 1.4 | 2 |
| Approximate dose in IU (factor IX) per kilogram body weight | 25 | 35 | 50 |
Dosing is based on body weight when it does not exceed 100 kg. In patients with body weight above 100 kg, the maximum single dose (IU of factor IX) should not exceed 2500 IU for INR values of 2.0–3.9, 3500 IU for INR values of 4.0–6.0, and 5000 IU for INR values >6.0.
Normalization of coagulation disorders caused by vitamin K antagonists is usually achieved approximately 30 minutes after injection. Concomitant administration of vitamin K should be considered in patients receiving Beriplex for urgent reversal of vitamin K antagonists, as the effect of vitamin K is typically observed after 4–6 hours.
Repeated dosing of Beriplex in patients requiring urgent reversal of vitamin K antagonists is not supported by clinical studies and therefore is not recommended.
These recommendations are based on clinical trials conducted in a limited number of subjects.
Monitoring of INR values during treatment is necessary, as efficacy and duration of action may vary among individual patients.
- Bleeding and perioperative prophylaxis in patients with congenital deficiencies of any vitamin K-dependent clotting factor when a specific clotting factor preparation cannot be used
The required dose of prothrombin complex concentrate is determined based on clinical studies:
- 1 IU of factor IX per kg of body weight results in an expected increase in plasma factor IX activity of 1.3% (0.013 IU/mL) relative to normal,
- 1 IU of factor VII per kg of body weight increases plasma factor VII activity by 1.7% relative to normal (0.017 IU/mL),
- 1 IU of factor II per kg of body weight increases plasma factor II activity by 1.9% relative to normal (0.019 IU/mL),
- 1 IU of factor X per kg of body weight increases plasma factor X activity by 1.9% relative to normal (0.019 IU/mL).
The dose of each clotting factor is expressed in international units (IU), consistent with the applicable standard for each clotting factor approved by the World Health Organization (WHO). Clotting factor activity in plasma is expressed as a percentage (relative to normal human plasma) or in international units (according to the international standard for the specific clotting factor in plasma).
One international unit (IU) of clotting factor activity equals the activity of that factor present in 1 mL of normal human plasma.
For example, the calculation of the required dose of factor X is based on the empirical observation that 1 IU of factor X per kg of body weight increases plasma factor X activity by 0.019 IU/mL.
The required dose is calculated using the following formula:
Required number of units = body weight [kg] × desired increase in factor X activity [IU/mL] × 53,
where 53 (mL/kg) is the reciprocal of the estimated recovery value.
It should be noted that these calculations are based on data from patients receiving vitamin K antagonists. Calculations based on data from healthy individuals would yield lower required doses.
If an individual recovery value is known, it should be used for calculations.
Product data are available from clinical trials conducted in healthy volunteers (N=15), in the reversal of vitamin K antagonist effects, and in the treatment of acute major bleeding or perioperative bleeding prophylaxis (N=98, N=43).
Children and adolescents
The safety and efficacy of the medicinal product Beriplex P/N 250 in children and adolescents have not yet been established in controlled clinical trials.
Elderly
Dosing and route of administration in elderly patients (>65 years of age) are consistent with general recommendations.
Administration method
General instructions
- The solution should be clear or slightly opalescent. After filtration and after reconstitution and withdrawal of the solution (see below), before administration, check whether it contains visible particles or discoloration. Do not use cloudy solutions or those containing precipitate or particles.
- Reconstitution and withdrawal from the vial must be performed under aseptic conditions.
Reconstitution
Bring the solvent to room temperature.
Ensure that the caps of the vials containing the powder and the solvent have been removed, disinfect the rubber stoppers with an aseptic solution, and allow the stoppers to dry before opening the Mix2Vial packaging.
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Administration and dosing
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Care should be taken to avoid blood entering the syringe filled with the product. This may cause
a reaction of the coagulation factors present in the product and the formation of fibrin clots, which
could be administered to the patient.
If more than one vial of Beriplex product is required, it is possible to combine several vials for administration as a single infusion using a commercially available administration set.
The Beriplex medicinal product solution must not be diluted.
The reconstituted solution should be administered intravenously (no faster than 8 ml/min*).
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.
Special warnings and precautions for use.
There are no clinical data available on the use of Beriplex P/N 1000 in postpartum haemorrhage due to vitamin K deficiency in newborns.
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*In clinical trials of Beriplex, patients weighing below 70 kg were given a recommended dosage with a maximum infusion rate of 0.12 ml/kg/min (below 8 ml/min).
Platelet count monitoring considerations:
Platelet count should be closely monitored.
Interactions with other medicinal products and other forms of interaction
When performing coagulation tests sensitive to the presence of heparin, the heparin dose contained in the product should be taken into account in the test results obtained from patients receiving high doses of prothrombin complex factors.