PLASMASAFE 200 ML Инфузионный раствор

Содержание инструкции

1. PLASMASAFE solution for infusion
   1. What is PLASMASAFE and what is it used for
   2. What you need to know before using PLASMASAFE
   3. How to use PLASMASAFE
   4. Possible side effects
   5. How to store PLASMASAFE
   6. Contents of the pack and other information

PLASMASAFE solution for infusion

Frozen human plasma
AB0 specific group
treated with solvent-detergent

Read this leaflet carefully before using this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If any side effects occur, including those not listed in this leaflet, ask your doctor or nurse. See section 4.

Contents of this leaflet:

• 1. What PLASMASAFE is and what it is used for
• 2. What you need to know before using PLASMASAFE
• 3. How to use PLASMASAFE
• 4. Possible side effects
• 5. How to store PLASMASAFE
• 6. Contents of the pack and other information

1. What is PLASMASAFE and what is it used for

PLASMASAFE is a human plasma solution, frozen AB0 specific group, containing all the normal
plasma components such as albumin, immunoglobulins and other globulins, coagulation factors,
complement factors and their inhibitors. The content and distribution of plasma proteins in
PLASMASAFE are comparable to those of fresh frozen plasma (FFP), i.e. 45-70 mg/ml.
PLASMASAFE presents coagulation activity values close to the corresponding values of normal human FFP
and each factor is present at a minimum concentration of 0.5 IU/ml.
Furthermore, as a result of solvent - detergent (SD) treatment and purification, the content
of lipids and lipoproteins is reduced. This has no effect on the indications of PLASMASAFE.
PLASMASAFE has the same indications as FFP and is used in the following therapies:

• Combined deficiencies of coagulation factors such as consumption coagulopathies (alteration of the blood coagulation mechanism), such as disseminated intravascular coagulation (DIC, acquired thrombo-hemorrhagic syndrome), or coagulopathies due to severe liver failure or massive transfusions;
• Replacement therapy in coagulation factor deficiencies, in emergency situations when a concentrate of a specific coagulation factor is not available, such as factor V or factor XI, or when a specific laboratory diagnosis is not possible;
• Resolution of fibrinolytic activity (dissolution of fibrin clots which can cause bleeding) and rapid resolution of the effect of oral anticoagulants (coumarin or

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indanedione) when the action of vitamin K is insufficient due to reduced liver function
or in emergency situations;

• Thrombotic Thrombocytopenic Purpura (TTP, severe acute blood disease), generally in association with plasmapheresis (therapeutic procedure that allows the separation of the liquid component of the blood, plasma, from the cellular component and the removal of substances present in it);
• In intensive plasmapheresis procedures, PLASMASAFE must be used exclusively to correct coagulation abnormalities during severe bleeding.

2. What you need to know before using PLASMASAFE

Do not use PLASMASAFE
if you are allergic (hypersensitive) to plasma proteins or any of the other ingredients
of this medicine (listed in section 6);
if you know you have antibodies against Immunoglobulin IgA (IgA deficiency with documented
presence of anti-IgA antibodies);
if you know you have low levels of protein S (a vitamin K-dependent protein in the blood);
if you have had previous reactions to human plasma products or fresh frozen plasma.

Warnings and precautions
Talk to your doctor or nurse before using PLASMASAFE.
Pay particular attention with PLASMASAFE

• if you have low blood levels of immunoglobulin A;
• if you have previously had allergic reactions to plasma proteins, including fresh frozen plasma;
• if you suffer from heart failure or pulmonary edema (fluid in the lungs);
• if you have an increased risk of thrombotic complications (blood clots), due to a potential increase in the risk of venous thromboembolism (partial or complete blockage of a vein, by a blood clot or thrombus).

PLASMASAFE must not be used:

• as a plasma expander in patients in whom no deficiency of coagulation factors has been documented;
• in cases of bleeding caused by von Willebrand disease (vWD disease due to a genetic dysfunction characterized by spontaneous bleeding) or other coagulation deficiencies when concentrates of specific factors are available;
• to correct hyperfibrinolysis (massive uncontrolled dissolution of fibrin clots that can cause bleeding) due to plasmin inhibitor deficiency (alpha2 antiplasmin) because dilution with SD-treated plasma, which contains low levels of alpha2 antiplasmin, may reduce alpha2 antiplasmin levels.

The doctor or another healthcare professional will monitor you closely and observe you carefully
during the entire infusion period with PLASMASAFE to verify that there are no reactions.
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As with any intravenous protein product, hypersensitivity reactions of type
allergic may occur.
Symptoms such as fever, skin manifestations (rash, erythematous rash and urticaria), feeling of cold/chills with or without fever, nausea
with or without vomiting, local edema (swelling) and allergic or anaphylactic reactions (severe and
rapid allergic reaction) may occasionally occur.
If you notice any of the symptoms listed during the administration of the product, you should immediately notify
the doctor or healthcare professional present, as these symptoms may be the
early signs of an allergic reaction.
In case of adverse reactions, the doctor will decide whether the infusion rate should be reduced or
the infusion stopped, depending on the type and severity of the adverse events
In case of shock, standard medical treatment for shock must be initiated.

Children
The safety and efficacy of PLASMASAFE in children have not yet been established.
In premature infants, the available data on the use of PLASMASAFE are very limited, therefore the
product should only be administered if the benefits are clearly evident compared to the
potential risks.

Viral safety of PLASMASAFE
Medicines prepared from human blood or plasma undergo a number of safety measures
to prevent the transmission of infections to patients. These measures include:

• careful selection of blood and plasma donors to ensure that potentially infected donors are excluded;
• testing of each donation and plasma pool for the presence of viruses;
• the introduction into the processing of blood and plasma of certain steps capable of inactivating or removing viruses. Despite these measures, when administering medicines prepared from human blood or plasma, the possibility of transmitting an infection cannot be completely excluded. This also applies to viruses, or other types of infectious agents, emerging or unknown. The measures taken are considered effective for enveloped viruses such as the human immunodeficiency virus (HIV), the hepatitis B virus (HBV), the hepatitis C virus (HCV) and for the non-enveloped hepatitis A virus (HAV). The measures taken may have limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection can be severe in pregnant women (fetal infection) and in individuals with a compromised immune system or who have some type of anemia (e.g. sickle cell anemia or hemolytic anemia).

It is strongly recommended that each time you receive a dose of PLASMASAFE, the name and
batch number of the product are recorded, in order to maintain traceability between the
patient and the batch of product used.
The doctor may recommend that you get vaccinated against hepatitis A and B if you receive
regularly/repeatedly medicines derived from blood or plasma.

Other medicines and PLASMASAFE
Tell your doctor or nurse if you are taking, have recently taken or might take
any other medicines.
During clinical studies, human plasma protein solution, which has the same pharmaceutical
form and qualitative-quantitative composition as PLASMASAFE, has been administered in association
with various medications and no interactions have been identified.
PLASMASAFE must not be mixed with other medicines due to the possibility of inactivation or
precipitation.
The product can be mixed with red blood cells and platelets.
To avoid the formation of clots, solutions containing calcium must not be administered through the same infusion line.
No interactions with other drugs are known.

PLASMASAFE with food, drinks and alcohol
No effects have been observed.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant, are planning to become pregnant or are breastfeeding
ask your doctor or pharmacist for advice before using this medicine.
The safety of PLASMASAFE use in pregnancy has not been established in controlled clinical
studies. The product should therefore only be administered during pregnancy or breastfeeding
if clearly indicated.
For the potential risk of parvovirus B19 transmission, see the “Warnings and
precautions” section.

Driving and operating machinery
After an outpatient infusion with PLASMASAFE, the patient should be kept at rest for
one hour.
PLASMASAFE does not alter or negligibly alters the ability to drive vehicles or operate
machinery.

PLASMASAFE contains sodium
This medicine contains up to a maximum of 0.92 g of sodium (the main component of table
salt) per 200 ml bag.
This is equivalent to 46% of the maximum recommended daily intake with the diet of an
adult.

3. How to use PLASMASAFE

PLASMASAFE can only be used in hospitals or clinics and nursing homes by
medical professionals or other healthcare operators.

• The administration of PLASMASAFE must be based on AB0 group compatibility.
• In emergency cases, PLASMASAFE group AB can be considered as universal plasma, given that it can be administered to any patient.

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For Instructions on correct Use and Dosage, refer to the section “The following information is
intended exclusively for doctors or healthcare operators”.
Treatment must begin under the supervision of a physician.
The dose and treatment regimen depend on the individual clinical situation and underlying
diseases, but 12-15 ml of PLASMASAFE /Kg of body weight represents a generally accepted starting dose (for an increase in the levels of the deficient coagulation factor of approximately
25%).
The doctor will determine the dose and treatment regimen suitable for you.

Use in children
The dosage in children and adolescents (0-18 years) is not different from that of adults since the
dosage for each indication is given per body weight and adjusted according to their clinical response.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Adverse reactions known to be associated with the administration of Fresh Frozen Plasma (FFP),
may also occur with PLASMASAFE and include:
Common:

• allergic reactions from acute to mild (e.g. urticaria, fever, chills, nausea, vomiting, abdominal or lower back pain) due to hypersensitivity to the infused proteins.

Uncommon:

• citrate toxicity which manifests through the following symptoms: fatigue, paresthesia (altered sensitivity of the limbs or other parts of the body), tremors and hypocalcemia (decreased amount of calcium in the blood) during plasma exchange procedures.

Rare:

• transfusional hemolytic reactions of an immediate or delayed type due to incompatibility between antibodies present in FFP and erythrocyte antigens of the recipient (therefore the administration of PLASMASAFE must be based on AB0 group compatibility);
• acute lung injury (a syndrome known as transfusion-related acute lung injury characterized by chills, fever, non-productive cough and dyspnea) caused by anti-leukocyte antibodies with high activity;
• post-transfusion passive purpura (PTP), induced by specific anti-platelet antibodies with high activity and characterized by dyspnea (difficulty breathing), skin rash, fever, generalized purpura (severe acute blood disease) and marked thrombocytopenia (number of platelets lower than normal).
• allergic reactions from acute to severe such as anaphylactic or anaphylactoid reactions, characterized for example by skin redness, hypotension, substernal pain, bronchospasm, dyspnea (difficulty breathing) and cardio-respiratory collapse, due to hypersensitivity to the infused proteins or to anti-IgA antibodies.

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Since PLASMASAFE does not contain whole cells (red blood cells, white blood cells and platelets) the
risk of immunization is reduced.
Infusion of PLASMASAFE may give rise to antibodies against coagulation factors.
High infusion rates can cause cardiovascular effects as a result of citrate toxicity
(decrease in plasma ionized calcium levels) especially in patients with disorders
of liver function.
The following data are based on adverse reactions observed in clinical studies conducted on a population of
199 patients treated with human plasma proteins that have the same pharmaceutical form and
qualitative and quantitative composition as PLASMASAFE:

Common:

• skin manifestations (rash, erythematous rash and urticaria)
• chills with or without fever
• fever
• localized edema (localized swelling)
• nausea with or without vomiting

Uncommon:

• pruritus (itching)
• pulmonary manifestations (cough, asthma and polypnea)
• hypocalcemia (decreased amount of calcium in the blood)
• anaphylactoid reactions (severe and rapid allergic reaction)

Additional side effects in children
No specific data are available for the pediatric population.

Reporting of side effects
If you get any side effects, even if not listed in this leaflet, tell your doctor or nurse. You can also
report side effects directly through https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the
safety of this medicine.

5. How to store PLASMASAFE

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 and on the packaging.
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The expiry date refers to the last day of that month.
The product must be stored at a temperature below or equal to -18°C and protected from light.
The product must be used within 4 hours of thawing if kept at 20°C ÷ 25°C or within 8
hours if kept at 4°C.
See the expiry date stated on the packaging.
The expiry date refers to the product in intact packaging, correctly stored.
After opening the bag, the product must be used immediately.
Do not dispose of any medicine in the drain or in household waste.
Ask your pharmacist how to dispose of medicines you no longer use. This will help to protect
the environment.

6. Contents of the pack and other information

What the contents arePLASMASAFE
In a 200 ml bag the active ingredient consists of 9 - 14 g of human plasma proteins
The other components are: disodium citrate dihydrate, disodium hydrogen phosphate, glycine.

Description of the appearanceof PLASMASAFE and contents of the pack
Solution for exclusive intravenous use.
The PLASMASAFE pack is a 200 ml bag.

Marketing Authorisation Holder
Kedrion S.p.A. - Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca).
Manufacturer
Kedrion S.p.A. - S.S. 7 bis Km 19,5, S. Antimo (Napoli).
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The following information is intended exclusively for doctors or healthcare professionals:
Warnings and Precautions
The administration of PLASMASAFE must be based on ABO blood group compatibility. In cases of
emergency, PLASMASAFE group AB can be considered as universal plasma, as it can be
administered to any patient.
PLASMASAFE must be used with cautionin the following conditions:

• IgA deficiency;
• Latent or manifest cardiac decompensation;
• Pulmonary edema;
• In patients with an increased risk of thrombotic complications due to a potential increase in the risk of venous thromboembolism resulting from reduced protein S activity in PLASMASAFE compared to fresh frozen plasma from a single donor;

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• In patients who may require massive transfusion, such as in liver transplantation or other conditions with complex hemostasis disorders, particular attention must be paid to symptoms indicating a tendency to excessive bleeding.

PLASMASAFE must notbe used:

• As a plasma expander in patients in whom no deficiency of coagulation factors has been documented;
• In cases of bleeding caused by von Willebrand's disease or other coagulation deficiencies when specific factor concentrates are available;
• To correct hyperfibrinolysis due to alpha2 antiplasmin deficiency, as dilution with SD plasma may reduce alpha2 antiplasmin levels.

Patients must be monitored for at least 20 minutes after administration.

Dosage
It is important to monitor the response, both clinically and by measuring

• prothrombin time (PT),
• partial thromboplastin time (PTT)
• and/or the dosage of specific coagulation factors.

Dosage for coagulation factor deficiencies:
Adequate hemostatic effect in mild and moderate bleeding or minor surgery in
patients with coagulation factor deficiencies is normally achieved after infusion of 5-20 ml of
PLASMASAFE/Kg of body weight (for an increase in the levels of the deficient coagulation factor of
10-33%).
In case of severe bleeding or major surgery, it is necessary to consult an expert hematologist.
Dosage for PTT and bleeding in intensive plasmapheresis procedures:
In patients with PTT, the entire plasma volume should be replaced with PLASMASAFE.
In case of severe bleeding during intensive plasmapheresis procedures, it is necessary to consult an
expert hematologist.
Paediatric population
The dosage in children and adolescents (0-18 years) is not different from that of adults because
the dosage for each indication is given per body weight and adjusted according to the clinical outcome
of the aforementioned conditions.

Route of administration
PLASMASAFE must be administered by intravenous infusion after thawing, as
described in the following section “Instructions for correct use”, using an infusion set
with filter. Aseptic technique must be used throughout the infusion.
Due to the risk of citrate toxicity, the infusion rate should not exceed 0.020-0.025
mmol of citrate/kg of body weight/minute.
The toxic effects of citrate can be minimized by administering calcium gluconate in
another vein.

Instructions for correct use
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• Thaw the product by keeping the bag in a water bath with good circulation at a temperature between 35°C - 37°C. It is important to ensure that the water does not contaminate the opening of the bag.
• The temperature in the water bath should never exceed 37°C and should never fall below 35°C. Bring the contents of the bag to a temperature of about 37°C before infusing.
• The temperature of PLASMASAFE should not be higher than 37°C.
• Thawing should not take more than 30 minutes.
• Remove the outer packaging and check that the bag has no leaks or breaks.
• Do not shake.
• Do not use solutions that are cloudy or contain deposits.

The thawed product must not be refrozen. Unused product must be discarded.

If more than the prescribed dose ofPLASMASAFEis administered
High doses or infusion rates can induce hypervolemia, pulmonary edema and/or
cardiac decompensation.
High infusion rates can cause cardiovascular effects as a result of citrate toxicity (decrease in plasma ionized calcium levels), especially in patients with impaired
liver function.
Emergency measures for adverse reactions
Depending on the type and severity of the adverse reactions, the infusion may be stopped and appropriate resuscitation measures must be applied, as defined by the general guidelines for shock therapy:

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Disposal
Unused medicinal product and waste materials derived from such medicinal product must be disposed of in
accordance with local regulations.
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