PLASMAGRADE 200 ML Инфузионный раствор

Содержание инструкции

1. PLASMAGRADE solution for infusion
   1. What is PLASMAGRADE and what is it used for
   2. What you need to know before using PLASMAGRADE
   3. How to use PLASMAGRADE
   4. Possible side effects
   5. How to store PLASMAGRADE
   6. Package contents and other information

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

1. What is PLASMAGRADE and what is it used for

PLASMAGRADE is a human plasma frozen AB0 specific group solution containing
all the normal components of plasma such as albumin, immunoglobulins and other globulins, coagulation factors, complement factors and their inhibitors. The content and distribution of
plasma proteins in PLASMAGRADE are comparable to those of fresh frozen plasma
(FFP), i.e. 45-70 mg/ml.
PLASMAGRADE 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 PLASMAGRADE.
PLASMAGRADE 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 for 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;

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• Resolution of fibrinolytic activity (dissolution of fibrin clots which can cause bleeding) and rapid resolution of the effect of oral anticoagulants (coumarin or indanedione type) 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 blood, plasma, from the cellular component and the removal of substances present in it);
• In intensive plasmapheresis procedures, PLASMAGRADE must be used exclusively to correct coagulation abnormalities during severe bleeding.

2. What you need to know before using PLASMAGRADE

Do not use PLASMAGRADE
if you are allergic (hypersensitive) to plasma proteins or to 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 previously experienced reactions to human plasma products or fresh frozen plasma.

Warnings and precautions
Talk to your doctor or nurse before using PLASMAGRADE.
Be particularly careful with PLASMAGRADE

• 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 obstruction of a vein by a blood clot or thrombus).

PLASMAGRADE 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 specific factor concentrates are available.
• to correct hyperfibrinolysis (massive uncontrolled dissolution of fibrin clots which can cause bleeding) due to plasmin inhibitor deficiency (alpha2 antiplasmin) because dilution with SD plasma treatment, which contains low levels of alpha2 antiplasmin, may reduce levels of alpha2 antiplasmin.

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The doctor or another healthcare professional will monitor you closely and observe you carefully
during the entire infusion period with PLASMAGRADE to verify that there are no
reactions.
As with any intravenous protein product, hypersensitivity reactions of an allergic type are possible.
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 aforementioned symptoms during the administration of the product, you should immediately inform
the doctor or healthcare professional present, as these symptoms may be the
first 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 should be initiated.

Children
The safety and efficacy of PLASMAGRADE in children have not yet been established.
In premature infants, available data on the use of PLASMASAFE ( which has the same pharmaceutical

form and qualitative-quantitative composition as PLASMAGRADE) are very limited, therefore,
the product should only be administered if the benefits are clearly evident compared to the
potential risks.

PLASMAGRADE 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 recommended maximum daily intake with the diet of an
adult.

Viral safety of PLASMAGRADE
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 some 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.

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Parvovirus B19 infection can be severe in pregnant women (fetal infection) and in
individuals whose immune system is depressed 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 PLASMAGRADE, 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 PLASMAGRADE
Tell your doctor or nurse if you are taking, have recently taken or might take
any other medicines.
During clinical studies, the human plasma protein solution with the same pharmaceutical
form and qualitative-quantitative composition as PLASMAGRADE, has been administered in
association with various medications and no interactions have been identified.
PLASMAGRADE should 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 should not be administered through the same infusion line.

PLASMAGRADE 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 use of PLASMAGRADE in pregnancy has not been established in controlled clinical
studies. The product should therefore be administered in pregnancy or during breastfeeding
only if clearly indicated.
For the potential risk of parvovirus B19 transmission, see the “Warnings and
precautions” section.

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

3. How to use PLASMAGRADE

PLASMAGRADE can only be used in hospitals or clinics and nursing homes by
medical professionals or other healthcare operators.
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• The administration of PLASMAGRADE must be based on AB0 group compatibility.
• In emergency cases, PLASMAGRADE group AB can be considered as universal plasma, as it can be administered to any patient. 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 PLASMAGRADE/Kg of body weight (for an increase in the levels of the
deficient coagulation factor of approximately 25%) represents a generally
accepted starting dose.
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 based on 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 PLASMAGRADE 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:

• immediate or delayed hemolytic transfusion reactions due to incompatibility between antibodies present in FFP and recipient red blood cell antigens (therefore, the administration of PLASMAGRADE 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 (low platelet count).
• allergic reactions from acute to severe such as anaphylactic or anaphylactoid reactions, characterized for example by skin flushing, hypotension, substernal pain, bronchospasm,

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dyspnea (difficulty breathing) and cardio-respiratory collapse, due to hypersensitivity to the
infused proteins or to anti-IgA antibodies.
Since PLASMAGRADE does not contain whole cells (red blood cells, white blood cells and platelets) the
risk of immunization is reduced.
The infusion of PLASMAGRADE 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 PLASMAGRADE:

Common:

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

Uncommon:

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

Additional adverse 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
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 PLASMAGRADE

Keep this medicine out of the sight and reach of children.
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Do not use this medicine after the expiry date which is stated on the label and on the packaging.
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.
Once the bag has been opened, the product must be used immediately.
Do not dispose of any medicine in wastewater or household waste.
Ask your pharmacist how to dispose of medicines you no longer use. This will help to protect
the environment.

6. Package contents and other information

What PLASMAGRADE contains
One 200 ml bag contains 9 - 14 g of human plasma proteins as the active ingredient
The other components are: disodium citrate dihydrate, disodium hydrogen phosphate, glycine.

Description of the appearance of PLASMAGRADE and contents of the pack
Solution for exclusive intravenous use.
The PLASMAGRADE 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 PLASMAGRADE must be based on ABO blood group compatibility. In
emergency cases, PLASMAGRADE group AB can be considered as universal plasma,
as it can be administered to any patient.
PLASMAGRADE must be used with cautionin the following conditions:

• IgA deficiency.
• Latent or manifest heart failure.
• Pulmonary edema.

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• In patients with an increased risk of thrombotic complications due to a potential increase in the risk of venous thromboembolism resulting from the reduced activity of protein S in PLASMAGRADE compared to fresh frozen plasma from a single donor.
• In patients who may require massive transfusion, such as in liver transplantation or other conditions with complex hemostasis disorders, particular attention should be paid to symptoms indicating a tendency to excessive bleeding.

PLASMAGRADE 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 concentrates of specific factors are available.
• To correct hyperfibrinolysis due to alpha2 antiplasmin deficiency, as dilution with SD plasma may reduce alpha2 antiplasmin levels.

Patients must be observed 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 to moderate bleeding or minor surgery in
patients with coagulation factor deficiencies is usually achieved after infusion of 5-20 ml
of PLASMAGRADE/kg body weight (for an increase in the level of the
deficient coagulation factor of 10-33%).
In cases 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 PLASMAGRADE.
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, as
the dosage for each indication is given by body weight and adjusted according to the clinical outcome
of the aforementioned conditions.

Route of administration
PLASMAGRADE 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 body weight/minute.
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The toxic effects of citrate can be minimized by administering calcium gluconate in
another vein.

Instructions for correct use

• 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 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 approximately 37°C before infusion.
• The temperature of PLASMAGRADE should not exceed 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 PLASMAGRADE than intended is administered
High doses or infusion rates may induce hypervolemia, pulmonary edema and/or
heart failure.
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 applied, as defined by the general guidelines for shock therapy:

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