Probumin

Package leaflet: Information for the user

Probumin 200 g/l solution for infusion

Human albumin
Please read this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What Probumin is and what it is used for

Probumin is a human albumin solution derived from human plasma (an important protein in human blood) and belongs to a class of medicines called "Blood substitutes and plasma protein fractions".
Probumin is used to restore and maintain circulating blood volume in patients who have lost blood and/or body fluids for any reason, when the use of a colloid is appropriate.
If you have any doubts about the use of Probumin, consult your doctor or pharmacist.

2. What you need to know before using Probumin

Do not use Probumin
If you are allergic (hypersensitive) to human albumin or to any of the other ingredients of this
medicinal product (listed in section 6; see also the section “Important information about some
excipients of Probumin” at the end of this section).

Warnings and precautions
Talk to your doctor or nurse before using Probumin.
If you have previously experienced symptoms of an allergic reaction (hypersensitivity, such as breathing
difficulties, feeling weak, or other symptoms) to human albumin, inform your doctor or nurse immediately.
Suspected allergic or anaphylactic reactions require immediate discontinuation of the infusion. In case
of shock, standard medical treatments for shock must be initiated.
Albumin should be administered with caution in conditions where hypervolemia (increased blood
volume) and its consequences, or hemo-dilution (i.e. blood dilution), may pose a particular risk to you.

• If you suffer from any of the following conditions, inform your doctor:
  • Decompensated heart failure (reduced cardiac performance)
  • Arterial hypertension (increased blood pressure)
  • Oesophageal varices (dilated veins in the oesophagus)
  • Pulmonary edema (fluid accumulation in the lungs)
  • Hemorrhagic diathesis (tendency to bleed)
  • Severe anemia (deficiency of red blood cells and/or oxygen-carrying substance)
  • Renal and post-renal anuria (absence of urine production)
    These conditions may contraindicate the therapeutic use of Probumin or may lead your doctor to adjust the dose or infusion rate to avoid complications.

Albumin solutions must not be diluted with water for injections, as this may cause haemolysis (rupture of red blood cells) in recipients.
If large volumes of blood need to be replaced, your doctor must monitor coagulation and hematocrit (the proportion of blood cells in the blood). Your doctor will take all necessary measures to adequately replace blood components (coagulation factors, electrolytes, platelets, and red blood cells).
Human albumin solution is more concentrated than plasma; therefore, when concentrated albumin is administered, your doctor must ensure you are adequately hydrated and must monitor you closely to prevent circulatory overload and hyperhydration (i.e. heart and circulation problems due to fluid accumulation).
If the dose and infusion rate are not adjusted according to your circulatory status, you may experience symptoms indicating increased blood volume (hypervolemia). If you notice any of the following symptoms, inform your doctor immediately, as the infusion must be stopped promptly: headache, dyspnea (difficulty breathing), jugular vein distension (swelling of the neck veins), increased blood pressure, increased venous pressure, pulmonary edema.

For athletes: using this medicine without therapeutic need constitutes doping and may lead to a positive anti-doping test.

Viral safety
When medicinal products are prepared from human blood or plasma, specific measures are taken to prevent transmission of infections to patients. These measures include:

• careful selection of blood and plasma donors to ensure potentially infected donors are excluded,
• testing of each donation and plasma pool for the presence of viruses/infections,
• inclusion of processing steps capable of inactivating or removing viruses during blood or plasma manufacturing.

Despite these measures, when administering medicinal products prepared from human blood or plasma, the possibility of transmitting infectious agents cannot be completely ruled out. This also applies to emerging or unknown viruses or other infectious agents.
No cases of viral infections have been reported with albumin produced using well-established processes and meeting European Pharmacopoeia standards.
It is strongly recommended that each time you receive a dose of Probumin, both the product name and batch number are recorded, to ensure traceability of the batch used.

Children
The safety and efficacy of Probumin in children have not been established in controlled clinical studies.
The use of human albumin in children is based solely on established medical practice. However, clinical experience with human albumin in children suggests that harmful effects are unlikely, provided particular attention is paid to the administered dose to avoid circulatory overload.

Other medicines and Probumin
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
No specific interactions between albumin and other medicines are known.
Probumin must not be mixed with other medicinal products, whole blood, or red blood cell concentrates (except with the diluents recommended in the section “The following information is intended exclusively for doctors or healthcare professionals”).

Pregnancy, breastfeeding and fertility

Pregnancy
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
The safety of Probumin use during pregnancy has not been established in controlled clinical studies. However, clinical experience with albumin suggests that harmful effects on the course of pregnancy, the fetus, or the newborn are unlikely.
In general, particular caution should be exercised when performing plasma volume replacement in pregnant patients.

Breastfeeding
It is not known whether Probumin is excreted in breast milk. Excretion of human albumin in milk has not been studied in animals. The decision whether to continue/stop breastfeeding or to continue/stop therapy with Probumin should be made by weighing the benefits of breastfeeding for the child against the benefits of Probumin therapy for the woman.

Fertility
No animal reproduction studies have been conducted with Probumin 200 g/l. However, albumin is a normal constituent of human blood.

Driving and using machines
No effects on the ability to drive or operate machinery have been observed.

Probumin contains sodium
This medicinal product contains 166.8 mg of sodium (main component of table salt) per 50 ml vial and 333.5 mg per 100 ml vial. This corresponds to 8.3% and 16.7% of the maximum daily dietary intake recommended for an adult, respectively.
This medicinal product contains potassium, less than 1 mmol (39 mg) per 50 ml or 100 ml vial, i.e. essentially ‘potassium-free’.

3. How to use Probumin

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.
Probumin must be administered intravenously (into a vein) by healthcare personnel (by a doctor or nurse).
Your doctor will decide how much product you will receive, the infusion rate, frequency, and duration of treatment with Probumin. All of this will be determined based on your clinical condition.
For instructions on correct use and dosage, refer to the section “The following information is intended exclusively for healthcare professionals”.

Use in children
The safety and efficacy of Probumin in children have not been established in controlled clinical studies, and its use in the pediatric population is based solely on established medical practice. However, clinical experience with albumin suggests that harmful effects in children are not expected.

If you use more Probumin than you should
If the dosage and infusion rate are too high, an increase in blood volume (hypervolemia) may occur. In this case, you may experience symptoms such as headache, dyspnea (difficulty breathing), jugular vein distension (i.e., swelling of the neck veins, which may indicate cardiovascular overload), increased blood pressure, increased central venous pressure, and pulmonary edema (fluid accumulation in the lungs). As soon as you notice any of these symptoms, inform your doctor immediately, as the infusion must be stopped immediately and your circulatory parameters must be closely monitored. Furthermore, depending on the severity of the clinical situation, urine output should be increased and cardiac function improved.
If you have any doubts about using this medicine, consult your doctor.

If you forget to use Probumin
If you have forgotten to take Probumin, inform your doctor immediately and follow their instructions.
Do not administer a double dose to make up for the missed dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
If any of the following side effects occur, contact your doctor immediately:

• Severe allergic reactions such as anaphylactic shock. In such cases, the infusion must be stopped and appropriate treatment initiated. These reactions may occur very rarely.

Other side effects:

• skin redness
• skin rashes (urticaria)
• fever
• nausea
• chills
• hypotension (low blood pressure)
• tremor
• dyspnea (difficulty breathing)

These mild reactions may occur rarely and usually resolve quickly by slowing down or stopping the infusion.
For information on viral safety, see section 2 "What you need to know before using Probumin".
Additional side effects in children and adolescents
There are no specific data available to assess the possible occurrence of different adverse reactions in this population.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist or nurse. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Probumin

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container after "Exp.".
The expiry date refers to the last day of that month.
Store below 30°C. Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
Do not use this medicine if you notice that the solution is cloudy or contains deposits. The presence of cloudiness or deposits may indicate that the protein is unstable or that the solution has been contaminated.
Once the container has been opened, the contents should be used immediately.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Probumin contains

• The active substance is human albumin. One millilitre of Probumin 200 g/l contains 200 mg of human plasma proteins, consisting of at least 95% human albumin.
• The other components are sodium chloride, sodium caprylate, sodium N-acetyltryptophanate and water for injections.

For further information on the components, see also “Probumin contains sodium” at the end of section 2.

Description of the appearance of Probumin and contents of the pack
Probumin is an infusion solution. It is a slightly viscous, clear, almost colourless, yellow, amber or green liquid.
Probumin 200 g/l; 50 ml vial
Probumin 200 g/l; 100 ml vial

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Grifols Italia S.p.A.
Via Torino, 15
56010 Vicopisano
Pisa – ITALY

Manufacturer:
Instituto Grifols, S.A.
Can Guasch, 2 - Parets del Vallès
08150 Barcelona - SPAIN

The following information is intended exclusively for physicians or healthcare professionals:

• Probumin must be administered intravenously, either directly or diluted with an isotonic solution (e.g. 5% glucose or 0.9% sodium chloride). Mixing with electrolyte solutions should be performed under aseptic conditions.
• Do not dilute albumin solutions with water for injections, as this may cause haemolysis in the recipient.
• Do not mix human albumin with other medicinal products, whole blood or red blood cell concentrates.
• Infusion must be administered intravenously using a sterile, pyrogen-free, single-use infusion set. Before inserting the infusion set into the vial stopper, disinfect the stopper with an antiseptic solution. Once the vial is opened, the contents should be infused immediately.
• The concentration of the albumin preparation, dosage and infusion rate must be determined according to the individual patient's needs.
• The required dose depends on the patient's physical condition, severity of trauma or illness, and ongoing losses of body fluids and proteins. The necessary dose should be determined based on the assessment of circulating volume adequacy, and not according to plasma albumin levels.
• The infusion rate should be established according to the patient's individual clinical condition and indication. During plasmapheresis, the infusion rate should be adjusted according to the removal rate.
• Hypervolaemia may occur if dosage and infusion rate are not adjusted to the patient's circulatory status. At the first signs of cardiovascular overload (headache, dyspnoea, jugular vein distension), increased arterial or venous blood pressure, or pulmonary oedema, the infusion must be stopped immediately.
• If large volumes are to be administered, the product should be warmed to room or body temperature before use.
• When administering concentrated albumin, ensure adequate hydration of the patient. Patients should be closely monitored to avoid circulatory overload and fluid overload.
• When administering albumin, the patient's electrolyte status should be monitored and normal electrolyte balance should be restored or maintained.
• Adequate replacement of other blood components (coagulation factors, electrolytes, platelets and red blood cells) must be ensured.