INTRATECT 50 g/l Solution

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Intratect, 50 g/l, Solution for Infusion
   1. Read the package leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Contents of the Package Leaflet
3. What is Intratect and what is it used for
   1. Intratect is used in adults, children, and adolescents (0-18 years) who have insufficient antibodies (replacement therapy) in the following cases:
   2. Intratect is also used in adults, children, and adolescents (0-18 years) for the treatment of inflammatory diseases (immunomodulation), such as:
4. Important information before using Intratect
   1. When not to use Intratect
   2. Warnings and precautions
   3. Before starting treatment with Intratect, discuss with your doctor, pharmacist, or nurse if:
   4. Warning - reactions
   5. Information on infectious agent transmission
   6. Intratect and other medicines
   7. Effect on laboratory tests
   8. Pregnancy and breastfeeding
   9. Driving and using machines
5. How to use Intratect
   1. Use in children and adolescents
   2. Use of a higher than recommended dose of Intratect
   3. If one infusion is missed
6. Possible side effects
   1. If you notice any of the following symptoms, inform your doctor immediately:
   2. This may be an allergic reaction or a severe allergic reaction (anaphylactic shock) or hypersensitivity.
   3. During clinical trials with Intratect (50 g/l), the following side effects were reported:
   4. The following side effects have been reported spontaneously for Intratect:
   5. Frequency not known (frequency cannot be estimated from available data)
   6. Human immunoglobulin preparations may generally cause the following side effects (in decreasing order of frequency):
   7. Reporting side effects
7. How to store Intratect
8. Contents of the pack and other information
   1. What Intratect contains
   2. What Intratect looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Date of last revision of the package leaflet: 28.05.2023
   5. Information intended for healthcare professionals only:
   6. Special precautions
   7. Dosage
   8. Immunomodulation in the following diseases:
   9. Method of administration
   10. Incompatibilities

Package Leaflet: Information for the User

Intratect, 50 g/l, Solution for Infusion

Human Normal Immunoglobulin (IVIg)

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

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

Contents of the Package Leaflet

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

1. What is Intratect and what is it used for

Intratect is a human blood-derived product that contains antibodies (the body's own defense substances) against diseases, available as a solution for infusion. The solution is ready for intravenous infusion (drip). Intratect contains human normal immunoglobulin (antibodies) from the blood of donors from a broad population spectrum, which may contain antibodies against most common infectious diseases. In cases where the level of immunoglobulin G (IgG) in the blood is low, an appropriate dose of Intratect may restore normal values.

Intratect is used in adults, children, and adolescents (0-18 years) who have insufficient antibodies (replacement therapy) in the following cases:

• Patients with congenital antibody deficiency (primary immunodeficiency syndromes, PID)
• Acquired antibody deficiency (secondary immunodeficiency syndrome, SID) in patients with severe or recurrent infections and ineffective antimicrobial treatment with proven failure of specific antibodies or low IgG levels <4 g l< li>

Intratect is also used in adults, children, and adolescents (0-18 years) for the treatment of inflammatory diseases (immunomodulation), such as:

• Primary immune thrombocytopenia (ITP, where the patient has a reduced platelet count), if the patient is scheduled for surgery in the near future or is at risk of bleeding.
• Guillain-Barré syndrome (a disease that damages nerves and can lead to generalized paralysis).
• Kawasaki disease (a disease that occurs in children, causing inflammation of many body organs and leading to enlargement of the heart's blood vessels) together with acetylsalicylic acid.
• Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic disease characterized by inflammation of the peripheral nerves, leading to muscle weakness and (or) numbness, mainly in the legs and upper limbs.
• Multifocal motor neuropathy (MMN) is a rare disease characterized by slow, progressive, asymmetric muscle weakness without sensory loss.

2. Important information before using Intratect

When not to use Intratect

• if the patient is allergic to human immunoglobulin or any of the other ingredients of this medicine (listed in section 6).
• if the patient has a deficiency of immunoglobulin A, especially if there are antibodies against immunoglobulin A in the blood, as this may lead to anaphylaxis.

Warnings and precautions

Before starting treatment with Intratect, discuss with your doctor, pharmacist, or nurse if:

• the patient has not received this medicine before or there has been a long interval (e.g., several weeks) since the last administration of the medicine (the patient must be closely monitored during infusion and for one hour after completion of infusion)
• the patient has recently received Intratect (the patient must be observed during infusion and for at least 20 minutes after infusion)
• the patient has an active infection or a concomitant chronic inflammatory condition
• the patient has had a reaction to other antibodies (in rare cases, there is a risk of allergic reactions)
• the patient has kidney disease
• the patient has received medicines that may harm the kidneys (in case of worsening kidney function, it may be necessary to discontinue treatment with Intratect) The doctor will take special precautions in patients with overweight, elderly, diabetic, or hypertensive patients, with low blood volume (hypovolemia), when blood viscosity is higher than normal (high blood viscosity), in immobilized patients, with vascular problems (vascular disease) or other risks of thrombotic events (blood clots).

Warning - reactions

The patient will be closely monitored during infusion of Intratect to ensure that no reaction (e.g., anaphylaxis) occurs. The doctor will ensure that the infusion rate of Intratect is appropriate for the individual patient. If the following reactions occur, such as headache, sudden heat, chills, muscle pain, wheezing, rapid heartbeat, back pain, nausea, low blood pressure, during infusion of Intratect, the doctor should be informed immediately. The infusion rate can be reduced or completely stopped. After infusion of Intratect, the patient may experience low white blood cell count (neutropenia), which resolves spontaneously within 7-14 days. In case of doubts about symptoms, the doctor should be consulted. After receiving immunoglobulins, in very rare cases, acute post-transfusion pulmonary injury (TRALI) may occur. This will lead to non-cardiogenic pulmonary edema. The patient experiences severe respiratory distress (respiratory distress syndrome), tachypnea, abnormally low oxygen levels in the blood (hypoxia), and elevated body temperature (fever). Symptoms usually occur within 1-6 hours of receiving treatment. The doctor should be informed immediately if the patient notices such reactions during infusion of Intratect. The doctor will immediately stop the infusion.

Information on infectious agent transmission

Intratect is manufactured from human plasma (the liquid part of the blood). When medicines are manufactured from human blood or plasma, it is important to prevent the transmission of infections to patients. Blood donors are tested for viruses. Manufacturers of these products also process the blood or plasma to inactivate or remove viruses. Despite these measures, when administering medicines prepared from human blood or plasma, it is not possible to completely eliminate the risk of transmitting an infection. The measures taken are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B and C viruses. The effectiveness of these measures may be limited for non-enveloped viruses, such as hepatitis A virus and parvovirus B19. The reason why immunoglobulins are not associated with hepatitis A or parvovirus B19 infections may be that the antibodies against these infectious agents present in the product have a protective effect. It is strongly recommended that, in each case of administering a dose of Intratect to a patient, the doctor records the name and batch number of the product, so that the patient can be linked to the specific batch of the product. In case of need, it will be possible to trace the patient and the batch of the product used.

Intratect and other medicines

Tell your doctor about all medicines you are taking or have recently taken, as well as any medicines you plan to take. Intratect may reduce the effectiveness of some vaccines, such as:

• measles
• rubella
• mumps
• chickenpox It may be necessary to wait up to 3 months before receiving some vaccines and up to 1 year before receiving the measles vaccine.

It is recommended to avoid concomitant use of loop diuretics with Intratect.

Effect on laboratory tests

Intratect may affect laboratory tests. If you are undergoing blood tests after receiving Intratect, inform the person taking the blood or your doctor that you are taking Intratect.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, ask your doctor for advice before taking this medicine. The doctor will decide whether Intratect can be used during pregnancy and breastfeeding.

Driving and using machines

Intratect has a minor influence on the ability to drive and use machines. Patients who have experienced side effects during treatment should wait until they have resolved before driving or operating machines.

3. How to use Intratect

Intratect is intended for intravenous administration (intravenous infusion). It is administered to the patient by a doctor or nurse. The dosage depends on the patient's health status and body weight. The doctor will decide what dose to administer. At the beginning of the infusion, the patient will receive Intratect at a low rate. Then, the doctor may gradually increase the infusion rate. The infusion rate and frequency of administration depend on the reason for administering Intratect to the patient. The medicinal product should be brought to room temperature or body temperature before use.

Use in children and adolescents

Dosage in children and adolescents (0-18 years) does not differ from that in adults, as the dosage for each indication is determined based on body weight and adjusted according to clinical results in the above diseases. In replacement therapy for patients with impaired immune systems (primary or secondary immunodeficiency), infusion is performed every 3-4 weeks. In the treatment of inflammatory conditions (immunomodulation), infusion may be performed as follows:

• Primary immune thrombocytopenia: in the treatment of an acute episode, the infusion is administered on the first day, after which the dose may be repeated once within 3 days. Alternatively, a reduced dose can be administered over 2 to 5 days.
• Guillain-Barré syndrome: the infusion is administered over 5 days.
• Kawasaki disease: the infusion should be administered as a single dose together with acetylsalicylic acid.
• Chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy: the treatment effect should be evaluated after each administration cycle.

Use of a higher than recommended dose of Intratect

Overdose may lead to fluid overload and excessive blood viscosity, especially in children, elderly patients, or patients with heart failure or impaired kidney function. The patient should drink enough fluids to avoid dehydration and inform the doctor about any health problems. If the patient thinks they have received too much Intratect, they should inform the doctor, who will decide whether to discontinue the medicine or whether other treatment is required.

If one infusion is missed

Intratect is administered to the patient in a hospital by a doctor or nurse, so the likelihood of missing a dose is low. However, the patient should inform the doctor if they think an infusion has been missed. In case of any further doubts about the use of this medicine, the patient should consult a doctor or nurse.

4. Possible side effects

Like all medicines, Intratect can cause side effects, although not everybody gets them. The frequencies of side effects were mainly calculated based on the number of treated patients, unless otherwise specified, e.g., based on the number of infusions.

If you notice any of the following symptoms, inform your doctor immediately:

• rash
• itching
• wheezing
• difficulty breathing
• swelling of the eyelids, face, lips, throat, or tongue
• very low blood pressure with symptoms such as dizziness, confusion, fainting, rapid heartbeat

This may be an allergic reaction or a severe allergic reaction (anaphylactic shock) or hypersensitivity.

During clinical trials with Intratect (50 g/l), the following side effects were reported:

Frequent(may occur in up to 1 in 10 infusions):

• headache
• fever Uncommon(may occur in up to 1 in 100 infusions):
• mild increase in red blood cell destruction in blood vessels (hemolysis)
• taste disorders
• high blood pressure
• superficial vein inflammation
• nausea
• vomiting
• abdominal pain
• rash with raised spots
• chills
• feeling of heat
• increased body temperature
• positive blood test results for antibodies against red blood cells

The following side effects have been reported spontaneously for Intratect:

Frequency not known (frequency cannot be estimated from available data)

• severe chest pain or pressure on the chest (angina pectoris)
• chills or shivering
• anaphylactic shock, allergic reaction
• difficulty breathing (dyspnea)
• low blood pressure
• back pain
• decreased white blood cell count (leukopenia)

Human immunoglobulin preparations may generally cause the following side effects (in decreasing order of frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate back pain
• decrease in red blood cell count due to destruction of these cells in blood vessels ((reversible) hemolytic reactions) and (rarely) hemolytic anemia requiring transfusion
• (rarely) sudden drop in blood pressure and, in sporadic cases, anaphylactic shock
• (rarely) transient skin reactions (including cutaneous lupus erythematosus - frequency not known)
• (very rarely) thromboembolic reactions, such as myocardial infarction, stroke, blood clots in pulmonary blood vessels (pulmonary embolism), blood clots in veins (deep vein thrombosis)
• cases of transient acute inflammation of the protective membranes covering the brain and spinal cord (reversible aseptic meningitis)
• cases of abnormal blood test results indicating kidney function disorders and (or) sudden kidney failure
• cases of acute post-transfusion pulmonary injury (TRALI), see also "Warnings and precautions"

If side effects occur, the infusion rate will be reduced or the infusion will be stopped.

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, please inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, 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. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Intratect

Keep the medicine out of the sight and reach of children. Do not use this medicine after the expiry date stated on the label and carton after "Expiry Date". After first opening, the product should be used immediately. Do not store above 25°C. Do not freeze. Store the vial in the outer carton to protect from light. Do not use this medicine if the solution is cloudy or contains sediment. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Intratect contains

• The active substance of Intratect is human immunoglobulin for intravenous use.

Intratect contains 50 g/l of human normal immunoglobulin, of which at least 96% is immunoglobulin G (IgG). The distribution of IgG subclasses is approximately: 57% IgG1, 37% IgG2, 3% IgG3, and 3% IgG4. The maximum content of immunoglobulin A (IgA) is 900 micrograms/ml.

• The other ingredients are glycine and water for injections.

What Intratect looks like and contents of the pack

Intratect is a solution for infusion. It is a clear or slightly opalescent (milky, resembling opal) solution, colorless to pale yellow. 20 ml, 50 ml, 100 ml, or 200 ml of solution in a vial (type II glass) with a stopper (bromobutyl) and cap (aluminum). Pack sizes: 1 vial containing 20 ml, 50 ml, 100 ml, or 200 ml of solution. Pack sizes: 3 vials containing 200 ml of solution. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Biotest Pharma GmbH, Landsteinerstrasse 5, 63303 Dreieich, Germany, Tel.: +49 6103 801-0, Fax: +49 6103 801-150, Email: [email protected]

Date of last revision of the package leaflet: 28.05.2023

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Information intended for healthcare professionals only:

Special precautions

Infusion-related reaction Some side effects (e.g., headache, sudden heat, chills, muscle pain, wheezing, rapid heartbeat, back pain, nausea, low blood pressure) may be related to the infusion rate. The recommended infusion rate should be strictly followed. During the infusion, patients should be closely monitored for any symptoms. All patients receiving IVIg require:

• adequate hydration before starting IVIg infusion
• monitoring of diuresis
• monitoring of serum creatinine levels
• avoidance of concomitant use of loop diuretics

It is strongly recommended that, in each case of administering a dose of Intratect to a patient, the doctor records the name and batch number of the product, so that the patient can be linked to the specific batch of the product. In case of shock, standard shock treatment should be applied. Aseptic meningitis syndrome (AMS) AMS has been reported in association with IVIg treatment. The syndrome usually occurs within a few hours to 2 days after IVIg treatment. In cerebrospinal fluid (CSF) examinations, pleocytosis with a cell count of up to several thousand cells/mm3, mainly granulocytes, and elevated protein levels of up to several hundred mg/dl have been frequently observed. AMS may occur more frequently with high-dose IVIg treatment (2 g/kg). Patients showing such objective and subjective symptoms should undergo a thorough neurological examination, including CSF examinations, to rule out other causes of meningitis. Discontinuation of IVIg treatment has led to remission of AMS within a few days without sequelae. Hemolytic anemia IVIg products may contain antibodies against blood groups, which can act as hemolysins and cause in vivo coating of red blood cells (RBC) with immunoglobulins, resulting in a positive direct antiglobulin test (Coombs test), and rarely - hemolysis. Hemolytic anemia may occur after IVIg treatment due to increased red blood cell sequestration. Patients treated with IVIg should be monitored for clinical signs and symptoms of hemolysis.

Dosage

Dosage and dosing schedule depend on the indication. Dosage should be individualized based on clinical response. Body weight-based dosage may need to be adjusted in patients with underweight or overweight. The recommended dosage is as follows:

Immunomodulation in the following diseases:

Primary immune thrombocytopenia:

• 0.8-1 g/kg on day 1; the dose can be repeated once within 3 days.
• 0.4 g/kg/day for 2-5 days. In case of relapse, treatment can be repeated.

Guillain-Barré syndrome:

0.4 g/kg/day for 5 days (may be repeated in case of relapse).

Kawasaki disease:

2.0 g/kg should be administered as a single dose. Patients should receive concomitant treatment with acetylsalicylic acid.

Chronic inflammatory demyelinating polyneuropathy (CIDP)

Initial dose: 2 g/kg divided over 2-5 consecutive days. Maintenance dose: 1 g/kg divided over 1-2 days every 3 weeks. The treatment effect should be evaluated after each administration cycle. If no effect is observed after 6 months, treatment should be discontinued. If treatment is effective, the decision to continue long-term treatment is made by the doctor based on the patient's response and reaction to maintenance treatment. It may be necessary to adjust the dosage and intervals between doses according to the individual course of the disease.

Multifocal motor neuropathy (MMN)

Initial dose: 2 g/kg divided over 2-5 consecutive days. Maintenance dose: 1 g/kg every 2-4 weeks or 2 g/kg every 4-8 weeks. The treatment effect should be evaluated after each administration cycle. If no effect is observed after 6 months, treatment should be discontinued. If treatment is effective, the decision to continue long-term treatment is made by the doctor based on the patient's response and reaction to maintenance treatment. It may be necessary to adjust the dosage and intervals between doses according to the individual course of the disease.

Children and adolescents

Dosage in children and adolescents (0-18 years) does not differ from that in adults, as the dosage for each indication is determined based on body weight and adjusted according to clinical results in the above diseases.

Method of administration

Intravenous administration Intratect should be administered as an intravenous infusion at an initial rate of 0.3 ml/kg body weight/hour for 30 minutes. See "Warnings and precautions". If a side effect occurs, the infusion rate should be reduced or the infusion stopped. If the product is well tolerated, the infusion rate can be gradually increased to a maximum of 1.9 ml/kg body weight/hour.

Incompatibilities

This medicinal product should not be mixed with other medicinal products or other IVIg products, as compatibility has not been tested.