INTRATECT 100 g/l Solution

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Intratect, 100 g/l, Solution for Infusion
   1. Read the package leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of Contents of the Package Leaflet:
3. What is Intratect 100 g/l and what is it used for
4. Important information before using Intratect 100 g/l
   1. When not to use Intratect 100 g/l:
   2. Warnings and precautions
   3. Before starting treatment with Intratect 100 g/l, discuss with your doctor, pharmacist, or nurse if:
   4. Warning - reactions
   5. Information on infectious agent transmission
   6. Intratect 100 g/l and other medicines
   7. Effect on laboratory tests
   8. Pregnancy and breastfeeding
   9. Driving and using machines
5. How to use Intratect 100 g/l
   1. Use in children and adolescents
   2. Overdose of Intratect 100 g/l
   3. Missed infusion of Intratect 100 g/l
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. The following side effects have been reported during clinical trials with Intratect 100 g/l (100 g/l):
   4. The following side effects have been reported spontaneously for Intratect 100 g/l:
   5. Frequency not known (frequency cannot be estimated from the available data)
   6. Human immunoglobulin products may generally cause the following side effects (in decreasing order of frequency):
   7. Reporting side effects
7. How to store Intratect 100 g/l
8. Contents of the pack and other information
   1. What Intratect 100 g/l contains
   2. What Intratect 100 g/l 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. Administration
   9. Incompatibilities

Package Leaflet: Information for the User

Intratect, 100 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 any not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Package Leaflet:

• 1. What is Intratect 100 g/l and what is it used for
• 2. Important information before using Intratect 100 g/l
• 3. How to use Intratect 100 g/l
• 4. Possible side effects
• 5. How to store Intratect 100 g/l
• 6. Contents of the pack and other information

1. What is Intratect 100 g/l and what is it used for

Intratect 100 g/l 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 100 g/l 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 100 g/l may restore normal values.
Intratect 100 g/l is used in adults, children, and adolescents (0-18 years) who do not have enough antibodies (replacement therapy) in the following cases:

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

Intratect 100 g/l 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 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 weakness of the limbs without sensory loss.

2. Important information before using Intratect 100 g/l

When not to use Intratect 100 g/l:

• If the patient is allergic to human immunoglobulin or any other component 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 100 g/l, 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 the infusion).
• The patient has recently received Intratect 100 g/l (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 100 g/l). 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 in cases of other risks of thrombotic events (blood clots).

Warning - reactions

The patient will be closely monitored during infusion of Intratect 100 g/l to ensure that no reaction (e.g., anaphylaxis) occurs. The doctor will ensure that the infusion rate of Intratect 100 g/l is appropriate for the individual patient.
In case of the following reactions, such as headache, sudden warmth, chills, muscle pain, wheezing, rapid heartbeat, back pain, nausea, and low blood pressure, during infusion of Intratect 100 g/l, inform your doctor immediately. The infusion rate can be reduced or completely stopped.
After infusion of Intratect 100 g/l, the patient may experience low white blood cell count (neutropenia), which resolves spontaneously within 7-14 days. In case of doubt about symptoms, consult your doctor.
After receiving immunoglobulins, in very rare cases, acute post-transfusion lung injury (TRALI) may occur. This will lead to non-cardiogenic pulmonary edema. The patient experiences severe breathing difficulties (respiratory distress syndrome), rapid breathing (tachypnea), abnormally low oxygen levels in the blood (hypoxia), and elevated body temperature (fever).
Symptoms usually occur within 1-6 hours after receiving treatment. Inform your doctor immediately if you notice such reactions during infusion of Intratect 100 g/l. The doctor will immediately stop the infusion.

Information on infectious agent transmission

Intratect 100 g/l is manufactured from human plasma (the liquid part of the blood). When medicines are made 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 transmission.
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 administration of Intratect 100 g/l 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, this allows tracing of the batch of the product used.

Intratect 100 g/l 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 100 g/l 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.

Concomitant use of loop diuretics with Intratect 100 g/l should be avoided.

Effect on laboratory tests

Intratect 100 g/l may affect laboratory tests. If you undergo blood tests after receiving Intratect 100 g/l, inform the person taking the blood or your doctor that you have received Intratect 100 g/l.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.
Your doctor will decide whether Intratect 100 g/l can be used during pregnancy and breastfeeding.

Driving and using machines

Intratect 100 g/l has a minor influence on the ability to drive and use machines. Patients who experience side effects during treatment should wait for them to resolve before driving or using machines.

3. How to use Intratect 100 g/l

Intratect 100 g/l is intended for intravenous administration (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 100 g/l at a slow rate. Then, the doctor may gradually increase the infusion rate.
The infusion rate and frequency of administration depend on the reason for administering Intratect 100 g/l 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 in 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 diseases (immunomodulation), infusion may be performed as follows:

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

Overdose of Intratect 100 g/l

Overdose may lead to fluid overload and increased 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 100 g/l, they should inform their doctor, who will decide whether to discontinue treatment or if other treatment is required.

Missed infusion of Intratect 100 g/l

Intratect 100 g/l 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 their doctor if they think an infusion has been missed.
In case of any further doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

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

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

• rash
• itching
• wheezing
• breathing difficulties
• 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.

The following side effects have been reported during clinical trials with Intratect 100 g/l (100 g/l):

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

• abnormal heart rhythm (palpitations)
• discomfort
• infusion-related reaction
• headache
• joint pain
• back pain
• bone pain Uncommon(may occur in up to 1 in 100 infusions):
• hypersensitivity
• fatigue
• chills
• hypothermia
• neurological disorders
• muscle pain
• skin pain
• rash
• increased blood flow to organs and tissues
• high blood pressure
• diarrhea
• abdominal pain

The following side effects have been reported spontaneously for Intratect 100 g/l:

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

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

Human immunoglobulin products 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
• decreased red blood cell count due to breakdown 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 erythema multiforme - frequency not known)
• (very rarely) thromboembolic reactions, such as heart attack, stroke, blood clots in blood vessels in the lungs (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 lung injury (TRALI), see also "Warnings and precautions"

In case of side effects, the infusion rate will be reduced or the infusion will be stopped.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, please inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +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 100 g/l

Keep this 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. These measures will help protect the environment.

6. Contents of the pack and other information

What Intratect 100 g/l contains

• The active substance of Intratect 100 g/l is human immunoglobulin for intravenous use.

Intratect 100 g/l contains 100 g/l of normal human immunoglobulin, of which at least 96% is immunoglobulin G (IgG). The distribution of the individual IgG subclasses is approximately: 57% IgG1, 37% IgG2, 3% IgG3, and 3% IgG4. The maximum content of immunoglobulin A (IgA) is 1800 micrograms/ml.

• Other ingredients are: glycine and water for injections.

What Intratect 100 g/l looks like and contents of the pack

Intratect 100 g/l is a solution for infusion. It is a clear or slightly opalescent (milky) solution, colorless or pale yellow.
10 ml, 25 ml, 50 ml, 100 ml, or 200 ml solution in a vial (type II glass) with a stopper (bromobutyl) and cap (aluminum).
Pack sizes: 1 vial containing 10 ml, 25 ml, 50 ml, 100 ml, or 200 ml solution.
Pack sizes: 3 vials containing 100 ml or 200 ml solution.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Biotest Pharma GmbH
Landsteinerstrasse 5
63303 Dreieich
Germany
Phone: +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 warmth, chills, muscle pain, wheezing, rapid heartbeat, back pain, nausea, and low blood pressure) may be related to the infusion rate. The recommended infusion rate must be strictly followed. During the infusion, patients must be closely monitored and carefully observed for any signs of an infusion-related reaction.
In all patients, IVIg administration requires:

• adequate hydration of the patient 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 administration of Intratect 100 g/l 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 used.
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 often been found.
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 resulted in 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 RBC 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 and adjusted according to clinical response. Body weight-based dosing may need to be adjusted in patients with underweight or overweight.
The recommended dosing is as follows:

Administration

Intravenous administration
Intratect 100 g/l 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". In case of a side effect, 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.
Replacement therapy:
In patients who have tolerated the infusion rate of 1.9 ml/kg/hour well, the rate can be gradually increased to 6 ml/kg/hour and, if well tolerated, further increased to a maximum of 8 ml/kg/hour.
Generally, doses and infusion rates should be individualized according to the patient's needs.

Incompatibilities

Do not mix the medicinal product with other medicinal products or other IVIg products, as compatibility has not been tested.