Intratect

Package leaflet: Information for the user

Intratect, 50 g/l, solution for infusion
Human normal immunoglobulin (IVIg)
Please read all of this leaflet carefully before this medicine is used, as it contains
important information for the patient.

• Keep this leaflet as you may need to read it again.
• If you have any further questions, please consult 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.

Contents of the leaflet

1. What Intratect is and what it is 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 Intratect is and what it is used for

Intratect is a preparation derived from human blood, containing antibodies (the body's own defence substances) against diseases, provided as a solution for infusion. The solution is ready for intravenous infusion (drip infusion).
Intratect contains human normal immunoglobulin (antibodies) from blood donors representing a broad population spectrum, which may include antibodies against most of the commonly occurring infectious diseases. When the level of immunoglobulin G (IgG) in the blood is low, an appropriate dose of Intratect can restore normal levels.
Intratect is used in adults, children and adolescents (0–18 years) who have insufficient antibody levels (replacement therapy) in the following conditions:

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

Intratect is also used in adults, children and adolescents (0–18 years) for the treatment of
inflammatory diseases (immunomodulation), e.g.:

• Immune thrombocytopenic purpura (ITP, in which the patient has a reduced number of blood platelets), if the patient is scheduled for surgery in the near future or is at risk of bleeding.
• Guillain-Barré syndrome (a disease damaging nerves and potentially leading to generalized paralysis).
• Kawasaki disease (a condition occurring in children causing systemic inflammation of multiple body organs and enlargement of coronary arteries), together with acetylsalicylic acid.
• Chronic inflammatory demyelinating polyneuropathy (CIDP). This is a chronic disease characterized by inflammation of peripheral nerves causing muscle weakness and (or) numbness, primarily in the legs and upper limbs.
• Multifocal motor neuropathy (MMN). This is a rare disease characterized by slow, progressive, asymmetric limb weakness without loss of sensation.

2. Important information before using Intratect

When not to use Intratect

• if the patient is allergic to human immunoglobulin or to any of the other ingredients of this medicine (listed in section 6).
• if the patient has immunoglobulin A deficiency, especially if antibodies against immunoglobulin A are present 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 previously received this medicine or there has been a long interval (e.g. several weeks) since the last dose (the patient must be closely monitored during and for one hour after the infusion)
• the patient has recently received Intratect (the patient should be observed during and for at least 20 minutes after the infusion)
• the patient has an active infection or a coexisting 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 or has had kidney disease
• the patient is taking medications that may damage the kidneys (if kidney function worsens, treatment with Intratect may need to be discontinued)

Special precautions should be taken by the doctor in patients who are overweight, elderly, have diabetes or high blood pressure, have low blood volume (hypovolemia), increased blood viscosity (high blood viscosity), are immobilized, have vascular disorders, or have other risk factors for thrombotic events (blood clots).

Note – Reactions
The patient will be closely monitored during Intratect infusion to ensure that no reaction occurs (e.g. anaphylaxis). The doctor will ensure that the infusion rate of Intratect is appropriate for the individual patient.
If any of the following reactions occur during Intratect infusion—such as headache, sudden feeling of warmth, chills, muscle pain, wheezing, rapid heartbeat, back pain, nausea, low blood pressure—inform the doctor immediately. The infusion rate may be reduced or the infusion stopped completely.
After Intratect infusion, the patient may experience low white blood cell count (neutropenia), which resolves spontaneously within 7–14 days. If in doubt about symptoms, contact the doctor.
After receiving immunoglobulins, acute transfusion-related lung injury (TRALI) may occur very rarely. This leads to fluid accumulation in the air spaces of the lungs unrelated to heart disease (non-cardiogenic pulmonary edema). The patient may experience severe breathing difficulties (respiratory distress syndrome), rapid breathing (tachypnea), abnormally low blood oxygen levels (hypoxia), and elevated body temperature (fever). Symptoms typically occur within 1–6 hours after treatment. Inform the doctor immediately if such reactions occur during Intratect infusion. The doctor will immediately stop the infusion.

Information on transmission of infectious agents
Intratect is manufactured from human plasma (the liquid part of blood). When medicines are made from human blood or plasma, it is important to prevent transmission of infections to patients. Blood donors are screened for viruses. Manufacturers of these products further process the blood or plasma to inactivate or remove viruses. Despite these measures, it cannot be completely excluded that medicines prepared from human blood or plasma might transmit infection.
The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV) and 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 immunoglobulins are not associated with hepatitis A or parvovirus B19 infections may be that the antibodies present in the product against these infectious agents are protective in nature.
It is strongly recommended that, whenever a patient receives a dose of Intratect, the doctor records the product name and batch number. The batch number identifies the source materials used in the product. This allows the patient to be linked to the source material if necessary.

Intratect and other medicines
Inform the doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Intratect may reduce the effectiveness of certain vaccines, such as those against:

• measles
• rubella
• mumps
• varicella

It may be necessary to wait up to 3 months before receiving certain vaccines and up to 1 year before receiving the measles vaccine.

Concomitant use of loop diuretics with Intratect should be avoided.

Effect on blood tests
Intratect may affect blood test results. If blood tests are performed after receiving Intratect, inform the person drawing the blood or the doctor that Intratect has been administered.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult the doctor before using this medicine.
The doctor will decide whether Intratect can be used during pregnancy and breastfeeding.

Driving and operating machinery
Intratect has a minor influence on the ability to drive and operate machinery.
Patients who experience adverse effects during treatment should wait until symptoms resolve before driving or operating machinery.

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 condition and body weight. The doctor will decide the amount to be administered.
At the beginning of the infusion, the patient will receive Intratect at a slow rate. Subsequently, the doctor may gradually increase the infusion rate.
The infusion rate and frequency of administration depend on the reason for which Intratect is being given 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 (aged 0–18 years) does not differ from that in adults, as the dosage in each indication is based on body weight and adjusted according to clinical response in the aforementioned diseases.
In replacement therapy for patients with impaired immune system (primary or secondary immunodeficiency), the infusion is administered every 3–4 weeks.
In the treatment of inflammatory conditions (immunomodulation), the infusion may be administered as follows:

• Immune thrombocytopenia: in the treatment of acute episodes, the infusion is given on the first day, and this dose may be repeated once within 3 days. Alternatively, a reduced dose may be administered over 2 to 5 days.
• Guillain-Barré syndrome: the infusion is administered over 5 days.
• Kawasaki disease: the infusion should be given 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.

Administration of a higher than recommended dose of Intratect
Overdose may lead to fluid overload and increased blood viscosity, particularly in children, elderly patients, or patients with heart failure or impaired kidney function.
The patient should drink sufficient fluids to avoid dehydration and should inform the doctor of any health problems. If the patient believes they have received too much Intratect, this should be reported to the doctor, who will decide whether to discontinue administration or whether other treatment is required.

If one infusion is missed
Intratect is administered to the patient in a hospital setting by a doctor or nurse, so the likelihood of missing a dose is low. However, the patient should inform the doctor if they believe an infusion has been missed.

If you have any further questions about the use of this medicine, please consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The frequencies listed below were generally calculated based on the number of treated
patients, unless otherwise stated (e.g. per infusion).
If you notice any of the symptoms listed below, you should immediately inform your doctor:

• skin 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 of Intratect (50 g/l), the following adverse reactions were reported:
Common (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 breakdown within blood vessels (hemolysis)
• taste disturbances
• high blood pressure
• superficial phlebitis
• nausea
• vomiting
• abdominal pain
• rash with raised spots
• chills
• feeling of warmth
• elevated body temperature
• positive blood test results for antibodies against red blood cells

The following adverse reactions have been reported spontaneously for Intratect:
Frequency not known (frequency cannot be estimated from the available data):

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

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

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and mild 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 cutaneous lupus erythematosus – frequency not known)
• (very rarely) thromboembolic events such as myocardial infarction, stroke, blood clots in lung 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 blood test results indicating impaired kidney function and (or) acute kidney failure
• cases of acute transfusion-related lung injury (TRALI), see also section "Warnings and precautions"

If adverse reactions occur, the infusion rate will be reduced or the infusion
will be stopped.
Reporting of adverse reactions
If any adverse effects occur, including any not listed in this
leaflet, you should inform your doctor, pharmacist or nurse. Adverse reactions can
be reported directly to the Department of Monitoring Adverse Drug Reactions 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the 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 under "Expiry".
After first opening, immediate use is recommended.
Do not store above 25 °C. Do not freeze.
Store the vial in the outer packaging to protect from light.
Do not use this medicine if the solution is cloudy or contains a precipitate.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Doing so helps protect the environment.

6. Contents of the pack and other information

What Intratect contains

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

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

• Other ingredients: 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, opal-like appearance), colourless to pale yellow solution.
20 ml, 50 ml, 100 ml or 200 ml solution in a vial (made of Type II glass) with a stopper (bromobutyl rubber) and a cap (aluminium).
Pack sizes: 1 vial containing 20 ml, 50 ml, 100 ml or 200 ml solution.
Pack sizes: 3 vials containing 200 ml solution each.
Not all pack sizes may be marketed.

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

Information intended exclusively for medical professionals:

Special precautions
Infusion-related reactions
Some adverse reactions (e.g., headache, sudden facial flushing, chills, muscle pain,
wheezing, tachycardia, back pain, nausea, and hypotension) may be related to
the infusion rate. The recommended infusion rate must be strictly followed. During the infusion,
patients must be carefully monitored and closely observed for any symptoms.
For all patients receiving IVIg, the following is required:

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

It is strongly recommended that, for each administration of the medicinal product Intratect to a patient,
the product name and batch number be recorded, enabling traceability between the patient and the specific batch of the
medicinal product.
In case of shock, standard procedures for shock therapy 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. Cerebrospinal fluid (CSF) analysis
often reveals pleocytosis up to several thousand cells/mm³, predominantly granulocytes, and elevated protein levels up to several hundred mg/dL.
AMS may occur more frequently with high-dose IVIg treatment (2 g/kg).
Patients presenting with such subjective and objective symptoms should undergo thorough neurological evaluation, including cerebrospinal fluid examination, to exclude other causes of meningitis.
Discontinuation of IVIg treatment led to AMS remission within a few days without sequelae.
Hemolytic anemia
IVIg products may contain blood group antibodies which can act as hemolysins and cause in vivo coating of red blood cells (RBCs) with immunoglobulins, resulting in a positive direct antiglobulin reaction (Coombs test), and rarely, hemolysis. Hemolytic anemia may occur after IVIg treatment due to enhanced sequestration of RBCs. Patients treated with IVIg should be monitored for clinical signs and symptoms of hemolysis.

Dosage
Dosage and dosing regimen depend on the indication.
Dosage should be individually adjusted according to clinical response. Dose based on body weight may require adjustment in patients who are underweight or overweight.
The following dosages are recommended:

Replacement therapy in primary immunodeficiency syndromes:
The dosing regimen should be established to achieve a serum IgG level of at least 6 g/L or within the normal reference range for age. (Serum IgG levels should be measured before each subsequent infusion.) It takes 3–6 months from initiation of therapy to reach IgG steady-state levels. The recommended initial dose is 0.4–0.8 g/kg body weight given as a single dose, followed by at least 0.2 g/kg body weight every 3–4 weeks.
The dose required to achieve a serum IgG level of 6 g/L is 0.2–0.8 g/kg body weight administered monthly. After reaching a steady-state IgG level, the interval between infusions may be 3 to 4 weeks.
Trough serum IgG levels should be monitored and evaluated together with the frequency of infections. To reduce the frequency of bacterial infections, it may be necessary to increase the dose and target a higher trough IgG level.

Replacement therapy in secondary immunodeficiencies:
Recommended dose: 0.2–0.4 g/kg every 3–4 weeks.
Trough serum IgG levels should be monitored and evaluated in conjunction with infection frequency. The dose should be appropriately adjusted to achieve optimal protection against infections. Dose increase may be necessary in patients with persistent infection, while dose reduction may be considered if the patient remains infection-free.

Immunomodulation in the following diseases:

Primary immune thrombocytopenia (ITP):
Two alternative treatment regimens exist:

• 0.8–1 g/kg on Day 1; dose may be repeated once within 3 days.
• 0.4 g/kg daily for 2–5 days. Treatment may be repeated in case of relapse.

Guillain-Barré syndrome:
0.4 g/kg/day for 5 days (repeat dosing may be considered in case of relapse).
Kawasaki disease:
2.0 g/kg should be administered as a single dose. Patients should receive concomitant acetylsalicylic acid therapy.
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Initial dose: 2 g/kg divided over 2–5 consecutive days
Maintenance doses: 1 g/kg divided over 1–2 consecutive days every 3 weeks.
Therapeutic response should be evaluated after each cycle. If no therapeutic effect is observed after 6 months, treatment should be discontinued.
If treatment is effective, the decision on long-term therapy should be made by the physician based on the patient's response and response to maintenance therapy. Dose and interval adjustments may be necessary according to the individual disease course.

Multifocal motor neuropathy (MMN)
Initial dose: 2 g/kg divided over 2–5 consecutive days.
Maintenance dose: 1 g/kg every 2 to 4 weeks or 2 g/kg every 4 to 8 weeks.
Therapeutic response should be evaluated after each cycle. If no therapeutic effect is observed after 6 months, treatment should be discontinued.
If treatment is effective, the decision on long-term therapy should be made by the physician based on the patient's response and response to maintenance therapy. Dose and interval adjustments may be necessary according to the individual disease course.

The recommended dosages are summarized in the table below:

Children and adolescents
Dosing in children and adolescents (aged 0–18 years) does not differ from dosing in adults,
since the dosage for each indication is determined based on body weight and must be
adjusted according to clinical outcomes in the aforementioned 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 an adverse reaction occurs, the infusion rate should be reduced or the infusion stopped. If the product is well tolerated,
the infusion rate may be gradually increased up to a maximum of 1.9 ml/kg body weight/hour.
Pharmaceutical incompatibilities
Do not mix this medicinal product with other medicinal products or other IVIg products,
as compatibility studies have not been conducted.