Intratect

Package leaflet: Information for the user

Intratect, 100 g/l, solution for infusion
Human normal immunoglobulin (IVIg)
Please read all of this leaflet carefully before this medicine is administered because it contains
important information for you.

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

Contents of the leaflet:

1. What Intratect 100 g/l is and what it is used for
2. Important information before administration of 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 Intratect 100 g/l is and what it is used for
Intratect 100 g/l is a preparation derived from human blood, containing antibodies (the body's own defensive substances) against diseases, available as a solution for intravenous infusion. The solution is ready for intravenous infusion (drip infusion).
Intratect 100 g/l contains human normal immunoglobulin (antibodies) from plasma of donors representing a broad population spectrum, which may contain antibodies against most common infectious diseases. When the level of immunoglobulin G (IgG) in the blood is low, an appropriate dose of Intratect 100 g/l can restore normal levels.
Intratect 100 g/l is used in adults, children, and adolescents (0–18 years) who have insufficient levels of antibodies (replacement therapy) in the following conditions:

• 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 therapy, with proven failure of specific antibody response or low IgG levels (< 4 g/l)

Intratect 100 g/l is also used in adults, children, and adolescents (0–18 years) for the treatment of
inflammatory diseases (immunomodulation), e.g.:

• Immune thrombocytopenia (ITP), in which the patient has a reduced number of 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 disease occurring in children causing systemic inflammation of multiple 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 leading to 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 administration of Intratect 100 g/l

Do not use Intratect 100 g/l:

• 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 (IgA) deficiency, especially if antibodies against IgA are present in the blood, as this may lead to anaphylaxis.

Warnings and precautions
Before starting treatment with Intratect 100 g/l, please 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 100 g/l (the patient must be observed during the infusion and for at least 20 minutes after the infusion)
• the patient has an active infection or coexisting chronic inflammatory condition
• the patient has previously experienced a reaction to other antibody products (in rare cases, there is a risk of allergic reactions)
• the patient has or has had kidney disease
• the patient is receiving medications that may damage the kidneys (if kidney function worsens, treatment with Intratect 100 g/l may need to be discontinued)
  Special precautions should be taken by the physician in overweight patients, elderly patients, those with diabetes or high blood pressure, those with low blood volume (hypovolemia), those with increased blood viscosity (high blood viscosity), immobilized patients, those with vascular diseases, or those with other risk factors for thrombotic events (blood clots).

Note – Reactions
The patient will be closely monitored during infusion of Intratect 100 g/l to ensure no reaction occurs (e.g., anaphylaxis). The physician will ensure that the infusion rate of Intratect 100 g/l is appropriate for the individual patient.
If any of the following reactions occur during infusion of Intratect 100 g/l—such as headache, sudden flush, chills, muscle pain, wheezing, rapid heartbeat, back pain, nausea, low blood pressure—please inform the doctor immediately. The infusion rate may be reduced or the infusion stopped completely.
After infusion of Intratect 100 g/l, 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, very rarely, acute transfusion-related lung injury (TRALI) may occur. This leads to non-cardiogenic accumulation of fluid in the air spaces of the lungs (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 appear within 1–6 hours after treatment. Please inform the doctor immediately if such reactions occur during infusion of Intratect 100 g/l. The doctor will immediately stop the infusion.

Information on transmission of infectious agents
Intratect 100 g/l is manufactured from human plasma (the liquid part of blood). When medicines are manufactured 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, when administering medicines prepared from human blood or plasma, the possibility of transmitting infection cannot be completely ruled out.
The measures taken are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus.
The effectiveness of these measures may be limited against 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 present in the product against these infectious agents are protective in nature.
It is strongly recommended that every time a patient receives a dose of Intratect 100 g/l, the doctor records the product name and batch number. The batch number identifies the source materials used in the product. This allows, if necessary, linking the patient to the source material used.

Intratect 100 g/l and other medicines
Please inform your doctor about all medicines currently or recently used, as well as any medicines the patient plans to use.
Intratect 100 g/l may reduce the effectiveness of certain vaccines, such as those against:

• measles
• rubella
• mumps
• varicella (chickenpox)
  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 100 g/l should be avoided.
Effect on blood tests
Intratect 100 g/l may affect blood test results. If undergoing blood tests after receiving Intratect 100 g/l, please inform the person drawing blood or the doctor that Intratect 100 g/l has been administered.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor before using this medicine.
The doctor will decide whether Intratect 100 g/l can be used during pregnancy and breastfeeding.
Driving and operating machinery
Intratect 100 g/l has a minor influence on the ability to drive and operate machinery. Patients who experience side effects during treatment should wait for these to resolve before driving or operating machinery.

3. How to use Intratect 100 g/l

Intratect 100 g/l 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 appropriate dose to administer.
At the beginning of the infusion, the patient will receive Intratect 100 g/l 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 100 g/l is being administered to the patient.
The medicinal product should be brought to room temperature or body temperature before use.

Use in children and adolescents
Dosing in children and adolescents (aged 0–18 years) does not differ from dosing 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 100 g/l
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 sufficient fluids to avoid dehydration and should inform the doctor of any health problems. If the patient believes they have received too high a dose of Intratect 100 g/l, this should be reported to the doctor, who will decide whether to discontinue the infusion or whether other treatment is required.

Missed infusion
Intratect 100 g/l is administered to the patient in a hospital setting by a doctor or nurse, so the likelihood of missing a dose is very low. However, the patient should inform the doctor if they believe an infusion has been missed.

If there are any further doubts regarding the use of this medicine, consult the 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 number of infusions).
If any of the following symptoms occur, 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, or rapid heartbeat

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

The following adverse reactions have been reported during clinical trials with Intratect 100 g/l (100 g/l):
Common (may occur in no more than 1 out of 10 infusions):

• irregular heartbeat (palpitations)
• discomfort
• infusion-related reaction
• headache
• joint pain
• back pain
• bone pain

Uncommon (may occur in no more than 1 out of 100 infusions):

• hypersensitivity
• fatigue
• chills
• hypothermia
• sensory disturbances
• muscle pain
• skin pain
• rash
• excessive blood flow to organs and tissues (hyperperfusion)
• high blood pressure
• diarrhoea
• abdominal pain

The following adverse reactions have been reported spontaneously for Intratect 100 g/l:
Frequency not known (frequency cannot be estimated from available data):

• severe chest pain or pressure on the chest (angina)
• chills or shivering
• shock (anaphylactic), allergic reaction
• difficulty breathing (dyspnoea)
• low blood pressure
• back pain
• decreased number of white blood cells (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 number of red blood cells due to their breakdown within blood vessels ((reversible) haemolytic reactions), and (rarely) haemolytic anaemia 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 the 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 kidney function disorders 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 adverse effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Intratect 100 g/l

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, 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 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 package and other information

What Intratect 100 g/l contains

• The active substance in Intratect 100 g/l is human immunoglobulin for intravenous administration.

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

• Other components: 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, opal-like),
colourless or pale yellow solution.
10 ml, 25 ml, 50 ml, 100 ml or 200 ml solution in a vial (type II glass) with a stopper
(bromobutyl) and a cap (aluminium).
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 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 reaction
Some adverse reactions (e.g., headache, sudden facial flushing, chills, muscle pain,
wheezing, tachycardia, back pain, nausea, and hypotension) may be related to
the rate of infusion. The recommended infusion rate must be strictly observed. 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 of the patient prior to initiation of 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
100 g/l, the name and batch number of the product be recorded, to enable traceability of the patient to the specific batch
of the medicinal product.
In case of shock, standard treatment procedures for shock management should be applied.
Aseptic meningitis syndrome (AMS)
AMS has been reported in association with IVIg therapy.
The syndrome typically occurs within several hours to 2 days after IVIg treatment. In cerebrospinal fluid (CSF) examinations,
pleocytosis is frequently observed, reaching up to several thousand cells/mm³, predominantly granulocytes, along with elevated protein concentrations 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 testing, to exclude other causes of meningitis.
Discontinuation of IVIg therapy resulted in AMS remission within a few days without sequelae.
Hemolytic anemia
IVIg products may contain blood group antibodies which may act as hemolysins and cause
in vivo coating of red blood cells (RBCs) with immunoglobulins, leading to a positive direct antiglobulin test (Coombs test), and rarely, hemolysis. Hemolytic anemia may occur following IVIg treatment due to enhanced sequestration of RBCs. Patients receiving IVIg should be monitored for clinical signs and symptoms of hemolysis.

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

Replacement therapy in primary immunodeficiency syndromes:
The dosing schedule should be established to achieve serum IgG levels of at least 6 g/L or within the normal reference range for age (IgG levels should be measured before each subsequent infusion). It takes 3–6 months from initiation of therapy to reach IgG steady-state concentration. The recommended initial dose is 0.4–0.8 g/kg body weight administered as a single dose, followed by at least 0.2 g/kg body weight every 3–4 weeks.
The dose required to achieve serum IgG levels of 6 g/L ranges from 0.2–0.8 g/kg body weight administered monthly. After reaching steady-state IgG levels, intervals between infusions may range from 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, dose increase and targeted elevation of trough serum IgG concentration may be necessary.

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 together with the frequency of infections. The dose should be appropriately adjusted to achieve optimal protection against infections. Dose increase may be necessary in patients with persistent infections, 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 are available:

• 0.8–1 g/kg on Day 1; the 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 adjustments and intervals between doses may need to be modified according to 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 adjustments and intervals between doses may need to be modified according to individual disease course.

The recommended dosages are summarized in the table below:

Children and adolescents
The dosing in children and adolescents (aged 0–18 years) does not differ from dosing in adults,
since the dosage in each indication is determined based on body weight and must be adjusted according to clinical response in the above-mentioned diseases.
Method of 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". 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.
Replacement therapy:
In patients who tolerated an infusion rate of 1.9 ml/kg/hour well, the rate may be gradually increased to 6 ml/kg/hour, and if still well tolerated, may be gradually increased up to a maximum of 8 ml/kg/hour.
In general, doses and infusion rates should be individually adjusted according to patient needs.
Pharmaceutical incompatibilities
Do not mix the medicinal product with other medicinal products or with other IVIg products, as compatibility studies have not been conducted.