Leaflet: information for the user

Intratect 50 g/l solution for infusion

Human normal immunoglobulin (IgIV)

Read this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

1. What is Intratect and what it is used for

2.What you need to know before starting to use Intratect

3.How to use Intratect

4.Possible side effects

5.Storage of Intratect

6.Contents of the pack and additional information

Intratectis a human blood extract that contains antibodies (the body's own defense substances) against diseases, presented in the form of a perfusion solution. The solution is ready for perfusion through a vein ("infusion").

Intratect contains normal human immunoglobulin (antibodies) that comes from blood donated by a wide range of the population and is very likely to contain antibodies against common infectious diseases. The appropriate doses of Intratect allow for the restoration of normal blood levels of immunoglobulin G (IgG) when they are reduced.

Intratect is administered to adults, children, and adolescents (0-18 years) who do not have enough antibodies (substitutive treatment) in cases of:

-patients born with a lack of antibodies (primary immunodeficiency syndrome, PIS)

-acquired lack of antibodies (secondary immunodeficiency syndrome, SIS) in patients with severe or recurrent infections and ineffective antibiotic treatment with demonstrated or proven insufficiency of specific antibodies or a low IgG level (<4g/l)

Intratect is also used in adults, children, and adolescents (0-18 years) to treat inflammatory diseases (immunomodulation), such as::

-primary immune thrombocytopenia (TIP, in which the patient has fewer platelets in the blood) if the patient is about to undergo surgery or is at risk of bleeding

-Guillain-Barré syndrome (a disease that damages nerves and can cause generalized paralysis)

-Kawasaki disease (a childhood disease that causes inflammation of various body organs and in which the heart arteries become enlarged), along with acetylsalicylic acid

-chronic inflammatory demyelinating polyneuropathy (CIDP). A chronic disease characterized by the inflammation of peripheral nerves, which causes muscle weakness and/or numbness, mainly in the legs and upper limbs.

-multifocal motor neuropathy (MMN). A rare disease characterized by the slow and progressive asymmetric weakness of the limbs, without sensory loss.

No use Intratect

-if you are allergic to human immunoglobulin or any of the other components of this medication (listed in section 6).

-if you have a deficiency of immunoglobulin A, particularly if you have antibodies against immunoglobulin A in your blood, as this may lead to anaphylaxis.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Intratect

-if you have not received this medication before or if it has been a long time (e.g., several weeks) since you last received it (you will require close monitoring during infusion and for at least one hour after it has finished)

-if you have recently received Intratect (you will require observation during infusion and for at least 20 minutes after infusion)

-if you have an active infection or a chronic underlying inflammation

-if you have had a reaction to other antibodies (in rare cases, you may be at risk of an allergic reaction)

-if you have kidney disease

-if you have received medications that can damage your kidneys (if kidney function worsens, treatment with Intratect may need to be suspended)

Your doctor will take special care if you are overweight, elderly, have diabetes, hypertension, decreased blood volume (hypovolemia), if your blood is thicker than normal (elevated blood viscosity), if you are bedridden or have been immobile for some time (immobilization), or have vascular problems (vascular diseases) or other risks of thrombotic episodes (blood clots).

Remember: reactions

You will be closely monitored during the Intratect infusion period to check for any reactions (e.g., anaphylaxis). Your doctor will ensure that the rate at which Intratect is infused is suitable for your case.

If you notice any of the following signs of a reaction, such as headache, hot flushes, chills, muscle pain, wheezing, rapid heart rate, lower back pain, nausea, or low blood pressure during Intratect infusion, inform your doctor immediately. The infusion rate may be reduced or stopped completely.

After Intratect infusion, you may experience a low white blood cell count (neutropenia), which will resolve spontaneously within 7 to 14 days. If you are unsure of your symptoms, consult your doctor.

In rare cases, acute lung injury related to transfusion (TRALI) may occur after receiving immunoglobulins. This causes the accumulation of non-cardiogenic fluid in the lung spaces (pulmonary edema). You may experience significant breathing difficulty (dyspnea), rapid breathing (tachypnea), an abnormally low oxygen concentration in your blood (hypoxia), and increased body temperature (fever). Symptoms usually appear between 1 and 6 hours after treatment. Inform your doctor immediately if you observe these reactions during Intratect infusion; they will stop the infusion immediately.

Information on the transmission of infectious agents

Intratect is prepared with human plasma (the liquid part of blood). When administering medications derived from plasma or human blood, certain measures must be taken to prevent infections from being transmitted to patients. These measures include a careful selection of donors to exclude those at risk of being carriers of infectious diseases, analysis of specific infection markers in individual donations and plasma mixtures, and inclusion of stages in the manufacturing process to eliminate/inactivate viruses. Despite this, the possibility of transmission of infectious agents cannot be completely ruled out when administering medications derived from human blood or plasma. This also applies to emerging or unknown viruses or other types of infections.

These measures are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus.

The measures taken may have limited value against non-enveloped viruses, such as hepatitis A virus and parvovirus B19.

Immunoglobulins have not been associated with the transmission of hepatitis A virus or parvovirus B19 infections, possibly due to the protective effect of the antibodies against these infections present in the medication.

It is strongly recommended that each time your doctor administers a dose of Intratect, they record your name and the batch number of the product. The batch number provides information on the specific starting materials used in your medication. If necessary, this will allow a connection to be established between you and the starting materials used.

Use of Intratect with other medications

Inform your doctor if you are using, have used recently, or may need to use any other medication.

Intratect may reduce the effectiveness of some vaccines, such as:

-measles vaccine

-rubella vaccine

-mumps vaccine

-varicella vaccine

You may need to wait three months to receive certain vaccines or up to one year to receive the measles vaccine.

Avoid concurrent use of loop diuretics with Intratect.

Effects on blood tests

Intratect may affect blood tests. If you have a blood test after receiving Intratect, inform the person taking the blood sample or your doctor that you have received Intratect.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor before using any medication.

Your doctor will decide if you can use Intratect during pregnancy or breastfeeding.

Driving and operating machinery

The influence of Intratect on your ability to drive and operate machinery is small. Patients who experience adverse reactions during treatment should wait until these resolve before driving or operating machinery.

Intratect is intended for intravenous administration (infusion into a vein) by a doctor or nurse. The dose will depend on your condition and body weight. The doctor will know the exact amount that should be administered to you.

At the beginning of the infusion, you will receive Intratect at a slow rate. Then, the doctor may gradually increase the infusion rate.

The infusion rate and frequency will depend on the reason you are receiving Intratect.

The medication should be brought to room temperature or body temperature before use.

Use in children and adolescents

The dosage in children and adolescents (0-18 years) is not different from that of adults, as the dosage for each indication is calculated based on body weight and adjusted according to the clinical outcome of the aforementioned diseases.

For replacement therapy in patients with a weakened immune system (primary or secondary immunodeficiency), the infusion is performed every 3-4 weeks.

For treating inflammatory diseases (immunomodulation), the infusion may be performed as follows:

• Primary immune thrombocytopenia: for acute episode treatment, a single infusion is performed on day 1; this dose may be repeated once in 3 days. Alternatively, a lower dose may be administered daily for 2 to 5 days.

• Guillain-Barré syndrome: the infusion will be performed over 5 days.

• Kawasaki disease: the infusion will be performed as a single dose along with acetylsalicylic acid.

• Chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy; the treatment effect should be evaluated after each cycle of administration.

If you receive more Intratect than you should

Overdose may cause fluid overload and increased blood viscosity, especially in children, elderly patients, or those with heart or kidney function impairment.Make sure to drink enough fluids to avoid dehydration and inform your doctor about any medical issues.If you believe you have received too much Intratect, inform your doctor, who will decide whether to suspend the infusion and apply a different treatment.

In case of overdose or accidental ingestion, call the Toxicology Information Service immediately at phone number 915620420.

If you forget a infusion

Intratect will be administered in the hospital by a doctor or nurse, so it is unlikely that any infusion will be missed. However, if you believe that a infusion has been omitted, inform your doctor.

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Unless otherwise specified, such as the number of infusions, the frequencies indicated below have been calculated based on the number of patients treated.

If you notice any of these side effects, inform your doctor immediately:

• eruption,
• itching,
• whistling in the chest (sibilance),
• difficulty breathing,
• swelling in the eyelids, face, lips, throat, or tongue,
• extremely low blood pressure with symptoms such as dizziness, confusion, fainting, rapid pulse

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

The following adverse reactions have been reported in clinical trials with Intratect 50 g/l:

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

• headache
• fever

Rare (may occur in up to 1 in 100 infusions):

• slight increase in red blood cell destruction in blood vessels (hemolysis)
• alteration of taste
• high blood pressure
• inflammation of a superficial vein
• nausea
• vomiting
• abdominal pain
• eruption with raised patches
• chills
• sensation of heat
• increased body temperature
• positive blood test for antibodies against red blood cells

The following adverse reactions have been reported spontaneously with Intratect:

Adverse reactions of unknown frequency (frequency cannot be estimated from available data)

• intense chest pain or pressure (angina pectoris)
• chills or tremors (chills)
• shock (anaphylactic), allergic reaction
• difficulty breathing (dyspnea)
• low blood pressure
• back pain
• decrease in white blood cell count (leucopenia)

Preparations of human immunoglobulin in general may cause the following adverse reactions (in decreasing frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate back pain
• destruction of red blood cells in blood vessels (reversible hemolytic reactions) and (rarely) hemolytic anemia requiring blood transfusion
• (rarely) sudden drop in blood pressure and in isolated cases anaphylactic shock
• (rarely) transient skin reactions (including cutaneous lupus erythematosus, unknown frequency)
• (very rarely) thromboembolic reactions such as heart attack (myocardial infarction), stroke, pulmonary embolism, deep vein thrombosis
• cases of acute and transient inflammation of the protective membranes covering the brain and spinal cord (aseptic meningitis)
• cases of abnormal blood test results indicating renal dysfunction and/or sudden kidney failure
• acute lung injury related to transfusion (LPAT), see also "Warnings and precautions"

If any side effect occurs, the infusion rate will be reduced or discontinued.

Reporting of adverse reactions

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Usehttps://www.notificaram.es.By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and the box after CAD.

It is recommended to use immediately after the first opening.

Do not store at a temperature above 25°C. Do not freeze.

Store the vial in the outer packaging to protect it from light.

Do not use this medication if the solution is cloudy or contains deposits.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment..

Composition of Intratect

-The active principle of Intratect is human immunoglobulin for intravenous administration.

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

-The other components are: glycine and water for injectable preparations.

Appearance of Intratect and packaging contents

Intratect is a perfusion solution. The solution is transparent or slightly opalescent (opal-like milky color) and colorless or pale yellow.

20 ml, 50 ml, 100 ml, or 200 ml of the solution in a vial (type II glass) with a stopper (bromobutyl) and a closure capsule (aluminum).

Package sizes: 1 vial with 20 ml, 50 ml, 100 ml, or 200 ml of solution.

Package sizes: 3 vials with 200 ml of solution.

Only some package sizes may be marketed.

Marketing authorization holder and responsible manufacturer

Biotest Pharma GmbH

Landsteinerstrasse 5

63303 Dreieich

Germany

Phone: + 49 6103 801-0

Fax: + 49 6103 801-150

Email:[email protected]

For more information about this medication, please contact the local representative of the marketing authorization holder:

Grifols Movaco, S.A.

Can Guasc, s/n – Parets del Vallès

08150 Barcelona

Spain

Last review date of thisleaflet: 05/2023

The detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

This information is intended solely for healthcare professionals:

Special precautions

Reaction related to perfusion

Some intense adverse reactions (e.g. headache, hot flashes, chills, myalgia, wheezing, tachycardia, lumbalgia, nausea, and hypotension) may be related to the perfusion rate. The recommended perfusion rate should be respected. The patient should be closely monitored and any symptoms that arise during perfusion should be carefully observed.

The administration of IgIV requires:

-adequate hydration before starting IgIV perfusion,

-monitoring of diuresis,

-monitoring of serum creatinine levels,

-avoiding concomitant use of diuretics.

It is strongly recommended that, each time Intratect is administered to a patient, the patient's name and the product batch number administered be recorded.

In case of shock, standard medical guidelines for shock treatment should be followed.

Asymptomatic Meningitis Syndrome (SMA)

There have been reports of SMA associated with IgIV treatment.

The syndrome usually begins several hours to 2 days after IgIV treatment. Cerebrospinal fluid (CSF) studies are often positive, showing pleocytosis of up to several thousand cells/mm³, predominantly granulocytic, and elevated protein levels of up to several hundred mg/dl.

SMA may occur more frequently in association with high-dose IgIV treatments (2 g/kg).

Patients showing these signs and symptoms should undergo a thorough neurological examination, including CSF studies, to rule out other causes of meningitis.

Discontinuation of IgIV treatment has resulted in the resolution of SMA within several days without sequelae.

Anemia Hemolytica

IgIV products may contain antibodies against blood groups that could act as hemolysins and induce in vivo glomerular coating of red blood cells with immunoglobulin, leading to a positive direct antiglobulin test (Coombs test) and, rarely, hemolysis. Hemolytic anemia may develop after IgIV treatment due to increased red blood cell sequestration. Clinically significant hemolysis signs and symptoms should be closely monitored in IgIV recipients.

Dosage

The dosage and regimen depend on the indication.

The dosage will be individualized for each patient based on clinical response. The weight-based dosage should be adjusted in patients with insufficient weight or obesity.

The following dosing regimens are provided as a guide:

Replacement therapy in primary immunodeficiency syndromes:

The dosing regimen should induce a minimum IgG level (measured before the next perfusion) of at least 6g/l or within the normal reference range for the patient's age. Three to six months of treatment are required to achieve equilibrium (steady-state IgG levels). The recommended initial dose is 0.4-0.8g/kg in a single administration, followed by at least 0.2g/kg every 3-4weeks.

The dose required to achieve a trough IgG level of 6g/l is approximately 0.2-0.8g/kg/month. The dosing interval, once equilibrium is achieved, varies between 3-4weeks.

Trough IgG levels should be measured and evaluated along with the incidence of infection. To reduce the rate of bacterial infections, it may be necessary to increase the dose and pursue higher trough levels.

Substitution therapy in secondary immunodeficiencies:

The recommended dose is 0.2-0.4g/kg every three to four weeks.

Trough IgG levels should be measured and evaluated along with the incidence of infection. The dose should be adjusted as necessary to achieve optimal protection against infections; in patients with persistent infection, it may be necessary to increase the dose; if the patient remains without infection, it may be considered to reduce the dose.

Immunomodulation in:

Primary immune thrombocytopenia:

There are two alternative treatment regimens:

-0.8-1 g/kg on day 1; this dose may be repeated once within three days,

-0.4 g/kg administered daily for 2-5days.

Treatment may be repeated in case of relapse.

Guillain-Barré Syndrome:

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

Kawasaki Disease:

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

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP):

Initial dose: 2g/kg divided over 2-5consecutive days

Maintenance dose: 1g/kg divided over 1-2consecutive days every 3weeks.

The effect of treatment should be evaluated after each cycle; treatment should be discontinued if no effect is observed after 6months. If treatment is effective, physicians should decide on long-term treatment based on the patient's response and maintenance response. Doses and intervals should be adapted according to the individual evolution of the disease.

Multifocal Motor Neuropathy (MMN):

Initial dose: 2g/kg divided over 2-5consecutive days

Maintenance dose: 1g/kg every 2-4weeks, or 2g/kg every 4-8weeks.

The effect of treatment should be evaluated after each cycle; treatment should be discontinued if no effect is observed after 6months. If treatment is effective, physicians should decide on long-term treatment based on the patient's response and maintenance response. Doses and intervals should be adapted according to the individual evolution of the disease.

The recommended dosing regimens are summarized in the following table:

Pediatric population

The dosing regimen in children and adolescents (0-18 years) is not different from that of adults, as the dosing regimen for each indication is calculated based on body weight and should be adjusted according to the clinical response of the aforementioned diseases.

Administration mode

Intravenous

Intratect should be perfused intravenously at an initial rate not exceeding 0.3ml/kg/hour for 30minutes. See "Warnings and precautions". If an adverse reaction occurs, the perfusion rate should be reduced or stopped. If well tolerated, the perfusion rate can be gradually increased to a maximum of 1.9ml/kg/hour.

Incompatibilities

Since there are no compatibility studies, this medication should not be mixed with any other medication or IgIV product.