Intratect 50 g/L solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Intratect 50 g/l solution for infusion

Normal human immunoglobulin (IgIV)

Read all of 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, ask your doctor, pharmacist or nurse.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Intratect is and what it is used for
2. What you need to know 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 human blood extract containing antibodies (the body's own defense substances) against diseases, presented as a solution for infusion. The solution is ready for intravenous infusion ("drip").

Intratect contains normal human immunoglobulin (antibodies) derived from blood donated by a large population group and is highly likely to contain antibodies against the most common infectious diseases. Appropriate doses of Intratect help restore blood levels of immunoglobulin G (IgG) to normal when they are reduced.

Intratect is administered to adults, children, and adolescents (0–18 years) who do not have sufficient antibodies (replacement therapy) in cases of:

• patients born with an antibody deficiency (primary immunodeficiency syndrome, PIS)
• acquired antibody deficiency (secondary immunodeficiency syndrome, SIS) in patients suffering from severe or recurrent infections and ineffective antibiotic treatment, with demonstrated specific antibody failure or low IgG levels (< 4 g/l)

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

• primary immune thrombocytopenia (ITP, in which the patient has a low platelet count in the blood) if the patient is about to undergo surgery or is at risk of bleeding
• Guillain-Barré syndrome (a disease that damages the nerves and may cause generalized paralysis)
• Kawasaki disease (a childhood illness causing inflammation of various body organs and enlargement of the heart arteries), in combination with acetylsalicylic acid
• chronic inflammatory demyelinating polyneuropathy (CIDP). A chronic disease characterized by inflammation of the peripheral nerves, causing muscle weakness and/or numbness, primarily in the legs and upper limbs.
• multifocal motor neuropathy (MMN). A rare disease characterized by slowly progressive, asymmetric weakness of the limbs, without sensory loss.

2. What you need to know before using Intratect

Do not use Intratect

• if you are allergic to human immunoglobulin or any of the other ingredients of this medicine (listed in section 6).
• if you have immunoglobulin A deficiency, particularly if you have antibodies against immunoglobulin A in your blood, as this may lead to anaphylaxis.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Intratect

• if you have never received this medicine before or if a long time has passed (e.g., several weeks) since your last dose (you will require close monitoring during infusion and for one hour after completion)
• if you have recently received Intratect (you will require monitoring during infusion and for at least 20 minutes after infusion)
• if you have an active infection or underlying chronic inflammation
• if you have previously experienced a reaction to other antibodies (in rare cases, you may be at risk of an allergic reaction)
• if you have or have had kidney disease
• if you have taken medications that may damage your kidneys (if kidney function worsens, treatment with Intratect may need to be discontinued)

Your doctor will exercise particular caution if you are overweight, elderly, have diabetes, low blood volume (hypovolemia), increased blood viscosity (high blood viscosity), are bedridden or have been immobile for some time (immobilization), or have blood vessel disorders (vascular diseases) or other risk factors for thrombotic events (blood clots).

Remember: Reactions

During the Intratect infusion, you will be closely monitored for any reactions (e.g., anaphylaxis). Your doctor will ensure that the infusion rate of Intratect is appropriate for your condition.

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

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

In very rare cases, transfusion-related acute lung injury (TRALI) may occur after receiving immunoglobulins. This causes fluid accumulation unrelated to heart function in the air spaces of the lungs (non-cardiogenic pulmonary edema). You may experience severe breathing difficulty (respiratory distress), rapid breathing (tachypnea), abnormally low oxygen levels in the blood (hypoxia), and increased body temperature (fever). Symptoms typically appear between 1 and 6 hours after treatment. Inform your doctor immediately if you experience these reactions during Intratect infusion; the infusion will be stopped immediately.

Information on transmission of infectious agents

Intratect is prepared from human plasma (the liquid part of blood). When medicines derived from human plasma or blood are administered, certain measures must be taken to prevent transmission of infections to patients. These measures include careful selection of donors to exclude those at risk of carrying infectious diseases, testing for specific markers of infection in individual donations and plasma pools, and inclusion of manufacturing steps designed to inactivate or remove viruses. Nevertheless, when medicines derived from human blood or plasma are administered, the possibility of transmitting infectious agents cannot be completely ruled out. This also applies to emerging viruses or those of unknown origin, as well as other types of infections.

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

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

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

It is strongly recommended that each time your doctor administers a dose of Intratect, they record your name and the product's batch number. The batch number provides information about the specific starting materials used for your medicine. This may allow a link to be established between you and the source material, if necessary.

Use of Intratect with other medicines

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.

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

• measles vaccine
• rubella vaccine
• mumps vaccine
• varicella vaccine

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

Avoid concomitant use of loop diuretics with Intratect.

Effects on blood tests

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

Pregnancy and breastfeeding

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

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

Driving and use of machines

The effect of Intratect on the ability to drive and operate machinery is minimal. Patients who experience adverse reactions during treatment should wait until these reactions have resolved before driving or operating machinery.

3. How to use Intratect

Intratect is intended for intravenous administration (infusion into a vein) by a physician or nursing staff. The dose will depend on your condition and body weight. Your doctor will determine the exact amount to administer.

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

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

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

Use in children and adolescents

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

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

For the treatment of inflammatory diseases (immunomodulation), the infusion may be administered as follows:

• Primary immune thrombocytopenia: for the treatment of an acute episode, an infusion is given on Day 1; this dose may be repeated once after 3 days. Alternatively, a lower dose may be administered daily for 2 to 5 days.

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

• Kawasaki disease: the infusion will be given 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 administration cycle.

If you receive more Intratect than you should

Overdose may cause fluid overload and increased blood viscosity, particularly in children, elderly patients, or those with impaired heart or kidney function. Make sure to drink sufficient fluids to avoid dehydration and inform your doctor of any medical problems. If you think you have received too much Intratect, inform your doctor immediately, who will decide whether to stop the infusion and initiate alternative treatment.

In case of overdose or accidental ingestion, contact the Toxicology Information Service immediately at telephone 915620420.

If you miss an infusion

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The frequencies listed below are generally based on the number of patients treated, unless otherwise specified (e.g., number of infusions).

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

• rash,
• itching,
• wheezing in the chest,
• difficulty breathing,
• swelling of the eyelids, face, lips, throat, or tongue,
• extremely low blood pressure with symptoms such as dizziness, confusion, fainting, or rapid pulse.

These could be signs of an allergic reaction or a severe allergic reaction (anaphylactic shock), or a hypersensitivity reaction.

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

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 destruction of red blood cells within blood vessels (hemolysis)
• altered sense of taste
• high blood pressure
• inflammation of a superficial vein
• nausea
• vomiting
• abdominal pain
• rash with raised spots
• chills
• sensation of warmth
• increased body temperature
• positive blood test result for antibodies against red blood cells

The following adverse effects have been reported spontaneously with Intratect:

Adverse effects with unknown frequency (frequency cannot be estimated from available data):

• severe chest pain or tightness (angina pectoris)
• rigors or shaking (chills)
• shock (anaphylactic), allergic reaction
• difficulty breathing (dyspnea)
• low blood pressure
• back pain
• decrease in white blood cell count (leukopenia)

Human immunoglobulin preparations in general may cause the following adverse effects (in decreasing frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate back pain
• decreased number of red blood cells due to their destruction in blood vessels (hemolytic reactions [reversible]) 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, frequency not known)
• (very rarely) thromboembolic events such as heart attack (myocardial infarction), stroke, blood clots in the lung vessels (pulmonary embolism), or clots in a vein (deep vein thrombosis)
• cases of acute transient inflammation of the protective membranes covering the brain and spinal cord (aseptic meningitis)
• cases of blood test results indicating kidney dysfunction and/or sudden kidney failure
• transfusion-related acute lung injury (TRALI)—see section "Warnings and precautions"

If any adverse reaction occurs, the infusion rate will be reduced or the infusion stopped.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Intratect

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 the carton following EXP.

It is recommended to use immediately after first opening.

Do not store above 25 °C. Do not freeze.

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

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Intratect

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

Intratect contains 50 g/L of normal immunoglobulin, of which at least 96% is immunoglobulin G (IgG). The IgG subclass distribution is approximately 57% IgG1, 37% IgG2, 3% IgG3, and 3% 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 contents of the container

Intratect is a solution for infusion. The solution is transparent or slightly opalescent (milky, opal-like appearance) and colorless or pale yellow.

20 mL, 50 mL, 100 mL, or 200 mL of solution in a vial (type II glass) with a stopper (bromobutyl rubber) and an aluminum seal.

Pack sizes of 1 vial containing 20 mL, 50 mL, 100 mL, or 200 mL of solution.

Pack sizes of 3 vials containing 200 mL of solution each.

Only certain 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]

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Grifols Movaco, S.A.
Can Guasc, s/n – Parets del Vallès
08150 Barcelona
Spain

Date of the most recent revision of this leaflet: 05/2023

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

Special precautions

Infusion-related reactions

Some severe adverse reactions (e.g., headache, flushing, chills, myalgia, chest tightness, wheezing, tachycardia, back pain, nausea, and hypotension) may be related to the infusion rate. The recommended infusion rate must be observed. The patient should be closely monitored and carefully observed for any symptoms arising during infusion.

Administration of IVIG requires, in all cases:

• adequate hydration prior to starting IVIG infusion,
• monitoring of urine output,
• monitoring of serum creatinine levels,
• avoidance of concomitant use of loop diuretics.

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

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

Aseptic Meningitis Syndrome (AMS)

AMS has been reported in association with IVIG treatment.

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

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

Patients presenting with these signs and symptoms should undergo a thorough neurological examination, including cerebrospinal fluid (CSF) studies, to exclude other causes of meningitis.

Discontinuation of IVIG treatment has resulted in resolution of AMS within several days, without sequelae.

Hemolytic anemia

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

Dosage

The dose and dosage regimen depend on the indication.

The dose should be individualized for each patient according to clinical response. Weight-based dosing should be adjusted in patients who are underweight or overweight.

The following dosage regimens are provided as guidance:

Replacement therapy in primary immunodeficiency syndromes:

The dosage regimen should aim to achieve a trough IgG level (measured just before the next infusion) of at least 6 g/L or within the normal reference range for the patient's age group. It may take 3–6 months of treatment to reach equilibrium (steady-state IgG levels). The recommended initial dose is 0.4–0.8 g/kg as a single infusion, followed by at least 0.2 g/kg every 3–4 weeks.

The dose required to achieve a trough IgG level of 6 g/L is approximately 0.2–0.8 g/kg/month. Once steady state is achieved, the dosing interval typically ranges from 3 to 4 weeks.

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

Replacement therapy in secondary immunodeficiencies:

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

Trough IgG levels should be measured and evaluated together with the incidence of infections. The dose should be adjusted as necessary to achieve optimal protection against infections; dose increases may be needed in patients with persistent infections, while dose reduction may be considered in patients remaining infection-free.

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 the following three days,
• 0.4 g/kg administered daily for 2–5 days.

Treatment may be repeated in case of relapse.

Guillain-Barré syndrome:

0.4 g/kg/day for 5 days (administration 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 administered over 2–5 consecutive days
Maintenance dose: 1 g/kg administered over 1–2 consecutive days every 3 weeks.

The effect of treatment should be evaluated after each cycle; treatment should be discontinued if no effect is observed after 6 months.

If treatment is effective, physicians should decide on long-term therapy based on patient response and maintenance response. Doses and intervals should be adjusted according to the individual course of the disease.

Multifocal motor neuropathy (MMN):

Initial dose: 2 g/kg administered over 2–5 consecutive days
Maintenance dose: 1 g/kg every 2 to 4 weeks, or 2 g/kg every 4 to 8 weeks.

The effect of treatment should be evaluated after each cycle; treatment should be discontinued if no effect is observed after 6 months.

If treatment is effective, physicians should decide on long-term therapy based on patient response and maintenance response. Doses and intervals should be adjusted according to the individual course of the disease.

The dosage recommendations are summarized in the following table:

Pediatric population

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

Method of administration

Intravenous route

Intratect must be administered intravenously at an initial infusion rate not exceeding 0.3 ml/kg/hour for 30 minutes. See “Warnings and precautions”. If an adverse reaction occurs, the infusion rate should be reduced or the infusion stopped. If well tolerated, the infusion rate may be gradually increased up to a maximum of 1.9 ml/kg/hour.

Incompatibilities

Due to the lack of compatibility studies, this medicinal product must not be mixed with any other medicinal product or with any other IgIV product.