Prospecto: information for the user

Intratect 100g/l solution for infusion

Human normal immunoglobulin (IgIV)

Read this prospect carefully before starting to use this medication, because it contains important information for you.

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

Intratect100g/lis a human blood extract containing antibodies (the body's own defense substances) against diseases, presented in a perfusion solution. The solution is ready for infusion into a vein ("drip").

Intratect100g/lcontains normal human immunoglobulin (antibodies) derived from blood donated by a wide population group and is very likely to contain antibodies against common infectious diseases. Appropriate doses ofIntratect100g/lallow for the restoration of normal blood levels of immunoglobulin G (IgG) when they are reduced.

Intratect100g/l is administered to adults, children, and adolescents(0–18 years)who do not have sufficient antibodies (substitutive treatment) in cases of:

• patientswho were bornwith a lack of antibodies (primary immunodeficiency syndrome, PIS)
• acquired lack of antibodies (secondary immunodeficiency syndrome, SIS) in patients suffering from severe or recurrent infections and ineffective antibiotic treatment with demonstrated or proven insufficiency of specific antibodies or a low IgG level (<4g/l)

Intratect100g/l 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 hemorrhage
• Guillain-Barré syndrome (a disease that damages nerves and can cause paralysis)
• Kawasaki disease (a childhood disease that causes inflammation of various body organs and in which the heart's arteries become enlarged), alongwith aspirin
• chronic inflammatory demyelinating polyneuropathy (CIDP). A chronic disease characterized by the inflammation of peripheral nerves, causing muscle weakness and/or numbness, mainly in the legs and upper limbs.
• multifocal motor neuropathy (MMN). A rare disease characterized by slow and progressive asymmetric weakness of the limbs, without sensory loss.

No useIntratect100g/l:

• 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 100 g/l100g/l

• 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 100 g/l (you will need to be observed 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 or have had kidney disease
• if you have received medications that can damage your kidneys (if kidney function worsens, treatment with Intratect 100 g/l may need to be suspended)

Your doctor will take special care if you are overweight, elderly, have diabetes, or have high blood pressure, 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 infusion of Intratect 100 g/l to check for any reactions (e.g., anaphylaxis). Your doctor will ensure that the rate at which Intratect 100 g/l is infused is appropriate for your case.

If you notice any of the following signs of a reaction, that is, headache, hot flushes, chills, muscle pain, wheezing, rapid heart rate, lower back pain, nausea, low blood pressure during the infusion of Intratect 100 g/l, inform your doctor immediately. The infusion rate may be reduced or stopped completely.

After the infusion of Intratect 100 g/l, 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 air spaces of the lungs (non-cardiogenic pulmonary edema). You may experience significant difficulty breathing (dyspnea), rapid breathing (tachypnea), an abnormally low oxygen concentration in the blood (hypoxia), and an elevated body temperature (fever). Symptoms usually appear between 1 and 6 hours after treatment. Inform your doctor immediately if you observe these reactions during the infusion of Intratect 100 g/l; they will stop the infusion immediately.

Information on the transmission of infectious agents

Intratect 100 g/l is prepared with human plasma (the liquid part of the 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 markers of infections in individual donations and plasma mixtures, and inclusion of stages in the manufacturing process to eliminate/inactivate viruses. Despite this, when administering medications derived from human blood or plasma, the risk of transmission of infectious agents cannot be completely ruled out. This also applies to emerging or unknown viruses or 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 value against non-enveloped viruses, such as hepatitis A virus and parvovirus B19.

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

We strongly recommend that each time your doctor administers a dose of Intratect 100 g/l, they record your name and the batch number of the product. The batch number provides information about 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 100 g/l with other medications

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

Intratect 100 g/l 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 100 g/l.

Effects on blood tests

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant or plan to become pregnant, consult your doctor before using this medication.

Your doctor will decide whether you can use Intratect 100 g/l during pregnancy or breastfeeding.

Driving and operating machinery

The influence of Intratect 100 g/l on your ability to drive and operate machinery is small.Patients who experience adverse reactions during treatment should wait until these have resolved before driving or operating machinery.

Intratect100g/lis 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 to administer.

At the beginning of the infusion, you will receiveIntratect100g/lat a slow rate. The doctor may then gradually increase the infusion rate.

The infusion rate and frequency will depend on the reason you are receivingIntratect100g/l.

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 mentioned diseases.

For replacement therapy in patients with a weakened immune system (primary or secondary immunodeficiency), the infusion is performed every3 to4 weeks.

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

• Primary immune thrombocytopenia: for acute treatment, an infusion is performed on day 1; this dose may be repeated once every 3 days. Alternatively, a lower dose may be administered daily for2 to5 days.
• Guillain-Barré syndrome: the infusion will be performed over 5 days.
• Kawasaki disease: the infusion will be performed as a single dosealong with aspirin.
• Chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy; the treatment effect should be evaluated after each cycle of administration.

If you receive more Intratect100g/l than you should

Overdose may cause fluid overload and increased blood viscosity, particularly in children, elderly patients, or those withheart or kidney function impairment. Ensure you drink enough fluids to avoid dehydration and inform your doctor of any medical issues. If you believe you have received too much Intratect100g/l, inform your doctor, who will decide whether to suspend the infusion and apply alternative treatment.

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

If you forget a dose

Intratect100g/l will be administered in the hospital by a doctor or nurse, so it is unlikely that any dose will be missed. However, if you believe a dose has been omitted, inform your doctor.

If you have any otherquestions 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.

The frequencies indicated below have been calculated based on the number of patients treated unless otherwise specified, for example, the number of infusions.

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

• eruption,
• itching,
• chest wheezing (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 side effects have been reported in clinical trials withIntratect 100 g/l:

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

• arrhythmia (palpitations)
• uncomfortable feeling
• reaction associated with infusion
• headache
• joint pain
• back pain
• bone pain

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

• hypersensitivity
• fatigue
• chills
• hypothermia
• sensory alteration
• muscle pain
• skin pain
• eruption
• excessive blood flow to organs or tissues
• high blood pressure
• diarrhea
• abdominal pain

The following side effects have been reported spontaneously with Intratect:

Unknown frequency (frequency cannot be estimated from available data)

• intense chest pain or pressure (angina pectoris)
• shivering or trembling (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 side effects(in decreasing frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate back pain
• decrease in red blood cell count due to destruction 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 asheart 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 renal insufficiency
• acute transfusion-related lung injury (TRALI), see also "Warnings and precautions"

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

Reporting of side effects

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 the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of thismedicine.

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 above25°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.

Medications should not be thrown away through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Intratect100g/l

• The active principle of Intratect100g/l is human immunoglobulin for intravenous administration. Intratect100g/l contains 100 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 1800 micrograms/ml.
• The other components are: glycine and water for injectable preparations.

Aspect of the product and content of the package

Intratect100g/l is a perfusion solution. The solution is transparent or slightly opalescent (opal-like milky color) and colorless or pale yellow.

10 ml, 25ml, 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 of 1 vial with 10 ml, 25 ml, 50 ml, 100 ml or 200 ml of solution.

Package sizes of 3 vials with 100 ml or 200 ml of solution.

Only some package sizes may be marketed.

Holder of the marketing authorization and responsible for manufacturing

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 this leaflet: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 doctors or healthcare professionals:

Special precautions

Reaction related to perfusion

Some severe adverse reactions (e.g. headache, hot flashes, chills, muscle pain, wheezing, tachycardia, lower back pain, 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 in all cases:

• adequate hydration before starting the perfusion of IgIV,
• monitoring of urine output,
• monitoring of serum creatinine levels,
• avoiding the 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 the treatment of shock should be followed.

Asymptomatic aseptic meningitis (AAM)

Aseptic meningitis associated with IgIV treatment has been reported.

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.

AAM may occur more frequently in association with high-dose IgIV treatments (2g/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 AAM within several days without sequelae.

Hemolytic anemia

IgIV 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 IgIV treatment due to increased red blood cell sequestration. Clinicians should monitor patients for signs and symptoms of hemolysis.

Dosage

The dosage and treatment 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 treatment regimens are provided as a guide:

Replacement therapy in primary immunodeficiency syndromes:

The treatment 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 steady-state is achieved, varies between3–4weeks.

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, a dose reduction may be considered.

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 2-5días.

Treatment may be repeated in case of relapse.

Guillain-Barré syndrome:

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

Kawasaki disease:

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

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP):

Initial dose: 2g/kg divided over 2-5días consecutivos

Maintenance dose: 1g/kg divided over 1–2días consecutivos every 3weeks.

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

If treatment is effective, doctors should decide on long-term treatment based on the patient's response and the response to maintenance.The doses and intervals should be adapted according to the individual evolution of the disease.

Multifocal motor neuropathy (MMN):

Initial dose: 2g/kg divided over 2–5días consecutivos

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, after 6months, no effect is observed.

If treatment is effective, doctors should decide on long-term treatment based on the patient's response and the response to maintenance.The 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 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 should be adjusted according to the clinical outcome of the aforementioned diseases.

Administration mode

Intravenous

Intratect100g/lshould be infused intravenously at an initial rate not exceeding 0.3ml/kg/hour for 30minutes. See "Warnings and precautions". If a reaction occurs, the infusion rate should be reduced or discontinued. If tolerated well, the infusion rate may be gradually increased to a maximum of 1.9ml/kg/hour.

Substitution therapy:

In patients who have tolerated the infusion rate of1.9ml/kg/h, it is possible to gradually increase the rate to6ml/kg/h and, if they continue to tolerate it well, to further increase to a maximum of8ml/kg/h.

In general, the dose and infusion rates should be adjusted individually according to the patient's needs.

Incompatibilities

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