INTRATECT 50 G/L SOLUTION FOR INFUSION

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, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Intratect and what is it used for
2. What you need to know before you use Intratect
3. How to use Intratect
4. Possible side effects
5. Storage of Intratect
6. Contents of the pack and other information

1. What is Intratect and what is it used for

Intratect is a human blood extract that contains antibodies (the body's own defense substances) against diseases, presented as a solution for infusion. The solution is ready for infusion into a vein ("drip").

Intratect contains normal human immunoglobulin (antibodies) derived from blood donated by a large group of the population and is very likely to contain antibodies against the most common infectious diseases. Adequate doses of Intratect allow the blood values of immunoglobulin G (IgG) to be restored to normal when they are reduced.

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

• patients born with 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 specific antibody deficiency or low IgG level (< 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, where 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 the nerves and can cause generalized paralysis)
• Kawasaki disease (a childhood disease that causes inflammation of various organs in the body and in which the heart's arteries increase in size), along with acetylsalicylic acid
• chronic inflammatory demyelinating polyneuropathy (CIDP). A chronic disease characterized by inflammation of the 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.

2. What you need to know before you use Intratect

Do not use Intratect

• if you are allergic to human immunoglobulin or to any of the other components of this medicine (listed in section 6).
• if you have a deficiency of immunoglobulin A, in particular, 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 medicine before or if it has been a long time (e.g., several weeks) since you last received it (you will need close monitoring during infusion and for up to one hour after it has finished)
• if you have recently received Intratect (you will need observation during infusion and for at least 20 minutes after infusion)
• if you have an active infection or underlying chronic 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 medicines that can damage your kidneys (if kidney function worsens, it may be necessary to stop treatment with Intratect)

Your doctor will be particularly careful if you are overweight, are elderly, have diabetes, or suffer from high blood pressure, decreased blood volume (hypovolemia), if your blood is thicker than normal (increased blood viscosity), are bedridden or have been immobile for some time (immobilization), or have problems with your blood vessels (vascular disease) or other risks of thrombotic episodes (blood clots).

Remember: reactions

During the Intratect infusion period, you will be closely monitored to check that you do not suffer any reaction (e.g., anaphylaxis). Your doctor will ensure that the rate at which Intratect is infused is suitable for you.

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

After Intratect infusion, you may have a low concentration of white blood cells (neutropenia), which resolves spontaneously within 7 to 14 days. If you are unsure of the symptoms, consult your doctor.

In very rare cases, acute lung injury related to transfusion (TRALI) may occur after receiving immunoglobulins. This causes the accumulation of non-cardiogenic fluid in the lungs' air spaces (non-cardiogenic pulmonary edema). You may experience significant difficulty breathing (respiratory distress), rapid breathing (tachypnea), abnormally low oxygen levels in the 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 interrupt the infusion immediately.

Information on the transmission of infectious agents

Intratect is prepared from human plasma (the liquid part of the blood). When medicines derived from human plasma or blood are administered, certain measures must be taken to prevent infections from being passed on to patients. These measures include careful selection of donors to exclude those at risk of carrying infectious diseases, testing for specific infection markers in individual donations and plasma pools, as well as inclusion of steps in the manufacturing process to eliminate/inactivate viruses. Despite this, when medicines derived from human blood or plasma are administered, the possibility of transmitting infectious agents cannot be completely excluded. 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 hepatitis A or parvovirus B19 infections, possibly due to the protective effect of the antibody content against these infections in the medicine.

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 for your medicine. If necessary, this will allow a connection to be established between you and the starting material used.

Using Intratect with other medicines

Tell your doctor if you are using, have recently used, or might use any other medicines.

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

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

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

Avoid concomitant use of loop diuretics with Intratect.

Effects on blood tests

Intratect may alter blood test results. If you have a blood test after receiving Intratect, inform the person taking the 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 using machines

Intratect has a minor influence on the ability to drive and use machines. Patients who experience adverse reactions during treatment should wait until they resolve before driving or operating machines.

3. How to use Intratect

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

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

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

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

Use in children and adolescents

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

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

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

• Primary immune thrombocytopenia: for the treatment of an acute episode, infusion is performed 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: infusion is performed over 5 days.

• Kawasaki disease: infusion is performed as a single dose along 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 thickening, especially in children, elderly patients, or those with heart or kidney function impairment. Make sure to drink enough fluid to avoid dehydration and inform your doctor about any medical problems. If you think you have received too much Intratect, tell your doctor, who will decide whether to stop the infusion and apply different treatment.

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

If you miss an 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 think you have missed an infusion, inform your doctor.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The frequencies indicated below are calculated based on the number of patients treated unless otherwise specified, e.g., the number of infusions.

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

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

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 with Intratect 50 g/l:

Common (may affect up to 1 in 10 infusions):

• headache
• fever

Uncommon(may affect up to 1 in 100 infusions):

• mild increase in red blood cell destruction in the blood vessels (hemolysis)
• altered sense of taste
• high blood pressure
• inflammation of a superficial vein
• nausea
• vomiting
• abdominal pain
• rash with raised patches
• chills
• feeling of heat
• increased body temperature
• positive blood test result for antibodies against red blood cells

The following side effects have been reported spontaneously with Intratect:

Frequency not known (frequency cannot be estimated from the available data)

• severe chest pain or tightness (angina)
• shivering or shaking (chills)
• anaphylactic shock, allergic reaction
• difficulty breathing (dyspnea)
• low blood pressure
• back pain
• decrease in the number of white blood cells (leucopenia)

Human immunoglobulin preparations 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 the number of red blood cells due to their destruction in the 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, frequency not known)
• (very rarely) thromboembolic reactions such as heart attack (myocardial infarction), stroke, blood clots in the lungs (pulmonary embolism), blood 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 also section "Warnings and precautions"

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

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use https://www.notificaram.es. By reporting side 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 which is stated on the label and carton after 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 no longer required. This will help protect the environment.

6. Container Content and Additional Information

Intratect Composition

• The active ingredient of 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 distribution by IgG subclasses 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 Container Content

Intratect is a solution for infusion. The solution is transparent or slightly opalescent (milky color like opal) 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 closing cap (aluminum).

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

Container sizes of 3 vials with 200 ml of solution.

Only some container 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 more 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 Last Revision of thisProspectus: 05/2023

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

This information is intended only for healthcare professionals:

Special Precautions

Infusion-related Reaction

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

The administration of IgIV requires in all cases:

• adequate hydration before starting IgIV infusion,
• monitoring of diuresis,
• monitoring of serum creatinine levels,
• avoiding concomitant use of loop diuretics.

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

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

Aseptic Meningitis Syndrome (AMS)

The occurrence of AMS associated with IgIV treatment has been reported.

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

AMS 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 exclude other causes of meningitis.

Discontinuation of IgIV treatment has resulted in the remission of AMS within several days without sequelae.

Hemolytic Anemia

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

Posology

The dose and dosing regimen depend on the indication.

The dose will be individualized for each patient based on the clinical response. The dose based on body weight should be adjusted in patients with insufficient weight or overweight.

The following dosing regimens are provided for guidance:

Replacement Therapy in Primary Immunodeficiency Syndromes:

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

The dose required to achieve an IgG trough level of 6 g/l is in the order of 0.2-0.8 g/kg/month. The dose interval, once the steady state is reached, varies between 3-4 weeks.

IgG trough 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 0.2-0.4 g/kg every 3 to 4 weeks.

IgG trough 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 infection-free, 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 the next three days,
• 0.4 g/kg administered daily for 2-5 days.

Treatment can be repeated in case of relapse.

Guillain-Barré Syndrome:

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

Kawasaki Disease:

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

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP):

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

Maintenance dose: 1 g/kg divided 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 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: 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.

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 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 posological recommendations are summarized in the following table:

Pediatric Population

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

Method of Administration

Intravenous Route

Intratect should be infused intravenously at an initial rate that does not exceed 0.3 ml/kg/hour for 30 minutes. See "Warnings and Precautions". If an adverse reaction occurs, the administration rate should be reduced or the infusion stopped. If well tolerated, the administration rate can be gradually increased up to a maximum of 1.9 ml/kg/hour.

Incompatibilities

As no compatibility study is available, this medicinal product must not be mixed with any other medicinal product or IgIV product.