Intratect

Package leaflet: Information for the user

Intratect 50 g/l infusion solution

Normal human immunoglobulin (IVIg)
Please 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 questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Intratect is and what it is used for
2. What you need to know before you use 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, and is available as a solution for infusion. The solution is ready to be administered into a vein ("intravenous infusion").
Intratect contains normal human immunoglobulin (antibodies) obtained from blood donated by a large group of donors, and therefore likely contains antibodies against the most common infectious diseases.
Adequate doses of Intratect can restore blood levels of immunoglobulin G (IgG) to normal when these levels are low.
Intratect is used in 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 syndromes, PID)
• acquired antibody deficiency (secondary immunodeficiency syndrome, SID) in patients suffering from severe or recurrent infections and ineffective antimicrobial treatment, with documented specific antibody deficiency or low IgG levels (< 4 g/l)

Intratect is also used in adults, children and adolescents (0–18 years) for the treatment of inflammatory disorders (immunomodulation), such as:

• primary immune thrombocytopenia (ITP, in which the patient has a reduced number of platelets), when 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 (in children it causes inflammation in various organs with dilation of the coronary arteries), in combination with acetylsalicylic acid
• chronic inflammatory demyelinating polyneuropathy (CIDP). This is 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). It is a rare condition characterized by slowly progressive, asymmetric limb weakness, without sensory loss.

2. What you need to know before using Intratect

Do not use Intratect

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Intratect if

• you have never used this medicine before or it has been a long time (several weeks) since you last received it (careful monitoring will be required during the infusion and for one hour after it ends)
• you have recently received Intratect (in which case you will need to be observed during the infusion and for at least 20 minutes after the infusion)
• you have an active infection or an underlying chronic inflammation
• you have previously had a reaction to other antibodies (in rare cases, there may be a risk of allergic reaction)
• you have or have had kidney disease
• you have been given medicines that may damage the kidneys (if kidney function worsens, treatment with Intratect may need to be stopped). Your doctor will pay particular attention if you are overweight, elderly, have diabetes or hypertension, have low blood volume (hypovolemia), increased blood thickness (hyperviscosity), are bedridden or immobile for a period of time (immobilization), have blood vessel disorders (vascular diseases), or other risk factors for developing thrombosis (blood clotting).

Be careful – reactions
You will remain under close observation throughout the entire Intratect infusion period to ensure that no reactions occur (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 during the Intratect infusion—inform your doctor immediately. The infusion rate may be slowed down or the infusion stopped completely.
After Intratect infusion, a low white blood cell count (neutropenia) may occur, which resolves spontaneously within 7–14 days. If you are uncertain about symptoms, consult your doctor.
In very rare cases, acute lung injury related to transfusion (TRALI) may occur after administration of immunoglobulins. This leads to 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), increased breathing rate (tachypnea), abnormally low oxygen levels in the blood (hypoxia), and elevated body temperature (fever). Symptoms usually appear within 1–6 hours after treatment. If such reactions occur during Intratect infusion, inform your doctor immediately; the infusion will be stopped immediately.

Information on transmission of infectious agents
Intratect is made from human plasma (the liquid part of blood). When medicines are made from human blood or plasma, it is important to prevent the transmission of infections to patients. Blood donors are tested for viruses and infections. In addition, manufacturers of these medicines treat the blood or plasma to inactivate or remove viruses. Despite these precautions, however, the possibility of transmitting infections cannot be completely ruled out when medicines derived from human blood or plasma are administered.
The precautions taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus.
The precautions taken may be less effective against non-enveloped viruses such as hepatitis A virus and parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, possibly because the antibodies against these infections contained in the product are protective.
It is strongly recommended that your doctor records the name and batch number of the product each time you are administered a dose of Intratect. The batch number provides information about the specific starting material used for the medicine you receive. If necessary, this allows traceability of the starting material used for you.

Other medicines and Intratect
Inform your doctor if you are currently taking, have recently taken, or might take any other medicines.
Intratect may reduce the effectiveness of certain vaccines, such as those for:

• measles
• rubella
• mumps
• varicella
  It may be necessary to wait up to 3 months before receiving certain vaccines, and 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, you must inform the person drawing the blood sample or your doctor that you have been treated with Intratect.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor for advice before taking this medicine.
Your doctor will decide whether Intratect can be used during pregnancy and breastfeeding.

Driving and using machines
Intratect may have a slight effect on the ability to drive or operate machinery. 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). It is administered by a doctor or nurse. The dose will depend on your health condition and body weight. Your doctor will determine the appropriate dose for you.
At the beginning of the infusion, Intratect will be administered slowly. Your doctor may subsequently increase the infusion rate gradually.
The infusion rate and frequency depend on the reason for which you are receiving Intratect.
The medicine must 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 in adults, since for each indication it depends on body weight and is adjusted according to the clinical outcome of the conditions mentioned above.
For replacement therapy in patients with immune system deficiency (primary or secondary immunodeficiency), the infusion is given every 3–4 weeks.
For the treatment of inflammatory disorders (immunomodulation), the infusion may be administered as follows:

• Primary immune thrombocytopenia: for treatment of an acute episode, one infusion is administered on day 1; this dose may be repeated once within 3 days. Alternatively, a lower dose may be administered daily for 2–5 days.
• Guillain-Barré syndrome: the infusion is administered for 5 days.
• Kawasaki disease: the infusion should be administered as a single dose in combination with acetylsalicylic acid.
• Chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy: the treatment effect should be evaluated after each administration cycle.

If you have been given more Intratect than you should have
An overdose may cause fluid overload and increased blood viscosity, particularly in children, elderly patients, or patients with impaired renal or cardiac function. Make sure to drink adequate amounts of fluids to avoid dehydration and inform your doctor of any health problems. If you think you have received an excessive amount of Intratect, inform your doctor, who will decide whether the infusion should be stopped and whether alternative treatment is required.

If an infusion has not been administered
Intratect will be administered to you in a hospital setting by a doctor or nurse, so it is unlikely that an infusion will be missed. However, inform your doctor if you think you have missed an infusion. If you have further questions about 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 everyone gets them.
The frequencies described below are generally based on the number of patients treated, unless otherwise specified (e.g., per number of infusions).
If you notice any of the following effects, inform your doctor immediately:

• skin 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 pulse.
  These may be signs of a severe allergic reaction (anaphylactic shock) or hypersensitivity reaction.

The following side effects were reported during clinical studies with Intratect 50 g/l:
Common (may occur in up to 1 in 10 people):

• headache
• fever

Uncommon (may occur in up to 1 in 100 people):

• slight increase in destruction of red blood cells within blood vessels (haemolysis)
• altered sense of taste
• high blood pressure
• inflammation of a superficial vein
• malaise (nausea)
• vomiting
• abdominal pain
• skin rash with raised spots
• chills
• hot flushes
• increased body temperature
• positive test for antibodies directed against red blood cells

The following side effects have been reported spontaneously with Intratect:
Not known (frequency cannot be estimated from the available data):

• severe chest pain or tightness in the chest (angina pectoris)
• chills or tremors (rigidity)
• shock (anaphylactic), allergic reaction
• difficulty breathing (dyspnoea)
• low blood pressure
• back pain
• decrease in white blood cell count (leucopenia)

Immunoglobulin human-based preparations may generally cause the following side effects
(in decreasing order of frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure and moderate backache
• reduction in red blood cell count due to breakdown of these cells in blood vessels (reversible haemolytic reactions) and (rarely) haemolytic anaemia requiring 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 blood vessels of the lung (pulmonary embolism), blood clots in a vein (deep vein thrombosis)
• cases of acute, temporary inflammation of the protective membranes covering the brain and spinal cord (reversible aseptic meningitis)
• cases of blood test results indicating impaired kidney function and/or acute kidney failure
• cases of acute transfusion-related lung injury (TRALI): see also section “Warnings and precautions”

If side effects occur, the infusion will be slowed down or completely stopped.
Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 after "Exp".
Immediate use after first opening is recommended.
Do not store above 25°C. Do not freeze.
Keep the vial in its carton to protect the medicine from light.
Do not use this medicine if the solution is cloudy or contains deposits.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Intratect contains
The active substance in Intratect is human immunoglobulin for intravenous administration.
Intratect contains 50 g/l of normal human immunoglobulin, of which at least 96% consists of
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 injections.

Description of the appearance of Intratect and contents of the pack
Intratect is a solution for infusion. The solution is clear or slightly opalescent (slightly milky), colourless or pale yellow.
20 ml, 50 ml, 100 ml or 200 ml of solution in vials (type II glass) with stopper (bromobutyl) and seal (aluminium).
Each pack contains 1 vial with 20 ml, 50 ml, 100 ml or 200 ml of solution.
Each pack contains 3 vials with 200 ml of 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]

For all information regarding this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Biotest Italia srl
Via Leonardo da Vinci, 43
20090 Trezzano sul Naviglio (Milan)
Italy
Tel.: 02 4844291
Fax: 02 4450141
Email: [email protected]

MANUFACTURE
Biotest AG, Landsteinerstrasse 5, D-63303 Dreieich, Germany

RELEASE OF BATCHES
Biotest Pharma GmbH, Landsteinerstrasse 5, D-63303 Dreieich, Germany

PACKAGING
Biotest AG, Landsteinerstrasse 5, D-63303 Dreieich, Germany

The following information is intended exclusively for healthcare professionals:

Special precautions
Infusion-related reaction
Certain adverse reactions (e.g., headache, flushing, chills, myalgia, wheezing, tachycardia, back pain, nausea, and arterial hypotension) may be related to the infusion rate. The recommended infusion rate must be strictly observed. Patients must be closely monitored and carefully observed for any symptoms during the infusion period.
In all patients, intravenous administration of IVIg requires:

• adequate hydration prior to initiation of IVIg infusion
• monitoring of urine output
• monitoring of serum creatinine levels
• avoidance of concomitant use of loop diuretics

Each time Intratect is administered to a patient, it is strongly recommended to record the product name and batch number.
In case of shock, apply standard medical treatments for shock.

Aseptic Meningitis Syndrome (AMS)
AMS has been reported in association with IVIg treatment.
The syndrome usually begins several hours to two days after IVIg treatment. Cerebrospinal fluid (CSF) analyses 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 with high-dose IVIg treatment (2 g/kg).
Patients presenting with such signs and symptoms should undergo a thorough neurological examination, including CSF studies, to exclude other causes of meningitis.
Discontinuation of IVIg treatment has led to resolution of AMS within a few days without sequelae.

Hemolytic anemia
IVIg products may contain blood group antibodies that can act as hemolysins and induce in vivo immunoglobulin binding to red blood cells (RBCs), resulting in a positive direct antiglobulin reaction (Coombs test) and, rarely, hemolysis. Hemolytic anemia may develop following IgIV therapy due to increased RBC sequestration. Patients treated with IVIg should be monitored for clinical signs and symptoms of hemolysis.

Dosage
The dose and dosing regimen depend on the indication.
Dose individualization may be necessary for each patient according to clinical response. Weight-based dosing may require adjustment in underweight or overweight patients.
The following dosages are suggested as a guide:

Replacement therapy in primary immunodeficiency syndromes:
The dosing regimen should achieve a minimum IgG level (measured just before the next infusion) of at least 6 g/L or within the normal reference range for age-specific population. It takes 3–6 months after initiation of therapy to reach steady-state IgG levels. The recommended initial dose is 0.4–0.8 g/kg administered as a single infusion, followed by at least 0.2 g/kg administered every 3–4 weeks.
The dose required to achieve a minimum IgG level of 6 g/L ranges from 0.2–0.8 g/kg/month.
Once steady-state is achieved, the interval between doses ranges from 3 to 4 weeks.
Trough IgG levels should be measured and evaluated in relation to the incidence of infection.
To reduce the rate of bacterial infections, it may be necessary to increase the dosage with the aim of achieving higher trough IgG levels.

Replacement therapy in secondary immunodeficiencies
The recommended dose is 0.2–0.4 g/kg every 3–4 weeks.
Trough IgG levels should be measured and evaluated in relation to the incidence of infection. The dose should be adjusted as needed to achieve optimal protection against infections; an increase may be necessary in patients with persistent infections, while dose reduction may be considered if the patient remains infection-free.

Immunomodulation in:

Immune thrombocytopenia (ITP)
Two alternative treatment regimens are available:

• 0.8–1 g/kg administered on Day 1; this dose may be repeated once every 3 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 (re-administration may be considered in case of relapse).

Kawasaki disease:
A single dose of 2.0 g/kg must be administered. 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 doses: 1 g/kg divided over 1–2 consecutive days every 3 weeks.
The effect of treatment should be evaluated after each cycle; if no effect is observed after 6 months, treatment should be discontinued.
If treatment is effective, long-term therapy is at the physician’s discretion, based on patient response and maintenance response. Dosage and administration intervals may need to be adjusted according to the individual course of the disease.

Multifocal motor neuropathy (MMN)
Initial dose: 2 g/kg divided over 2–5 consecutive days.
Maintenance dose: 1 g/kg every 2–4 weeks or 2 g/kg every 4–8 weeks.
The effect of treatment must be evaluated after each cycle; if no effect is observed after 6 months, treatment must be discontinued.
If treatment is effective, long-term therapy is at the physician’s discretion, based on patient response and maintenance response. Dosage and administration intervals may need to be adjusted according to the individual course of the disease.

The recommended dosages are summarized in the following table:

Paediatric population
The dosage in children and adolescents (0–18 years) does not differ from that in adults, as for each indication it depends on body weight and must be adjusted according to the clinical outcome of the above-mentioned conditions.
Method of administration
Intravenous use
Intratect must be administered intravenously at an initial rate not exceeding 0.3 ml/kg/hour for 30 minutes. See "Warnings and precautions". In case of an adverse reaction, reduce the infusion rate or stop the infusion. If well tolerated, the infusion rate may be gradually increased up to a maximum of 1.9 ml/kg/hour.
Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products or with any other product containing IVIg.

Package leaflet: Information for the user

Intratect 100 g/l solution for infusion

Normal human immunoglobulin (IVIg)
Please read this leaflet carefully before using this medicine because it contains important information for you.

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

Contents of this leaflet:

1. What Intratect 100 g/l is and what it is used for
2. What you need to know before using 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 human blood extract containing antibodies (natural defense substances of the body) against diseases, and is available as an infusion solution. The solution is ready to be administered into a vein (“intravenous infusion”).
Intratect 100 g/l contains normal human immunoglobulin (antibodies) obtained from blood donated by a large group of donors, and therefore likely contains antibodies against the most common infectious diseases. Adequate doses of Intratect 100 g/l can restore blood levels of immunoglobulin G (IgG) to normal when these are low.
Intratect 100 g/l is used in adults, children and adolescents (0–18 years) who have insufficient
antibodies (replacement therapy) in the following cases:

• patients born with antibody deficiency (primary immunodeficiency syndromes, PID)
• acquired antibody deficiency (secondary immunodeficiency syndrome, SID) in patients suffering from severe or recurrent infections with ineffective antimicrobial treatment and documented defect in 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 disorders (immunomodulation), such as:

• primary immune thrombocytopenia (immune thrombocytopenia, ITP, in which the patient has a reduced number of platelets), when the patient is scheduled to undergo surgery in the near future or is at risk of bleeding
• Guillain-Barré syndrome (a disease that damages the nerves and may cause generalized paralysis)
• Kawasaki disease (in children causes inflammation in various organs with dilation of the coronary arteries), in combination with acetylsalicylic acid
• chronic inflammatory demyelinating polyneuropathy (CIDP). This is 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). It is a rare condition characterized by slowly progressive, asymmetric limb weakness, without sensory loss.

2. What you should know before using Intratect 100 g/l

Do not use Intratect 100 g/l

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Intratect 100 g/l if:

• You have never used this medicine before or a long time has passed (several weeks) since you last received it (careful monitoring will be required during the infusion and for one hour after it ends).
• You have recently received Intratect 100 g/l (in this case, you will need to be observed during the infusion and for at least 20 minutes afterwards).
• You have an active infection or underlying chronic inflammation.
• You have previously had a reaction to other antibodies (in rare cases, there may be a risk of allergic reaction).
• You have or have had kidney disease.
• You have been given medicines that may damage the kidneys (if kidney function worsens, treatment with Intratect 100 g/l may need to be stopped). Your doctor will pay particular attention if you are overweight, elderly, have diabetes or hypertension, have low blood volume (hypovolemia), increased blood viscosity (hyperviscosity), are bedridden or immobile for a period of time (immobilization), or have blood vessel disorders (vascular diseases) or other risk factors for developing thrombosis (blood clotting).

Take care – reactions
You will remain under close observation throughout the entire period of infusion with Intratect 100 g/l to ensure that no reactions occur (e.g. anaphylaxis). Your doctor will ensure that the infusion rate of Intratect 100 g/l 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 during the infusion of Intratect 100 g/l—inform your doctor immediately. The infusion rate may be slowed or the infusion stopped completely.
After infusion of Intratect 100 g/l, a low white blood cell count (neutropenia) may occur, which resolves spontaneously within 7–14 days. If you are uncertain about symptoms, consult your doctor.
In very rare cases, acute lung injury related to transfusion (TRALI) may occur after administration of immunoglobulins. This leads to fluid accumulation in the air spaces of the lungs unrelated to heart function (non-cardiogenic pulmonary edema). You may experience severe difficulty breathing (respiratory distress), increased respiratory rate (tachypnea), abnormally low oxygen levels in the blood (hypoxia), and elevated body temperature (fever). Symptoms typically appear within 1–6 hours after treatment. If such reactions occur during infusion of Intratect 100 g/l, report them immediately to your doctor, who will immediately stop the infusion.

Information on transmission of infectious agents
Intratect 100 g/l is derived from human plasma (the liquid component of blood). When medicines are made from human blood or plasma, it is important to minimize the risk of transmitting infections to patients. Blood donors are tested for viruses and other infections. In addition, manufacturers process the blood or plasma to inactivate or remove viruses. Despite these precautions, however, the possibility of transmitting infections cannot be completely ruled out when medicines derived from human blood or plasma are administered.
The precautions 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.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, possibly because the antibodies against these infections present in the product are protective.
Your doctor is strongly advised to record the name and batch number of the product each time a dose of Intratect 100 g/l is administered to you. The batch number provides information about the specific starting material used for the medicine you receive. If necessary, it will thus be possible to trace back the source material used for your treatment.

Other medicines and Intratect 100 g/l
Inform your doctor if you are currently taking, have recently taken, or might take any other medicines.
Intratect 100 g/l may reduce the effectiveness of certain vaccines, such as those for:

• measles
• rubella
• mumps
• varicella

It may be necessary to wait up to 3 months before receiving certain vaccines, and up to one year before receiving the measles vaccine. Avoid concomitant use of loop diuretics with Intratect 100 g/l.

Effects on blood tests
Intratect 100 g/l may affect blood test results. If you undergo blood testing after receiving Intratect 100 g/l, inform the person drawing the blood sample or your doctor that you have been treated with Intratect 100 g/l.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before taking this medicine.
Your doctor will decide whether Intratect 100 g/l can be used during pregnancy and breastfeeding.

Driving and using machines
Intratect 100 g/l may have a minor effect on the ability to drive vehicles or operate machinery. Patients who experience adverse reactions during treatment should wait until these symptoms have resolved before driving or operating machinery.

3. How to use Intratect 100 g/l

Intratect 100 g/l is intended for intravenous administration (infusion into a vein). It is administered by a doctor or nurse. The dose will depend on your medical condition and body weight. Your doctor will determine the appropriate dose for you.
At the beginning of the infusion, Intratect 100 g/l will be administered slowly. Your doctor may subsequently increase the infusion rate gradually.
The infusion rate and frequency depend on the reason why you are receiving Intratect 100 g/l.
The medicine should be warmed 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 in adults, as for each indication it depends on body weight and is adjusted according to the clinical response to the above-mentioned conditions.
For replacement therapy in patients with immune system deficiency (primary or secondary immunodeficiency), the infusion is given every 3–4 weeks.
For treatment of inflammatory disorders (immunomodulation), the infusion may be administered as follows:

• Immune thrombocytopenia: for treatment of an acute episode, one infusion is given on day 1; this dose may be repeated once within 3 days. Alternatively, a lower dose may be administered daily for 2–5 days.
• Guillain-Barré syndrome: the infusion is administered for 5 consecutive days.
• Kawasaki disease: the infusion should be given as a single dose in combination with acetylsalicylic acid.
• Chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy: the treatment effect should be evaluated after each administration cycle.

If you have been given more Intratect 100 g/l than you should have
An overdose may cause fluid overload and increased blood viscosity, especially in children, elderly patients, or patients with impaired renal or cardiac function. Make sure you drink adequate amounts of fluids to avoid dehydration and inform your doctor of any health problems. If you think you have received an excessive amount of Intratect 100 g/l, inform your doctor, who will decide whether the infusion should be stopped and whether alternative treatment is required.

If an infusion has not been administered
Intratect 100 g/l will be administered to you in a hospital setting by a doctor or nurse, so it is unlikely that an infusion will be missed. However, inform your doctor if you think you have missed an infusion.
If you have any further questions about 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 will experience them.
The frequencies reported below are generally based on the number of patients treated, unless otherwise specified (e.g., per number of infusions).
If you notice any of the following effects, inform your doctor immediately:

• skin 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 pulse
  These may be signs of a severe allergic reaction (anaphylactic shock) or hypersensitivity reaction.

The following side effects have been reported in clinical studies with Intratect 100 g/l:
Common (may affect up to 1 in 10 infusions):

• abnormal heartbeat (palpitations)
• feeling unwell
• infusion-related reaction
• headache
• joint pain
• back pain
• bone pain

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

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

The following side effects have been spontaneously reported with Intratect:
Not known (frequency cannot be estimated from the available data):

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

Preparations containing human immunoglobulins may generally cause the following side effects
(listed in decreasing order of frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate lower back pain
• reduced number of red blood cells due to their breakdown within blood vessels (reversible hemolytic reactions) and (rarely) hemolytic anemia requiring 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 blood vessels of the lung (pulmonary embolism), blood clots in a vein (deep vein thrombosis)
• cases of temporary acute inflammation of the protective membranes covering the brain and spinal cord (reversible aseptic meningitis)
• cases of blood test results indicating impaired kidney function and/or acute kidney failure
• cases of acute transfusion-related lung injury (TRALI): see also section “Warnings and precautions”

If side effects occur, the infusion will be slowed down or stopped completely.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. You may also report side effects directly via
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Intratect 100 g/l

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 after Exp.
Immediate use after first opening is recommended.
Do not store above 25°C. Do not freeze. Keep the vial in its carton to protect the medicine from light.
Do not use this medicine if the solution is cloudy or contains deposits.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents 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% consists of
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 1800 micrograms/ml.
The other components are: glycine and water for injections.

Description of the appearance of Intratect 100 g/l and contents of the pack
Intratect 100 g/l is a solution for infusion. The solution is clear or slightly opalescent (slightly milky), colourless or pale yellow.
10 ml, 25 ml, 50 ml, 100 ml or 200 ml of solution in vials (Type II glass) with stopper (bromobutyl) and
seal (aluminium).
Each pack contains 1 vial with 10 ml, 25 ml, 50 ml, 100 ml or 200 ml of solution.
Each pack contains 3 vials with 100 ml or 200 ml of 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]

For all information regarding this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Biotest Italia srl
Via Leonardo da Vinci, 43
20090 Trezzano s/N (Milan)
Italy
Tel.: 02 4844291
Fax: 02 4450141
Email: [email protected]

MANUFACTURER
Biotest AG, Landsteinerstrasse 5, D-63303 Dreieich, Germany

BATCH RELEASE
Biotest Pharma GmbH, Landsteinerstrasse 5, D-63303 Dreieich, Germany

PACKAGING
Biotest AG, Landsteinerstrasse 5, D-63303 Dreieich, Germany

The following information is intended exclusively for healthcare professionals:

Special precautions
Infusion-related reaction
Certain adverse reactions (e.g., headache, flushing, chills, myalgia, wheezing, tachycardia, back pain, nausea, and arterial hypotension) may be related to the infusion rate. The recommended infusion rate must be strictly observed. Patients must be closely monitored and carefully observed for any symptoms during the infusion period.
In all patients, intravenous administration of IVIg requires:

• adequate hydration before starting IVIg infusion
• monitoring of urine output
• monitoring of serum creatinine levels
• avoidance of concomitant use of loop diuretics

Each time Intratect 100 g/l is administered to a patient, it is strongly recommended to record the product name and batch number.
In case of shock, apply standard medical treatments for shock.

Aseptic Meningitis Syndrome (AMS)
AMS has been reported in association with IVIG treatment.
The syndrome usually begins within a few hours to two days after IVIG treatment. Cerebrospinal fluid (CSF) analyses are frequently positive, showing pleocytosis up to several thousand cells per 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 treatment (2 g/kg).
Patients presenting with such signs and symptoms should undergo a thorough neurological examination, including CSF studies, to exclude other causes of meningitis.
Discontinuation of IVIG treatment has led to resolution of AMS within a few days, without sequelae.

Hemolytic anemia
IVIG products may contain blood group antibodies that can act as hemolysins and induce immunoglobulin binding to red blood cells (RBCs) in vivo, causing a positive direct antiglobulin reaction (Coombs test) and, rarely, hemolysis. Hemolytic anemia may develop following IgIV therapy due to increased sequestration of RBCs. Patients treated with IVIG should be monitored for clinical signs and symptoms of hemolysis.

Dosage
The dose and dosing regimen depend on the indication.
Dosage may need to be individualized for each patient according to clinical response. Weight-based dosing may require adjustment in underweight or overweight patients.
The following dosages are suggested as a guide:

Replacement therapy in primary immunodeficiency syndromes:
The dosing regimen should achieve a minimum IgG level (measured just before the next infusion) of at least 6 g/L or within the normal reference range for the age of the population. Three to six months are required after initiation of therapy to reach equilibrium (steady-state IgG levels). The recommended initial dose is 0.4–0.8 g/kg administered as a single dose, followed by at least 0.2 g/kg administered every 3–4 weeks.
The dose required to achieve a minimum IgG level of 6 g/L is approximately 0.2–0.8 g/kg/month.
Once equilibrium is reached, the interval between doses ranges from 3 to 4 weeks.
Minimum IgG levels should be measured and evaluated in relation to the incidence of infection.
To reduce the rate of bacterial infection, it may be necessary to increase the dosage and aim for higher trough IgG levels.

Replacement therapy in secondary immunodeficiencies
The recommended dose is 0.2–0.4 g/kg every 3–4 weeks.
Minimum IgG levels should be measured and evaluated in relation to the incidence of infection. The dose should be adjusted as needed to achieve optimal protection against infections; an increase may be necessary in patients with persistent infections, while a dose reduction may be considered if the patient remains infection-free.

Immunomodulation in:

Primary immune thrombocytopenia
There are two alternative treatment schedules:

• 0.8–1 g/kg administered on day 1; this dose may be repeated once every 3 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 (re-administration may be considered in case of relapse).

Kawasaki disease:
A single dose of 2.0 g/kg must be administered. 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 doses: 1 g/kg divided over 1–2 consecutive days every 3 weeks.
The effect of treatment should be evaluated after each cycle; if no effect is observed after 6 months, treatment should be discontinued.
If treatment is effective, long-term therapy is at the physician’s discretion, based on the patient’s response and maintenance response. Dosage and administration intervals may need to be adjusted according to the individual course of the disease.

Multifocal motor neuropathy (MMN)
Initial dose: 2 g/kg divided over 2–5 consecutive days.
Maintenance dose: 1 g/kg every 2–4 weeks or 2 g/kg every 4–8 weeks.
The effect of treatment should be evaluated after each cycle; if no effect is observed after 6 months, treatment should be discontinued.
If treatment is effective, long-term therapy is at the physician’s discretion, based on the patient’s response and maintenance response. Dosage and administration intervals may need to be adjusted according to the individual course of the disease.

The recommended dosages are summarized in the following table:

Paediatric population
The dosage in children and adolescents (0–18 years) is not different from that in adults,
since for each indication it depends on body weight and must be adjusted according to the clinical outcome of the conditions mentioned above.
Method of administration
Intravenous use
Intratect 100 g/l must be infused intravenously at an initial rate of no more than 0.3 ml/kg/hour for
30 minutes. See "Warnings and precautions". In case of adverse reaction, reduce the infusion rate or stop the infusion. If well tolerated, the infusion rate may be gradually increased up to a maximum of 1.9 ml/kg/hour.
Replacement therapy:
In patients who have well tolerated the infusion at a rate of 1.9 ml/kg/hour, the rate may be gradually increased to 6 ml/kg/hour and, if the infusion is still well tolerated, the rate may be further gradually increased up to a maximum of 8 ml/kg/hour.
In general, dosage and infusion rate must be adjusted to the individual patient's needs.
Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products nor with any other product containing IVIg.