IG 50 G/L Infusion solution

Зміст інструкції

1. Ig VENA 50 g/l Solution for infusion
   1. What is Ig VENA and what is it used for
   2. What you need to know before using Ig VENA
   3. How to use Ig VENA
   4. Possible side effects
   5. How to store Ig VENA
   6. Contents of the pack and other information
2. Ig VENA 50 g/l Solution for Infusion
   1. What is Ig VENA and what is it used for
   2. What you need to know before using Ig VENA
   3. How to use Ig VENA
   4. Possible side effects
   5. How to store Ig VENA
   6. Contents of the pack and other information

Ig VENA 50 g/l Solution for infusion

Normal human immunoglobulin (IVIg) for intravenous use
Read this leaflet carefully before using this medicine as it contains
important information for you.

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

Contents of this leaflet:

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

1. What is Ig VENA and what is it used for

Ig VENA is a human normal immunoglobulin solution for intravenous use. Immunoglobulins are human antibodies that are also present in the blood.
Ig VENA is used for:

Treatment of adults, children and adolescents (0-18 years) who do not have sufficient antibodies
(replacement therapy) in the following cases:

• 1. Patients with congenital deficiency in antibody production (primary immunodeficiency syndromes).
• 2. Patients with acquired deficiency in antibody production (secondary immunodeficiencies) who suffer from severe or recurrent infections due to various medical conditions (for example, oncological or autoimmune diseases or for the consequent treatment of these diseases). These patients have been treated with antibiotics that have proven ineffective and have not had a sufficiently positive increase in IgG antibody titers after vaccination (pneumococcal vaccines with polysaccharide and polypeptide antigens) or have a level of IgG in their blood < 4 g/l.

Treatment of adults, children and adolescents (0-18 years) with certain inflammatory diseases
(immunomodulation) in the following situations:

• 1. Patients who do not have sufficient platelets (Primary Immune Thrombocytopenia, ITP) and who are at high risk of bleeding or before surgery to correct the platelet count.
• 2. Patients with Guillain Barrè syndrome. This is an acute disease, characterized by inflammation of the peripheral nerves, which causes severe muscle weakness, particularly in the legs and upper limbs.

• 3. Patients with Kawasaki disease (in combination with acetylsalicylic acid). This is an acute disease that mainly affects young children, characterized by inflammation of blood vessels throughout the body.
• 4. Patients affected by Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). This chronic disease is a rare disorder of the peripheral nerves characterized by a gradual increase in weakness of the legs and, to a lesser extent, the arms.
• 5. Patients with Multifocal Motor Neuropathy (MMN). This is a rare condition that affects motor nerves and is characterized by asymmetrical, slowly progressive limb weakness without sensory loss.

2. What you need to know before using Ig VENA

Do not use Ig VENA
If you are allergic (hypersensitive) to human immunoglobulins or to any of the other
ingredients of this medicine (listed in section 6).
If you have antibodies directed against IgA-type immunoglobulins in your blood, as the
administration of a product containing IgA may cause a severe allergic reaction.

Warnings and precautions
Talk to your doctor or nurse before using Ig VENA.
Your doctor or another healthcare professional will monitor you closely and observe you carefully
during the entire infusion period with Ig VENA to ensure that no reactions occur.
Some adverse reactions may occur more frequently:

• if the infusion rate is too high;
• if you have uncontrolled symptoms of untreated infections (e.g. fever) or symptoms of chronic inflammation;
• if you are receiving normal human immunoglobulins for the first time;
• in rare cases where the type of human normal immunoglobulin medicinal product has been changed, or when a long interval has passed since the previous infusion.
• In some conditions, immunoglobulins may increase the risk of myocardial infarction, stroke, pulmonary embolism or deep vein thrombosis as they increaseblood viscosity.Therefore, your doctor will pay particular attention in the following circumstances:
• if you are overweight,
• if you are elderly,
• if you suffer from diabetes,
• if you have high blood pressure (hypertension),
• if your blood volume is too low (hypovolemia),
• if you have or have had problems with blood vessels (vascular diseases),
• if you have an increased tendency to blood clotting (inherited or acquired thrombophilic disorders),
• if you suffer from thrombotic episodes,
• if you suffer from diseases that increase blood density (viscosity),
• if you have had a prolonged period of immobility,
• if you have or have had kidney problems or if you are taking medicines that can damage the kidneys (nephrotoxic medicines), as cases of acute renal failure have been reported. In case of kidney damage, the doctor will consider interrupting the treatment.
• You may be allergic (hypersensitive) to immunoglobulins (antibodies) without knowing it.

This can happen even if you have already received normal human immunoglobulins in the past and
tolerated previous administrations. This is particularly likely if
you do not have enough IgA-type immunoglobulins (IgA deficiency with anti-IgA antibodies).
In these rare cases, allergic (hypersensitivity) reactions such as
low blood pressure or shock may occur.
If an adverse reaction occurs, the doctor will decide whether to reduce the administration rate or to
stop the infusion. The doctor will also decide on the necessary treatment based on the nature
and severity of the adverse effect.
In case of shock, the doctor must perform the standard treatment for shock. Tell your doctor if
you suffer from any of the conditions described above, the doctor will use particular caution when prescribing and
administering Ig VENA.
Viral safety
Medicines prepared from human blood or plasma undergo a number of
safety measures to prevent the transmission of infections to patients. These measures
include careful selection of blood or plasma donors to ensure that potentially infected donors are excluded and testing of each donation and plasma pool for
detection of the presence of viruses. Manufacturers of these medicines also introduce some steps into
the processing of blood or plasma that are capable of inactivating or removing pathogens.
Despite these measures, the possibility of transmitting an infection cannot be completely excluded when administering medicines prepared from human blood or plasma.
This also applies to viruses, or other types of infectious agents, emerging or unknown.
The measures taken are considered effective for enveloped viruses such as the human immunodeficiency virus (HIV), the hepatitis B virus (HBV), the hepatitis C virus (HCV) and
the non-enveloped hepatitis A virus (HAV). The measures taken have limited value against non-enveloped viruses such as parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, this
may be due to the fact that the antibodies against these infections, which are contained in the product,
have a protective capacity.
It is strongly recommended to record the trade name and batch number whenever you
receive a dose of Ig VENA, so that you have documentation of the batches used.

Children and adolescents
Mild and transient glycosuria (presence of glucose in the urine) without clinical signs has been
observed in pediatric patients after administration of Ig VENA. This event may be
related to the maltose contained in Ig VENA, since, in the renal tubules, maltose is
hydrolyzed to glucose, which is reabsorbed and excreted in the urine generally only in small
amounts. Glucose reabsorption is an age-dependent mechanism. The transient increase
in maltose in the plasma may exceed the kidney's ability to reabsorb sugar and result in a
positive urine glucose test.

Other medicines and Ig VENA
Tell your doctor if you are taking, have recently taken or might take any other
medicines.
Normal human immunoglobulins for intravenous use must not be mixed with other
medicinal products, or with other IVIg products.
Live attenuated virus vaccines
The administration of immunoglobulin may alter the efficacy of live attenuated virus vaccines for a period of at least 6 weeks and up to
3 months, such as those for measles, rubella, mumps and
varicella. An interval of three months must elapse after the administration of this product
before vaccination with live attenuated virus vaccines. In the case of measles, this
weakening of the response may last up to a year. Therefore, in patients receiving
the measles vaccine, the antibody level must be checked.
Loop diuretics (a group of medicines that increase urine production)
Avoid concomitant use of loop diuretics.
Blood tests
Ig VENA may interfere with some blood tests due to the temporary increase in various
antibodies that are passively transferred into your blood after the infusion of immunoglobulins; this increase in antibodies may cause some blood tests to have a result that
may be incorrect. Passive transfer of antibodies against red blood cell antigens, e.g.
A, B, D (determining the blood group), may interfere with some serological tests for red blood cell antibodies, for example the direct antiglobulin test (DAT, direct Coombs test).
Blood glucose tests
Some blood glucose measurement systems (for example, those based on pyrroloquinoline quinone glucose dehydrogenase (GDH-PQQ) or the colorimetric glucose-oxidoreductase method)
falsely recognize the maltose (100 mg/ml) contained in Ig VENA as glucose. This can
result in a reading of falsely elevated blood glucose values during the infusion and for a period
of approximately 15 hours after the end of the infusion and, consequently, in inadequate
insulin administration, causing a life-threatening or even fatal hypoglycemia.
Furthermore, cases of real hypoglycemia may not be treated if the hypoglycemic state is masked by
falsely elevated glucose values. Consequently, during the administration of Ig VENA or
other parenteral products containing maltose, blood glucose measurement must be performed with
glucose-specific methods. The instructions for use of the blood glucose measurement system, including
those of the test strips, must be carefully checked to establish whether the system is
appropriate for use in patients treated with parenteral products containing maltose. If there are
doubts, contact the manufacturer of the measurement system to determine
appropriateness for use in conjunction with parenteral products containing maltose.
Children and adolescents
Although specific interaction studies have not been conducted in the pediatric population, no differences are expected compared to adult patients.

Pregnancy, breastfeeding and fertility

• If you are pregnant, suspect you are pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor for advice before taking this medicine. The doctor will decide whether it is appropriate to use Ig VENA during pregnancy and breastfeeding.
• Clinical studies with Ig VENA have not been conducted in pregnant women. Human immunoglobulin products for intravenous use have been shown to cross the placenta in increasing amounts during the third trimester. However, medicines containing antibodies have been used for years in pregnant women and have been shown not to be expected to have adverse effects on the course of pregnancy, the fetus and the newborn.
• If you are breastfeeding and are being treated with Ig VENA, the antibodies contained in the product may pass into breast milk. Therefore, your baby may be protected from some infections.
• Clinical experience with immunoglobulins suggests that no harmful effects on fertility are to be expected.

Driving and using machines
The ability to drive vehicles or use machines may be impaired by some adverse reactions
associated with Ig VENA. Patients who experience adverse reactions during treatment should
wait for them to resolve before driving vehicles or using machines.

Ig VENA contains maltose and sodium
The product contains 100 mg of maltose per ml.
This medicinal product contains approximately 69 mg of sodium per litre. This should be taken into consideration for
patients who are on a controlled sodium diet.

3. How to use Ig VENA

Ig VENA can only be used in hospital or in clinics and nursing homes by healthcare professionals
doctors or other healthcare operators.
The dose and treatment regimen depend on the indication; the doctor will determine the dose and
treatment regimen suitable for You.
At the beginning of the infusion you will receive Ig VENA with a low infusion rate. If you tolerate it well, the
doctor may gradually increase the infusion rate.

Use in children and adolescents
The dosage in children and adolescents (0-18 years) is not different from that of adults
because the dosage for each indication is given per body weight and adjusted based on the
patient's clinical response.

If you use more Ig VENA than you should
If you are given more Ig VENA than you should, fluid overload may occur and
the blood may become too thick (hyperviscous); this is particularly manifested in patients
at risk, especially elderly patients or those with impaired cardiac or renal function.
If you have any doubts 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 gets them.
The side effects reported below may generally occur after treatment with
immunoglobulins:

• chills, headache, dizziness, fever, vomiting, nausea, allergic reactions, arthralgia (joint pain), low blood pressure and moderate back pain have been reported occasionally;
• isolated cases of temporary reduction of red blood cells (reversible hemolytic anemia/hemolysis);
• a sudden drop in blood pressure has been reported rarely and, in some isolated cases, hypersensitivity reactions (anaphylactic shock) may occur, even when the patient has not shown reactions to previous administrations;
• rare cases of transient skin reactions have been observed;
• very rarely, thromboembolic reactions (blood clot formation) have been observed, which can cause myocardial infarction, stroke, pulmonary vein obstruction (pulmonary embolism) and deep vein thrombosis;
• cases of transient non-infectious meningitis (reversible aseptic meningitis);
• an increase in blood creatinine levels and/or cases of sudden renal failure have been reported;
• cases of acute transfusion-related lung injury (TRALI).

The side effects reported during the administration of Ig VENA in clinical studies and those
reported after the medicine has been marketed are listed below in decreasing order of
frequency.
Common (may affect up to 1 in 10 patients):

• Back pain
• Nausea
• Generalized weakness, fatigue, fever
• Muscle pain
• Headache, drowsiness

Frequency not known (cannot be estimated from available data):

• Non-infectious meningitis
• Destruction and consequent lack of red blood cells
• Allergic reactions and life-threatening allergic shock
• Confusional state
• Stroke, dizziness, involuntary tremor, numbness and tingling of the skin or a limb
• Heart attack, bluish or purplish discoloration of the skin, rapid heartbeat, slow heartbeat, irregular heartbeat
• Blood clots in major veins and blood vessels, low blood pressure, high blood pressure, pallor
• Blood clots in a major artery of the lungs, abnormal fluid volume in the lungs, difficulty breathing with shortness of breath and cough
• Vomiting, diarrhea, abdominal pain
• Rapid swelling of the skin, urticaria, redness and inflammation of the skin, rash, itching, eczema, excessive sweating
• Pain in muscles and joints, back pain, neck pain, musculoskeletal stiffness
• Sudden renal failure
• Inflammation of the vein at the injection site, chills, chest pain or discomfort, facial swelling, general feeling of illness
• Increased creatinine levels in the blood

Additional side effects in children and adolescents
The frequency, type and severity of adverse reactions in children are expected to be the same as
those in adults.
Mild and transient glycosuria (presence of glucose in the urine) without clinical significance has
been observed in children after administration of Ig VENA.
For information on viral safety see section 2 “ Before using Ig VENA”.

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. You can also report side effects directly
through the national reporting system at:
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 Ig VENA

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 the outer packaging after “Exp.”. The expiry date refers to the last day of the month.
Store in a refrigerator (2  C - 8  C).
Once the infusion container has been opened, the contents must be used immediately.
Keep the vial in the outer packaging.
Do not freeze.
Do not use this medicine if you notice that the solution is cloudy or contains deposits
or presents a colour change.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Ig VENA contains
The active ingredient of Ig VENA is normal human immunoglobulin.
One ml of solution contains 50 mg of normal human immunoglobulin.
The solution contains human proteins in an amount of 50 g/l, of which at least 95% consists of
immunoglobulin G (IgG).
The subclasses of immunoglobulin G (IgG) have the following distribution:
IgG 62.1 %
IgG 34.8 %
IgG 2.5 %
IgG 0.6 %
The maximum content of IgA is 50 micrograms/ml.
Produced from plasma of human donors.
The other components are maltose and water for injections.

Description of the appearance of Ig VENA and contents of the pack
Ig VENA is a solution for infusion, contained in single vials of 20 ml. The solution is
clear or slightly opalescent, colourless or pale yellow.
Pack:
1 vial containing 1 g/20 ml.

Marketing authorisation holder and manufacturer
Marketing authorisation holder:
Kedrion S.p.A. - Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca) - ITALY.
Manufacturer: Kedrion S.p.A., 55027 Bolognana, Gallicano (Lucca) - ITALY.

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:

The following information is intended exclusively for physicians or healthcare professionals:
Instructions for correct use

• Before administration, bring the product to room or body temperature.
• Before administration, visually inspect the solution for particles or chromatic alterations. Do not use turbid solutions or those with deposits.
• Normal human immunoglobulin must be infused intravenously at an initial rate of 0.46 - 0.92 ml/kg/h (10 - 20 drops per minute) for 20 - 30 minutes. In case of adverse reaction, it is necessary to reduce the administration rate or stop the infusion. If well tolerated, the administration rate may be gradually increased up to a maximum of 1.85 ml/kg/h (40 drops/minute).
• In patients with PID who tolerate the infusion rate of 0.92 ml/kg/h, the administration rate may be gradually increased to 2 ml/kg/h, 4 ml/kg/h, up to a maximum of 6 ml/kg/h, every 20-30 minutes and only if the patient tolerates the infusion well.
• In general, the dosage and infusion rate must be individually adapted according to the patient's needs. Depending on body weight, dosage and the onset of adverse reactions, the patient may not reach the maximum infusion rate. In case of adverse reaction, the infusion must be stopped immediately and resumed applying the most appropriate rate for the patient.

Special populations
In paediatric patients (0-18 years) and in the elderly (> 64 years), the initial administration rate should be 0.46 – 0.92 ml/kg/h (10 - 20 drops per minute) for 20-30
minutes. If well tolerated and based on the patient's clinical condition, the infusion rate may be gradually increased up to a maximum of 1.85 ml/kg/h (40
drops/minute).

Particular precautions
Some serious adverse reactions to the product may be due to the infusion rate.
Potential complications can often be avoided by ensuring:

• that patients are not sensitive to normal human immunoglobulin by administering the product slowly at the beginning (with an infusion rate between 0.46 and 0.92 ml/kg/h);
• that patients are carefully monitored for any symptom during the infusion period. In particular, patients receiving human normal immunoglobulin for the first time, patients who have changed type of IVIg product and patients for whom a long interval has elapsed since the previous infusion, must be monitored during the first infusion and for the first hour after the first infusion, to identify potential signs of adverse reactions. All other patients should be observed for at least 20 minutes after administration. In all patients, the administration of IVIg requires:
• adequate hydration before the start of IVIg infusion;
• monitoring of urine volume;
• monitoring of serum creatinine level;
• avoiding the concomitant use of loop diuretics. In case of adverse reaction, the administration rate must be reduced or the infusion must be stopped. The necessary treatment depends on the nature and severity of the undesirable effect. In case of shock, standard medical treatment for shock must be performed.

Infusion reaction
Some 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 carefully followed. Patients
must be closely monitored and carefully observed for any symptoms during the
infusion period.
Adverse reactions may occur more frequently

• in patients receiving normal human immunoglobulin for the first time or, in rare cases, when the human immunoglobulin-based product is changed or in the case of a long interval from the previous infusion
• in patients with untreated infection or chronic inflammation

Children and adolescents
No specific measures or monitoring are required for the paediatric population.
No difference is expected in the paediatric population (0-18 years).
Thromboembolism
Clinical evidence demonstrates a relationship between the administration of IVIg and thromboembolic events such as myocardial infarction, stroke (including stroke), pulmonary embolism and deep vein thrombosis, which are presumed to be related to a relative increase in blood viscosity due to a high influx of immunoglobulin in patients at risk.
Caution should be exercised in prescribing and infusing IVIg in obese patients and in patients with pre-existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus and a history of vascular diseases or thrombotic episodes, patients with hereditary or acquired thrombophilic disorders, patients immobilised for a prolonged period, patients severely hypovolemic, patients with diseases that increase blood viscosity).
In patients at risk for thromboembolic adverse reactions, IVIg-based products should be administered at the minimum feasible infusion rate and dose.
Acute renal insufficiency
Cases of acute renal insufficiency have been reported in patients who have received IVIg. In most cases, risk factors have been identified and include pre-existing renal insufficiency, diabetes mellitus, hypovolemia, overweight, concomitant administration of nephrotoxic drugs or age over 65 years.
Renal parameters should be assessed before IVIg infusion, in particular in patients considered potentially at risk of developing acute renal insufficiency, and again at appropriate intervals. In patients at risk of acute renal insufficiency, IVIg-based products should be administered at the minimum feasible infusion rate and dose.
If changes in renal function occur, discontinuation of IVIg treatment should be considered. Although cases of renal dysfunction and acute renal insufficiency have been linked to the use of many medicinal products based on IVIg containing various excipients such as sucrose, glucose and maltose, those containing sucrose as a stabilizer represent a very high percentage of the total number. In at-risk patients, the use of IVIg medicinal products that do not contain these excipients may be considered.
Aseptic meningitis syndrome (AMS)
Aseptic meningitis syndrome may occur in association with IVIg treatment.
Generally, the syndrome begins after a period ranging from several hours to 2 days after IVIg treatment. Studies on cerebrospinal fluid often show positive pleocytosis up to several thousand cells per mm , especially granulocytes, and high protein levels, up to several hundred mg/dl.
AMS may occur more frequently in association with high doses of IVIg (2 g/kg).
Patients presenting with such signs and symptoms should receive a complete neurological examination, including cerebrospinal fluid studies, to exclude other causes of meningitis.
Discontinuation of IVIg treatment has led to remission of AMS within a few days, without consequences.
Hemolytic anemia
IVIg-based products may contain blood group-specific antibodies that may act as hemolysins and induce in vivo coating of red blood cells with immunoglobulins, causing a positive direct antiglobulin reaction (Coombs' test) and, rarely, hemolysis.
Hemolytic anemia may develop following IVIg therapy due to increased sequestration of red blood cells. Patients receiving IVIg should be monitored for detection of clinical signs and symptoms of hemolysis.
Neutropenia/Leukopenia
A transient decrease in neutrophil count and/or episodes of neutropenia, sometimes severe, have been reported after treatment with IVIg. This usually occurs within a few hours or days after IVIg administration and resolves spontaneously within 7-14 days.
Transfusion-related acute lung injury (TRALI)
A few cases of acute non-cardiogenic pulmonary edema (transfusion-related acute lung injury, TRALI) have been reported in patients receiving IVIg. TRALI is characterized by severe hypoxia, dyspnea, tachypnea, cyanosis, fever and hypotension. Symptoms associated with TRALI typically appear during the transfusion or within 6 hours of the transfusion, usually within 1-2 hours. Therefore, patients receiving IVIg should be monitored and IVIg infusion should be immediately stopped if any pulmonary adverse reactions occur. TRALI is a life-threatening condition requiring immediate admission to the intensive care unit.
This product contains 100 mg of maltose per ml as an excipient. Interference of maltose with blood glucose tests may lead to an overestimation of glucose values and, consequently, to inadequate insulin administration, which may cause a life-threatening state of hypoglycemia and patient death. In addition, cases of real hypoglycemia may not be treated if the hypoglycemic state is masked by falsely elevated glucose values. For further details see section “Blood glucose testing”.

Dosage recommendations
Replacement therapy must be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency.
Dosage
The dose and dosage regimen depend on the indication. The dose must be individualized for each patient based on clinical response. Weight-based dosing may require adjustment in underweight or overweight patients.
The following dosage regimens can be used as a reference.

Replacement therapy in primary immunodeficiency syndromes
The dosage regimen should induce the achievement of a baseline IgG level (measured before the next infusion) of at least 6 g/L or within the normal reference range for the patient's age. It takes 3 to 6 months from the start of therapy to reach equilibrium (steady-state 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 administered every 3-4 weeks. The dose required to reach a baseline level of 6 g/L of IgG is in the range of 0.2 – 0.8 g/kg/month. The interval between doses varies from 3 to 4 weeks after steady state has been reached. Baseline IgG levels should be measured and evaluated together with the incidence of infections. It may be necessary to increase the dose and achieve higher baseline levels to reduce the frequency of bacterial infections.

Secondary immunodeficiencies
The recommended dose is 0.2 – 0.4 g/kg every 3 - 4 weeks.
Baseline IgG levels should be measured and evaluated together with 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 infection; a decrease in the dose may be considered when the patient remains infection-free.

Primary immune thrombocytopenia
There are two alternative treatment regimens:

• 0.8 - 1 g/kg administered on day 1; this dose may be repeated once within 3 days;
• 0.4 g/kg per day for 2 - 5 days. Treatment may be repeated in case of relapses.

Guillain Barré syndrome
0.4 g/kg/day for 5 days (possible repetition of the dosage in case of relapse).

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

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
Initial dose: 2 g/kg divided into 2-5 consecutive days.
Maintenance doses: 1 g/kg in 1-2 consecutive days every 3 weeks.
The effect of treatment should be evaluated after each cycle; if no effect of treatment is observed after 6 months, treatment should be discontinued.
If therapy is effective, its long-term administration is at the discretion of the physician based on the patient's response and maintenance response. The dosage and intervals may need to be adjusted based on the individual course of the disease.

Multifocal motor neuropathy (MMN)
Initial dose: 2 g/kg administered in 2-5 consecutive days.
Maintenance doses: 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 of treatment is observed after 6 months, treatment should be discontinued.
If therapy is effective, its long-term administration is at the discretion of the physician based on the patient's response and maintenance response. The dosage and intervals may need to be adjusted based on the individual course of the disease.
The recommended doses are summarized in the following table:

Use in children and adolescents
The dosage in children and adolescents (0-18 years) is not different from that of adults because the dosage for each indication is given by body weight and adjusted based on the clinical outcome of the aforementioned conditions.
Hepatic insufficiency
There is no evidence to require a dose adjustment.
Renal insufficiency
No dose adjustment unless clinically justified.
Elderly
No dose adjustment unless clinically justified.

CIDP
Due to the rarity of the disease and, consequently, the small overall number of patients, experience in the use of intravenous immunoglobulins in children with CIDP is limited; therefore, only literature data are available. However, published data consistently demonstrate that treatment with IVIg is equally effective in children and adults, in line with what happens for the indications recognized for IVIg.

Ig VENA 50 g/l Solution for Infusion

Normal human immunoglobulin (IVIg) for intravenous use
Read this leaflet carefully before using this medicineas it contains
important information for you.

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

Contents of this leaflet:

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

1. What is Ig VENA and what is it used for

Ig VENA is a human normal immunoglobulin solution for intravenous use. Immunoglobulins are human antibodies that are also present in the blood.
Ig VENA is used for:

Treatment of adults, children and adolescents (0-18 years) who do not have sufficient antibodies
(replacement therapy) in the following cases:

• 1. Patients with congenital deficiency in antibody production (primary immunodeficiency syndromes).
• 2. Patients with acquired deficiency in antibody production (secondary immunodeficiencies) who suffer from severe or recurrent infections due to various medical conditions (for example, oncological or autoimmune diseases or for the consequent treatment of these diseases). These patients have been treated with antibiotics that have proven ineffective and have not had a sufficiently positive increase in IgG antibody titers after vaccination (pneumococcal vaccines with polysaccharide and polypeptide antigens) or have a level of IgG in their blood < 4 g/l.

Treatment of adults, children and adolescents (0-18 years) with certain inflammatory diseases
(immunomodulation) in the following situations:

• 1. Patients who do not have sufficient platelets (Primary Immune Thrombocytopenia, ITP) and who are at high risk of bleeding or before surgery to correct the platelet count.
• 2. Patients with Guillain Barrè syndrome. This is an acute disease, characterized by inflammation of the peripheral nerves, which causes severe muscle weakness, especially in the legs and upper limbs.
• 3. Patients with Kawasaki disease (in combination with acetylsalicylic acid). This is an acute disease that mainly affects young children, characterized by inflammation of blood vessels throughout the body.

• 4. Patients affected by Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). This chronic disease is a rare disorder of the peripheral nerves characterized by a gradual increase in weakness of the legs and, to a lesser extent, the arms.
• 5. Patients with Multifocal Motor Neuropathy (MMN). This is a rare condition that affects motor nerves and is characterized by asymmetrical, slowly progressive limb weakness without loss of sensation.

2. What you need to know before using Ig VENA

Do not use Ig VENA
If you are allergic (hypersensitive) to human immunoglobulins or to any of the other
ingredients of this medicine (listed in section 6).
If you have antibodies against IgA type immunoglobulins in your blood, as the
administration of a product containing IgA may cause a severe allergic reaction.

Warnings and precautions
Talk to your doctor or nurse before using Ig VENA.
Your doctor or another healthcare professional will monitor you closely and observe you carefully
during the entire infusion period with Ig VENA to check for any reactions.
Some adverse reactions may occur more frequently:

• if the infusion rate is too high;
• if you have uncontrolled symptoms of untreated infections (e.g. fever) or symptoms of chronic inflammation;
• if you are receiving normal human immunoglobulins for the first time;
• in rare cases if you have changed the type of human normal immunoglobulin medicinal product, or if a long time has passed since the previous infusion.
• In some conditions, immunoglobulins may increase the risk of myocardial infarction, stroke, pulmonary embolism or deep vein thrombosis because they increase theviscosity of the blood.Therefore, your doctor will be particularly careful in the following circumstances:
• if you are overweight,
• if you are elderly,
• if you suffer from diabetes,
• if you have high blood pressure (hypertension),
• if the blood volume is too low (hypovolemia),
• if you have or have had problems with blood vessels (vascular diseases),
• if you have an increased tendency to blood clotting (inherited or acquired thrombophilic disorders),
• if you suffer from thrombotic episodes,
• if you suffer from diseases that increase blood density (viscosity),
• if you have had a prolonged period of immobility,
• if you have or have had kidney problems or if you are taking medicines that can damage the kidneys (nephrotoxic medicines), as cases of acute renal failure have been reported. In case of kidney damage, the doctor will consider interrupting the treatment.
• You may be allergic (hypersensitive) to immunoglobulins (antibodies) without knowing it.This can happen even if you have already received normal human immunoglobulins in the past and have tolerated previous administrations. This is particularly possible if you do not have enough IgA type immunoglobulins (IgA deficiency with anti-IgA antibodies).

In these rare cases, allergic (hypersensitivity) reactions such as a
drop in blood pressure or shock may occur.
If an adverse reaction occurs, the doctor will decide whether to reduce the administration rate or to
stop the infusion. In addition, the doctor will decide on the necessary treatment based on the nature
and severity of the adverse effect.
In case of shock, the doctor must perform the standard treatment for shock. Tell your doctor if
you suffer from any of the conditions described above, the doctor will use particular caution when prescribing and
administering Ig VENA.
Viral safety
Medicines that are prepared from human blood or plasma are subjected to a number of
safety measures to prevent the transmission of infections to patients. These measures
include careful selection of blood or plasma donors to ensure that potentially infected donors are excluded and testing of each donation and plasma pool for
the possible presence of viruses. Manufacturers of these medicines also introduce some steps into the
processing of blood or plasma that are capable of inactivating or removing pathogens.
Despite these measures, when administering medicines prepared from human blood or plasma,
the possibility of transmitting an infection cannot be completely excluded. This also applies to
viruses, or other types of infectious agents, emerging or unknown.
The measures taken are considered effective for enveloped viruses such as the human immunodeficiency virus (HIV), the hepatitis B virus (HBV), the hepatitis C virus (HCV) and
the non-enveloped hepatitis A virus (HAV). The measures taken have limited value against non-enveloped viruses such as parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, this
may be due to the fact that the antibodies against these infections, which are contained in the product,
have a protective capacity.
It is strongly recommended to record the trade name and batch number whenever you
receive a dose of Ig VENA, so that you have documentation on the batches used.

Children and adolescents
Mild and transient glycosuria (presence of glucose in the urine) without clinical signs has been
observed in pediatric patients after administration of Ig VENA. This event may be
related to the maltose contained in Ig VENA, since, in the renal tubules, maltose is
hydrolyzed to glucose, which is reabsorbed and excreted in the urine generally only in small
amounts. Glucose reabsorption is an age-dependent mechanism. The transient increase
in maltose in the plasma may exceed the kidney's ability to reabsorb sugar and result in a
positive glucose test in the urine.

Other medicines and Ig VENA
Tell your doctor if you are taking, have recently taken or might take any other
medicines.
Normal human immunoglobulins for intravenous use must not be mixed with other
medicinal products, or with other IVIg products.
Live attenuated virus vaccines
The administration of immunoglobulin may alter for a period of at least 6 weeks and up to
3 months the effectiveness of live attenuated virus vaccines such as those for measles, rubella, mumps and
chickenpox. After the administration of this product, an interval of three months
must elapse before vaccination with live attenuated virus vaccines. In the case of measles, this
weakening of the response may last up to a year. Therefore, in patients receiving the
measles vaccine, the antibody level must be checked.
Loop diuretics (a group of medicines that increase urine production)
Avoid concomitant use of loop diuretics.
Blood tests
Ig VENA may interfere with some blood tests due to the temporary increase of various
antibodies that are passively transferred into your blood after the infusion of immunoglobulins; this increase in antibodies may cause some blood tests to have a result that
may not be correct. Passive transmission of antibodies against red blood cell antigens, e.g.
A, B, D (determining the blood group), may interfere with some serological tests for red blood cell antibodies, for example the direct antiglobulin test (DAT, direct Coombs test).
Blood glucose tests
Some blood glucose measurement systems (for example, those based on pyrroloquinoline quinone glucose dehydrogenase (GDH-PQQ) or the colorimetric glucose-oxidoreductase method)
falsely recognize the maltose (100 mg/ml) contained in Ig VENA as glucose. This can
result in a reading of falsely elevated blood glucose values during the infusion and for a period
of approximately 15 hours after the end of the infusion and, consequently, in inadequate
insulin administration, causing a life-threatening or even fatal hypoglycemia.
Furthermore, cases of real hypoglycemia may not be treated if the hypoglycemic state is masked by
falsely elevated glucose values. Consequently, during the administration of Ig VENA or
other parenteral products containing maltose, blood glucose measurement must be performed with
glucose-specific methods. The instructions for use of the blood glucose measurement system, including
those of the test strips, must be carefully checked to establish whether the system is
appropriate for use in patients treated with parenteral products containing maltose. If there are
doubts, contact the manufacturer of the measurement system to determine
appropriateness for use in conjunction with parenteral products containing maltose.
Children and adolescents
Although specific interaction studies have not been conducted in the pediatric population, differences compared to adult patients are not expected.

Pregnancy, breastfeeding and fertility

• If you are pregnant, suspect you are pregnant, or are planning to become pregnant, or if you are breastfeeding, ask your doctor for advice before taking this medicine. The doctor will decide whether it is appropriate to use Ig VENA during pregnancy and breastfeeding.
• Clinical studies with Ig VENA have not been conducted in pregnant women. Human immunoglobulin products for intravenous use have been shown to cross the placenta increasingly during the third trimester. However, medicines containing antibodies have been used for years in pregnant women and have been shown not to be expected to have adverse effects on the course of pregnancy, the fetus and the newborn.
• If you are breastfeeding and are being treated with Ig VENA, the antibodies contained in the product may pass into breast milk. Therefore, your baby may be protected from some infections.
• Clinical experience with immunoglobulins suggests that no adverse effects on fertility are expected.

Driving and using machines
The ability to drive vehicles or use machines may be altered by some adverse reactions
associated with Ig VENA. Patients who experience adverse reactions during treatment must
wait for their resolution before driving vehicles or using machines.

Ig VENA contains maltose and sodium
The product contains 100 mg of maltose per ml.
This medicinal product contains approximately 69 mg of sodium per litre. This should be taken into consideration for
patients who are on a controlled sodium diet.

3. How to use Ig VENA

Ig VENA can only be used in hospital or clinics and nursing homes by medical professionals or other healthcare operators.
The dose and treatment regimen depend on the indication; the doctor will determine the appropriate dose and
treatment regimen for you.
At the beginning of the infusion, you will receive Ig VENA with a low infusion rate. If you tolerate it well, the
doctor may gradually increase the infusion rate.

Use in children and adolescents
The dosage in children and adolescents (0-18 years) is not different from that of adults
because the dosage for each indication is given per body weight and adjusted based on the
patient's clinical response.

If you use more Ig VENA than you should
If you are given more Ig VENA than you should, fluid overload may occur and
the blood may become too thick (hyperviscous); this is particularly manifested in at-risk patients, especially in elderly patients or with impaired cardiac or renal function.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
The side effects reported below may generally occur after treatment with
immunoglobulins:

• Chills, headache, dizziness, fever, vomiting, nausea, allergic reactions, arthralgia (joint pain), decreased blood pressure and moderate back pain have been reported occasionally;
• Isolated cases of temporary reduction of red blood cells (reversible hemolytic anemia/hemolysis);
• A sudden drop in blood pressure has been reported rarely and, in some isolated cases, hypersensitivity reactions (anaphylactic shock) may occur, even when the patient has not shown reactions to previous administrations;
• Rare cases of transient skin reactions have been observed;
• Very rarely, thromboembolic reactions (blood clot formation) have been observed, which can cause myocardial infarction, stroke, pulmonary vein obstruction (pulmonary embolism) and deep vein thrombosis;
• Cases of transient non-infectious meningitis (reversible aseptic meningitis);
• An increase in blood creatinine levels and/or cases of sudden renal failure have been reported;
• Cases of acute transfusion-related lung injury (TRALI).

The side effects reported during the administration of Ig VENA in clinical studies and those
reported after the medicine is marketed are listed below in decreasing order of
frequency.
Common (may affect up to 1 in 10 patients):

• Back pain
• Nausea
• Generalized weakness, fatigue, fever
• Muscle pain
• Headache, drowsiness

Frequency not known (cannot be estimated from available data):

• Non-infectious meningitis
• Destruction and subsequent lack of red blood cells
• Allergic reactions and life-threatening allergic shock
• Confusional state
• Stroke, dizziness, involuntary tremor, numbness and tingling of the skin or a limb
• Heart attack, bluish or purplish discoloration of the skin, rapid heartbeat, slow heartbeat, irregular heartbeat
• Blood clots in major veins and blood vessels, low blood pressure, high blood pressure, pallor
• Blood clots in a major artery of the lungs, abnormal fluid volume in the lungs, difficulty breathing with shortness of breath and cough
• Vomiting, diarrhea, abdominal pain
• Rapid swelling of the skin, urticaria, redness and inflammation of the skin, rash, itching, eczema, excessive sweating
• Pain in muscles and joints, back pain, neck pain, musculoskeletal stiffness
• Sudden kidney failure
• Inflammation of the vein at the injection site, chills, chest pain or discomfort, facial swelling, general feeling of discomfort
• Increased creatinine levels in the blood

Additional side effects in children and adolescents
The frequency, type and severity of adverse reactions in children are expected to be the same as
those in adults.
Mild and transient glycosuria (presence of glucose in the urine) without clinical significance
has been observed in children after administration of Ig VENA.
For information on viral safety see section 2 “ Before using Ig VENA”.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please
tell your doctor or nurse. You can also report side effects directly
through the national reporting system at:
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 Ig VENA

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 the outer
packaging after “Exp.”. The expiry date refers to the last day of the month.
Store in a refrigerator (2  C - 8  C).
Before use and within the expiry date, the product may be stored at room
temperature, not exceeding 25°C, for a maximum of 6 consecutive months. After this period the
product must be discarded. In any case, the product must no longer be stored in a refrigerator if
stored at room temperature.
Record the date of start of storage at room temperature on the outer box.
Once the infusion container has been opened, the contents must be used
immediately.
Keep the vial in the outer packaging.
Do not freeze.
Do not use this medicine if you notice that the solution is cloudy or contains deposits
or presents a change in color.
Do not dispose of any medicine in the wastewater and household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Ig VENA contains
The active ingredient of Ig VENA is normal human immunoglobulin.
One ml of solution contains 50 mg of normal human immunoglobulin.
The solution contains human proteins in an amount of 50 g/l of which at least 95% consists of
immunoglobulin G (IgG).
The subclasses of immunoglobulin type G (IgG) have the following distribution:
IgG 62.1 %
IgG 34.8 %
IgG 2.5 %
IgG 0.6 %
The maximum content of IgA is 50 micrograms/ml.
Produced from human donor plasma.
The other components are maltose and water for injections.

Description of the appearance of Ig VENA and contents of the pack
Ig VENA is a solution for infusion, contained in single vials of 50, 100 or 200 ml, with
extendable hanger (vial + extendable hanger). The solution is clear or slightly
opalescent, colorless or pale yellow.
Pack sizes:

Single packs:
1 vial containing 2.5 g/50 ml
1 vial containing 5 g/100 ml
1 vial containing 10 g/200 ml.

Multiple packs:
Multiple pack consisting of 2 single packs of 1 vial of 10 g/200 ml
Multiple pack consisting of 3 single packs of 1 vial of 10 g/200 ml.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Marketing authorisation holder:
Kedrion S.p.A. - Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca) - ITALY.
Manufacturer: Kedrion S.p.A., 55027 Bolognana, Gallicano (Lucca) - ITALY.

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:

The following information is intended exclusively for doctors or healthcare professionals:
Instructions for correct use

• Before administration, bring the product to room or body temperature.
• Before administration, visually inspect the solution for particles or color changes. Do not use turbid solutions or those with deposits.
• Normal human immunoglobulin must be infused intravenously at an initial rate of 0.46 - 0.92 ml/kg/h (10 - 20 drops per minute) for 20 - 30 minutes. In case of adverse reaction, the infusion rate must be reduced or the infusion stopped. If well tolerated, the infusion rate may be gradually increased up to a maximum of 1.85 ml/kg/h (40 drops/minute).
• In patients with PID who tolerate an infusion rate of 0.92 ml/kg/h, the infusion rate may be gradually increased to 2 ml/kg/h, 4 ml/kg/h, up to a maximum of 6 ml/kg/h, every 20-30 minutes and only if the patient tolerates the infusion well.
• In general, the dosage and infusion rate must be individually adapted according to the patient's needs. Depending on body weight, dosage and the onset of adverse reactions, the patient may not reach the maximum infusion rate. In case of an adverse reaction, the infusion must be stopped immediately and resumed using the most appropriate rate for the patient.

Special populations
In pediatric patients (0-18 years) and the elderly (> 64 years), the initial infusion rate
should be 0.46 – 0.92 ml/kg/h (10 - 20 drops per minute) for 20-30
minutes. If well tolerated and based on the patient's clinical condition, the infusion rate
may be gradually increased up to a maximum of 1.85 ml/kg/h (40
drops/minute).
Instructions for use of the extendable hanger

• 1. Initial condition of the vial with the hanger label
• 2. Invert the vial
• 3. Rotate the lower edge of the hanger label upwards to extend it
• 4. Suspend the vial from the support

Special precautions
Some serious adverse reactions to the product may be due to the infusion rate.
Potential complications can often be avoided by ensuring:

• that patients are not sensitive to normal human immunoglobulin by administering the product slowly at the beginning (with an infusion rate between 0.46 and 0.92 ml/kg/h);
• that patients are carefully monitored for any symptoms during the infusion period. In particular, patients receiving human immunoglobulin for the first time, patients who have changed to a different IVIg product type, and patients for whom a long time has passed since the previous infusion, must be monitored during the first infusion and for the first hour after the first infusion to detect potential signs of adverse reactions. All other patients should be observed for at least 20 minutes after administration. In all patients, the administration of IVIg requires:
• adequate hydration before the start of the IVIg infusion;
• monitoring of urine output;
• monitoring of serum creatinine levels;
• avoiding the concomitant use of loop diuretics.

In case of an adverse reaction, the administration rate must be reduced or the infusion must
be stopped. The necessary treatment depends on the nature and severity of the adverse
effect. In case of shock, standard medical treatment for shock must be performed.
Infusion reaction
Some adverse reactions (e.g. headache, flushing, chills, myalgia, wheezing, tachycardia, back pain, nausea and hypotension) may be related to the infusion rate. The recommended infusion rate must be carefully followed. Patients
must be closely monitored and carefully observed for any symptoms during the
infusion period.
Adverse reactions may occur more frequently

• in patients receiving normal human immunoglobulin for the first time or, in rare cases, when the human immunoglobulin product is changed or after a long interval from the previous infusion
• in patients with untreated infection or chronic inflammation

Children and adolescents
No specific measures or monitoring are required for the pediatric population.
No difference is expected in the pediatric population (0-18 years).
Thromboembolism
There is clinical evidence demonstrating a relationship between the administration of IVIg and thromboembolic events such as myocardial infarction, stroke (including stroke), pulmonary embolism and deep vein thrombosis, which are presumed to be related to a relative increase in blood viscosity due to a high influx of immunoglobulin in patients at risk.
Caution should be exercised when prescribing and infusing IVIg in obese patients and in patients with
pre-existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus
and a history of vascular diseases or thrombotic episodes, patients with hereditary or
acquired thrombophilic disorders, patients immobilized for a prolonged period, severely hypovolemic patients,
patients with diseases that increase blood viscosity).
In patients at risk for thromboembolic adverse reactions, IVIg-based products must be
administered at the lowest practicable infusion rate and dose.
Acute renal failure
Cases of acute renal failure have been reported in patients who have received IVIg. In
most cases, risk factors have been identified and include pre-existing renal insufficiency, diabetes mellitus, hypovolemia, overweight, concomitant administration of
nephrotoxic drugs or age over 65 years.
Renal parameters must be assessed before IVIg infusion, in particular in patients
considered potentially at risk of developing acute renal failure, and at appropriate intervals.
In patients at risk of acute renal failure, IVIg-based products must be
administered at the lowest practicable infusion rate and dose.
If changes in renal function occur, discontinuation of
treatment with IVIg should be considered. Although cases of renal dysfunction and acute renal failure have
been linked to the use of many medicinal products based on IVIg containing various excipients
such as sucrose, glucose and maltose, those containing sucrose as a stabilizer
represent a very high percentage of the overall number. In at-risk patients, it may be
considered to use medicinal products based on IVIg that do not contain these
excipients.
Aseptic meningitis syndrome (AMS)
Aseptic meningitis syndrome may occur in association with IVIg treatment.
Generally, the syndrome begins after a period ranging from several hours to 2 days after treatment
with IVIg. Studies on cerebrospinal fluid are often positive for pleocytosis up to several
thousands of cells per mm , especially granulocytes, and high protein levels, up to several
hundreds of mg/dl.
AMS may occur more frequently in association with high doses of IVIg (2 g/kg).
Patients presenting with such signs and symptoms should receive a complete neurological examination,
including cerebrospinal fluid studies, to exclude other causes of meningitis.
Discontinuation of IVIg treatment has led to remission of AMS within a few days,
without consequences.
Hemolytic anemia
IVIg-based products may contain blood group-specific antibodies that may act
as hemolysins and induce in vivo coating of red blood cells with immunoglobulins,
causing a positive direct antiglobulin test (Coombs' test) and, rarely, hemolysis.
Hemolytic anemia may develop following IVIg therapy due to increased
red blood cell sequestration. Patients receiving IVIg should be monitored for
detection of clinical signs and symptoms of hemolysis.
Neutropenia/Leukopenia
A transient decrease in neutrophil count and/or episodes of neutropenia, sometimes severe, have
been reported after treatment with IVIg. This usually occurs within a few hours or days
after IVIg administration and resolves spontaneously within 7-14 days.
Transfusion-related acute lung injury (TRALI)
A few cases of acute non-cardiogenic pulmonary edema (transfusion-related acute lung injury, TRALI) have been reported in patients receiving IVIg. TRALI is characterized by
severe hypoxia, dyspnea, tachypnea, cyanosis, fever and hypotension. Symptoms associated with TRALI
typically appear during the transfusion or within 6 hours of the transfusion, usually within 1-2
hours. Therefore, patients receiving IVIg should be monitored and IVIg infusion should
be immediately stopped if adverse pulmonary reactions occur. TRALI is
a life-threatening condition requiring immediate admission to
intensive care unit.
This product contains 100 mg of maltose per ml as an excipient. Interference of maltose
with blood glucose testing may lead to an overestimation of glucose values and, consequently, to
inadequate insulin administration, which may cause a life-threatening state of hypoglycemia and death of the patient. In addition, cases of real hypoglycemia may not be treated
if the hypoglycemic state is masked by falsely elevated glucose values. For further details
see section “ Blood glucose testing”.

Dosage recommendations
Replacement therapy should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency.
Posology
The dose and dosage regimen depend on the indication. The dose must be individualized for each patient based on clinical response. Weight-based dosing may require adjustment in underweight or overweight patients.
The following dosage regimens can be used as a reference.

Replacement therapy in primary immunodeficiency syndromes
The dosage regimen should induce the achievement of a baseline IgG level (measured before the next infusion) of at least 6 g/L or within the normal reference range for the patient's age. From the start of therapy, 3 to 6 months are required to reach equilibrium (steady-state 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 administered every 3-4 weeks. The dose required to reach a baseline level of 6 g/L of IgG is in the range of 0.2 – 0.8 g/kg/month. The interval between doses varies from 3 to 4 weeks after steady state has been reached. Baseline IgG levels should be measured and evaluated together with the incidence of infections. It may be necessary to increase the dose and achieve higher baseline levels to reduce the frequency of bacterial infections.

Secondary immunodeficiencies
The recommended dose is 0.2 – 0.4 g/kg every 3 - 4 weeks.
Baseline IgG levels should be measured and evaluated together with 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 infection; a decrease in dose may be considered when the patient remains infection-free.

Primary immune thrombocytopenia
There are two alternative treatment regimens:

• 0.8 - 1 g/kg administered on day 1; this dose may be repeated once within 3 days;
• 0.4 g/kg per day for 2 - 5 days. Treatment may be repeated in case of relapses.

Guillain Barré syndrome
0.4 g/kg/day for 5 days (possible repetition of the dosage 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 polyradiculoneuropathy (CIDP)
Initial dose: 2 g/kg divided into 2-5 days consecutively.
Maintenance doses: 1 g/kg in 1-2 days consecutively every 3 weeks.
The effect of treatment should be evaluated after each cycle; if no effect of treatment is observed after 6 months, treatment should be discontinued.
If therapy is effective, its long-term administration is at the physician's discretion based on the patient's response and maintenance response. The dosage and intervals may need to be adjusted based on the individual course of the disease.

Multifocal motor neuropathy (MMN)
Initial dose: 2 g/kg administered in 2-5 days consecutively.
Maintenance doses: 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 of treatment is observed after 6 months, treatment should be discontinued.
If therapy is effective, its long-term administration is at the physician's discretion based on the patient's response and maintenance response. The dosage and intervals may need to be adjusted based on the individual course of the disease.
The recommended doses are summarized in the following table:

Use in children and adolescents
The dosage in children and adolescents (0-18 years) is not different from that of adults because the dosage for each indication is given by body weight and adjusted based on the clinical outcome of the aforementioned conditions.
Hepatic impairment
There is no evidence to require a dose adjustment.
Renal impairment
No dose adjustment unless clinically justified.
Elderly
No dose adjustment unless clinically justified.

CIDP
Due to the rarity of the disease and, consequently, the small overall number of patients, experience in the use of intravenous immunoglobulins in children with CIDP is limited; therefore, only literature data are available. However, published data consistently demonstrate that treatment with IVIg is equally effective in children and adults, in line with what happens for indications recognized for IVIg.