Product Information for the User

Privigen 100 mg/ml (10%) Infusion Solution

Normal Human Immunoglobulin (IgIV)

Read this entire product information carefully before starting to use the medication, as it contains important information for you.

• Keep this product information, as you may need to refer to it again.
• If you need advice or more information, consult your pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this product information. See section 4.

What is Privigen

Privigen belongs to a class of medications called human normal immunoglobulins. Immunoglobulins are also known as antibodies and are blood proteins that help the body fight infections.

How Privigen works

Privigen contains immunoglobulins that have been prepared from the blood of healthy individuals. The medication works in exactly the same way as the naturally occurring immunoglobulins in human blood.

What is Privigen used for

Privigen is used for the treatment of adults and children (0-18 years) in the following situations:

1. To increase low levels of immunoglobulins in the blood to normal values (restorative treatment):

1. To treat some inflammatory disorders (immunomodulation). There are 5 groups:
   1. Patients who do not have a sufficient number of platelets in the blood (Immune thrombocytopenic purpura (ITP)), and:

who are at risk of bleeding or who will undergo surgery soon.

• Read this section carefully. Before Privigen is administered to you, you and your doctor must consider the information provided.

Do not use Privigen

• if you are allergic to human immunoglobulins or proline.
• if you have developed antibodies against IgA immunoglobulins in your blood.
• if you have hyperprolinemia type I or II (a genetic disorder that causes high levels of the amino acid proline in the blood). This is an extremely rare condition. Worldwide, only a few families with this disease are known.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Privigen.

What circumstances increase the risk of adverse reactions?

• Inform your doctor or healthcare professional before treatment if any of the following circumstances apply to you:

• You receive this medication in high doses over 1 or several days and have blood group A, B, or AB or have an underlying inflammatory disease. In these circumstances, immunoglobulins have been frequently described as increasing the risk of destruction of red blood cells (hemolysis).
• You are overweight, elderly, have diabetes, have been bedridden for a prolonged period, have high blood pressure, have low blood volume (hypovolemia), have vascular problems (vascular diseases), have an increased tendency to blood coagulation (thrombophilia or thrombotic episodes), or have a disease or disorder that makes your blood more dense (hyperviscosity syndrome). In these circumstances, immunoglobulins may increase the risk of heart attack, stroke, pulmonary embolism, or blockage of a leg blood vessel, although this is extremely rare.

• You are diabetic. Although Privigen does not contain sugar, it may be diluted with a special sugar solution (5% glucose), which may affect the patient's blood sugar levels.
• You have or have had previous kidney problems or take medications that can damage your kidneys (nephrotoxic medications). In these circumstances, immunoglobulins may increase the risk of rapid loss of renal function (acute renal failure) although this is extremely rare. Renal failure with fatal outcome has occurred in isolated cases related to hemodialysis.

What type of supervision is required during infusion?

For your personal safety, Privigen treatment will be performed under the supervision of your doctor or healthcare professional. You will be observed throughout the infusion and for at least 20 minutes after its completion. In some cases, special precautions may be necessary. Some examples of these circumstances are as follows:

• You receive Privigen at a high infusion rateor if
• You are receiving Privigen for the first time or after a prolonged interruption of treatment (for example, several months).

In these cases, you will be closely monitored throughout the infusion and for at least one hour after its completion.

When may it be necessary to slow down or stop the infusion?

• You may be allergic (hypersensitive) to immunoglobulins without knowing it.

However, real allergic reactions are extremely rare. These may occur even if you have previously received human immunoglobulins and tolerated them well. This may occur especially if you have developed antibodies against IgA immunoglobulins. In these extremely rare cases, allergic reactions may occur, such as a sudden drop in blood pressure or shock (see also section 4 "Possible adverse reactions").

• In extremely rare cases, a transfusion-related acute lung injury (TRALI) may occur after administering immunoglobulins. This will result in the accumulation of fluid in the air spaces of the lungs (non-cardiogenic pulmonary edema) unrelated to the heart. You will recognize TRALI by severe difficulty breathing (dyspnea), blue skin (cyanosis), abnormally low oxygen levels in the blood (hypoxia), low blood pressure (hypotension), and increased body temperature (fever). Symptoms usually appear during or within 6 hours after receiving the treatment.

?Inform your doctor or healthcare professional immediately if you notice these reactions during the Privigen infusion. They will decide whether to slow down the infusion rate or stop it completely.

Blood tests

• Inform your doctor about your treatment with Privigen before blood tests are performed.

After receiving Privigen, the results of certain blood tests (serological tests) may be altered for some time.

Information on safety regarding infections

Privigen is made from human blood plasma (the liquid part of the blood). When medications are made from blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These measures are as follows:

• meticulous selection of blood or plasma donors to exclude those with a risk of transmitting infections,
• examination of each donation and plasma mixtures to check for the absence of signs of viruses or infections.
• inclusion of steps in the blood or plasma processing that may inactivate or eliminate viruses.

Despite these measures, administering medications prepared from blood or plasma cannot completely exclude the possibility of transmitting an infection. This is also true for any unknown or emerging virus or any other type of infection.

The measures taken are considered effective for enveloped viruses, such as HIV, hepatitis B virus, and hepatitis C virus, and for non-enveloped viruses, such as hepatitis A virus and parvovirus B19.

Immunoglobulins have not been associated with hepatitis A virus or parvovirus B19 infections, possibly because the antibodies against these infections, which are contained in the product, are protective.

• It is strongly recommended that each time you receive a dose of Privigen, the name and batch number of the product be noted, in order to maintain a record of the batches used.

Use of Privigen with other medications

• Inform your doctor or healthcare professional if you are using, have used recently, or may need to use any other medication.

Concomitant use of medications that increase the excretion of water from your body (diuretics) should be avoided during Privigen treatment. Your doctor will decide whether to use or continue diuretic treatment.

Vaccinations

• Inform the doctor who prescribed the vaccine about your treatment with Privigen before vaccination.

After receiving Privigen, the effectiveness of some vaccines may be reduced. The affected vaccines are those with live and attenuated viruses, such as measles, mumps, rubella, and varicella vaccines. These vaccinations should be postponed for at least three months after the last Privigen infusion. In the case of the measles vaccine, this alteration may persist for up to one year. Therefore, the doctor who prescribed the vaccine should check the effectiveness of the measles vaccine.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication. Your doctor will decide whether you can receive Privigen during pregnancy or while breastfeeding.

However, in pregnant women and breastfeeding women, medications containing antibodies have been used. Long-term clinical experience has shown that no adverse effects should be expected during pregnancy or on the newborn.

If you receive Privigen while breastfeeding, the antibodies present in this medication will also be found in breast milk. Therefore, your baby will also receive the protective antibodies.

Driving and operating machinery

During Privigen treatment, patients may experience effects such as dizziness or nausea that may affect their ability to drive and operate machinery. If this occurs, do not drive or operate machinery until the effects have disappeared.

Privigen contains proline

Do not take it if you have hyperprolinemia (see also section 2, "What you need to know before Privigen is administered to you")

• Inform your doctor before starting treatment.

Sodium content

This medication contains less than 2.3 mg of sodium (main component of table salt/for cooking) per 100 ml. This is equivalent to 0.12% of the maximum daily intake of 2 g of sodium recommended for an adult.

Privigen is indicated only for intravenous infusion. It is administered generally by your doctor or healthcare professional.

Your doctor will calculate the correct dose for you, taking into account your weight, the specific circumstances listed in section 2, "Warnings and Precautions," and your response to treatment. The dose calculation for children and young patients is not different from that of adults. At the beginning of the infusion, you will receive Privigen at a slow infusion rate. If you tolerate this well, your doctor may gradually increase the infusion rate.

If You Receive More Privigen Than You Should

It is unlikely that an overdose will occur, since Privigen is generally administered only under medical supervision. If, despite this, you receive more Privigen than you should, your blood may become too thick (more dense), which could increase the risk of developing blood clots. This may occur especially if you are a high-risk patient, for example, if you are elderly or have kidney or heart disease. Inform your doctor if you know you have medical problems.

Like all medicines, this medicine can have side effects, although not everyone will experience them. Possible side effects can be reduced or even prevented if Privigen is administered at a slow infusion rate. Such side effects can occur even if you have previously received human immunoglobulins and tolerated them well.

In very rare and isolated cases, the following adverse reactions have been described with immunoglobulin preparations:

• Severe hypersensitivity reactions, such as a sudden drop in blood pressure or anaphylactic shock (for example, you may feel dizzy, lightheaded, experience fainting while standing, feel cold in your hands and feet, perceive an abnormal heartbeat or chest pain, or have blurred vision), even if you have not shown hypersensitivity in previous infusions,

• Inform your doctor or healthcare professional immediately if you notice such symptoms during the infusion of Privigen. They will decide if it is necessary to reduce the infusion rate or stop it completely.

• Formation of blood clots that can travel through the bloodstream (thromboembolic reactions) and can cause, for example: myocardial infarction (for example, when you have a sudden chest pain or shortness of breath), stroke (for example, when you have a sudden episode of muscle weakness, loss of sensation or balance, loss of alertness, or difficulty speaking), blood clots in the arteries of the lungs (for example, when you have chest pain, difficulty breathing, or coughing up blood), deep vein thrombosis (for example, when you have redness, warmth, pain on examination, or swelling in one or both legs),
• Chest pain, chest discomfort, breathing difficulty caused by acute lung injury due to transfusion (TRALI)

• • Inform your doctor or healthcare professional immediately if you experience any of the symptoms mentioned above. Anyone who experiences such symptoms should be immediately transported to the emergency department of a hospital for the corresponding evaluation and appropriate treatment.
• Transient non-infectious meningitis (reversible aseptic meningitis)

• Increased concentration of creatinine in the blood
• Proteinuria
• Acute renal failure

• Transient decrease in red blood cells (reversible hemolytic anemia or hemolysis), anemia, leukopenia, anisocytosis (including microcytosis).

The routine laboratory tests may frequently reveal changes in liver function (hyperbilirubinemia), as well as changes in blood counts (for example, positive direct Coombs test), increased alanine aminotransferase, increased aspartate aminotransferase, increased lactate dehydrogenase in blood).

Very common(may occur in more than 1 in 10 patients):

Headache (including sinus headache, migraine, headache, tension headache, pain (including back pain, limb pain, joint and bone pain (arthralgia), neck pain, facial pain), fever (including chills), flu-like illness (including rhinitis, sore throat, oral and pharyngeal vesicles, throat constriction).

Common(may occur in up to 1 in 10 patients):

Transient reduction in red blood cell count (anemia), decrease in red blood cells (hemolysis including hemolytic anemia) β, reduction in white blood cell count (leukopenia), hypersensitivity, dizziness (including vertigo), high blood pressure (hypertension), redness (including warmth, flushing), low blood pressure (hypotension), including decreased blood pressure), breathing difficulty (dyspnea, including chest pain, chest discomfort, painful breathing), stomach discomfort (nausea), vomiting, soft stools (diarrhea), stomach pain, skin disorder (including rash, itching (pruritus), urticaria, maculopapular rash, skin redness (erythema), skin peeling (exfoliation), muscle pain (including muscle cramps and stiffness), fatigue, physical weakness (asthenia), muscle weakness.

Routine laboratory tests may frequently reveal changes in liver function (hyperbilirubinemia), as well as changes in blood counts (for example, positive direct Coombs test), increased alanine aminotransferase, increased aspartate aminotransferase, increased lactate dehydrogenase in blood).

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

Transient non-infectious meningitis (reversible aseptic meningitis), irregular shape of red blood cells (microscopic detection), increased platelet count in the blood (thrombocytosis), drowsiness, chills (shivering), palpitations, tachycardia, thromboembolic events, lack of blood supply to the lower extremities that causes, for example, pain when walking (peripheral vascular disorder), presence of excess serum proteins in the urine (proteinuria, including increased creatinine in blood), pain at the injection site (including infusion site discomfort).

In isolated cases (post-marketing experience), the following have been observed in patients treated with Privigen: abnormally low count of white blood cells called neutrophils (decreased neutrophil count), anaphylactic shock, breathing difficulty due to lung injury caused by transfusion (TRALI), and acute renal failure.

• The cases of hemolytic anemia after the completion of the controlled clinical study were observed with a significantly reduced frequency due to improvements in the manufacturing process of Privigen.

• Inform your doctor or healthcare professional if you experience any side effects, even if they are not listed in this leaflet.

See section 2, "What you need to know before starting to use Privigen" for more information on the circumstances that increase the risk of side effects.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet. You can alsoreport them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more informationon the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the outer packaging and on the vial label after “EXP”. The expiration date is the last day of the month indicated.
• As the solution does not contain preservatives, the healthcare professional must infuse it as soon as possible after the first opening of the vial.
• Do not store at a temperature above 25 °C.
• Do not freeze.
• Keep the vial in the outer carton to protect it from light.
• Do not use this medication if you notice that the solution is cloudy or if it contains particles floating in the solution.

Composition of Privigen

• Theactive principleis normal human immunoglobulin (antibodies of the IgG type). Privigen contains 100 mg/ml (10%) of human protein, of which at least 98% is IgG.

The approximate percentage of IgG subclasses is as follows:

IgG169%

IgG226%

IgG33%

IgG42%

This medicine contains traces of IgA (not more than 25 micrograms/ml).

• Theother components (excipients)are the amino acid proline, water for injection, and hydrochloric acid or sodium hydroxide (to adjust the pH).

Appearance of the product and contents of the package

Privigen is presented as a perfusion solution.

The solution is clear or slightly opalescent, and colorless to pale yellow.

Package sizes:

1 vial (2.5 g/25 ml, 5 g/50 ml, 10 g/100 ml, 20 g/200 ml or 40 g/400 ml)

3 vials (10 g/100 ml or 20 g/200 ml)

Only some package sizes may be commercially available.

Marketing authorization holder and responsible manufacturer

CSL Behring GmbH

Emil-von-Behring-Strasse 76

D-35041 Marburg

Germany

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this summary:

The detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

-------------------------------------------------------------------------------------------------------------------------

This information is intended solely for healthcare professionals:

Dosage and administration

The recommended dosages are summarized in the following table:

Administration

Intravenous route.

Human normal immunoglobulin should be infused intravenously at an initial infusion rate of 0.3 ml/kg body weight over approximately 30 minutes. If tolerated well, the infusion rate may be increased gradually to 4.8 ml/kg body weight per hour.

In patients with primary immunodeficiency who have tolerated well the infusion rate of 4.8 ml/kg body weight per hour, the infusion rate may be increased gradually even further, up to a maximum of 7.2 ml/kg body weight per hour.

If a pre-dilution prior to infusion is desired, Privigen may be diluted with a 5% glucose solution to obtain a final concentration of 50 mg/ml (5%).

Special precautions

In case of adverse reaction, the infusion rate should be reduced or the infusion should be stopped.

It is strongly recommended that, each time Privigen is administered to a patient, the name and batch number of the product should be noted, in order to maintain a link between the patient and the batch of the product.

Incompatibilities

This medicine should not be mixed with other medicines, except those mentioned in the following section.

Special precautions for disposal and other manipulations

The medicine should be brought to room temperature or body temperature before use. For the administration of Privigen, a perfusion line with ventilation should be used. The stopper should be pierced always in the center, within the marked area.

The solution should be clear or slightly opalescent and colorless or pale yellow. Solutions that are turbid or have deposits should not be used.

If a dilution is desired, it is recommended to use a 5% glucose solution. To obtain a solution of immunoglobulin of 50 mg/ml (5%), 100 mg/ml (10%) of Privigen should be diluted with an equal volume of 5% glucose solution. Strict aseptic technique should be followed during the dilution of Privigen.

Once the vial has been pierced in aseptic conditions, its contents should be used quickly. Since the solution does not contain preservatives, Privigen should be infused as soon as possible.

The disposal of unused medicine and all materials that have been in contact with it, will be carried out in accordance with local regulations.