PRIVIGEN 100 MG/ML SOLUTION FOR INFUSION

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Privigen 100 mg/ml (10%) solution for infusion

normal human immunoglobulin (IgIV)

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

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

Leaflet contents:

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

1. What Privigen is and what it is used for

What is Privigen

Privigen belongs to a class of medicines called normal human 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 blood taken from healthy individuals. The medicine works in exactly the same way as the immunoglobulins naturally present in human blood.

What Privigen is used for

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

1. To increase abnormally low blood immunoglobulin levels to normal values (replacement therapy):

   1. Patients who were born with a reduced or absent ability to produce immunoglobulins (primary immunodeficiencies or PID).
   2. Patients with acquired immunodeficiency (AID) who suffer from severe or recurrent infections, ineffective antimicrobial treatment, and proven specific antibody failure (PSAF)* or serum IgG level of <4 g/l.

2. To treat certain inflammatory disorders (immunomodulation). There are 5 groups:

   1. Patients who do not have enough platelets in their blood (immune thrombocytopenic purpura (ITP)), and: who are at risk of bleeding or who are about to undergo surgery.
   2. Patients with Guillain-Barré syndrome. This is an acute disease characterized by inflammation of the peripheral nerves causing severe muscle weakness, mainly in the lower and upper limbs.
   3. Patients with Kawasaki disease. This is an acute disease affecting mainly young children and characterized by inflammation of blood vessels throughout the body.
   4. Patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This is a chronic disease characterized by inflammation of the peripheral nerves causing muscle weakness and numbness, mainly in the legs and upper extremities.
   5. Patients with multifocal motor neuropathy (MMN). This is a motor nerve disease with slowly progressive weakness of the arms and legs.

2. What you need to know before using Privigen

• Read this section carefully. Before you are administered Privigen, you and your doctor should consider the information provided.

Do not use Privigen

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

Warnings and precautions

What circumstances increase the risk of adverse reactions?

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

• You receive this medicine at high doses over one or several days and have blood group A, B, or AB, or have an underlying inflammatory disease. Under these circumstances, immunoglobulins have frequently been associated with an increased 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, low blood volume (hypovolemia), have blood vessel problems (vascular diseases), have an increased tendency for blood clotting (thrombophilia or thrombotic episodes), or suffer from a disease or disorder that makes your blood thicker (blood hyperviscosity). Under these circumstances, immunoglobulins may increase the risk of heart attack (myocardial infarction), stroke, blood clots in the lung (pulmonary embolism), or blockage of a blood vessel in the leg, although very rarely.

• You have diabetes. Although Privigen does not contain sugar, it may be diluted with a special sugar solution (5% glucose), which could affect your blood sugar levels.

• You have or have previously had kidney problems or are taking medications that may harm your kidneys (nephrotoxic drugs). Under these circumstances, immunoglobulins may increase the risk of rapid, severe loss of kidney function (acute renal failure), although only very rarely. Fatal loss of kidney function has occurred in isolated cases related to hemodialysis.

What type of monitoring is required during infusion?

For your personal safety, treatment with Privigen 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 it ends. In some cases, special precautions may be necessary. Examples include:

• you are receiving Privigen at a high infusion rate, or
• you are receiving Privigen for the first time or after a prolonged interruption of treatment (e.g., several months).

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

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

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

However, true allergic reactions are very 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-type immunoglobulins. In these very rare cases, allergic reactions such as a sudden drop in blood pressure or shock may occur (see also section 4, "Possible side effects").

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

• Immediately inform your doctor or healthcare professional if you notice any of these reactions during the infusion of Privigen. They will decide whether the infusion rate should be reduced or the infusion stopped completely.

Blood tests

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

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

Safety information regarding infections

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

• careful selection of blood or plasma donors to exclude those at risk of transmitting infections,
• testing of each donation and plasma pools for signs of viruses or infections,
• inclusion of steps in the manufacturing process that can inactivate or remove viruses.

Despite these measures, when administering medicines prepared from human blood or plasma, the possibility of transmitting an infection cannot be completely ruled out. This also applies to any unknown or emerging viruses or other types of infections.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as against non-enveloped viruses such as hepatitis A virus and parvovirus B19.

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

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

Use of Privigen with other medicines

• Inform your doctor or healthcare professional if you are taking, have recently taken, or might need to take any other medicines.

Concomitant use of medicines that increase water excretion from your body (loop diuretics) should be avoided during treatment with Privigen. Your doctor will decide whether you should use or continue treatment with loop diuretics.

Vaccines

• Before vaccination, inform the doctor administering the vaccine about your treatment with Privigen.

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

Pregnancy and breastfeeding

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

However, medicines containing antibodies have been used in pregnant and breastfeeding women. Long-term clinical experience has shown that harmful effects during pregnancy or on the newborn are not expected.

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

Driving and using machines

During treatment with Privigen, patients may experience effects such as dizziness or nausea, which may affect the ability to drive or use machines. If this occurs, you should not drive or use machines until these effects have subsided.

Privigen contains proline

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

• Inform your doctor before starting treatment.

Sodium content

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

3. How to use Privigen

Privigen is intended for intravenous infusion only (infusion into a vein). It is usually administered by your doctor or healthcare professional.

Your doctor will calculate the correct dose for you based on your body weight, the specific circumstances listed in section 2, "Warnings and precautions," and your response to treatment. Dose calculation for children and young patients is not different from that for 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

An overdose is unlikely since Privigen is generally administered only under medical supervision. Nevertheless, if you receive more Privigen than you should, your blood may become too thick (increased viscosity), which could increase the risk of developing blood clots. This is especially possible if you are a patient at risk, for example, if you are elderly or if you have kidney or heart disease. Inform your doctor if you know you have medical conditions.

4. Possible adverse effects

Like all medicines, this medicine can have adverse effects, although not everyone experiences them. Possible adverse effects may be reduced or even avoided if Privigen is administered at a slow infusion rate. Such adverse effects may 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 reported with immunoglobulin preparations:

• severe hypersensitivity reactions, such as a sudden drop in blood pressure or anaphylactic shock (for example, you may feel dizzy, lightheaded, faint 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 previously shown hypersensitivity during prior infusions,

• Immediately inform your doctor or healthcare professional if you notice such symptoms during Privigen infusion. They will decide whether the infusion rate should be reduced or whether the infusion should be stopped completely.

• formation of blood clots that may travel through the bloodstream (thromboembolic reactions), which may cause, for example: myocardial infarction (for example, sudden chest pain or shortness of breath), stroke (for example, 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, chest pain, difficulty breathing, or coughing up blood), deep vein thrombosis (for example, redness, warmth, tenderness on palpation, or swelling in one or both legs),

• chest pain, chest discomfort, painful breathing due to transfusion-related acute lung injury (TRALI)

• Immediately inform your doctor or healthcare professional if you experience any of the symptoms listed above. Anyone experiencing such symptoms should be immediately transferred to a hospital emergency department for appropriate evaluation and treatment.

• transient non-infectious meningitis (reversible aseptic meningitis)

• Immediately inform your doctor or healthcare professional if you experience the following symptoms: severe headache, neck stiffness, drowsiness, fever, increased sensitivity of the eyes to light (photophobia), nausea and vomiting, after receiving intravenous immunoglobulins. These symptoms could indicate aseptic meningitis, a non-infectious inflammation of the protective membranes surrounding the brain and spinal cord. If you experience a recurrence of aseptic meningitis during intravenous immunoglobulin treatment, your doctor will assess whether your symptoms have appeared or worsened, which may indicate progression to brain swelling (cerebral edema). Your doctor will decide whether further tests are needed and whether to continue the Privigen infusion.

• increased blood creatinine concentration

• proteinuria

• acute renal failure

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

Adverse effects observed in controlled clinical studies and post-marketing experience are listed in decreasing order of frequency:

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

Headache (including sinus headache, migraine, head discomfort, tension headache), pain (including back pain, limb pain, joint and bone pain (arthralgia), neck pain, facial pain), fever (including chills), flu-like illness (including runny nose (nasopharyngitis), sore throat (pharyngolaryngeal pain), mouth and throat blisters (oropharyngeal blisters), throat tightness.

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

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

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

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

Transient non-infectious meningitis (reversible aseptic meningitis), abnormal shape of red blood cells (microscopic detection), presence of elevated platelet counts in blood (thrombocytosis), drowsiness, chills (tremors), palpitations, tachycardia, thromboembolic events, inadequate blood supply to the lower limbs causing, for example, pain while walking (peripheral vascular disorder), presence of excess serum proteins in urine (proteinuria, including increased blood creatinine), pain at injection site (including discomfort at infusion site).

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

β Cases of hemolytic anemia after completion of the controlled clinical study were observed at a significantly reduced frequency due to improvements in the manufacturing process of Privigen.

• If you experience any adverse effects, consult your doctor or healthcare professional, even if these are adverse effects not listed in this leaflet.

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

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Privigen

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the outer packaging and on the label of the vial after “EXP”. The expiry date refers to the last day of the month indicated.
• Since the solution does not contain preservatives, healthcare professionals should administer it as soon as possible after the first opening of the vial.
• Do not store above 25 °C.
• Do not freeze.
• Keep the vial in the outer carton to protect it from light.
• Do not use this medicine if you notice that the solution is cloudy or contains particles floating in it.

6. Contents of the container and other information

Composition of Privigen

• The active substance is human normal immunoglobulin (IgG-type antibodies). Privigen contains 100 mg/ml (10%) human protein, of which at least 98% is IgG.

The approximate percentage of IgG subclasses is as follows:

This medicine contains traces of IgA (no more than 25 micrograms/ml).

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

Appearance of the medicinal product and content of the container

Privigen is presented as a solution for infusion.

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

Container 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 certain container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

CSL Behring GmbH
Emil-von-Behring-Strasse 76
D-35041 Marburg
Germany

Further information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary:

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

This information is intended for healthcare professionals only:

Dosage and method of administration

Dosage recommendations are summarized in the following table:

Method of administration

Intravenous route.

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

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

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

Special precautions

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

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

Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in the following section.

Special precautions for disposal and other handling

The medicine should be brought to room or body temperature before use. A vented infusion set must be used for the administration of Privigen. The stopper must always be pierced in the center, within the marked area.

The solution should be clear or slightly opalescent and colourless or pale yellow. Solutions that are cloudy or contain deposits must not be used.

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

Once the vial has been pierced under aseptic conditions, its contents should be used promptly. Because the solution contains no preservatives, Privigen should be infused as soon as possible.

Any unused medicinal product and materials that have come into contact with it should be disposed of in accordance with local requirements.