Privigen

Package leaflet: Information for the user

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

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or healthcare professionals.
• If you get any side effects, talk to your doctor or healthcare professionals. This includes any possible side effects not listed in this leaflet.

Contents of this leaflet:

1. What Privigen is and what it is used for
2. What you need to know before being given Privigen
3. How to use Privigen
4. Possible side 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 Privigen is
Privigen belongs to a class of medicines called normal human immunoglobulins.
Immunoglobulins, also known as antibodies, are blood proteins that help the body fight infections.

How Privigen works
Privigen contains immunoglobulins prepared from the blood of 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 conditions:

A) To increase very low levels of immunoglobulins in your blood up to normal values (replacement therapy):

1. Patients born with a reduced or absent ability to produce immunoglobulins (primary immunodeficiencies (PID)).
2. Patients with acquired immunodeficiency (SID) who suffer from severe or recurrent infections, ineffective antimicrobial treatment, and confirmed specific antibody deficiency or serum IgG levels <4 g/l.

B) To treat certain inflammatory diseases (immunomodulation). There are 4 categories of patients:

1. Patients who have too few platelets in their blood (primary immune thrombocytopenia (ITP)) and who are at high risk of bleeding or who will undergo surgery in the near future.
2. Patients with Guillain-Barré syndrome. This is an acute disease characterized by inflammation of the peripheral nerves, causing severe muscle weakness, particularly in the legs and upper limbs.
3. Patients with Kawasaki disease. This is an acute illness that mainly affects young children and is 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/or numbness, mainly in the legs and upper limbs.
5. Patients with multifocal motor neuropathy (MMN). This is a slowly progressive disease of the motor nerves causing weakness in the arms and legs.

2. What you should know before being given Privigen

Read this section carefully. The information provided here should be taken into account by you and your doctor before administration of Privigen.
DO NOT take Privigen

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

Warnings and precautions
Circumstances that increase the risk of adverse reactions
Before treatment, inform your doctor or healthcare providers if any of the following circumstances apply to you:

• you receive the medicine at high doses for one day or several days and you have blood group A, B, or AB and/or have an underlying inflammatory disease. In these cases, immunoglobulins have commonly been observed to increase the risk of red blood cell destruction (hemolysis).
• you are overweight, elderly, diabetic, have been confined to bed for a prolonged period, have high blood pressure, reduced blood volume (hypovolemia), blood vessel problems (vascular diseases), an increased tendency for blood to clot (thrombophilia or thrombotic episodes), or have a disease or condition that makes your blood thicker (hyperviscous). In these cases, immunoglobulins may increase the risk of heart attack (myocardial infarction), stroke, formation of blood clots in the lungs (pulmonary embolism), or in the legs, although very rarely.
• you are diabetic. Although Privigen does not contain sugars, it may be diluted with a specific sugar solution (5% glucose), which could affect your blood sugar levels.
• you have, or have previously had, kidney problems or are taking medicines that may damage the kidneys (nephrotoxic drugs). In these cases, immunoglobulins may increase the risk of rapid and severe loss of kidney function (acute kidney failure), although only very rarely. Loss of kidney function leading to death has occurred in isolated cases associated with hemolysis.

Monitoring required during infusion
For your safety, treatment with Privigen will be administered under the supervision of a doctor or healthcare professionals. You will generally be monitored throughout the entire intravenous infusion and for at least 20 minutes afterward. In certain circumstances, special precautions may be necessary. These circumstances may occur: if you receive Privigen at a high infusion rate, or
if you are receiving Privigen for the first time or after a long interruption of treatment (e.g., several months).
In these cases, you will be closely observed throughout the infusion and for at least 1 hour after the infusion ends.

Need to slow down or stop the infusion rate

• You may be allergic (hypersensitive) to immunoglobulins without knowing it. However, true allergic reactions are rare. Such reactions may occur even if you have previously received human immunoglobulins and tolerated them well. This possibility is particularly relevant if you have developed antibodies against IgA-type immunoglobulins. In these rare cases, allergic reactions such as sudden drop in blood pressure or shock may occur (see also section 4 “Possible side effects”).
• Very rarely, transfusion-related acute lung injury (TRALI) may occur after receiving immunoglobulins. This causes fluid accumulation in the air spaces of the lung unrelated to heart function (non-cardiogenic pulmonary edema). You will recognize TRALI by severe breathing difficulty (respiratory distress), bluish skin color (cyanosis), excessively low oxygen levels in the blood (hypoxia), low blood pressure (hypotension), and increased body temperature (fever). Symptoms typically appear during or within 6 hours after treatment. Inform your doctor or healthcare providers immediately if you notice these reactions during the infusion of Privigen. They will decide whether to reduce the infusion rate or stop the infusion completely.

Blood tests
Before undergoing any blood tests, inform your doctor that you are being treated with Privigen.
After administration of Privigen, results of certain blood tests (serological tests) may be altered for a certain period of time.

Safety information regarding infections
Privigen is made from human blood plasma (plasma is the liquid part of blood).
For medicines derived from human blood or plasma, certain safety measures are implemented to prevent transmission of infections to patients. These safety measures include:
careful selection of plasma and blood donors to exclude individuals who may carry infections,
testing of each donation and pooled plasma from multiple donors for signs of viruses/infections,
inclusion in the manufacturing process of steps for inactivation or removal of potential viruses.

Despite these measures, when administering medicines derived from human blood or plasma, the risk of transmitting infections can never be completely excluded. This applies even to unknown or new 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, and against non-enveloped viruses such as hepatitis A virus and Parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, possibly because the antibodies directed against these infections contained in the medicine are protective.

• It is recommended to record the brand name and batch number each time a dose of Privigen is administered, in order to maintain documentation of the batches used.

Other medicines and Privigen
Inform your doctor or healthcare providers if you are taking, have recently taken, or might take any other medicines.
Concomitant use of medicines that increase water elimination from the body (loop diuretics) should be avoided during treatment with Privigen. Your doctor will decide whether to use or continue treatment with loop diuretics.

Vaccinations
Before vaccination, inform the healthcare provider administering the vaccine that you are being treated with Privigen.
After administration of Privigen, the effectiveness of certain vaccinations may be impaired. This applies particularly to vaccinations with live attenuated viruses, such as those against measles, mumps, rubella, and varicella. These vaccinations should be postponed until at least three months after the last infusion of Privigen. For measles vaccination, reduced effectiveness may persist up to 1 year. Therefore, the healthcare provider administering the measles vaccine should verify its effectiveness.

Pregnancy and breastfeeding
Inform your doctor or healthcare providers if you are pregnant, planning to become pregnant, or breastfeeding. Your doctor will decide whether Privigen can be administered during pregnancy or breastfeeding.
However, medicines containing antibodies have been used during pregnancy and breastfeeding. Long-term experience has shown that harmful effects during pregnancy or on the newborn are not expected.
If you are given Privigen during breastfeeding, the antibodies contained in the medicine will pass into breast milk. Therefore, the baby may also receive protective antibodies.

Driving and use of machines
During treatment with Privigen, patients may experience effects such as dizziness or nausea, which could impair the ability to drive or operate machinery. In such cases, do not drive or operate machinery until these effects have disappeared.

Privigen contains proline
Do not take this medicine if you have hyperprolinemia (see also section 2 “What you should know before being given Privigen”).
Inform your doctor before treatment.

Sodium content
This medicine contains less than 2.3 mg of sodium (a main component of table salt) per 100 mL. This is equivalent to 0.12% of the maximum daily intake recommended in an adult's diet.

3. How to use Privigen

Privigen is intended for intravenous infusion (intravenous infusion) only. It is normally
administered by a doctor or healthcare professionals.
Your doctor will calculate the correct dose based on your body weight, the specific circumstances listed in
section 2 “Warnings and precautions”, and your response to treatment. The dose calculation for
children and young people is not different from that for adults. At the beginning of the infusion, you will receive
Privigen at a low infusion rate. If you tolerate it well, your doctor may gradually increase the
infusion rate.
If you receive more Privigen than you should
Overdose is very unlikely to occur, as Privigen is generally administered under medical supervision. However, if you do receive more Privigen than necessary, your blood may become too thick (hyperviscous), which may increase the risk of developing blood clots. This may occur especially in patients at risk, for example elderly patients or patients with heart or kidney disease. Inform your doctor if you have any known medical conditions.

4. Possible side effects

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

Possible side effects may be reduced or even avoided if Privigen is infused at a low infusion rate. These side effects may occur even if you have previously received human immunoglobulins and tolerated them well.

In rare and isolated cases, the following side effects related to immunoglobulin-based preparations have been reported:

• Severe hypersensitivity reactions, such as sudden drop in blood pressure or anaphylactic shock (i.e., dizziness, vertigo, fainting upon standing, cold hands and feet, sensation of irregular heartbeat or chest pain, or blurred vision), even if you have not previously shown hypersensitivity reactions to prior infusions.
  Inform your doctor or healthcare professionals immediately if you notice any of these signs during Privigen infusion. They will decide whether to reduce the infusion rate or discontinue the infusion completely.

• Blood clot formation, which may travel through the bloodstream (thromboembolic reactions) and may cause, for example, myocardial infarction (e.g., sudden chest pain or shortness of breath), stroke (e.g., sudden muscle weakness, loss of sensation and/or balance, reduced alertness, or difficulty speaking), clots in the pulmonary arteries (e.g., chest pain, difficulty breathing, or coughing up blood), or deep vein thrombosis (e.g., redness, warmth, pain, excessive tenderness, or swelling in one or both legs).

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

  Inform your doctor or healthcare professionals immediately if you experience any of these symptoms. Any person presenting these symptoms must be immediately transferred to a hospital emergency department for diagnosis and treatment.

• Transient non-infectious meningitis (reversible aseptic meningitis): Inform your doctor or healthcare professionals immediately if you have a stiff neck and one or more of the following symptoms: fever, nausea, vomiting, headache, excessive sensitivity to light, or mental disturbances.
• Increased creatinine levels in the blood,
• Proteinuria,
• Acute renal failure, transient reduction in red blood cells (hemolytic anemia/reversible hemolysis), anemia, leukopenia, anisocytosis (including microcytosis).

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

Very common (may occur in more than 1 in 10 patients):
Headache (including sinus headache, migraine, sensation of head discomfort, tension headache), pain (including back pain, limb pain, joint and bone pain (arthralgia), neck pain, facial pain), fever (including chills), influenza-like illness (including runny nose (rhinorrhea), pharyngitis (pharyngo-laryngodynia), blisters in the mouth and throat (oropharyngeal blisters), throat tightness.

Common (may occur in up to 1 in 10 patients):
Temporary decrease in red blood cells (anemia), destruction of red blood cells (hemolysis, including hemolytic anemia), decrease in white blood cells (leukopenia), hypersensitivity, dizziness (including vertigo), high blood pressure (hypertension), hot flushes (including hot flashes, hyperemia), hypotension (including decreased blood pressure), shortness of breath (dyspnea including chest pain, chest discomfort, painful breathing), stomach ache (nausea), vomiting, loose stools (diarrhea), stomach pain, skin reactions (including rash, pruritus, urticaria, maculopapular rash, redness of the skin (erythema), skin peeling (exfoliative dermatitis)), muscle pain (including muscle cramps and stiffness), fatigue (tiredness), physical weakness (asthenia), muscle weakness.

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

Uncommon (may occur in up to 1 in 100 patients):
Transient non-infectious meningitis (reversible aseptic meningitis), abnormal red blood cell shape (microscopic detection), presence of an elevated number of platelets in the blood (thrombocytosis), drowsiness, chills (tremor), palpitations, tachycardia, thromboembolic events, inadequate blood supply to the lower limbs leading to symptoms such as pain while walking (peripheral vascular disorder), presence of excess serum proteins in the urine (proteinuria, including increased blood creatinine), injection site pain (including discomfort at the 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.

Cases of hemolytic anemia following completion of controlled studies have been observed at a significantly reduced frequency due to improvements in the manufacturing process of Privigen.

If you experience any side effect, including those not listed in this leaflet, consult your doctor or healthcare professionals.

For more detailed information on circumstances that increase the risk of side effects, please also refer to section 2 "What you should know before you are given Privigen".

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor, nurse, or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 carton and on the label of the vial after "Exp.". The expiry date refers to the last day of that month.
• Since the solution does not contain preservatives, healthcare professionals should infuse it as soon as possible after opening the vial.
• Do not store above 25 °C.
• Do not freeze.
• Store the vial in its outer packaging to protect it from light.
• Do not use this medicine if you notice that the solution is cloudy or contains particles.

6. Package contents and other information

What Privigen contains
The active substance is normal human immunoglobulin (IgG antibodies). Privigen
contains 100 mg/ml (10%) human proteins, of which at least 98% consists of IgG.
The approximate distribution of IgG subclasses is as follows:
IgG ....................... 69 %
IgG ....................... 26 %
IgG ......................... 3 %
IgG ......................... 2 %
This medicinal product contains trace amounts of IgA (not more than 25 micrograms/ml).
The other components (excipients) are the amino acid proline, water for injectable solutions, and
hydrochloric acid or sodium hydroxide (for pH adjustment).

Description of the appearance of Privigen and contents of the pack
Privigen is a solution for infusion.
The solution is clear or slightly opalescent, colourless to pale yellow.
Pack 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).
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
D-35041 Marburg
Germany
For further information on Privigen, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Luxembourg/Luxemburg
CSL Behring NV CSL Behring NV
Tél/Tel: +32 15 28 89 20 Tél/Tel: +32 15 28 89 20

България Magyarország
МагнаФарм България CSL Behring Kft.
Тел: +359 2 810 3949 Tel: +36 1 213 4290

Česká republika Malta
CSL Behring s.r.o. AM Mangion Ltd.
Tel: +42 702 137 233 Tel: +356 2397 6333

Danmark Nederland
CSL Behring ApS CSL Behring B.V.
Tlf: +45 4520 1420 Tel: +31 85 111 96 00

Deutschland Norge
CSL Behring GmbH CSL Behring AB
Tel: +49 69 30584437 Tlf: +46 8 544 966 70

Eesti Österreich
CSL Behring GmbH CSL Behring GmbH
Tel: +49 69 30584437 Tel: +43 1 80101 2463

Ελλάδα Polska
CSL Behring ΕΠΕ CSL Behring Sp. z o.o.
Τηλ: +30 210 7255 660 Tel: +48 22 213 22 65

España Portugal
CSL Behring S.A. CSL Behring Lda
Tel: +34 933 67 1870 Tel: +351 21 782 62 30

France România
CSL Behring SA Prisum International Trading srl
Tél: +33 1 53 58 54 00 Tel: +40 21 322 01 71

Hrvatska Slovenija
Marti Farm d.o.o. NEOX s.r.o.
Tel: +385 1 5588297 Tel: +386 41 42 0002

Ireland Slovenská republika
CSL Behring GmbH CSL Behring s.r.o.
Tel: +49 69 30517254 Tel: +421 911 653 862

Ísland Suomi/Finland
CSL Behring AB CSL Behring AB
Sími: +46 8 544 966 70 Puh/Tel: +46 8 544 966 70

Italia Sverige
CSL Behring S.p.A. CSL Behring AB
Tel: +39 02 34964 200 Tel: +46 8 544 966 70

Κύπρος United Kingdom
CSL Behring ΕΠΕ CSL Behring UK Ltd.
Τηλ: +30 210 7255 660 Tel: +44 1444 447405

Latvija
CSL Behring GmbH
Tel: +49 69 30584437

Lietuva
CSL Behring GmbH
Tel: +49 69 30584437

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/.

The following information is intended for healthcare professionals only:
Dosage and method of administration
The recommended dosages are summarised in the table below:

Route of administration
For intravenous use.
Infuse normal human immunoglobulin intravenously at an initial infusion rate of 0.3 ml/kg body weight/hour for approximately 30 minutes. If well tolerated, the infusion rate may be gradually increased to 4.8 ml/kg/hour.
In patients with primary immunodeficiency syndromes (PID) who have tolerated infusion at a rate of 4.8 ml/kg/hour, the rate may be further gradually increased up to a maximum of 7.2 ml/kg/hour.
If dilution prior to infusion is desired, Privigen may be diluted with 5% glucose solution to a final concentration of 50 mg/ml (5%).
Special precautions
In case of adverse reactions, reduce the infusion rate or stop the infusion.
It is recommended to record the trade name and batch number each time Privigen is administered to a patient, in order to be able to link the patient to the product batch.
Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in the following paragraph.
Special precautions for disposal and handling
Bring the product to room temperature or body temperature before use. Use an infusion set with an air vented drip chamber for administration of Privigen. Pierce the center of the stopper 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 desired, a 5% glucose solution is recommended. To obtain an immunoglobulin solution of 50 mg/ml (5%), 100 mg/ml of Privigen (10%) must be diluted with an equal volume of glucose solution. Perform dilution under strictly aseptic conditions.
Once the vial has been pierced under aseptic conditions, the contents should be used promptly. Since the solution does not contain preservatives, Privigen should be infused as soon as possible.
Any unused medicinal product and waste material derived from such medicinal product should be disposed of in accordance with local regulations.