KIOVIG 100 mg/ml SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

KIOVIG100mg/ml solution for infusion

human normal immunoglobulin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of thepackage leaflet:

1. What is KIOVIG and what is it used for
2. What you need to know before you use KIOVIG
3. How to use KIOVIG
4. Possible side effects
5. Storage of KIOVIG
6. Contents of the pack and further information

1. What is KIOVIG and what is it used for

KIOVIG belongs to a group of medicines called immunoglobulins. These medicines contain human antibodies, which are also present in the blood. Antibodies help to fight infections. Medicines like KIOVIG are used in patients who do not have enough antibodies in the blood and often suffer from frequent infections. These medicines can also be used in patients who need additional antibodies to treat certain inflammatory disorders (autoimmune diseases).

KIOVIG is used for

Treatment of patients who do not have enough antibodies (replacement therapy). Thereare five groups:

1. Patient with a congenital lack of antibody production (primary immunodeficiency syndromes).
2. Patient with secondary immunodeficiencies (SID) who suffer from severe or recurrent infections, ineffective antimicrobial treatment, and a deficiency of specific antibodies (PSAF) or IgG in serum <4 g/l.

*PSAF = inability to increase at least 2 times the antibody titre against pneumococcal polysaccharide vaccine and polymeric antigen vaccines.

Treatment of patients with certain inflammatory disorders (immunomodulation).

Thereare five groups:

1. Patient who do not have enough platelets in the blood (primary immune thrombocytopenia) and are at high risk of bleeding or are about to undergo surgery.
2. Patient with a disease characterized by inflammation of multiple nerves throughout the body (Guillain-Barré Syndrome).
3. Patient with a disease that causes multiple inflammation of various organs in the body (Kawasaki disease).
4. Patient with a rare disease characterized by asymmetric and progressive weakness of the limbs without sensory loss (multifocal motor neuropathy, MMN).
5. Patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

2. What you need to know before you use KIOVIG

Do not useKIOVIG

If you are allergic to immunoglobulins or any of the other ingredients of this medicine (listed in section 6).

For example, if you have an immunoglobulin A deficiency, in which case you may have anti-immunoglobulin A antibodies in your blood. Since KIOVIG contains trace amounts of immunoglobulin A (up to 0.14 mg/ml), you may develop an allergic reaction.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start using KIOVIG.

Required monitoring period during infusion

• You will be closely monitored during the KIOVIG infusion period to avoid an allergic reaction. Your doctor will ensure that the infusion rate of KIOVIG is suitable for you.
• If KIOVIG is administered at a high rate, if you have a disorder characterized by a low level of antibodies in the blood (hypo- or agammaglobulinemia), if you have not received this medicine before, or if it has been a long time (e.g., several weeks) since you last received it, there may be a higher risk of side effects. In these cases, you will be closely monitored during and for one hour after the infusion.
• If you have previously received KIOVIG and have recently received the last treatment, you will only be observed during the infusion and for at least 20 minutes after the infusion.

When to stop or reduce the infusion rate

In rare cases, the body may have previously reacted to certain antibodies and, therefore, be sensitized to medicines containing antibodies. This can occur especially if you have an immunoglobulin A deficiency. In these rare cases, you may experience allergic reactions such as a sudden drop in blood pressure or shock, even if you have previously received treatment with medicines containing antibodies.

If you experience an allergic reaction during the KIOVIG infusion, inform your doctor immediately. Depending on the doctor's decision, the infusion rate may be reduced or interrupted.

Special patient groups

• Your doctor will take special precautions if you are overweight, elderly, diabetic, or have high blood pressure, low blood volume (hypovolemia), or vascular problems. In these cases, immunoglobulins may increase the risk of myocardial infarction, stroke, pulmonary embolism, or deep vein thrombosis, although this is very rare.

Tell your doctor if you are diabetic. Although KIOVIG does not contain sugar, it can be diluted with a special sugar solution (5% glucose), which may affect your blood sugar levels.

• Your doctor will also take special care if you have or have had kidney problems or have received medicines that may have damaged your kidneys (nephrotoxic medicines), as there is a very rare possibility of severe kidney failure.

Tell your doctor if you have or have had kidney problems. Your doctor will choose the appropriate intravenous immunoglobulin for you.

Information on the original material of KIOVIG

KIOVIG is made from human plasma (the liquid part of the blood). When medicines are made from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These measures include careful selection of donors to exclude those at risk of carrying infectious diseases, testing for specific infection markers in individual donations and plasma pools, as well as inclusion of steps in the manufacturing process to eliminate/inactivate viruses. Despite this, when medicines derived from human blood or plasma are administered, the possibility of transmitting infectious agents cannot be completely excluded. This also applies to emerging or unknown viruses or other types of infections.

The measures taken for the manufacture of KIOVIG are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and for non-enveloped viruses such as hepatitis A virus and parvovirus B19. KIOVIG also contains certain antibodies that may prevent infection with hepatitis A virus and parvovirus B19.

Using KIOVIG with other medicines

Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines.

If you have been given a vaccine in the last six weeks and up to three months, the infusion of immunoglobulins like KIOVIG may alter the effectiveness of some live virus vaccines such as measles, rubella, mumps, and chickenpox. Therefore, after administration of immunoglobulins, you may need to wait up to 3 months before receiving a live attenuated virus vaccine. You may need to wait up to 1 year after receiving immunoglobulins before receiving the measles vaccine.

Effects on blood tests

KIOVIG contains a wide range of different antibodies, some of which may interfere with blood tests. If you have a blood test after receiving KIOVIG, please inform the analyst or your doctor that you have received the medicine.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
• No clinical studies have been conducted with KIOVIG in pregnant or breastfeeding women. However, medicines containing antibodies have been used in pregnant or breastfeeding women, and this has shown that they do not expect harmful effects during pregnancy or for the baby.
• If you are breastfeeding and receive KIOVIG, the antibodies in the medicine may also be found in breast milk. Therefore, your baby may be protected against certain infections.

Driving andusing machines

Patient may experience reactions (e.g., dizziness or nausea) during treatment with KIOVIG that could affect the ability to drive and use machines. If this happens, wait until the reactions have disappeared.

3. How to use KIOVIG

KIOVIG is for intravenous administration (infusion into a vein). It will be given to you by your doctor or nurse. The dose and frequency of infusion may vary depending on your situation and body weight.

At the start of the infusion, you will receive KIOVIG at a low rate. Your doctor may gradually increase the infusion rate depending on whether you tolerate it well.

Use in children and adolescents

In children and adolescents (0 to 18 years), the same indications, dose, and infusion frequency are used as in adults.

If you use more KIOVIG than you should

If you receive more KIOVIG than you should, the blood may become thicker (hyperviscosity). This can occur especially if you are a patient at risk (e.g., an elderly patient or a patient with kidney problems). Make sure to drink enough fluids to avoid dehydration and inform your doctor if you have medical problems.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some side effects, such as headache or redness, can be avoided by reducing the infusion rate.

The list of side effects observed in treatment with KIOVIG is described below:

• Very common side effects (may affect more than 1 in 10 people):

Headache, high blood pressure, nausea, rash, local reactions (e.g., pain, swelling, or other reactions at the infusion site), fever, fatigue.

• Common side effects (may affect up to 1 in 10 people):

Bronchitis, common cold, low red blood cell count, swollen lymph nodes, decreased appetite, difficulty sleeping, anxiety, dizziness, migraine, numbness or tingling of the skin or a limb, decreased sense of touch, eye inflammation, increased heart rate, flushing, cough, runny nose, chronic cough or wheezing (asthma), nasal congestion, sore throat, difficulty breathing, diarrhea, vomiting, abdominal pain, indigestion, bruising, itching, and hives, dermatitis, skin redness, back pain, joint pain, pain in arms or legs, muscle pain, muscle cramps, muscle weakness, chills, fluid accumulation under the skin, flu-like illness, chest pain or discomfort, lack of strength or feeling of weakness, malaise, chills, and shaking.

• Uncommon side effects (may affect up to 1 in 100 people):

Chronic nasal infection, fungal infections, various infections (of the nose and throat, kidney, or bladder), inflammation of the membranes covering the brain, severe allergic reactions, thyroid disorders, excessive response to stimuli, memory impairment, speech difficulties, bad taste, balance disturbance, involuntary tremor, eye pain or swelling, vertigo, fluid in the middle ear, peripheral coldness, vein inflammation, nose and throat inflammation, abdominal distension, rapid skin inflammation, acute skin inflammation, cold sweat, increased skin reaction to sunlight, excessive sweating even during sleep, muscle twitching, excess protein in the urine, chest tightness, feeling of heat, feeling of burning, swelling, increased respiratory rate, changes in blood test results.

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

Red blood cell destruction, severe life-threatening allergic shock, transient stroke, stroke, low blood pressure, heart attack, blood clot in a major vein, blood clot in the main artery of the lung, fluid accumulation in the lung, positive Coombs test result, decreased oxygen saturation in blood, transfusion-related acute lung injury.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V.

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

5. Storage of KIOVIG

• 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 carton after EXP. The expiry date is the last day of the month stated.
• Do not use this medicine if you notice particles or discoloration.
• Do not store above 25°C.
• Do not freeze.
• Keep the container in the outer carton to protect from light.

6. Container Contents and Additional Information

KIOVIG Composition

• The active ingredient of KIOVIG is normal human immunoglobulin.
• 1 ml of KIOVIG contains 100 mg of human protein, of which at least 98% is immunoglobulin G (IgG).
• The other components (excipients) are glycine and water for injectable preparations.

Product Appearance andContainer Contents

KIOVIG is a solution for infusion in vials of 10, 25, 50, 100, 200, or 300 ml. The solution is transparent or slightly opalescent, colorless or pale yellow.

Not all presentations may be marketed.

Marketing Authorization Holder:

Takeda Manufacturing Austria AG

Industriestrasse 67

A-1221 Vienna

Austria

Tel.: +800 66838470

E-mail: medinfoEMEA@shire.com

Manufacturer:

Baxalta Belgium Manufacturing SA

Boulevard René Branquart, 80

B-7860 Lessines

Belgium

Date of Last Revision of this Leaflet.

Other Sources of Information

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

This information is intended only for healthcare professionals:

Method of Administration

• KIOVIG should only be administered intravenously. Other routes of administration have not been evaluated.
• KIOVIG should be infused intravenously at an initial rate of 0.5 ml/kg body weight/h for 30 minutes. If well tolerated, the infusion rate may be gradually increased to a maximum of 6 ml/kg body weight/h. Clinical data from a limited number of patients also indicate that adult patients with PID may tolerate an infusion rate of up to 8 ml/kg body weight/h.
• If dilution to lower concentrations is required prior to infusion, KIOVIG may be diluted with a 5% glucose solution to a final concentration of 50 mg/ml (5% immunoglobulin).
• Any case of adverse reaction related to infusion should be treated by reducing the infusion rate or stopping it.

Special Precautions

• Any case of adverse reaction related to infusion should be treated by reducing the infusion rate or stopping it.
• It is recommended to record the name and batch number of the product each time KIOVIG is administered.

Incompatibilities

This medicinal product must not be mixed with other medicinal products.

Special Precautions for Storage

• Immediate use after dilution is recommended. The stability of KIOVIG after dilution with a 5% glucose solution to a final concentration of 50 mg/ml (5% immunoglobulin) has been demonstrated for 21 days at 2°C to 8°C and for 28°C to 30°C; however, these studies did not include the aspect of microbial contamination and safety.

Handling and Disposal Instructions

• The product should reach room or body temperature before use.
• KIOVIG should be inspected visually before administration to verify the absence of particles and discoloration. Only a transparent or slightly opalescent and colorless or pale yellow solution should be used. Do not use if particles or discoloration are observed.
• If dilution is necessary, a 5% glucose solution is recommended. To obtain a 50 mg/ml (5%) immunoglobulin solution, KIOVIG 100 mg/ml (10%) should be diluted with an equal volume of glucose solution. The risk of microbial contamination during dilution should be minimized.
• Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

Dosing Recommendations