Kiovig

Package leaflet: Information for the user

KIOVIG, 100 mg/ml solution for infusion

Normal human immunoglobulin
Please 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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful to them.
• If you get any side effects, including any not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What KIOVIG is and what it is used for

KIOVIG belongs to a class of medicines called immunoglobulins. These medicines contain
human antibodies, which are also naturally present in blood. Antibodies help the body
fight infections, and medicines such as KIOVIG are used in patients who do not have sufficient
antibody levels in the blood and are prone to frequent infections. They may also be
used in patients who require additional antibodies for the treatment of certain inflammatory
diseases (autoimmune diseases).

KIOVIG is used for

Treatment of patients who lack sufficient antibodies (replacement therapy). There are five groups:

1. Patients with congenital antibody synthesis deficiency (primary immunodeficiency syndromes).
2. Patients affected by blood cancer (chronic lymphocytic leukemia) leading to insufficient antibody production and recurrent infections when they do not respond to preventive antibiotic therapy.
3. Patients with bone marrow cancer (multiple myeloma) and insufficient antibody production, suffering from recurrent infections that have not responded to vaccination against certain bacteria (pneumococci).
4. Children and adolescents (aged 0–18 years) born with AIDS and suffering from recurrent bacterial infections.
5. Patients with poor antibody production due to allogeneic bone marrow transplantation.

Treatment of patients with certain inflammatory diseases (immunomodulation). There are five groups:

1. Patients with low platelet counts (primary immune thrombocytopenia, ITP) who are at high risk of bleeding or who are about to undergo surgery.
2. Patients with a disease associated with widespread inflammation of nerves throughout the body (Guillain-Barré syndrome).
3. Patients with a disease causing inflammation in multiple organs of the body (Kawasaki disease).
4. Patients affected by a rare condition characterized by slowly progressive, asymmetric limb weakness without loss of sensation (multifocal motor neuropathy, MMN).
5. Patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

2. What you need to know before using KIOVIG

Do not use KIOVIG
If you are allergic to immunoglobulins or to any of the other ingredients of this medicine
(listed in section 6).
For example, if you suffer from immunoglobulin A (IgA) deficiency, this may indicate the presence of antibodies
against immunoglobulin A in your blood. Since KIOVIG contains very small amounts of
immunoglobulin A (less than 0.14 mg/ml), an allergic reaction may occur.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using KIOVIG.

Duration of monitoring during infusion

• You will be closely monitored during the infusion period with KIOVIG to ensure that no reactions occur. Your doctor will carefully adjust the infusion rate of KIOVIG according to your individual needs.
• If KIOVIG is administered at a high rate, if you have a condition with low levels of antibodies in the blood (hypo- or agammaglobulinemia), if you have never taken this medicine before, or if a long period (e.g., several weeks) has passed since your last dose, the risk of adverse effects is higher. In these cases, you will be closely monitored during the infusion and for one hour after the infusion is completed.
• If you have previously received KIOVIG and your last dose was recent, you will be observed only during the infusion and for at least 20 minutes after the infusion.

When infusion must be slowed down or stopped
In rare cases, your body may have previously reacted to specific antibodies and thus may be
sensitive to medicines containing antibodies. This occurs particularly if you have immunoglobulin A deficiency. In these rare cases, you may experience allergic reactions such as sudden
drop in blood pressure or shock, even if you have previously been treated with antibody-containing
medicines.
If you experience a reaction during KIOVIG infusion, inform your doctor immediately.
Depending on the doctor's decision, the infusion rate may be reduced or the infusion
stopped.

Specific patient groups

• Your doctor will exercise particular caution if you are overweight, elderly, diabetic, have high blood pressure, reduced blood volume (hypovolemia), or have blood vessel problems (vascular diseases). In these conditions, immunoglobulins may increase the risk of myocardial infarction, stroke, pulmonary embolism, or deep vein thrombosis, although this occurs only very rarely. Inform your doctor if you have diabetes. Although KIOVIG does not contain glucose or sucrose, it may be diluted in a specific sugar-based solution (5% glucose) which could affect your blood sugar levels.
• Your doctor will also be particularly cautious if you have or have previously had kidney problems, or if you are taking medicines that may damage the kidneys (nephrotoxic medicines), as there is a minimal risk of acute kidney failure. Inform your doctor if you have kidney disease. Your doctor will select the intravenous immunoglobulin most appropriate for your condition.

Information about the active substance in KIOVIG
KIOVIG is a medicine derived from human plasma (the liquid component of blood). When
medicines are produced from human blood or plasma, several safety measures are applied to prevent transmission of infections to patients. These include careful selection of blood and plasma donors to ensure potential carriers of infections are excluded, and testing of each donation and plasma pool to detect the presence of viruses and infections. Manufacturers of these medicines apply processing procedures that inactivate or remove viruses during production. Nevertheless, whenever medicines prepared from human blood or plasma are administered, the possibility of transmitting an infection cannot be completely ruled out. This also applies to unknown or emerging viruses or other types of infections.
The measures taken in the production of KIOVIG are considered effective against lipid-enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as against non-lipid-enveloped viruses such as hepatitis A virus and parvovirus B19. KIOVIG also contains specific antibodies that may prevent infection from hepatitis A virus and parvovirus B19.

Other medicines and KIOVIG
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
If you have been vaccinated within the last six to three months, the infusion of immunoglobulins such as KIOVIG may interfere with the effectiveness of certain live virus vaccines, such as those against measles, rubella, mumps, and varicella. Therefore, after receiving immunoglobulins, you should wait up to three months before receiving a live attenuated virus vaccine. Before receiving the measles vaccine, you should wait up to one year after receiving immunoglobulins.

Effects on blood tests
KIOVIG contains a wide variety of antibodies, some of which may affect the results of blood tests. If you undergo blood testing after receiving KIOVIG, inform the person performing the test or your doctor that you have taken this medicine.

Pregnancy, breastfeeding, and fertility

• If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
• Clinical studies with KIOVIG have not been conducted in pregnant or breastfeeding women. However, antibody-containing medicines have been used in pregnant and breastfeeding women, and no harmful effects on the course of pregnancy or the child have been observed.
• If you are breastfeeding while being treated with KIOVIG, the antibodies contained in the product may pass into breast milk. Therefore, the infant may be protected against potential infections.

Driving and using machines
During treatment with KIOVIG, patients may experience reactions (e.g., dizziness or nausea) that could affect their ability to drive or operate machinery. In such cases, wait until these symptoms have resolved before driving or operating machinery.

3. How to use KIOVIG

KIOVIG must be administered intravenously (infusion into a vein). It is administered by a physician or nurse. The dose and frequency of infusion depend on the patient's general health and body weight.
At the beginning of the infusion, KIOVIG is given at a low rate. Depending on the patient's reaction, the physician may gradually increase the infusion rate.
Use in children and adolescents
The same indications, dosage, and infusion frequency used in adults apply to children and adolescents (age: 0–18 years).
If you use more KIOVIG than you should
If you receive more KIOVIG than prescribed, the blood may become too thick (hyperviscosity). This is particularly likely in at-risk patients, such as elderly patients or those with kidney problems. Make sure to drink sufficient fluids to avoid dehydration, and inform your doctor if any medical problems occur.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. Some side effects, such as headache or flushing, may be reduced by decreasing the infusion rate.
Below is a list of side effects reported with KIOVIG:

• 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, reduced appetite, difficulty sleeping, anxiety, dizziness, migraine, numbness or tingling of the skin or of a limb, reduced sense of touch, eye inflammation, rapid heartbeat, flushing, cough, runny nose, chronic cough or wheezing (asthma), nasal congestion, sore throat, shortness of breath, diarrhea, vomiting, abdominal pain, indigestion, bruising, itching, 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 energy or feeling weak, malaise, shaking chills.
• Uncommon side effects (may affect up to 1 in 100 people): chronic nasal infection, fungal infection, various infections (of the nose and throat, kidneys or bladder), sterile inflammation of the membranes covering the brain, severe allergic reactions, thyroid disorders, excessive response to stimuli, memory impairment, speech difficulties, unusual taste in mouth, impaired balance, involuntary tremor, eye pain or swelling, dizziness, middle ear effusion, cold sensation in extremities, vein inflammation, swelling of throat and ear, abdominal distension, rapid skin swelling, acute skin inflammation, cold sweating, increased skin reaction to sunlight, excessive sweating including during sleep, muscle twitching, excess serum proteins in urine, chest tightness, feeling of warmth, burning sensation, swelling, increased respiratory rate, changes in blood test results.
• Side effects with unknown frequency (cannot be estimated from available data): destruction of red blood cells, life-threatening allergic shock, transient stroke, stroke, low blood pressure, heart attack, blood clot in a major vein, blood clot in a major artery, fluid accumulation in the lungs, positive Coombs test results, decreased oxygen saturation in the blood, transfusion-related acute lung injury.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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 KIOVIG

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the label and carton following “Exp.” The expiry date refers to the last day of the month.
• Do not use this medicine if you notice any particles or discoloration.
• Do not store above 25°C.
• Do not freeze.
• Keep the container in the outer packaging to protect the medicine from light.

6. Package contents and other information

What KIOVIG contains

• The active substance in KIOVIG is human normal immunoglobulin.
• 1 ml of KIOVIG contains 100 mg of human proteins (100 mg/ml), of which at least 98% are immunoglobulin G (IgG).
• The other components (excipients) are glycine and water for injections.

Description of the appearance of KIOVIG and package contents
KIOVIG is an infusion solution contained in glass vials of 10, 25, 50, 100, 200 or 300 ml. The solution is clear or slightly opalescent and colourless or pale yellow.
Not all presentations may be marketed.

Marketing Authorization Holder
Baxter AG
Industriestrasse 67
A-1221 Vienna
Austria
Tel.: +44(0)1256 894 959
E-mail: [email protected]

Manufacturer
Baxalta Belgium Manufacturing SA
Boulevard René Branquart, 80
B-7860 Lessines
Belgium
Baxter SA
Boulevard René Branquart 80
B-7860 Lessines
Belgium

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

The following information is intended exclusively for healthcare professionals:

Method of administration

• KIOVIG must be administered exclusively by intravenous infusion. 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 up to a maximum of 6 ml/kg body weight/h. Clinical data from a limited number of patients confirm 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 5% glucose solution to achieve a final concentration of 50 mg/ml (5% immunoglobulin).
• Only infusion-related adverse events should be managed by reducing the infusion rate or stopping the infusion.

Special precautions

• Any infusion-related adverse event should be managed by reducing the infusion rate or stopping the infusion.
• It is recommended that whenever KIOVIG is administered, the product name and batch number be recorded.

Incompatibilities
The medicinal product must not be mixed with other medicinal products.

Special storage precautions

• After dilution to lower concentrations, the product should be used immediately. The stability of KIOVIG after dilution with 5% glucose solution to a final concentration of 50 mg/ml (5% immunoglobulin) has been demonstrated for 21 days at temperatures between 2°C and 8°C as well as between 28°C and 30°C; however, these studies did not include microbial contamination and safety aspects.

Instructions for handling and disposal

• The product should be brought to room or body temperature before use.
• KIOVIG should be visually inspected for particulate matter or discoloration prior to administration. Administer only clear or slightly opalescent, colourless or pale yellow solutions. Do not use if particulate matter or discoloration is present.
• If dilution is required, a 5% glucose solution is recommended. To obtain a 50 mg/ml (5%) immunoglobulin solution, 100 mg/ml KIOVIG (10%) should be diluted with an equal volume of glucose solution. Minimizing the risk of microbial contamination during dilution is recommended.
• Any unused product or waste material should be disposed of in accordance with local regulations.

Dose recommendations

dì = day