KIOVIG 100 mg/ml solution for infusion

KIOVIG belongs to a class of medications called immunoglobulins. These medicines contain human antibodies, which are also present in your blood. Antibodies help your body to fight infections. Medicines like KIOVIG are used in patients who do not have enough antibodies in their blood and tend to get frequent infections. They can also be used in patients who need additional antibodies for the cure of certain inflammatory disorders (autoimmune diseases).

KIOVIG is used for

Treatment of patients who do not have sufficient antibodies (replacement therapy). There are five groups:

1. Patients with inborn lack of antibody production (primary immunodeficiency syndromes).

2. Patients with a cancer of the blood (chronic lymphocytic leukaemia) that leads to a lack of antibody production and recurrent infections when preventative antibiotics have failed.

3. Patients with cancer of the bone marrow (multiple myeloma) and lack of antibody production with recurrent infections who have failed to respond to a vaccine against certain bacteria (pneumococci).

4. Children and adolescents (age 0 to 18) with AIDS from birth and recurrent bacterial infections.

5. Patients with low antibody production following transplantation of bone marrow cells from another person.

Treatment of patients with certain inflammatory disorders (immunomodulation). There are three groups:

1. Patients who do not have enough blood platelets (primary immune thrombocytopenia, ITP), and who are at high risk of bleeding or will have surgery in the near future.

2. Patients with a disease that is associated with multiple inflammations of the nerves in the whole body (Guillain Barré syndrome).

3. Patients with a disease which results in multiple inflammations of several organs of the body (Kawasaki disease).

KIOVIG must not be used

If you are allergic (hypersensitive) to immunoglobulins or to any other ingredient of KIOVIG.

For example, if you have an immunoglobulin A deficiency, you may have antibodies against immunoglobulin A in your blood. Since KIOVIG contains trace amounts of immunoglobulin A (less than 0.14 mg/ml), you might get an allergic reaction.

Take special care with KIOVIG

How long monitoring is required during the infusion

• You will be carefully observed during the infusion period with KIOVIG to make sure that you do not suffer a reaction. Your doctor will make sure that the rate at which KIOVIG is infused is suitable for you.
• If KIOVIG is administered at a high rate, if you suffer from a condition with low antibody levels in your blood (hypo- or agammaglobulinemia), if you have not received this medicine before or if there has been a long interval (e.g. several weeks) since you last received it, there may be a higher risk of side effects. In such cases, you will be closely monitored during your infusion and for an hour after your infusion has stopped.
• If you have already received KIOVIG previously and received the last treatment recently, then you will only be observed during the infusion and for at least 20 minutes after your infusion.

When slowing or stopping the infusion may be required

In rare cases your body may have previously reacted to specific antibodies and therefore will be sensitive to medicines containing antibodies. This may happen particularly if you suffer from immunoglobulin A deficiency. In these rare cases, you may get allergic reactions such as a sudden fall in blood pressure or shock even if you have already received treatment with medicines containing antibodies in the past.
If you experience a reaction during the infusion of KIOVIG, tell your doctor immediately. Depending on your doctor?s decision the rate of infusion can be slowed or the infusion can be stopped altogether.

Special patient groups

• Your doctor will take special care if you are overweight, elderly, diabetic, or if you suffer from high blood pressure, low blood volume (hypovolaemia), or problems with your blood vessels (vascular diseases). In these conditions, immunoglobulins may increase the risk of cardiac infarction, stroke, lung embolism, or deep vein thrombosis, although only in very rare cases. Tell your doctor if you are diabetic. Although KIOVIG does not contain sugar, it may be diluted with a special sugar solution (5% glucose), which could affect your blood sugar level.
• Your doctor will also take special care if you have or had previously problems with your kidneys, or if you receive medicinal products that may harm your kidney (nephrotoxic medicinal products), as there is a very rare chance of acute kidney failure. Please tell your doctor if you have a kidney disorder. Your doctor will choose the appropriate intravenous immunoglobulin for you.

Information on the source material of KIOVIG

KIOVIG is made from human plasma (the liquid part of blood). When medicines are made from human blood or plasma, a number of measures are put in place to prevent infections being passed on to patients. These include careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded, and the testing of each donation and pools of plasma for signs of virus/infections. Manufacturers of these products also include steps in the processing of the blood or plasma that can inactivate or remove viruses. Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging 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 the non-enveloped hepatitis A virus and parvovirus B19. KIOVIG also contains certain antibodies that can prevent an infection with hepatitis A virus and parvovirus B19.

Taking other medicines

• Please inform your doctor if you are taking, or have recently taken any other medicines, including medicines obtained without a prescription.
• If you have received a vaccination during the last six weeks and up to three months, the infusion of immunoglobulins like KIOVIG may impair the effect of some live virus vaccines such as measles, rubella, mumps and chicken pox. Therefore, after receiving immunoglobulins you may have to wait up to 3 months before receiving your live-attenuated vaccine. You may have to wait for up to 1 year after receiving immunoglobulins before you receive your measles vaccine.

Effects on blood tests

KIOVIG contains a wide variety of different antibodies, some of which can affect blood tests. If you have a blood test after receiving KIOVIG, please inform the person taking your blood or your doctor that you have received the medication.

Pregnancy and breast-feeding

• Please inform your doctor if you are pregnant or breast-feeding. Your doctor will decide if KIOVIG may be used during pregnancy and breast-feeding.
• No clinical trials have been made with KIOVIG in pregnant or breast-feeding women. However, medicines that contain antibodies have been used in pregnant or breast-feeding women, and it has been shown that there are no harmful effects on the course of pregnancy or the baby to be expected.
• If you are breast-feeding and receive KIOVIG, the antibodies of the medicine can also be found in the breast milk. Therefore, your baby may be protected from certain infections.

Driving and using machines

Patients may experience reactions (for example dizziness or nausea) during the treatment with KIOVIG, which might affect the ability to drive and use machines. If this happens, you should wait until the reactions have disappeared.

KIOVIG is intended for intravenous administration (infusion into a vein). It is given to you by your doctor or nurse. Dose and frequency of the infusion will vary depending on your condition and your body weight.

At the beginning of your infusion you will receive KIOVIG at a slow rate. Dependent on how comfortable you are, your doctor may then gradually increase the infusion rate.

Use in children

The same indications, dose and frequency of infusion as for adults apply for children (age 0 to 18).

If you use more KIOVIG than you should

If you get more KIOVIG than you should, your blood may become too thick (hyperviscous). This could particularly happen when you are a patient at risk, e.g. an elderly patient or a patient having problems with your kidneys. Be sure that you take adequate fluids so you are not dehydrated and notify your physician if you are known to have medical problems.

Like all medicines, KIOVIG can cause side effects, although not everybody gets them. Certain side effects, e.g. headache or flushing, may be reduced by slowing the infusion rate.

Below is a list of side effects reported with KIOVIG:

• Very common side effects (affects more than 1 user in 10): headache and fever.
• Common side effects (affects 1 to 10 users in 100): Bronchitis, common cold, dizziness, migraine, vertigo, rapid heartbeat, flushing, high blood pressure, cough, runny nose, diarrhoea, nausea, vomiting, itching, rash and hives, pain in your back, muscles, arms or legs, tiredness, influenza-like illness, pain and swelling at the infusion site, stiffness.
• Uncommon side effects (affects 1 to 10 users in 1,000): Chronic infection of the nose, fungal infections, various infections (of the nose and throat, kidney or bladder), low red blood cell count, swollen lymph glands, disorder of the thyroid, anxiety, memory impairment, burning sensation, difficulty in speaking, unusual taste in the mouth, difficulty in sleeping, eye inflammation, eye pain or swelling, fluid in middle ear, peripheral coldness, vein inflammation, chronic cough or wheezing (asthma), ear and throat swelling, sore throat, rapid swelling of the skin, acute inflammation of the skin, cold sweat, contusion, muscle cramps, chest tightness, feeling hot, indisposition, changes to blood test results.
• Rare side effects (affects 1 to 10 users in 10,000): Sterile inflammation of the layers lining the brain.
• Frequency not known (cannot be estimated from available data): Destruction of red blood cells, serious allergic reaction including life-threatening allergic shock, transient stroke, involuntary trembling, blood clot in a major vein, low blood pressure, accumulation of fluid in the lung, shortness of breath, abdominal pain, excessive sweating, chest pain, positive result of Coombs test, decreased oxygen saturation in blood, transfusion-related acute lung injury.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

• Keep out of the reach and sight of children.
• Do not use KIOVIG after the expiry date which is printed on the label and carton after EXP. The expiry date refers to the last day of that month.
• Do not use if particulate matter or discolouration is observed.
• Store in a refrigerator (2°C ? 8°C).
• Do not freeze.
• Keep the container in the outer carton in order to protect from light.
• KIOVIG may be stored at room temperature (not more than 25°C) for up to 1 year. Record date of transfer to room temperature and the end of the 1 year period on the outer carton. Once stored at room temperature KIOVIG must not be returned to the refrigerator and must be discarded, if not used by the end of the 1 year period.

What KIOVIG contains

The active substance of KIOVIG is human normal immunoglobulin.
1 ml of KIOVIG contains 100 mg of human protein of which at least 98% is immunoglobulin G (IgG). The other ingredients are glycine and water for injections.

What KIOVIG looks like and contents of the pack

KIOVIG is a solution for infusion in 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 Authorisation Holder

Baxter AG
Industriestrasse 67
A-1221 Vienna
Austria

Manufacturer

Baxter S.A.
Boulevard René Branquart, 80
B-7860 Lessines
Belgium

For any further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiqueBelgiëBelgien Baxter Belgium SPRL Bd. de la PlainePleinlaan 5 B-1050 BruxellesBrusselBrüssel TélTel 32 2 650 1711 Luxembourg Baxter Belgium SPRL Bd. de la Plaine 5 B-1050 Bruxelles, Belgique TélTel 32 2 650 1711

Magyarország Baxter Hungary Kft Népfürd u. 22 H-1138 Budapest Tel. 361 202 19 80 . 45 2, . 2 1404 , Te. 359 2 9808482

eská republika BAXTER CZECH spol.s.r.o. Karla Englie 32016CZ-150 00 Praha 5 Tel. 420 225 774 111 Malta Baxter Healthcare Ltd Wallingford Road Compton Berkshire RG20 7QW, United Kingdom Tel. 44 1635 206345

Nederland Baxter B.V. Kobaltweg 49 NL-3542 CE Utrecht Tel 31 30 2488911 Ko Baxter Hellas ... 34 GR-163 41 30-210-99 87 000

Danmark Baxter AS Gydevang 43 DK-3450 Allerød Tlf 45 48 16 64 00 Norge Baxter AS Gjerdrumsvei 11 N-0484 Oslo Tlf 47 22 58 4800

Deutschland Baxter Deutschland GmbH Edisonstraße 4 D-85716 Unterschleißheim Tel 49 89 31701 0 Österreich Baxter Healthcare GmbH Stella-Klein-Löw-Weg 15 A-1020 Wien Tel. 43 1 71120 0

Polska Baxter Polska Sp. z o.o. ul. Kruczkowskiego 8 PL-00-380 Warszawa Tel. 48 22 4883 777 Eesti AS Oriola Kungla 2 EE-76505 Saue Harjumaa Tel. 372 6 515 100

Baxter Hellas ... 34 GR-163 41 30 210 99 87 000 Portugal Baxter Médico Farmacêutica Lda Sintra Business Park Zona Industrial da Abrunheira, Edifício 10 P-2710-089 Sintra Tel 351 21 9252500

España Baxter S.L. Pouet de Camilo, 2E-46394 Ribarroja del Turia Valencia Tel 34 96 2722800 România FARMACEUTICA REMEDIA S.A. B-dul Metalurgiei, nr. 78, sector 4, 041836, Bucuresti, România Tel-Fax 40 21 321 16 40

France Baxter S.A.S 6 Avenue Louis Pasteur F-78310 Maurepas Tél 33 1 3461 5050 Slovenija Baxter d.o.o. elezna cesta 18 SI-1000 Ljubljana Tel. 386 1 420 16 80

Ireland Baxter Healthcare Ltd Unit 7 Deansgrange Industrial Estate IRL Blackrock, Dublin Tel 353 1 2065500 Slovenská republika Baxter AG, o. z. Dúbravská cesta 2 SK-841 04 Bratislava Tel 421 2 59418455

Ísland Icepharma hf Lynghalsi 13 IS-110 Reykjavík Sími 354 540 8000 SuomiFinland Baxter Oy PL 270 Valimotie 15 A FIN-00381 Helsinki PuhTel 358 9 8621111

Italia Baxter S.p.A. Piazzale dellIndustria 20 I-00144 Roma Tel 39 06 324911 Sverige Baxter Medical AB Torshamnsgatan 35 S-164 40 Kista Tel 46 8 6326400

Latvija Baxter AG Latvijas filile Dzelzavas iela 117 RGA LV-1021 Tel. 371 6 7784784 United Kingdom Baxter Healthcare Ltd Wallingford Road Compton Berkshire RG20 7QW Tel 44 1635 206345

Lietuva

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Tel.: + 370 5 269 16 91

This leaflet was last approved in

The following information is intended for medical or healthcare professionals only:

Method of administration

• KIOVIG must 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 bodyweight/hour for 30 minutes. If well tolerated, the rate of administration may gradually be increased to a maximum of 6 ml/kg bodyweight/hour. Clinical data obtained from a limited number of patients also indicate that adult PID patients may tolerate an infusion rate of up to 8 ml/kg BW/hr.
• If dilution to lower concentrations is required prior to infusion, KIOVIG may be diluted with 5% glucose solution to a final concentration of 50 mg/ml (5% immunoglobulin).
• Any infusion-related adverse events should be treated by lowering infusion rates or by stopping the infusion.

Special precautions

• Any infusion-related adverse events should be treated by lowering the infusion rate or by stopping the infusion.
• It is recommended that every time KIOVIG is administered, the name and batch number of the product is recorded.

Incompatibilities

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

Special precautions for storage

• After dilution to lower concentrations, immediate use is recommended. The in-use 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 as well as at 28°C to 30°C; however, these studies did not include the microbial contamination and safety aspects.

Instructions for handling and disposal

• The product must be brought to room or body temperature before use.
• KIOVIG should be inspected visually for particulate matter and discoloration prior to administration. Only clear to slightly opalescent and colourless to pale yellow solutions are to be administered. Do not use if particulate matter or discolouration is observed.
• If dilution is required, 5% glucose solution is recommended. For obtaining an immunoglobulin solution of 50 mg/ml (5%), KIOVIG 100 mg/ml (10%) should be diluted with an equal volume of the glucose solution. It is recommended that during dilution the risk of microbial contamination is minimised.
• Any unused product or waste material should be disposed of in accordance with local requirements.

Dose recommendations

Indication Dose Frequency of injections Replacement therapy in primary immunodeficiency - starting dose 0.4 0.8 gkg thereafter every 3 4 weeks to obtain IgG 0.2 0.8 gkg trough level of at least 5 6 gl 0.2 0.4 gkg Replacement therapy in secondary immunodeficiency every 3 4 weeks to obtain IgG trough level of at least 5 6 gl Children and adolescents with AIDS 0.2 0.4 gkg every 3 4 weeks 0.2 0.4 gkg every 3 4 weeks to obtain IgG trough level above 5gl Hypogammaglobulinaemia 4 gl in patients after allogeneic haematopoietic stem cell transplantation Immunomodulation Primary immune thrombocytopenia 0.8 1 gkg on day 1, possibly repeated once within 3 days or 0.4 gkgd for 2 5 days Guillain Barré syndrome 0.4 gkgd for 5 days Kawasaki disease 1.6 2 gkg in divided doses for 2 5 days in association with acetylsalicylic acid or 2 gkg in one dose in association with acetylsalicylic acid d day