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PACKAGE LEAFLET: INFORMATION FOR THE USER

Subcuvta

Human Normal Immunoglobulin

160 g/l Solution for Injection

Active substance: Human Normal Immunoglobulin

In this leaflet:

1.    What SUBCUVIA is and what it is used for

2.    Before you use SUBCUVIA

3.    How to use SUBCUVIA

4.    Possible side effects

5.    Storing SUBCUVIA

6.    Further information

1. WHAT SUBCUVIA IS AND WHAT IT IS USED FOR

SUBCUVIA belongs to a class of medicines called immunoglobulins. These medicines contain antibodies which are normally found in your blood. Antibodies are proteins that help you to fight infection by neutralizing bacteria, viruses, and other foreign bodies. SUBCUVIA is used in the treatment of certain diseases that are caused by a lack of antibodies in your blood. These types of diseases are called antibody deficiency syndromes. If you do not have enough antibodies, you become vulnerable to frequent infections. Regular and sufficient doses of SUBCUVIA can correct this lack of antibodies.

Adults and children can be prescribed SUBCUVIA as antibody replacement therapy. The most common reasons for people being prescribed antibody replacement therapy are:

•    People who are born with an inability to make their own antibodies (congenital agammaglobulin-aemia),

•    People who cannot make enough own immune anti bodies (hypogammaglobulinaemia),

•    People who have a mixed group of reasons for not making enough own immune antibodies (common variable immunodeficiency),

•    People whose blood and other body systems are unable to make sufficient antibodies (severe combined immunodeficiency),

•    People who cannot make a particular class of antibody (IgG subclass deficiencies) with recurrent infections

In addition, SUBCUVIA is used for antibody replacement therapy with certain severe blood diseases, such as cancers of the bone marrow:

•    myeloma

•    chronic lymphatic leukaemia

These cancers can lead to severe secondary (acquired) antibody deficiencies and recurrent infections.

2. BEFORE YOU USE SUBCUVIA

Do NOT use SUBCUVIA You MUST NOT use SUBCUVIA

•    If you are allergic (hypersensitive) to immunoglobulins or any of the other ingredients of SUBCUVIA (see Section 6 - “What SUBCUVIA contains”)

•    You must not inject SUBCUVIA into a blood vessel (intravascularly)

•    You must not inject SUBCUVIA into a muscle (intramuscularly) if you have severe platelet deficiency (low platelets) or other blood clotting disorders.

Take special care with SUBCUVIA

The following is very important and should be

considered before you receive or use SUBCUVIA:

•    Infusion speed: the correct infusion speed is i mportant (see Section 3, HOW TO USE SUB-CUVIA). You are more likely to get side effects if the infusion is too fast.

•    Side effects are more frequent if you

-    are using SUBCUVIA for the first time

-    have received another immunoglobulin and have been switched to SUBCUVIA

-    have not used SUBCUVIA treatment for more than 8 weeks.

•    Immunoglobulin A (IgA) deficiency: if you suffer from a deficiency with anti-IgA antibodies. There is an increased risk of allergic reactions.

•    Severe allergic reactions (anaphylaxis). You may experience severe allergic reactions with a fall in blood pressure. These reactions are rare but they can occur even if you have not previously had problems with similar treatments.

•    Please tell your doctor that you have been using SUBCUVIA before you have a blood test. This is because SUBCUVIA may affect the results of the test.

•    SUBCUVIA contains 1.2 mg sodium per ml. This should be taken into account if you are on a low sodium diet.

Home treatment

Before you start home treatment you should assign a guardian person. This guardian should help you keep an eye on potential side effects. During the infusion you must look out for first signs of side effects (for further details see section 3. “HOW TO USE SUBCUVIA”). If you experience any, you or your guardian must stop the infusion immediately and contact a doctor. If you experience a severe side effect, you must seek emergency treatment immediately.

Viral Safety

When medicines are made from human blood or plasma, certain measures are put in place to prevent the spread of infection. These measures include careful selection of blood and plasma donors to make sure that people who are at risk of carrying infections are not donors. Donated blood and plasma is tested for viruses and other infections. The blood and plasma is also treated to inactivate or remove viruses. However, it cannot be guaranteed that infection will not be transmitted. This also applies to any unknown or emerging viruses or other types of infections. The measures taken are considered effective for some viruses such as human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus. However, they may not be effective against other viruses such as hepatitis A virus and parvovirus B19. Parvovirus B19 infection can be serious for pregnant women because of its potential effect on the unborn child and for individuals with immunodeficiency or increased red blood cell turnover (e.g., haemolytic anaemia). Immunoglobulins have not been associated with infections from hepatitis A and parvovirus B19.

It is strongly recommended that you keep a record of the batch number and expiry date every time you receive a dose of SUBCUVIA.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription, or if you have received a vaccination in the last 6 weeks.

•    SUBCUVIA may reduce the effect of some live virus vaccines such as measles, rubella, mumps and chicken pox. Therefore, after receiving SUBCUVIA, you may have to wait for up to 3 months before receiving certain vaccines. You may have to wait for up 1 year after receiving SUBCUVIA before you can receive a measles vaccine.

•    Do not mix SUBCUVIA with other medicinal products.

Pregnancy and breast-feeding

Please tell your doctor, if you are pregnant or breast-feeding. Your doctor will decide if SUBCUVIA may be used during pregnancy or breast-feeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

No effects on ability to drive and use machines have been observed.

3. HOW TO USE SUBCUVIA Starting of treatment

Your treatment will be started by your doctor. At first, SUBCUVIA will be injected slowly. You will then be watched carefully for at least 20 minutes to see if you have any side effects. Once the doctor has found the right dose for you, you may be allowed to give the treatment to yourself at home.

Home treatment

Your doctor will show you how to use the syringe driver, and the infusion techniques. Your doctor will also teach you how to recognize severe adverse effects and what to do if these occur. You will also be shown how to keep the treatment diary. You will be allowed to start home treatment as soon as you show that you can give yourself the treatment. You may start home treatment as long as you do not have any severe side effects.

Preparations

•    Always use SUBCUVIA exactly as your doctor has instructed you. You should check with your doctor if you are unsure.

•    Assign a guardian person who can watch you for potential side effects during the infusion and for at least 20 minutes after you received SUBCUVIA. These side effects could be a low blood pressure or allergic reaction. Your doctor will give you and your guardian detailed instructions. These include information to recognize an allergic reaction as soon as possible. Early symptoms of an allergic reaction include:

-    fall in blood pressure (hypotension)

-    increased pulse rate

-    vomiting (being sick)

-    cold sweat

-    chills

-    sensation of heat

-    hives

-    itching

-    difficulty in breathing.

During the infusion you must look out for first signs of allergic reactions. If you experience any of the above symptoms you or your guardian must stop the infusion immediately and contact a doctor. If you have severe symptoms, you must seek emergency treatment immediately.

•    You should bring the solution to room temperature (25°C) or body temperature (37°C) before use.

•    Do not use heating devices to warm up the medicine.

•    Do not use solutions that are more than just slightly cloudy. The solution will be clear and pale yellow to light brown. During storage it may show formation of slight turbidity or a small amount of particulate matter.

•    Do not reuse a vial once the stopper has been punctured.

Infusion

1.    Infusion sites are the abdomen, the thighs or the buttocks. You should position the needle at an angle of 45 to 90 degrees.

2.    Infuse SUBCUVIA subcutaneously (under the skin). You must make sure that SUBCUVIA is not infused into a blood vessel because this can lead to a shock (See Section 2 - Take special care with SUBCUVIA).

3.    Please keep strictly to the dosage and infusion speed your doctor instructed you to use. The usual starting speed is 10 ml/h/pump. The infusion speed can be increased by 1 ml/h/pump after each new infusion up to a maximum of 20 ml/h/pump. You can use more than one pump at the same time.

4.    Change the infusion site every 5 - 15 ml.

5.    Use each syringe only once.

6.    Sometimes it is not possible to give SUBCUVIA subcutaneously (under the skin). When this happens, SUBCUVIA may be given to you intramuscularly (into a muscle). Intramuscular administration must be given by your doctor or nurse.

7.    Keep a full record of SUBCUVIA dosing by attaching the self-adhesive label into your dosing diary.

Disposal

Dispose of any unused product or waste material as instructed by your doctor or pharmacist. Do not put the cover back on used needles. Put used needles, syringes and vials into the puncture-proof container and keep it out of the reach and sight of children. Dispose of the full puncture-proof container as instructed by your doctor. Never put the unused needles and syringes into your household waste bin.

If you use more SUBCUVIA than you should

You should strictly keep to the dosage and infusion speed your doctor instructed you to use. Please tell your doctor if you accidentally used more SUBCUVIA than instructed.

There are no known symptoms of an overdose.

If you forget to use SUBCUVIA

Do not infuse a double dose to make up for a forgotten dose. Just infuse your next dose as usual and make a note in your diary that you missed a dose.

If you stop using SUBCUVIA

Tell your doctor if you decide to stop treatment and the reasons why.

If you have any more questions on the use of this product, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

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

If you notice one of the following side effects, contact your doctor immediately:

•    a sudden fall in blood pressure. This side effect occurs rarely or in 1 to 10 out of 10,000 treated patients.

•    laboured breathing (dyspnoea), chest tightness, flushing of the face and skin, feeling of heat, and skin rash (urticaria). These could be signs of a severe allergic reaction (anaphylactic shock and anaphylactoid reaction) and can occur even if the patient has shown no hypersensitivity to previous administration. These side effects occur very rarely or in less than 1 out of 10,000 treated patients.

The following side effects may also occur during the use of SUBCUVIA:

Common side effects, occurring in 1 to 10 out of 100 treated patients:

•    bleeding    at    the    injection    side    (injection    site

haemorrhage)

•    injection    site    pain

•    bruising    at    the    injection    site    (injection    site

haematoma)

•    redness    at    the    injection    site    (injection    site

erythema)

•    chills

Uncommon side effects, occurring in 1 to 10 out of 1,000 treated patients:

•    dizziness

•    headache

•    nausea

•    itching at the injection site or generally (pruritus)

•    redness of the skin (erythema)

•    injection site swelling

•    pain

•    tiredness (fatigue)

•    feeling hot

Rare side effects, occurring in 1 to 10 out of

10.000    treated patients:

•    tremor

•    increased heart rate (tachycardia)

•    coldness in the extremities such as the hands or feet (peripheral coldness)

•    pain in the stomach area (abdominal pain)

•    pain in one or more joints (arthralgia)

•    stiffness in the muscles and joints (musculoskeletal stiffness)

•    pain in one or more muscles (myalgia)

•    injection site rash

•    increased levels of alanine aminotransferase

Side effects with unknown frequencies/OR: Very rare side effects, occurring in less than 1 out of

10.000    treated patients:

•    allergic reactions (hypersensitivity reactions)

•    sensation of prickling, tingling or creeping on the skin (paraesthesia)

•    abnormally low blood presure (hypotension)

•    abnormally high blood pressure (hypertension)

•    flushing

•    pallor

•    vomiting

•    swelling of the face

•    skin rash (urticaria)

•    rash with red spots covered with bumps (rash maculopapular)

•    inflammation of the skin due to an allergy (dematitis allergic)

•    excessive sweating (hyperhidrosis)

•    back pain

•    chest discomfort

•    fever (pyrexia)

•    feeling poorly (malaise)

•    injection site reaction

•    injection site urticaria

•    hardening of the injection site (injection site induration)

•    injection site warmth Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5. HOW TO STORE SUBCUVIA

•    Keep out of the reach and sight of children.

•    Do not use SUBCUVIA after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month.

•    Store at 2°C - 8°C (in a refrigerator).

•    Do not store above 25°C.

•    Do not freeze.

•    SUBCUVIA may be stored at room temperature (not more than 25°C) for up to 3 months. Record the date of transfer to room temperature and the end of the 3 month period on the outer carton. Once SUBCUVIA has been stored at room temperature, it must not be returned to the refrigerator. It must be discarded if not used by the end of the 3 month period.

•    Keep the vial in the outer carton to protect it from light.

•    Do not use SUBCUVIA if the solution appears foggy or milky. It should be clear or slightly cloudy.

•    Once a vial has been opened, the product must be used immediately.

•    Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION What SUBCUVIA contains

The active substance is human normal immunoglobulin.

It contains 16% (160 g/l) of human protein of which at least 90% is immunoglobulin G (IgG). The IgG sub class contents are:

•    IgG1 45 - 75%

•    IgG2 20 - 45%

•    IgG3 3 - 10%

•    IgG4 2 - 8%

Maximum IgA content 4.8 g/l

The other ingredients are Glycine, Sodium chloride and Water for injections.

What SUBCUVIA looks like and contents of the pack

SUBCUVIA is a solution for injection in a vial (0.8 g/5 ml or 1.6 g/10 ml; pack sizes of 1 vial or 20 vials). The liquid preparation is clear and pale yellow to light brown. Slight cloudiness or a small number of visible particles may form during storage. Do not use if the solution is more than just slightly cloudy.

Marketing Authorisation Holder

Baxter Healthcare Ltd

Caxton Way

Thetford

Norfolk

IP24 3SE

United Kingdom

Manufacturer

Baxter AG Industriestrasse 67 A-1220 Vienna Austria

This leaflet was last revised in January 2014

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

Posology and method of administration Posology

Treatment should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency.

The dosage may need to be individualised for each patient dependent on the pharmacokinetic and clinical response. The following dosage regimens are given as a guideline.

The dosage should be adjusted to maintain a trough level of at least 4 - 6 g/L of circulating IgG. The dosage regimen using the subcutaneous route should achieve a sustained level of IgG (measured before the next infusion). A loading dose of at least 0.2 - 0.5 g/kg given during the course of one week (0.1 - 0.15 g/kg bodyweight at any given day) may be required. After steady state IgG levels have been attained, maintenance doses are administered at repeated intervals to reach a cumulative monthly dose of the order of 0.4 - 0.8 g/kg. Trough levels should be measured in order to adjust the dose and dosage interval.

The subcutaneous route is the method of choice for the SUBCUVIA administration.

SUBCUVIA may also be injected by the intramuscular route. In such cases, the cumulative monthly dose should be divided up into weekly, or bi-weekly applications, in order to keep the injected volume low. To further minimize the discomfort for the patient, each single dosage may need to be injected at different anatomic sites.

Method of administration

Human normal immunoglobulin is administered via the subcutaneous or intramuscular route. SUBCUVIA should be administered via the subcutaneous route. In exceptional cases, where the subcutaneous administration is not possible, SUBCUVIA can be given intramuscularly.

The product should be brought to room or body temperature before use.

Do not use heating devices.

Subcutaneous infusion

for home treatment should be initiated by a physician experienced in the guidance of patients for home treatment. The patient must be instructed in the use of a syringe driver, infusion techniques, the keeping of treatment diary, recognition of and measures to be taken in case of severe adverse events. It is recommended to use an initial administration speed of 10 ml/h/pump.

The infusion speed can be enhanced for 1 ml/h/pump every subsequent infusion. The recommended maximum speed is 20 ml/h/pump. More than one pump can be used simultaneously. The infusion site should be changed every 5 - 15 ml.

Potential complications can often be avoided by ensuring that:

•    patients are not sensitive to human normal immunoglobulin by first injecting the product slowly.

•    patients are carefully monitored for any symptoms throughout the infusion period. In particular, patients naive to human normal immunoglobulin, patients switched from an alternative product or when there has been a long interval since the previous infusion should be monitored during the first infusion and for the first hour after the first infusion, in order to detect potential adverse signs. All other patients should be observed for at least 20 minutes after administration.

Intramuscular injection must be given by a physician or nurse.

Incompatibilities

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

SUBCUVIA is a trademark of Baxter International Inc./ Baxter Healthcare S.A. Baxter is a trademark of Baxter International Inc.

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