Flebogamma Dif 50 mg/ml solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Flebogamma DIF 50 mg/ml solution for infusion

Human normal immunoglobulin (IVIg)

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet:

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

1. What Flebogamma DIF is and what it is used for

What Flebogamma DIF is

Flebogamma DIF contains human normal immunoglobulin, a highly purified protein derived from human plasma (a component of blood from donors). This medicine belongs to a class of medicines called intravenous immunoglobulins. These are used to treat conditions in which the immune system does not function properly in response to disease.

What Flebogamma DIF is used for

Replacement therapy in adults, children and adolescents (2–18 years) who lack sufficient antibodies (Flebogamma DIF is used in replacement therapy). There are two groups:

• Patients with Primary Immunodeficiency Syndrome (PIS), a congenital deficiency of antibodies (group 1).

• Patients with Secondary Immunodeficiency Syndrome (SIS) in patients who suffer from severe or recurrent infections that do not respond to antimicrobial treatment and who have demonstrated specific antibody deficiency (PSAF)* or a serum level of <4 g/l (group 2).

*PSAF = inability to double the IgG antibody titre in response to pneumococcal polysaccharide and polypeptide vaccines.

Treatment in adults, children and adolescents (2–18 years) at risk in whom active measles vaccination is contraindicated or not recommended.

Treatment in adults, children and adolescents (2–18 years) with certain autoimmune conditions (immunomodulation). These are classified into five groups:

• Primary immune thrombocytopenia, in which the number of platelets in the bloodstream is drastically reduced. Platelets are an important component in the blood clotting process, and a low platelet count may cause bleeding and bruising. This product is also used in patients at high risk of bleeding or prior to surgical intervention, to increase the platelet count.

• Guillain-Barré syndrome, in which the immune system attacks the nerves and prevents them from functioning properly.

• Kawasaki disease (in this case together with acetylsalicylic acid), a childhood disease in which blood vessels (arteries) throughout the body become enlarged.

• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a rare and progressive disease causing weakness in the limbs, numbness, pain and fatigue.

• Multifocal motor neuropathy (MMN), a rare disease causing slowly progressive asymmetric weakness in the limbs without sensory loss.

2. What you need to know before using Flebogamma DIF

Do not use Flebogamma DIF

• If you are allergic to human immunoglobulins or to any other component of this medicine (listed in section 6).

• If you have IgA immunodeficiency in blood or have developed antibodies to IgA.

• If you have fructose intolerance, a rare genetic condition in which the enzyme needed to break down fructose is not produced. In infants and young children (0–2 years), hereditary fructose intolerance (HFI) may be undiagnosed and could be fatal; therefore, they must not receive this medicine. (See special precautions regarding excipients at the end of this section).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Flebogamma DIF.

Some adverse reactions may occur more frequently:

• if administered at a high infusion rate,
• if you are receiving Flebogamma DIF for the first time, if you have switched from another normal human immunoglobulin product (IgIV), or if a long time has passed (e.g. several weeks) since your last infusion. You will be closely monitored for at least one hour after infusion to detect possible adverse reactions.

Allergic reactions are uncommon. These may occur in isolated cases if you have insufficient IgA-type immunoglobulins in blood or if anti-IgA antibodies have developed.

Patients with pre-existing risk factors

Please inform your doctor if you have any other medical condition and/or disease, as increased monitoring is required in patients with pre-existing risk factors for thrombotic events (blood clot formation). In particular, inform your doctor if you have:

• diabetes
• high blood pressure
• history of vascular disease or thrombotic events
• overweight
• reduced blood volume
• diseases that increase blood viscosity
• age over 65 years

Patients with kidney problems

If you have kidney disease and are receiving Flebogamma DIF for the first time, you may experience kidney problems.

Your doctor will consider existing risk factors in your case and take appropriate measures, such as reducing the infusion rate or stopping treatment.

Effects on blood tests

After receiving Flebogamma DIF, the results of certain blood tests (serological tests) may be altered for some time. If you undergo blood testing after receiving Flebogamma DIF, please inform the laboratory staff or your doctor that you have received this medication.

Special safety precautions

When medicines are prepared from human blood or plasma, several measures are taken to prevent possible transmission of infections to patients. These measures include:

• careful selection of blood and plasma donors to ensure exclusion of donors at risk of infections,

• testing of each donation and plasma pool for possible viruses or infections,

• inclusion of several steps in the manufacturing process that can inactivate or eliminate viruses.

Despite these measures, when medicines made from human blood or plasma are administered, the possibility of transmitting infections cannot be completely ruled out. This also applies to unknown or emerging viruses and 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, as well as 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 against these infections contained in the medicine are protective.

It is highly recommended that each time Flebogamma DIF is administered to a patient, the name of the medicine and the batch number (indicated on the label and box after "Lote") be recorded, in order to maintain a link between the patient and the product batch.

Children and adolescents

Vital signs (body temperature, blood pressure, heart rate, and respiratory rate) should be monitored during Flebogamma DIF infusion.

Using Flebogamma DIF with other medicines

• Inform your doctor or pharmacist if you are taking or have recently taken any other medicines.

• Effects on vaccines: Flebogamma DIF may reduce the effectiveness of certain types of vaccines (live attenuated virus vaccines). For rubella, mumps, and varicella, a period of up to 3 months should elapse after receiving this medicine before these vaccines are administered. For measles, the interval is up to 1 year.

• Concomitant use of drugs that increase water excretion from the body (loop diuretics) should be avoided during treatment with Flebogamma DIF.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using any medicine.

Driving and using machines

Patients may experience reactions (such as dizziness or nausea) during treatment that could affect their ability to drive or operate machinery.

Flebogamma DIF contains sorbitol

Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disease, this medicine must not be given. Patients with HFI cannot break down fructose, which may lead to serious adverse effects.

Consult your doctor before receiving this medicine if you (or your child) have HFI or if your child cannot consume sweet foods or drinks because they cause dizziness, vomiting, or unpleasant effects such as bloating, stomach cramps, or diarrhea.

Flebogamma DIF contains sodium

This medicine contains less than 7.35 mg of sodium (main component of table/cooking salt) per 100 ml. This corresponds to 0.37% of the maximum daily intake of 2 g of sodium recommended for adults.

3. How to use Flebogamma DIF

Flebogamma DIF is for intravenous administration (injection into a vein). You may self-administer it if you have previously received full training from hospital staff or a healthcare professional. You must perform the infusion exactly as you have been instructed in order to avoid contamination with germs. You must never administer the injection alone; a healthcare professional experienced in drug preparation, cannulation, administration, and monitoring of adverse reactions must always be present.

The dose you receive will depend on your condition and your body weight, and will be calculated by your doctor (see section “Instructions for healthcare professionals” at the end of the leaflet).

At the beginning of the infusion, you will receive Flebogamma DIF at a slow rate (0.01–0.02 ml/kg/min). If you tolerate it well, your doctor may gradually increase the infusion rate (up to 0.1 ml/kg/min).

Use in children over 2 years of age

The dose in children is not considered to differ from that in adults, as it depends on the child's condition and body weight.

If you receive more Flebogamma DIF than you should

If you receive more Flebogamma DIF than prescribed, your body may experience fluid overload. This is especially possible if you are at risk, for example if you are elderly or have cardiac or renal problems. Contact your doctor immediately.

If you forget to use Flebogamma DIF

Contact your doctor or pharmacist immediately and follow their instructions.

Do not administer a double dose to make up for a missed dose.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, Flebogamma DIF may cause adverse effects, although not everyone experiences them.

In isolated cases, the following adverse reactions have been reported with immunoglobulin preparations. Seek immediate medical help if you experience any of the following reactions during or after infusion:

• Sudden drop in blood pressure and, in isolated cases, anaphylactic shock (symptoms include skin rash, hypotension, palpitations, wheezing, cough, sneezing, and difficulty breathing, among others), even in patients who have not previously shown hypersensitivity to prior administrations.
• Cases of transient non-infectious meningitis (symptoms include headache, photophobia or sensitivity to light, and neck stiffness).
• Cases of temporary reduction in the number of red blood cells in blood (reversible hemolytic anemia/hemolysis).
• Cases of transient skin reactions (skin-related adverse effects).
• Increase in serum creatinine levels (a test measuring kidney function) and/or acute kidney failure (symptoms include lower back pain, fatigue, and reduced urine output).
• Thromboembolic reactions such as myocardial infarction (chest pressure with sensation of rapid heartbeat), stroke (weakness in facial, arm, or leg muscles, difficulty speaking or understanding speech), pulmonary embolism (shortness of breath, chest pain, and fatigue), and deep vein thrombosis (pain and swelling in a limb).
• Cases of transfusion-related acute lung injury (TRALI) causing hypoxia (lack of oxygen), dyspnea (difficulty breathing), tachypnea (rapid breathing), cyanosis (lack of oxygen in blood), fever, and hypotension.

Other adverse effects:

Frequent (may affect up to 1 in 10 infusions):

• headache
• fever (elevated body temperature)
• tachycardia (increased heart rate)
• hypotension

Uncommon (may affect up to 1 in 100 infusions):

• bronchitis
• nasopharyngitis
• dizziness
• hypertension
• increase in blood pressure
• wheezing
• productive cough
• abdominal pain (including upper abdominal pain)
• diarrhea
• vomiting
• nausea
• urticaria
• pruritus (itching)
• skin rash
• back pain
• myalgia (muscle pain)
• arthralgia (joint pain)
• rigors (chills)
• pain
• reaction at injection site
• positive Coombs test
• decrease in blood pressure

Rare (may affect up to 1 in 1,000 infusions):

• hypersensitivity
• abnormal behaviour
• migraine
• blood pressure fluctuations
• erythema (skin redness)
• cough
• asthma
• dyspnea (difficulty breathing)
• epistaxis (nosebleed)
• nasal discomfort
• laryngeal pain
• contact dermatitis
• hyperhidrosis (excessive sweating)
• skin rash
• muscle spasms
• neck pain
• limb pain
• urinary retention
• weakness (fatigue)
• chest pain
• reaction at infusion site (skin redness, extravasation, swelling, and pain)
• reaction at injection site (including injection site edema, pain, itching, and swelling)
• peripheral edema
• increased alanine aminotransferase (liver transaminase)

Other adverse effects in children and adolescents

The incidence of headache, fever, increased heart rate, and decreased blood pressure was observed to be higher in children than in adults.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Flebogamma DIF

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.

Do not store above 30 °C. Do not freeze.

The solution should be clear or slightly opalescent. Do not use this medicine if the solution is cloudy or contains sediment.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Flebogamma DIF

• The active substance is human normal immunoglobulin (IVIG). One ml contains 50 mg of human normal immunoglobulin, of which at least 97% is IgG.

Each 10 ml vial contains: 0.5 g of human normal immunoglobulin
Each 50 ml vial contains: 2.5 g of human normal immunoglobulin
Each 100 ml vial contains: 5 g of human normal immunoglobulin
Each 200 ml vial contains: 10 g of human normal immunoglobulin
Each 400 ml vial contains: 20 g of human normal immunoglobulin

The percentage distribution of IgG subclasses is approximately 66.6% IgG1, 28.5% IgG2, 2.7% IgG3, and 2.2% IgG4. The IgA content is less than 50 micrograms/ml.

• The other components are sorbitol and water for injections (see section 2 for more information on the components).

Appearance of the product and contents of the container

Flebogamma DIF is a solution for infusion. The solution is transparent or slightly opalescent, colorless or pale yellow.

Flebogamma DIF is available in vials of 0.5 g/10 ml, 2.5 g/50 ml, 5 g/100 ml, 10 g/200 ml, and 20 g/400 ml.

Pack size: 1 vial
Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Instituto Grifols, S.A.
Can Guasc, 2 - Parets del Vallès
08150 Barcelona - Spain

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet: MM/YYYY

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

This information is intended for healthcare professionals only (see section 3 for more information):

Dosage and method of administration

The dose and dosing regimen depend on the indication.

The dosing regimen may need to be individualized for each patient according to clinical response. Dosing based on body weight may require adjustment in patients with low body weight or those who are overweight. The following dosing regimen may be used as a general guide.

The recommended dosage is described in the following table:

Flebogamma DIF must be administered intravenously at an initial rate of 0.01–0.02 ml/kg/min for the first thirty minutes. If well tolerated, the infusion rate may be gradually increased up to a maximum of 0.1 ml/kg/min.

In the clinical trial conducted in patients with chronic ITP, a significant increase in mean platelet levels (64,000/µl) was achieved, although normal levels were not reached.

Paediatric population

As the dosage for each indication is based on body weight and adjusted according to the clinical response to the conditions indicated above, the dosage in children does not differ from that indicated for adults.

Incompatibilities

Flebogamma DIF must not be mixed with other medicinal products or intravenous solutions and should be administered using a separate intravenous line.

Special precautions

Sorbitol

Patients with hereditary fructose intolerance (HFI) must not receive this medicinal product unless strictly necessary.

Infants and children (under 2 years of age) may be undiagnosed for hereditary fructose intolerance (HFI). Intravenous medicinal products (containing sorbitol/fructose) may be potentially fatal and are contraindicated in this population unless there is an absolute clinical need and no alternative is available.

Before administration of this medicinal product, the patient's medical history should be carefully reviewed for symptoms of HFI.

It is highly recommended that each time Flebogamma DIF is administered, the name of the medicinal product and the batch number used should be recorded, in order to maintain traceability between the patient and the product batch.

Handling and disposal instructions

The product should reach room temperature (not exceeding 30°C) before use.

The solution should be clear or slightly opalescent. Do not use Flebogamma DIF if the solution is cloudy or contains particulate matter.

Any unused medicinal product and all materials that have come into contact with it must be disposed of in accordance with local regulations.