Prospecto: information for the user

Flebogamma DIF50mg/ml solution for infusion

Human normal immunoglobulin (IgIV)

Read this prospectus carefully before starting to use this medication,because it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• This medication has been prescribed only for you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist or nurse, even if they do not appear in this prospectus. See section 4.

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

2.What you need to know before starting to use Flebogamma DIF

3.How to use Flebogamma DIF

4.Possible adverse effects

5.Storage of Flebogamma DIF

6.Contents of the package and additional information

What is Flebogamma DIF

Flebogamma DIF contains normal human immunoglobulin, a highly purified protein extracted from human plasma (a part of blood from donors). This medication belongs to a class of medications called intravenous immunoglobulins. These are used to treat conditions in which the immune system does not function correctly against diseases.

What is Flebogamma DIF used for

Treatment 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 (SIP), a congenital deficiency of antibodies (group 1).

• Patients with Secondary Immunodeficiency Syndrome (SIS) in patients who suffer from severe or recurrent infections, who do not respond to antimicrobial treatment and who haveshown a deficiency of specific antibodies (PSAF)*or a serum level of <4

*PSAF= inability to double the titre of IgG antibodies against pneumococcal polysaccharide and polypeptide antigens.

Treatment of adults, children, and adolescents (2 – 18 years) who are susceptible in whom active vaccination against measles is contraindicated or not recommended.

Treatment in adults, children, and adolescents (2-18 years) with certain autoimmune disorders (immunomodulation). They are classified into five groups:

• Primary immune thrombocytopenia, when the number of platelets in the bloodstream is drastically reduced. Platelets are an important part in the coagulation process, and a reduced number of platelets can cause bleeding and bruises. This product is also used in patients with a high risk of bleeding or before a surgical intervention, to increase the number of platelets.

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

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

• Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), a rare and progressive disease that causes weakness in the limbs, numbness, pain, and fatigue.

• Multifocal Motor Neuropathy (MMN), a rare disease that causes slow, asymmetric, progressive weakness in the limbs without sensory loss.

No use Flebogamma DIF

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

• If you have a deficiency of IgA immunoglobulin in your blood or have developed antibodies to IgA.

• If you have fructose intolerance, a rare genetic disorder that consists of not producing the enzyme responsible for breaking down fructose. In babies and young children (0-2 years), hereditary fructose intolerance (HFI) may not have been diagnosed and could be fatal, so they should not receive this medication. (See special precautions on excipients at the end of this section).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Flebogamma DIF.

Some adverse reactions may occur more frequently:

• if administered at a high infusion rate.
• if you receive Flebogamma DIF for the first time, or have changed from a normal human immunoglobulin product (IgIV), or have had a long period of time (e.g. several weeks) since the last infusion. You will be closely monitored for up to one hour after the infusion to detect possible adverse reactions.

Allergic reactions are rare. These may occur in isolated cases if you do not have sufficient IgA immunoglobulin in your blood or if antibodies anti-IgA have developed.

Patients with pre-existing risk factors

Please inform your doctor if you have any other pathological condition and/or disease, as a greater control 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
• obesity
• decreased blood volume
• diseases that increase blood viscosity
• 65 years of age or older

Patients with kidney problems

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

Your doctor will consider the existing risk factors in your case and take the necessary 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 have a blood test after receiving Flebogamma DIF, please inform the analyst or your doctor that you have received this medication.

Special safety precautions

When medications are prepared from human blood or plasma, a series of measures must be taken to prevent the possible transmission of infections to patients. These measures include:

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

• analysis of each donation and plasma mixture to detect possible viruses or infections,

• inclusion of a series of steps in the processing of blood or plasma that may inactivate or eliminate viruses.

Despite these measures, when administering medications prepared from human blood or plasma, it cannot be ruled out that infections may be transmitted. This also applies to unknown or emerging viruses and other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and for non-enveloped viruses of hepatitis A and parvovirus B19.

Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, possibly because the antibodies against these infections, as contained in the medication, are protective.

It is highly recommended that each time Flebogamma DIF is administered to a patient, the name of the medication and the batch number administered (indicated on the label and box after Lot) be recorded to maintain a relationship between the patient and the product batch.

Children and adolescents

Monitor vital signs (body temperature, blood pressure, heart rate, and respiratory rate) during the infusion of Flebogamma DIF.

Use of Flebogamma DIF with other medications

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

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

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

Pregnancy and breastfeeding

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

Driving and operating machinery

Patients may experience reactions (such as dizziness or nausea) during treatment that may affect their ability to drive and 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 disorder, you should not receive this medication. Patients with HFI cannot break down fructose, which can cause severe adverse effects.

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

Flebogamma DIF contains sodium

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

Flebogamma DIF is for intravenous administration (injection into a vein). It can be administered by yourself if you have previously received complete training from hospital staff or a healthcare professional. You must perform the infusion exactly as you have been taught to avoid the presence of germs. Never administer an injection by yourself, always have a healthcare professional with experience in preparing medications, cannulation, administration, and monitoring adverse reactions present.

The dose you receive will depend on your illness and your weight and will be calculated by your doctor (see section “Instructions for Healthcare Professionals” at the end of the prospectus).

At the beginning of the infusion, you will receive Flebogamma DIF at a low 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 old

The dose in children is not considered to be different from that of adults, as it depends on the illness and the child's weight.

If you receive more Flebogamma DIF than you should

If you receive more Flebogamma DIF than you should, your body may suffer from fluid overload. This can occur especially if you are a high-risk patient, for example if you are elderly or have heart or kidney problems. Consult your doctor immediately.

If you forgot to use Flebogamma DIF

Consult your doctor or pharmacist immediately and follow their instructions.

Do not administer a double dose to compensate for a missed dose.

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

Like all medicines, Flebogamma DIF can cause side effects, although not everyone will experience them.

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

• Brisk drop in blood pressure, and in isolated cases, anaphylactic shock (whose signs are skin rash, hypotension, palpitations, wheezing while breathing, cough, sneezing, and difficulty breathing, among others), even in patients who have not shown hypersensitivity to previous administrations.
• Temporal non-infectious meningitis (whose signs are headache, fear or sensitivity to light, neck stiffness).
• Temporary reduction in the number of red blood cells in the blood (reversible hemolytic anemia/hemolysis).
• Transient skin reactions (skin adverse effects).
• Increased levels of serum creatinine (test that measures kidney function) and/or acute kidney failure (whose signs are back pain, fatigue, decreased urine output).
• Thromboembolic reactions such as myocardial infarction (pressure in the chest area with a sensation that the heart is beating very quickly), stroke (weakness in the face, arms, or legs, difficulty speaking or understanding others when they speak), pulmonary embolism (shortness of breath, chest pain, and fatigue), and deep vein thrombosis (pain and swelling in a limb).
• Acute lung injury caused by transfusion (TRALI) that causes hypoxia (lack of oxygen), dyspnea (difficulty breathing), tachypnea (rapid breathing), cyanosis (lack of oxygen in the blood), fever, and hypotension.

Other side effects:

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

• Headache
• Fever (increase in body temperature)
• Tachycardia (increase in heart rate)
• Hypotension

Occasional (may affect 1 infusion in 100):

• Bronchitis
• Nasopharyngitis
• Dizziness
• Hypertension
• Increased blood pressure
• Wheezing while breathing
• Productive cough
• Upper abdominal pain (including upper abdominal pain)
• Diarrhea
• Vomiting
• Nausea
• Urticaria
• Pruritus (itching)
• Skin rash
• Back pain
• Myalgia (muscle pain)
• Arthralgia (joint pain)
• Rigidity (sensation of shivering)
• Pain
• Reaction at the injection site
• Positive Coombs test
• Decreased blood pressure

Rare (may affect 1 infusion in 1000):

• Hypersensitivity
• Abnormal behavior
• Migraine
• Fluctuations in blood pressure
• Erythema (skin redness)
• Cough
• Asthma
• Dyspnea (difficulty breathing)
• Nasal hemorrhage
• Nasal discomfort
• Laryngeal pain
• Contact dermatitis
• Hypohidrosis (excessive sweating)
• Skin rash
• Muscle spasms
• Neck pain
• Pain in the limb
• Urinary retention
• Weakness (fatigue)
• Chest pain
• Reaction at the infusion site (skin redness, extravasation, swelling, and pain)
• Reaction at the injection site (including edema at the injection site, pain, itching, and swelling)
• Peripheral edema
• Increased alanine aminotransferase (hepatic transaminase)

Other side effects in children and adolescents

It was observed that the proportion of headache, fever, increased heart rate, and decreased blood pressure was higher in children than in adults.

Reporting of side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it ispossibleside effects that do not appear in this prospectus.You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and carton after CAD.

Do not store at a temperature above 30 °C. Do not freeze.

The solution must be transparent or slightly opalescent. Do not usethis medicationif the solution is cloudy or has sediment.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of containers and medications that you no longer need. In this way, you will help protect the environment.

Composition ofFlebogamma DIF

-The active principle is human normal immunoglobulin (IgIV). One ml contains 50mg of human normal immunoglobulin, of which at least 97% is IgG.

Each vial of 10ml contains: 0.5g of human normal immunoglobulin

Each vial of 50ml contains: 2.5g of human normal immunoglobulin

Each vial of 100ml contains: 5g of human normal immunoglobulin

Each vial of 200ml contains: 10g of human normal immunoglobulin

Each vial of 400 ml contains: 20 g of human normal immunoglobulin

The percentage 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 remaining components are sorbitol and water for injectable preparations (see section 2 for more information on components).

Appearance of the product and contents of the container

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

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

Container size: 1vial

Only some container sizes may be marketed.

Marketing authorization holder and responsible manufacturer

Instituto Grifols, S.A.

Can Guasc, 2 - Parets del Vallès

08150 Barcelona - Spain

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet: MM/AAAA

For more detailed information about this medicinal product, please visit the website of the European Medicines Agency:http://www.ema.europa.eu.

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

Dosage and administration

The dosage and administration regimen depend on the indication.

It may be necessary to individualize the administration regimen for each patient based on clinical response. The dosage based on body weight may require adjustment in patients with low body weight or obesity. The following administration regimen may be used as a guideline.

The recommended dosage is described in the following table:

Flebogamma DIF should be administered intravenously at an initial rate of0.01‑0.02ml/kg/min for the first 30 minutes. If tolerated well, the administration rate may be increased gradually to a maximum of 0.1ml/kg/min.

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

Pediatric population

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

Incompatibilities

Flebogamma DIF should not be mixed with other medications or intravenous solutions and should be administered using a separate intravenous route.

Special precautions

Sorbitol

Patients with hereditary fructose intolerance (HFI) should not receive this medication unless absolutely necessary.

Babies and children (under 2 years) may not be diagnosed with hereditary fructose intolerance (HFI). Intravenous medications (containing sorbitol/fructose) may be potentially fatal and should be contraindicated for this population unless there is an absolute clinical need and no alternative is available.

Before receiving this medication, the patient's medical history should be thoroughly reviewed for symptoms of HFI.

It is highly recommended that each time Flebogamma DIF is administered to a patient, the name of the medication and the batch number administered be recorded to maintain a relationship 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 transparent or slightly opalescent. Do not use Flebogamma DIF if the solution is turbid or contains sediment.

The disposal of unused medication and all materials that have come into contact with it should be carried out in accordance with local regulations.