Package Insert: Information for the User

Gamunex 100mg/ml Infusion Solution

Normal Human Immunoglobulin (IgIV)

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others who may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section4.

Contents of the Package and Additional Information

What isGamunex

Gamunex contains highly purified normal human immunoglobulin (antibodies) as a protein extracted from human plasma (a part of the blood of donors).This medication belongs to a group of medications called intravenous immunoglobulins, which are used to treat diseases in which the body's defense system that allows fighting diseases does not function correctly.

For what it is usedGamunex

Treatment in adults, children, and adolescents (0-18 years) who lack sufficient antibodies (replacement therapy) such as:

• Patients with primary immunodeficiency syndrome (SIP), a congenital deficiency of antibodies.
• Patients with acquired immunodeficiency (AID) with severe or recurrent infections, ineffective antibiotic treatment, and demonstrated deficiency of specific antibodies or a serum IgG level <4 g/l.

Treatment in adults, children, and adolescents (0-18 years) who are susceptible and have been exposed to measles or have a risk of future exposure to measles and in whom active immunization against measles is contraindicated or not recommended.

Treatment in adults, children, and adolescents (0-18 years) with certain autoimmune diseases (immunomodulation). They are classified into five groups:

• Primary immune thrombocytopenia, a condition in which the number of platelets in the bloodstream is drastically reduced. Platelets are an important part of the coagulation process, and a reduced number of platelets can cause unwanted bleeding and bruising. This medication is also used in patients with a high risk of bleeding or before a surgical intervention, to correct the number of platelets.
• Guillain-Barré syndrome, a condition in which the immune system attacks the nerves and prevents them from functioning correctly.
• Kawasaki disease (in this case, in combination 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 gradual and progressive weakness in the limbs without sensory loss.

Treatment in adults 18 years or older with:

Severe acute exacerbations of myasthenia gravis. Myasthenia gravis is a disease that causes muscle weakness; exacerbations mainly affect swallowing, speech, and breathing.

No useGamunex

• If you are allergic to normal human immunoglobulins or any of the other components of this medication (including those listed in section6);
• If you do not have sufficient IgA immunoglobulins in your blood and have developed antibodies against IgA.

Warnings and Precautions

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

Reactions to Infusion and Hypersensitivity

Certain adverse reactions may be related to the infusion rate. Therefore, the recommended infusion rate should be followed (see“Information for Healthcare Professionals” at the end of this leaflet).

Certain adverse effects may occur more frequently:

• at high infusion rates;
• in patients with complete absence of gamma globulins or low levels of gamma globulin (agammaglobulinemia or hypogammaglobulinemia) with or without IgA deficiency;
• in patients receiving normal human immunoglobulin for the first time or, in rare cases, when changing the immunoglobulin medication or after a prolonged period without treatment.

The possible complications can often be avoided by ensuring that:

• You are not hypersensitive to human immunoglobulin by administering the initial infusion of Gamunex slowly,
• You are closely monitored for any symptoms during the infusion period. Especially if it is the first time you receive human immunoglobulin, if you have been changed from another immunoglobulin or if you have been without treatment for a certain period, you should be monitored for possible adverse effects during the first infusion and for one hour after the infusion.

In case of adverse effects, the infusion rate should be reduced or the infusion should be suspended until the symptoms disappear. If the symptoms persist even after suspending the infusion, appropriate treatment should be started. In case of anaphylactic shock (anaphylactic shock with a strong drop in blood pressure), the treatment with the medication should be immediately interrupted and standard medical treatment for shock should be initiated.

Patients with Renal Problems and Other Risk Factors

Cases of renal dysfunction and acute renal failure have been reported in relation to the intravenous administration of immunoglobulins. You are at special risk if you have certain risk factors such as pre-existing renal dysfunction (renal insufficiency), diabetes (diabetes mellitus), or reduced blood volume (hypovolemia). Other circumstances that are considered risk factors are obesity or simultaneous treatment with medications that are harmful to the kidneys and/or if you are over 65years old. In any case, you should take the following precautions:

• Drink plenty of fluids to ensure adequate fluid intake before starting treatment;
• Your doctor should monitor the amount of urine and measure renal function;
• Do not use certain medications that can increase urine production (thiazide diuretics) simultaneously.

The infusion rate in your case should be as slow as possible and the immunoglobulin should be used at the lowest possible concentration. If renal dysfunction occurs, your doctor will consider suspending treatment with immunoglobulin.

Hemolysis (Abnormal Destruction of Red Blood Cells)

It is frequently reported that immunoglobulins increase the risk of destruction of red blood cells (hemolysis) in adults and children. If you are administered high doses of IgIV on the same day or over several days and your blood group is A, B, or AB and/or you have an underlying inflammatory condition, you may be at higher risk of red blood cell destruction (hemolysis).

In post-marketing reports, it has been observed that high-dose IgIV indications in children, especially Kawasaki disease, are associated with a higher number of reports of hemolytic reactions than in other IgIV indications in children.

You should see a doctor if you develop pallor (pale skin), lethargy (feeling of weakness), dark urine, shortness of breath, or palpitations (rapid heart rate).

Cases of renal insufficiency associated with hemolysis with a fatal outcome have been reported.

Information on Safety with Respect to Infections

When medications are manufactured from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These measures include:

• Meticulous selection of blood or plasma donors to ensure that those with a risk of transmitting infections are excluded,
• Analysis of each donation and plasma mixtures to detect possible viruses or infections,
• Inclusion of steps in the blood or plasma processing that can 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 HIV, hepatitis B virus, and hepatitis C virus. The measures taken may have limited value for non-enveloped viruses such as hepatitis A virus and/or parvovirus B19. Immunoglobulins have not been associated with infections by hepatitis A virus or parvovirus B19, possibly because the antibodies against these infections, which are contained in the product, are protective.

This medication contains less than 1mmol of sodium (23mg) per single dose (up to a maximum of 2g/kg); this is, essentially “sodium-free”.

It is strongly recommended that, each time you are administered a dose of this medication, you note the name and batch number of the product, in order to maintain a record of the batches used.

Other Medications and Gamunex

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

You should avoid concomitant use of medications that increase the elimination of water from your body (thiazide diuretics) during treatment with Gamunex.

Effects on Vaccines: Gamunex may reduce the effectiveness of certain types of vaccines (live attenuated virus vaccines). In the case of measles, mumps, and chickenpox, a period of up to 3months should elapse between administration of this medication and administration of these vaccines. In the case of measles, the period may be up to 1year.

Pregnancy and Breastfeeding

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

Driving and Operating Machinery

You may experience dizziness or other reactions that may affect your ability to drive and operate machinery. If this occurs, you should wait until these symptoms disappear before driving or operating machinery.

The doctor will inject Gamunex into your veins (intravenous administration).

The dose you receive will depend on your disease and body weight, and will be determined by your doctor (see the section “Information for Healthcare Professionals” at the end of this leaflet).

At the beginning of the infusion, you will receive Gamunex at a slow rate. Then, depending on how you feel, the doctor may gradually increase the infusion rate.

If you interrupt treatment with Gamunex

If you interrupt treatment with this medication, your clinical condition may worsen. Talk to your treating doctor if you want to prematurely interrupt treatment with this medication.

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

Like all medicines,this medicinecan cause side effects, although not everyone will experience them.

In rare and isolated cases, the following side effects have been reported with immunoglobulin preparations.Seek immediate medical attention if you experience any of the following side effects during or after infusion:

• Sudden drop in blood pressure, and in isolated cases, anaphylactic shock (whose signs are hives, low blood pressure, rapid or irregular heartbeat, wheezing, cough, sneezing, and difficulty breathing, among others), even if you have not shown any allergic reaction in a previous administration.
• Temporal non-infectious meningitis (whose signs are headache, fear or intolerance to light, neck stiffness).
• Transient decrease in the number of red blood cells in the blood (reversible hemolytic/hemolysis).
• Transient skin reactions.
• Increased serum creatinine levels (a test that measures kidney function) and/or acute kidney failure (whose signs are lower back pain, fatigue, decreased urine output).
• Thromboembolic reactions such as, for example, myocardial infarction (pressure around the chest with a sensation that the heart is beating too quickly), stroke (muscle weakness in the face, arm, or leg, problems speaking or understanding what others are saying), pulmonary embolism (shortness of breath, chest pain, and fatigue), deep vein thrombosis (pain and swelling in a limb).
• Acute transfusion-related lung injury (TRALI) that causes hypoxia (lack of oxygen), difficulty breathing, rapid breathing, blue discoloration of the skin or mucous membranes, fever, and low blood pressure.

In clinical trials conducted with Gamunex, the following side effects were observed:

The following side effects were frequent (can affect up to 1 in 10 infusions):

• Headache
• Fever

The following side effects were infrequent (can affect up to 1 in 100 infusions):

• Dizziness
• Urticaria (hives, redness, itching of the skin)
• Pruritus (itching)
• Hives
• Nausea
• Vomiting
• High blood pressure
• Pharyngitis (inflammation of the throat)
• Cough
• Stuffy nose
• Wheezing
• Joint pain
• Back pain
• Flu-like syndrome
• Fatigue
• Chills
• Asthenia (weakness)
• Muscle pain

The following side effects wererare(can affect up to 1 in 1,000 infusions):

• Hemolytic anemia (destruction of red blood cells)
• Dyspnea (difficulty breathing)
• Sinusitis
• Dermatitis (inflammation of the skin) or contact dermatitis
• Angina (chest pain)
• Discomfort
• Reaction at the injection site
• Urethritis (pain or difficulty urinating)
• Upper respiratory tract viral infection (disease caused by an acute infection that affects the upper respiratory tract, including the nose, paranasal sinuses, and throat)
• Lymphocytosis (increase in the number of a specific type of white blood cell)
• Hypersensitivity (allergic reaction)
• Photophobia (sensitivity of the eyes to light)
• Hypertensive crisis (sudden increase in blood pressure)
• Hypemia (increase in blood flow)
• Hemoglobinuria (abnormally high concentrations of the protein that transports oxygen in the blood in the urine)
• Increased blood pressure
• Presence of free hemoglobin (hemoglobin circulating outside of red blood cells)
• Increased red blood cell sedimentation rate (increase in the rate of settling of red blood cells in a test tube)

What measures should be taken in case of side effects

If side effects occur, the infusion rate should be reduced or the infusion should be suspended until the signs of the side effects have disappeared. If the signs persist even after suspending the infusion, appropriate treatment should be administered.

In the case of a severe hypersensitivity reaction with a drop in blood pressure and dyspnea to the point of presenting a severe generalized allergic reaction (anaphylactic shock), the use of this medication should be immediately suspended and appropriate measures should be taken.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSpanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box and on the vial. The shelf life is 3 years.

Store in refrigerator (2 - 8°C). Do not freeze. Keep the vial in the outer box.

The medication can be stored in its outer box for a single period of up to 6 months at room temperature (maximum 25°C). In this case, the medication's shelf life expires at the end of these 6 months, regardless of the original expiration date. The new expiration date must be noted on the outer box. However, the new expiration date must not be later than the expiration date printed. It cannot be refrigerated again.

Once the individual package is opened, the contents must be used immediately. Any remainder must be discarded. It is not permitted to continue storing the medication, not even in the refrigerator, due to possible germ invasion.

Composition of Gamunex

The active principle is normal human immunoglobulin (IgIV). One ml of this medication contains 100mg of protein with a content of IgG of at least 98%. In water for injection.

A vial of 10ml contains: 1g of normal human immunoglobulin

A vial of 50ml contains: 5g of normal human immunoglobulin

A vial of 100ml contains: 10g of normal human immunoglobulin

A vial of 200ml contains: 20g of normal human immunoglobulin

A vial of 400ml contains: 40g of normal human immunoglobulin

The percentage of IgG subclasses is approximately 62.8% (IgG1), 29.7% (IgG2), 4.8% (IgG3) and 2.7% (IgG4).

The maximum content of IgA is 84 micrograms/ml.

The other components are glycine and water for injection.

Appearance of the product and contents of the package

Gamunex is a perfusion solution. The solution is transparent to slightly opalescent and colorless to pale yellow.

Gamunexis presented in vial sizes of 10ml, 50ml, 100ml, 200ml and 400ml. The box contains a glass vial with a stopper (chlorobutyl), a label with a detachable part that becomes a handle and a leaflet.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

Grifols Deutschland GmbH
Colmarer Straße 22
60528 Frankfurt
Germany

Tel.:+49 69/660 593 100

Responsible for manufacturing:

Instituto Grifols, S.A.

Can Guasc, 2 – Parets del Vallès

08150 Barcelona

Spain

Local representative:

Instituto Grifols, S.A.

Can Guasc, 2 – Parets del Vallès

08150 Barcelona

Spain

This medication is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Germany, Austria, Belgium, Cyprus, Ireland, Luxembourg, Netherlands, Poland, Portugal, United Kingdom (Northern Ireland):Gamunex 10% 100mg/ml

Denmark, Slovakia, Spain, Finland, France, Hungary, Italy, Norway, Czech Republic, Sweden:Gamunex 100mg/ml

Greece:Gaminex 10% 100mg/ml

Last review date of this leaflet:September 2022.

The detailed information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

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This information is intended solely for healthcare professionals:

Use only transparent or slightly opalescent and colorless or pale yellow perfusion solutions free of particles – do not agitate. Before perfusion, allow Gamunex to reach room temperature or body temperature (e.g. by placing it in a water bath at a maximum temperature of 37°C).

The vials are supplied with a label with a detachable handle (Fig.1). After introducing the perfusion equipment (Fig.2), invert the vial and fold back the part of the label corresponding to the handle (Fig.3).Press firmly with your fingerto create afoldin each side where the handle joins the rest of the label (Fig.4). Hang the vial from the hanger using the resulting handle (Fig.5).

Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5

Dosage and administration

The dose and dosing regimen depend on the indication.

It may be necessary to individualize the dose for each patient based on clinical response.The dose based on body weight may need to be adjusted in patients with low weight or obesity.The following dosing regimens are provided as a guide.

The recommended dosage is summarized in the following table:

Administration

By intravenous route.

Normal human immunoglobulin should be administered by intravenous route at an initial rate of 0.6-1.2ml/kg/h for 0.5h.In case of adverse reaction, the rate of administration should be reduced or the perfusion interrupted.If well tolerated, the rate of administration can be gradually increased to a maximum of 4.8-8.4ml/kg/h.

Pediatric population

The dosage in children and adolescents (0-18years) is not different from that of adults, as the dosage for each indication is calculated based on body weight and adjusted according to the clinical outcome of the aforementioned diseases.

Gamunex should not be mixed with other perfusion solutions or with other medications. If it is necessary to dilute before perfusion, a 50mg/ml glucose solution can be used. Do not dilute with saline solutions.

It should be avoided to administer Gamunex and heparin simultaneously through a single-lumen administration device.

The routes through which Gamunex is perfused can be irrigated with a 50mg/ml glucose solution or with a 9mg/ml sodium chloride solution, and should not be irrigated with heparin.

The heparinized route through which Gamunex has been administered should be irrigated with a 50mg/ml glucose solution or with a 9mg/ml sodium chloride solution, and should not be irrigated with heparin.