Product Information for the User

GAMMAGARD S/D 10 g, powder and solvent for solution for infusion

Human Normal Immunoglobulin

Read this entire product information carefully before starting to use the product,because it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

1. What is GAMMAGARD S/D and what is it used for

2. What you need to know before starting to use GAMMAGARD S/D

3. How to use GAMMAGARD S/D

4. Possible adverse effects

5. Storage of GAMMAGARD S/D

6. Contents of the pack and additional information

GAMMAGARD S/Dbelongs to a class of medications called immunoglobulins. These medications contain human antibodies, which are also present in the blood. Antibodies help to fight infections. Medications likeGAMMAGARD S/Dare used when there are not enough antibodies in the blood. These patients often suffer from frequent infections.GAMMAGARD S/Dcan also be used when additional antibodies are needed for the treatment of certain inflammatory disorders (autoimmune diseases).

GAMMAGARD S/D10 g is used for

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

1.Patients with a congenital lack of antibody production (primary immunodeficiency syndromes (IDP)) such as:

• congenital agammaglobulinemia or hypogammaglobulinemia,
• common variable immunodeficiency,
• severe combined immunodeficiencies,
• Wiskott-Aldrich syndrome

2.Patients with blood cancer (chronic lymphocytic leukemia) that causes a lack of antibody production and recurrent infections when preventive antibiotic treatment has failed.

3Patients with bone marrow cancer (multiple myeloma) and lack of antibody production with recurrent infections in whom response to vaccine against certain bacteria (pneumococci) has failed.

4Children and adolescents (0 to18 years) with congenital HIV infection and frequent infections.

5Patients with low antibody production after a bone marrow cell transplant from another person.

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

1.Patients who do not have enough platelets in the blood (idiopathic/primary thrombocytopenic purpura, PTI) and with a high risk of bleeding or who are about to undergo a surgical procedure soon.

2.Patients with a disease that causes multiple organ inflammation in the body (Kawasaki disease).

3.Patients with a disease characterized by multiple nerve inflammation throughout the body (Guillain Barré syndrome).

No useGAMMAGARDS/D

• If you are allergic (hypersensitive) to immunoglobulins or to any of the other components of this medication (listed in section 6).
• If you have a deficiency of immunoglobulin A. You may have anti-immunoglobulin A antibodies in your blood. GAMMAGARD S/D contains very small amounts of immunoglobulin A and you may develop an allergic reaction.

Warnings and precautions

Required monitoring period during infusion

• You will be closely monitored during the infusion period of GAMMAGARD S/D to prevent an allergic reaction. Your doctor will ensure that the infusion rate of GAMMAGARD S/D is appropriate for your case.

You may be at a higher risk of adverse effects:

• if GAMMAGARD S/D is administered at a high rate,
• if you have a condition characterized by low levels of antibodies in the blood (hypogammaglobulinemia),
• if you have not received this medication before or
• if it has been a long time (for example, several weeks) since the last time you received it.

In these cases, you will be closely monitored during the infusion and for one hour after the infusion has ended, as there may be a higher risk of adverse effects.

If you have received GAMMAGARD S/D recently, you will only be observed during the infusion and for at least 20 minutes after the infusion.

When to stop or reduce the infusion rate

In rare cases, your body may be sensitized to medications containing antibodies. This can occur, especially if you have a deficiency of immunoglobulin A. In these rare cases, you may experience allergic reactions such as a sudden drop in blood pressure or shock, even if you have received this medication before.

• If you experience any of the following symptoms, inform your doctor or nurse immediately:
• Sudden wheezing, difficulty breathing, or chest tightness
• Headache
• Fever
• Swelling of the eyelids, face, lips, or blood vessels
• Blisters or red spots with itching on the skin
• Itching all over the body

Depending on your doctor's decision, the infusion rate may be reduced or stopped.

Special patient groups

Your doctor must take extra precautions if you are overweight, elderly, diabetic, immobile, using estrogen, have a permanent vascular catheter, or are prone to thrombosis.

Your doctor will closely monitor you if you have:

• high blood pressure
• low blood volume (hypovolemia)
• increased blood viscosity or vascular problems (vascular diseases including heart failure or thrombotic episodes)
• excessive coagulation or coagulation disorders

In these cases, immunoglobulins may increase the risk of myocardial infarction, stroke, pulmonary embolism, or deep vein thrombosis, although this is rare.

Inform your doctor if you are diabetic.

This medication contains glucose. GAMMAGARD S/D does not contain sucrose or maltose.

Patients with diabetes mellitus should note that a 5% (50 mg/ml) solution of GAMMAGARD S/D contains 400 mg of glucose per gram of IgG. A 70 kg patient receiving a dose of 1 g/kg of IgG would receive 28 grams of glucose or 112 calories. This may affect your blood sugar level.

Your doctor will also take special care if you have or have had kidney problems

• if you receive medications that may damage your kidneys (nephrotoxic medications), as there is a rare risk of acute renal failure. Inform your doctor if you have or have had kidney problems.

The protein content may increase, causing increased blood viscosity

Information about the original material of GAMMAGARD S/D

GAMMAGARD S/D is manufactured from human plasma (the liquid part of the blood). When medications are made from blood or human plasma, a number 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 infection and the analysis of each donation and plasma mixture to detect possible viruses or infections. Manufacturers of these products also include 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 blood or human plasma, it cannot be ruled out that infections may be transmitted. This applies also to unknown or emerging viruses and other types of infections.

The measures taken are considered effective for encapsulated viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), and for non-encapsulated hepatitis A virus (HAV). The measures taken may have limited value for non-encapsulated viruses such as parvovirus B19.

Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections possibly because the antibodies against these infections, which are present in the product, are protective.

It is recommended that each time you receive GAMMAGARD S/D, the name of the medication and batch number administered be recorded to maintain a record of the batches used.

Use of GAMMAGARD S/D with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication or if you have been vaccinated in the last six weeks.

The infusion of immunoglobulins such as GAMMAGARD S/D may alter the effectiveness of some live virus vaccines such as measles, rubella, mumps, and varicella. Therefore, you may need to wait until 3 months after receiving these medications before receiving a live attenuated virus vaccine. You may need to wait until 1 year after receiving immunoglobulins before receiving the measles vaccine.

Effects on blood tests

GAMMAGARD S/D contains a wide variety of different antibodies, some of which may interfere with blood tests. If you have a blood test, please inform the analyst or your doctor that you have received GAMMAGARD S/D.

The administration of Gammagard S/D may result in false-positive readings in tests that depend on the detection of beta-D-glucans for the diagnosis of fungal infections; this may persist for several weeks after the infusion of the product.

Pregnancy, lactation, and fertility

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

• No clinical trials have been conducted with GAMMAGARD S/D in pregnant women or breastfeeding women. Clinical experience with antibody-containing medications has shown that adverse effects are not expected during pregnancy or for the child.
• If you are breastfeeding, the antibodies in GAMMAGARD S/D may be found in breast milk. Therefore, your baby may be protected against certain infections.
• The effects of GAMMAGARD S/D on fertility have not been established.

Driving and operating machinery

Patients may experience reactions (e.g., dizziness or nausea) during treatment with GAMMAGARD S/D that may affect their ability to drive and operate machinery.

If this occurs, wait until the reactions have disappeared.

Gammagard S/D 10 g containssodium and glucose

This medication contains 668 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 34% of the recommended daily maximum sodium intake for an adult.

This medication contains glucose. Patients with diabetes mellitus should note that a 5% (50 mg/ml) solution of GAMMAGARD S/D contains 400 mg of glucose per gram of IgG. A 70 kg patient receiving a dose of 1 g/kg of IgG would receive 28 grams of glucose or 112 calories. This may affect your blood sugar level.

GAMMAGARDS/Dis for intravenous administration (intravenous injection). It will be administered by your doctor or nurse. The dose and infusion frequency may vary depending on your condition and body weight.

At the beginning of the infusion, you will receive GAMMAGARDS/Dat a low rate. Your doctor may gradually increase the infusion rate depending on whether you tolerate it well.

Use in children

In children (0 to18 years) the same indications, doses, and infusion frequencies are used as in adults.

If you use moreGAMMAGARDS/Dthan you should

If you receive moreGAMMAGARDS/Dthan you should, the blood may thicken (hyperviscosity). The more the blood thickens, the harder it is for it to be transported through the blood vessels of your body, therefore, less oxygen will be carried to vital organs, such as the brain, lungs, etc. This may occur especially in high-risk patients (for example, elderly patients or patients with kidney or heart problems). Make sure to take the right liquids to avoid dehydration and inform your doctor if you have any health problems.

In case of overdose or accidental administration, consult the Toxicological Information Service. Phone 915 620 420.

Like all medicines,GAMMAGARDS/Dcan cause side effects,although not everyone will experience them. However, possible side effects can be reduced by decreasing the infusion rate.

The following side effects may occur generally after treatment with immunoglobulins (medicines such as GAMMAGARDS/D):

• Frequent (may affect up to 1 in 10 people):chills, headache, fever, vomiting, nausea.
• Possible (may affect up to 1 in 100 people): mild lower back pain.
• Rare(may affect up to 1 in 1000 people):cases of sudden drop in blood pressure, symptoms similar to eczema (transient skin reactions).
• Unknown frequency (cannot be estimated from available data):allergic reactions, even in patients who have not had reactions to previous infusions; reversible aseptic meningitis; temporary reduction in the number of red blood cells in the blood; transient increases in liver function values (transaminases) and creatinine levels in the blood and kidney failure; formation of blood clots in veins that have resulted in heart attack, stroke, lung damage, and deep vein thrombosis; joint pain; low blood pressure.

The following side effects are described below, which some patients have reported withGAMMAGARDS/Din clinical trials and side effects reported during post-marketing experience:

• Frequent (may affect up to 1 in 10 people): headache, redness, nausea, vomiting, fatigue, chills, fever.
• Possible (may affect up to 1 in 100 people): flu, anxiety, agitation, abnormal drowsiness, blurred vision, feeling heartbeats, difficulty breathing, nasal bleeding, diarrhea, upper abdominal pain, stomach discomfort, inflammation of the mouth, itching, skin rashes, cold sweats, excessive sweating, back pain, muscle cramps, arm and leg pain, chest pain, chest discomfort, abnormal sensations, feeling cold, feeling hot, flu-like symptoms, redness at the injection site, medication leakage from the injection site, injection site pain, nausea/vomiting sensation, pain, high blood pressure, blood pressure alterations, loss of appetite.
• Unknown frequency (cannot be estimated from available data): inflammation of the brain membranes not caused by bacterial infection, red blood cell destruction, decrease in red blood cell count, decrease in platelet count, lymph node inflammation, allergic reactions of all severity, including anaphylactic shock, nervousness, dizziness, abnormal skin sensations, involuntary tremors, seizures, cerebral hemorrhage, transient ischemic stroke, migraine, loss of consciousness, light intolerance, visual disturbances, eye pain, central retinal artery occlusion, heart attack, blue discoloration of the skin, tachycardia, bradycardia, high blood pressure, pallor, low blood pressure, vein inflammation, vessel occlusion, cough, throat constriction, decreased blood oxygen levels, hyperventilation, chest palpitations, respiratory tract spasms, pulmonary vessel occlusion, pulmonary edema, digestive disturbances, abdominal pain, non-transmissible liver inflammation, skin redness, skin eruptions, skin inflammation, deep skin allergic inflammation, muscle and joint pain, kidney failure, generalized weakness, body tissue swelling, injection and infusion site reactions, positive Coombs test result.

If you consider that any of the side effects you are experiencing are severe or if you notice any side effect not mentioned in this prospectus, inform your doctor or pharmacist.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for 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 medicine.

• Keep out of sight and reach of children.
• Do not use this medication after the expiration date shown on the packaging after CAD. The expiration date is the last day of that month.
• Do not use if particles or discoloration are observed.
• Do not store above 25°C.
• Do not freeze.

Keep the packaging in the outer container to protect it from light.

Composition ofGAMMAGARD S/D

The active ingredient ofGAMMAGARD S/Dis normal human immunoglobulin.

GAMMAGARD S/Dcan be reconstituted with sterile water for injection as a 5% protein solution (50 mg/ml) or a 10% protein solution (100 mg/ml). At least 90% is immunoglobulin G (IgG).

The other components are human albumin, glycine, sodium chloride, and monohydrate glucose.

Appearance of the product and contents of the package

GAMMAGARD S/D is a white or slightly yellowish lyophilized powder, substantially free of visible foreign particles. GAMMAGARD S/D is available in 5 g and 10 g packages.

Each package contains

• a vial of 10 g powder
• 192 ml of water for injection
• a sterile transfer device
• a sterile administration set with filter

Marketing authorization holder and manufacturer:

Marketing authorization holder:

Baxalta Innovations GmbH

Industriestrasse 67

1221 Vienna

Austria

Manufacturer:

Baxalta Belgium Manufacturing SA

Boulevard René Branquart, 80 (Lessines)

B-7860-Belgium

Local representative:

Takeda Farmacéutica España S.A.

Calle Albacete, 5, 9th floor,

Edificio Los Cubos

28027 Madrid

Spain

Phone: +34 91 790 42 22

This leaflet was approved in January 2021.

The detailed and updated information on 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 ONLY FOR DOCTORS OR HEALTHCARE PROFESSIONALS

Special precautions during storage

GAMMAGARD S/D has been shown to be stable in chemical and physical use for 24 hours at room temperature. From a microbiological point of view, the product should be used immediately. The time and storage conditions before use are the responsibility of the user and should not normally exceed 24 hours at 2-8°C, when the reconstitution has been carried out in controlled and validated aseptic conditions.

Reconstitution: Use an aseptic technique:

After reconstitution, only transparent or slightly opalescent and colorless or yellowish solutions will be administered.

Bring the vial of powder and the vial of water for injection (solvent) to room temperature. Maintain this temperature until the dissolution is complete.

A.Solution at 5%

1. Remove the protectors from the vials and clean the stoppers with germicidal solution.

2.Remove the protector that covers the needle of the transfer device. Do not touch the needle.

3a. Place the vial of solvent on a flat surface.

Use the exposed end of the needle to

perforate the vial of solvent through the center of the stopper.

WARNING: If the needle is not inserted in the center of the

stopper, it may come loose and the vacuum will be lost.

3b. Ensure that the neck of the vial is fully seated in

The transfer device by pressing firmly on the transfer device.

Remove the protector that covers the other end of the needle while

holding the transfer device. Do not touch the needle.

4. Maintain the vial of solvent with the transfer device connected at an angle with respect to the vial of powder to prevent the solvent from spilling.

NOTE: Do not place the vial of solvent down as the solvent may spill.

5a. Perforate the vial of powder through the center of

the stopper while quickly inverting the vial of solvent

to prevent the solvent from spilling.

WARNING: If the needle is not inserted in the

center of the stopper, it may come loose and the

vacuum will be lost.

5b. Ensure that the neck of the vial is fully seated in

the transfer device by pressing firmly on the vial of solvent.

6. After all the solvent has passed into the

vial of powder, remove the transfer device and the empty vial of solvent. Immediately turn the vial of concentrate to mix the contents completely.

WARNING: Do not shake. Avoid foam formation.

After a single use, discard the transfer device.

B. Solution at 10%

1. Remove the protectors from the vials and clean the stoppers with germicidal solution.
2. To prepare a 10% solution, it is necessary to extract half of the solvent volume. Table 2 describes the solvent volume to be extracted from each vial to obtain a 10% solution before connecting the transfer device. Using an aseptic technique, remove the unnecessary solvent volume using a sterile hypodermic syringe and needle. Discard the syringe and needle containing the solvent not required.
3. Using the residual solvent in the solvent vial, follow steps 2-6 described in section A.

TABLE 2

10 g

Concentrationvial

5%For reconstitution at 5% do not extract any solvent volume

10%96 ml

Administration. Use an aseptic technique

Follow the instructions for use of the administration set included in the package. If another administration set is used, ensure it contains a similar filter.

Instructions for use and handling

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

The complete dissolution should be achieved in 30 minutes.

The resulting solution should be transparent or slightly opalescent and colorless or yellowish. Do not use solutions that are turbid or contain sediments. The reconstituted product should be visually inspected before administration to verify the absence of particles and coloration.

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

Discard the administration set after a single use.

Administration route

Intravenous.

If possible, it is recommended to administer the 10% solution of GAMMAGARD S/D through the antecubital veins. This may reduce the likelihood of discomfort at the infusion site.

GAMMAGARD S/D at 5% (50 mg/ml) should be administered intravenously at an initial rate of 0.5 ml/kg/h. In general, it is recommended that patients receiving GAMMAGARD S/D for the first time or switching from another intravenous immunoglobulin to GAMMAGARD S/D, initiate treatment at the lowest infusion rate and then increase to the maximum rate if previously tolerated at intermediate infusion rates.

If tolerated well, the infusion rate of the 5% solution can be gradually increased to a maximum of 4 ml/kg/h. When switching from a 5% solution to a 10% solution, the infusion rate of the 10% solution should be initially low to maintain comparable IgG protein delivery. In many patients, it is possible to gradually increase the infusion rate of the 10% solution to 8 ml/kg/h. The infusion rate will be adjusted individually according to the patient's tolerance.

Special precautions

Incompatibilities

GAMMAGARD S/D should not be mixed with other medications. It is recommended to administer GAMMAGARD S/D separately from other medications received by the patient.