Gammaplex S/D 5 g, powder and solvent for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

GAMMAGARD S/D 5 g, powder and solvent for solution for infusion

Human normal immunoglobulin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• 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 GAMMAGARD S/D is and what it is used for
2. What you need to know before using GAMMAGARD S/D
3. How to use GAMMAGARD S/D
4. Possible side effects
5. How to store GAMMAGARD S/D
6. Contents of the pack and other information

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

GAMMAGARD S/D belongs to a class of medicines called immunoglobulins. These medicines contain human antibodies, which are also present in blood. Antibodies help fight infections. Medicines such as GAMMAGARD S/D are used when patients do not have enough antibodies in their blood. These patients often suffer from frequent infections. GAMMAGARD S/D may also be used when additional antibodies are needed to treat certain inflammatory disorders (autoimmune diseases).

GAMMAGARD S/D 5 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 (PID)) such as:

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

2. Patients with blood cancer (chronic lymphocytic leukemia) causing insufficient antibody production and recurrent infections when preventive antibiotic treatment has failed.

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

4. Children and adolescents (0 to 18 years) with congenital AIDS and frequent infections.

5. Patients with low antibody production following allogeneic bone marrow stem cell transplantation.

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 immune thrombocytopenia, ITP) and who are at high risk of bleeding or who are about to undergo surgery.

2. Patients with a disease causing widespread inflammation of various organs in the body (Kawasaki disease).

3. Patients with a disease characterized by widespread inflammation of nerves throughout the body (Guillain-Barré syndrome).

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

Do not use GAMMAGARD S/D

• If you are allergic (hypersensitive) to immunoglobulins or to any of the other components of this medicine (listed in section 6).
• If you have immunoglobulin A deficiency. 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 GAMMAGARD S/D infusion period to prevent allergic reactions. Your doctor will ensure that the infusion rate of GAMMAGARD S/D is appropriate for your condition.

There may be an increased risk of adverse effects:

• if GAMMAGARD S/D is administered at a high rate,
• if you have a disorder characterized by low levels of antibodies in the blood (hypo- or agammaglobulinemia),
• if you have not received this medicine before, or
• if a long period (e.g., several weeks) has passed 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 recently received GAMMAGARD S/D, you will only be observed during the infusion and for at least 20 minutes after the infusion.

When it is necessary to stop or reduce the infusion rate

In rare cases, your body may be sensitized to medicines containing antibodies. This may occur especially if you have immunoglobulin A deficiency. In these rare cases, you may experience allergic reactions such as a sudden drop in blood pressure or shock, even if you have previously received treatment with antibody-containing medicines.

• If you notice 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
• Itchy lumps or red spots on the skin
• Itching all over the body

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

Special patient groups

Your doctor should exercise extreme caution if you are overweight, elderly, diabetic, immobilized, using estrogens, have a permanent vascular catheter, or have a tendency to develop thrombosis.

Your doctor will monitor you carefully if you have:

• high blood pressure
• low blood volume (hypovolemia)
• increased blood viscosity or blood vessel disorders (vascular diseases including low cardiac output 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 very rare.

Inform your doctor if you are diabetic.

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

Patients with diabetes mellitus should be aware 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 exercise special caution

• if you have or have had kidney problems
• if you are taking medications that may harm your kidneys (nephrotoxic drugs), as there is a very rare possibility of acute kidney failure. Inform your doctor if you have or have had kidney problems.

Protein content may increase, causing higher blood viscosity

Information about the original material of GAMMAGARD S/D

GAMMAGARD S/D is manufactured from human plasma (the liquid component of blood). When medicines are prepared from human blood or plasma, a number of measures must be taken to prevent the potential transmission of infections to patients. These measures include careful selection of blood and plasma donors to ensure exclusion of donors at risk of carrying infections, and testing of each individual donation and pooled plasma for the presence of viruses or infections. Additionally, manufacturers of these products incorporate several stages in the processing of blood or plasma that can inactivate or eliminate viruses. Despite these measures, when medicines prepared 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 (HBV), and hepatitis C virus (HCV), as well as against the non-enveloped hepatitis A virus (HAV). However, the measures may have limited effectiveness against non-enveloped viruses such as parvovirus B19.

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

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

Use of GAMMAGARD S/D with other medicines

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

The infusion of immunoglobulins such as GAMMAGARD S/D may alter the effectiveness of certain live virus vaccines, such as those for measles, rubella, mumps, and varicella. Therefore, after receiving these medications, you may need to wait up to 3 months before receiving an attenuated live virus vaccine. You may need to wait up to 1 year after receiving immunoglobulins before administration of 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 are undergoing a blood test, please inform the laboratory staff or your doctor that you have been administered GAMMAGARD S/D.

Administration of Gammagard S/D may result in false-positive readings in tests that rely on the detection of beta-D-glucans for the diagnosis of fungal infections; this effect may persist for several weeks following infusion of the product.

Pregnancy, breastfeeding, and fertility

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

• Clinical trials with GAMMAGARD S/D have not been conducted in pregnant or breastfeeding women. Years of clinical experience with antibody-containing medicines have shown that harmful effects during pregnancy or on the child are not expected.
• If you are breastfeeding, antibodies from GAMMAGARD S/D may be present 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 could affect their ability to drive and operate machinery.

If this were to happen, wait until the reactions have subsided.

Gammagard S/D 5 g contains sodium and glucose

This medicine contains 334 mg of sodium (the main component of table/cooking salt) per vial. This corresponds to 7% of the maximum recommended daily sodium intake for an adult.

This medicine contains glucose. Patients with diabetes mellitus should be aware 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, which may affect their blood sugar levels.

3. How to use GAMMAGARD S/D

GAMMAGARD S/D is for intravenous administration (injection into a vein). It will be administered to you by your doctor or nurse. The dose and frequency of infusion may vary depending on your condition and body weight.

At the beginning of the infusion, you will receive GAMMAGARD S/D at a low rate. Your doctor may gradually increase the infusion rate depending on how well you tolerate it.

Use in children

In children (0 to 18 years of age), the same indications, doses, and frequency of infusion are used as in adults.

If you use more GAMMAGARD S/D than you should

If you receive more GAMMAGARD S/D than recommended, your blood may thicken (hyperviscosity). The thicker the blood becomes, the more difficult it is for it to flow through the blood vessels in your body, resulting in reduced oxygen delivery to vital organs such as the brain, lungs, etc. This is especially likely to occur in at-risk patients (for example, elderly patients or patients with kidney or heart problems). Make sure you drink adequate fluids to avoid dehydration and inform your doctor if you have any health problems.

In case of overdose or accidental administration, contact the Toxicology Information Service. Telephone: 915 620 420.

4. Possible adverse effects

Like all medicines, GAMMAGARD S/D may cause adverse effects, although not everyone experiences them. However, possible adverse effects can be reduced by decreasing the infusion rate.

The following adverse effects may generally occur after treatment with immunoglobulins (medicines such as GAMMAGARD S/D):

• Common (may affect up to 1 in 10 people): chills, headache, fever, vomiting, nausea.
• Uncommon (may affect up to 1 in 100 people): mild lower back pain.
• Rare (may affect up to 1 in 1,000 people): cases of sudden drop in blood pressure, eczema-like symptoms (transient skin reactions).
• Frequency not known (cannot be estimated from available data): allergic reactions, even in patients who have not previously shown reactions to infusions; temporary inflammation of the membranes surrounding the brain (reversible aseptic meningitis); temporary reduction in the number of red blood cells in blood; transient increases in liver function test values (transaminases) and increased blood creatinine levels and renal failure; formation of blood clots in veins resulting in heart attack, stroke, lung damage, and deep vein thrombosis; joint pain; low blood pressure.

The following adverse effects have been reported by some patients treated with GAMMAGARD S/D in clinical trials and during post-marketing experience:

• Common (may affect up to 1 in 10 people): headache, flushing, nausea, vomiting, fatigue, chills, fever.
• Uncommon (may affect up to 1 in 100 people): flu, anxiety, restlessness, abnormal drowsiness, blurred vision, palpitations, difficulty breathing, nosebleed, diarrhea, upper abdominal pain, stomach discomfort, mouth inflammation, itching, skin rash, cold sweat, excessive sweating, back pain, muscle cramps, arm and leg pain, chest pain, chest discomfort, abnormal sensation, feeling cold, feeling hot, flu-like symptoms, redness at injection site, leakage of medication from the infusion site, pain at injection site, nausea/vomiting sensation, pain, high blood pressure, blood pressure changes, loss of appetite.
• Frequency not known (cannot be estimated from available data): inflammation of the brain membranes not caused by bacterial infection, destruction of red blood cells, decreased number of red blood cells, decreased platelet count, lymph node swelling, allergic reactions of varying severity including anaphylactic shock, nervousness, dizziness, abnormal skin sensation, involuntary tremor, seizures, cerebral hemorrhage, stroke (transient), migraine, loss of consciousness, light intolerance, visual disturbance, eye pain, central retinal vessel occlusion, heart attack, bluish discoloration of the skin, increased heart rate, decreased heart rate, high blood pressure, pallor, low blood pressure, vein inflammation, blood vessel occlusion, cough, throat tightness, decreased blood oxygen levels, hyperventilation, chest tightness, bronchospasm, pulmonary vessel occlusion, pulmonary edema, digestive disturbance, abdominal pain, liver inflammation (non-transmissible), skin redness, skin eruptions, skin inflammation, allergic inflammation of the deep skin layers, muscle and joint pain, renal failure, generalized weakness, body tissue swelling, injection and infusion site reactions, positive Coombs test result.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of GAMMAGARD S/D

• Keep out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the container after EXP. The expiry date refers to 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 container in the outer packaging to protect it from light.

6. Contents of the container and additional information

Composition of GAMMAGARD S/D

The active substance in GAMMAGARD S/D is human normal immunoglobulin.

GAMMAGARD S/D can be reconstituted with sterile water for injections to prepare a protein solution at 5% (50 mg/ml) or 10% (100 mg/ml). At least 90% is immunoglobulin G (IgG).

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

Appearance of the product and contents of the pack

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

Each pack contains

• one vial of 5 g powder
• 96 ml of water for injections
• one sterile transfer device
• one 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
Tel: +34 91 790 42 22

This leaflet was approved in January 2021.

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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THIS INFORMATION IS INTENDED FOR MEDICAL OR HEALTHCARE PROFESSIONALS ONLY

Special precautions for storage

Chemical and physical in-use stability of reconstituted GAMMAGARD S/D has been demonstrated for 24 hours at room temperature. From a microbiological standpoint, the product should be used immediately; the time and conditions of storage prior to use are the responsibility of the user and should normally not exceed 24 hours at 2–8°C, provided reconstitution has been carried out under controlled and validated aseptic conditions.

Reconstitution: Use aseptic technique:

After reconstitution, only clear or slightly opalescent, colorless or yellowish solutions should be administered.

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

• 5% solution
  1. Remove the caps from the vials and disinfect the stoppers with a germicidal solution.
  2. Remove the protector covering the spike of the transfer device. Do not touch the spike.

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

Use the exposed end of the spike to puncture the solvent vial through the center of the stopper.

CAUTION: if the spike is not inserted into the center of the stopper, the stopper may become dislodged and the vacuum lost.

3b. Ensure the neck of the vial is fully seated by firmly pressing the transfer device down.

Remove the protector covering the other end of the spike while holding the transfer device. Do not touch the spike.

4. Hold the solvent vial with the transfer device attached at an angle relative to the powder vial to prevent solvent from leaking out.

Note: do not place the solvent vial upside down, as the solvent may spill.

5a. Puncture the powder vial through the center of the stopper while quickly inverting the solvent vial to prevent leakage of solvent.

CAUTION: if the spike is not inserted into the center of the stopper, the stopper may become dislodged and the vacuum lost.

5b. Ensure the neck of the vial is fully seated by firmly pressing the solvent vial.

6. After all the solvent has passed into the powder vial, remove the transfer device and the empty solvent vial. Immediately rotate the concentrate vial to fully mix the contents.

CAUTION: do not shake. Avoid foaming.

After single use, discard the transfer device.

• 10% solution
  1. Remove the caps from the vials and disinfect the stoppers with a germicidal solution.
  2. To prepare a 10% solution, half of the solvent volume must be removed. Table 2 describes the volume of solvent to be removed from each vial to achieve a 10% solution before connecting the transfer device. Using aseptic technique, remove the unnecessary volume of solvent using a sterile hypodermic syringe and needle. Discard the syringe and needle containing the excess solvent.
  3. Using the residual solvent in the solvent vial, follow steps 2–6 described in section A.

TABLE 2

5 g

Vial concentration

5% For 5% reconstitution, do not remove any solvent

10% 48 ml

Administration: Use aseptic technique

Follow the instructions for use provided in the leaflet accompanying the administration set included in the pack. 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.

Complete dissolution should be achieved within 30 minutes.

The resulting solution should be clear or slightly opalescent and colorless or yellowish. Do not use solutions that are cloudy or contain sediment. The reconstituted product should be inspected visually before administration to confirm the absence of particles and discoloration.

Disposal of unused medicine and all materials that have been in contact with it must be carried out in accordance with local regulations.

Discard the transfer device after single use.

Route of administration

Intravenous route.

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

GAMMAGARD S/D 5% (50 mg/ml) must 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, start treatment at the lowest infusion rate and then gradually increase to the maximum rate, provided they have previously tolerated several infusions at intermediate rates.

If well tolerated, the infusion rate of the 5% solution may be gradually increased up 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 initially be low to maintain a comparable IgG protein infusion rate. In many patients, the infusion rate of the 10% solution may be gradually increased up to 8 ml/kg/h. The infusion rate should be individually adjusted according to patient tolerability.

Special precautions

Any adverse reaction related to the infusion should be managed by reducing or stopping the infusion.

Each time GAMMAGARD S/D is administered, it is recommended to record the product name and batch number.

Incompatibilities

GAMMAGARD S/D must not be mixed with other medicinal products. It is recommended to administer GAMMAGARD S/D separately from other medications the patient may be receiving.

Recommended dosage

INDICATION	DOSE	INJECTION/INFUSION FREQUENCY
Replacement therapy in primary immunodeficiency Replacement therapy in secondary immunodeficiency Congenital AIDS Hypogammaglobulinemia (< 4 g/l) in patients who have received an allogeneic hematopoietic stem cell transplant	Initial dose: 0.4 – 0.8 g/kg Maintenance: 0.2–0.8 g/kg 0.2–0.4 g/kg 0.2–0.4 g/kg 0.2–0.4 g/kg	every 3–4 weeks to achieve a trough IgG level of at least 5–6 g/l every 3–4 weeks to achieve a trough IgG level of at least 5–6 g/l every 3–4 weeks every 3–4 weeks to achieve a trough IgG level above 5 g/l
Immunomodulation: Primary immune thrombocytopenia Guillain-Barré syndrome Kawasaki disease	0.8–1 g/kg or 0.4 g/kg/day 0.4 g/kg/day 1.6–2 g/kg or 2 g/kg	on day 1, may be repeated once within the following three days for 2–5 days for 5 days in several doses over 2–5 days, together with acetylsalicylic acid as a single dose, together with acetylsalicylic acid