Gammaplex 10 g, powder and solvent for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

GAMMAGARD S/D 10 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 side effects, talk to your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of this 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 naturally present in blood. Antibodies help the body 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 can also be used when additional antibodies are needed to treat certain inflammatory disorders (autoimmune diseases).

GAMMAGARD S/D 10 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 (PIDs)) 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 who have shown no response to vaccination against certain bacteria (pneumococci).

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

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

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

1. Patients who have too few 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 GAMMARD 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

Monitoring period required 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 previously received this medicine, 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 blood 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% solution (50 mg/ml) 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 care

• 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.

The protein content may increase, leading to higher blood viscosity.

Information on the Original Material of GAMMAGARD S/D

GAMMAGARD S/D is manufactured from human plasma (the liquid portion 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 the 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 other infections. In addition, manufacturers of these products incorporate several processing steps that can inactivate or remove viruses. Despite these measures, when administering medicines prepared from human blood or plasma, 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 effectiveness of these measures may be limited for non-enveloped viruses such as parvovirus B19.

Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, possibly because 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 used should be recorded to maintain a record of the batches utilized.

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 past six weeks.

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 administration of these products, 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 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 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 lead to false-positive results in tests that rely on the detection of beta-D-glucans for the diagnosis of fungal infections; this effect may persist for weeks following infusion of the product.

Pregnancy, lactation, 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 medicinal products 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 disappeared.

Gammagard S/D 10 g contains sodium and glucose

This medicine contains 668 mg of sodium (the main component of table/cooking salt) per vial. This corresponds to 34% of the maximum daily recommended 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 those with kidney or heart problems). Make sure you drink adequate fluids to avoid dehydration, and inform your doctor if you experience any health problems.

In case of overdose or accidental administration, contact the Toxicology Information Service at telephone number 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 1000 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 values (transaminases) and increased blood creatinine levels with renal failure; blood clot formation in veins leading to heart attack, stroke, lung damage, and deep vein thrombosis; joint pain; low blood pressure.

The following are adverse effects reported by some patients receiving GAMMAGARD S/D in clinical trials and during post-marketing experience:

• Very common (may affect more than 1 in 10 people): none.

• 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-like illness, anxiety, agitation, abnormal drowsiness, blurred vision, palpitations, breathing difficulty, nosebleed, diarrhea, upper abdominal pain, stomach discomfort, mouth inflammation, itching, skin rash, cold sweat, excessive sweating, back pain, muscle cramps, pain in arms and legs, chest pain, chest discomfort, abnormal sensation, feeling cold, feeling hot, flu-like symptoms, redness at injection site, leakage of medication from the vein at injection site, pain at injection site, nausea/vomiting sensation, pain, high blood pressure, blood pressure disturbances, 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, swollen lymph nodes, allergic reactions of varying severity including anaphylactic shock, nervousness, dizziness, abnormal skin sensation, involuntary tremor, seizures, brain 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 wheezing, bronchospasm, pulmonary blood vessel occlusion, pulmonary edema, digestive disturbances, abdominal pain, liver inflammation (non-transmissible), skin redness, skin rashes, 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.

If you consider any of the adverse effects you experience to be severe, or if you notice any adverse effects not listed in this leaflet, inform your doctor or pharmacist.

Reporting of adverse effects

If you experience any type of 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 Medicinal Products: 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 of GAMMAGARD S/D is normal human immunoglobulin.

GAMMAGARD S/D can be reconstituted with sterile water for injectable preparations into a 5% (50 mg/ml) or 10% (100 mg/ml) protein solution. 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 10 g vial of powder
• 192 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 summary of product characteristics was approved in January 2021.

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

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THIS INFORMATION IS INTENDED FOR 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:

Only clear or slightly opalescent, colorless or yellowish solutions should be administered after reconstitution.

Allow the vial of powder and the vial of water for injections (diluent) to reach room temperature. 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 diluent vial on a flat surface.

Use the exposed end of the spike to

pierce the diluent vial through the center of the stopper.

CAUTION: If the spike is not inserted into the center of the

stopper, it may become detached and the vacuum may be lost.

3b. Ensure the vial neck is fully seated in

the device by firmly pressing the transfer device.

Remove the protector covering the other end of the spike while

holding the transfer device. Do not touch the spike.

1. Hold the diluent vial with the transfer device attached at an angle relative to the powder vial to prevent the diluent from spilling.

Note: Do not invert the diluent vial as the diluent may spill.

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

stopper while quickly inverting the diluent vial

to prevent the diluent from spilling.

CAUTION: If the spike is not inserted into the

center of the stopper, it may become detached and the

vacuum may be lost.

5b. Ensure the vial neck is fully seated in

the device by firmly pressing the diluent vial.

1. After all the diluent has passed into the

powder vial, remove the transfer device and the empty diluent vial. Immediately rotate the concentrate vial to completely mix the contents.

CAUTION: Do not shake. Avoid foam formation.

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 diluent volume must be removed. Table 2 describes the volume of diluent to be removed from each vial to achieve a 10% solution before connecting the transfer device. Using aseptic technique, remove the unnecessary volume of diluent using a sterile hypodermic syringe and needle. Discard the syringe and needle containing the excess diluent.
  3. Using the remaining diluent in the diluent vial, follow steps 2–6 described in section A.

TABLE 2

10 g

Vial concentration

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

10% 96 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 visually inspected before administration to confirm the absence of particles and discoloration.

Disposal of unused medicine and all materials that have come into 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 gradually increase to the maximum rate, provided they have previously tolerated several infusions at intermediate infusion 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 gradually be 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 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 maintain 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