Gamunex

Package leaflet: Information for the user

Gamunex

100 mg/ml solution for infusion
normal human immunoglobulin (IVIg)
Please 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.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Gamunex is and what it is used for
2. What you need to know before using Gamunex
3. How to use Gamunex
4. Possible side effects
5. How to store Gamunex
6. Contents of the pack and other information

1. What Gamunex is and what it is used for

What Gamunex is
Gamunex contains normal human immunoglobulin (antibodies) as a highly purified protein extracted from human plasma (a component of blood from donors). This medicine belongs to a group of medicines called intravenous immunoglobulins, used in the treatment of conditions in which the body's defense system against diseases does not function properly.

What Gamunex is used for
Treatment of adults, children and adolescents (0–18 years) who do not have sufficient levels of antibodies (replacement therapy), such as:

• Patients with primary immunodeficiency syndromes (PID), a congenital deficiency of antibodies
• Patients with acquired immunodeficiency (SID) with severe or recurrent infections, ineffective antimicrobial treatment, and demonstrated inability to produce specific antibodies or serum IgG levels < 4 g/L

Treatment of susceptible adults, children and adolescents (0–18 years) who have been exposed to measles or are at risk of measles exposure, and in whom active measles vaccination is not indicated or contraindicated.

Treatment of adults, children and adolescents (0–18 years) with certain autoimmune disorders (immunomodulation). There are five groups:

• Primary immune thrombocytopenia (ITP), a condition in which the number of platelets in the bloodstream is greatly reduced. Platelets play an important role in the blood clotting process, and a low platelet count may cause unwanted bleeding and bruising. The medicine is also used in patients at high risk of bleeding, or prior to surgery, to correct platelet count.
• Guillain-Barré syndrome, in which the immune system damages nerves and impairs their proper function.
• Kawasaki disease (in this case together with acetylsalicylic acid therapy), a childhood illness in which blood vessels (arteries) throughout the body become inflamed and dilated.
• Chronic inflammatory demyelinating polyneuropathy (CIDP), a rare and progressive disease causing limb weakness, numbness, pain and fatigue.
• Multifocal motor neuropathy (MMN), a rare disease causing slowly progressive weakening of the limbs without sensory loss.

Treatment of adults aged 18 years and older with:

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

2. What you should know before using Gamunex

Do not use Gamunex

• If you are allergic to normal human immunoglobulin or to any of the other ingredients of this medicine (listed in section 6).
• If you have very low levels of immunoglobulin A (IgA) in your blood and have developed antibodies against IgA.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Gamunex.
Infusion-related reactions and hypersensitivity
Some adverse effects may be related to the rate of infusion. Therefore, the recommended infusion rate must be followed (see “Information for healthcare professionals” at the end of this leaflet).
Some adverse effects may occur more frequently:

• if the infusion rate is too high,
• in patients with complete absence of gammaglobulins or low levels of gammaglobulins (agammaglobulinemia or hypogammaglobulinemia), with or without IgA deficiency,
• in patients receiving normal human immunoglobulin for the first time, or, rarely, when switching from another immunoglobulin product, or after a prolonged interval without treatment.

Potential complications can often be avoided by ensuring:

• that you are not hypersensitive to human immunoglobulin, by initially administering Gamunex slowly.
• that you are closely monitored for symptoms during the infusion period. In particular, if you are receiving human immunoglobulin for the first time, if you switch immunoglobulin products, or if you have not received treatment for a period of time, you should be closely observed for possible adverse effects during the first infusion and for one hour thereafter.

If adverse effects occur, the infusion rate should be reduced or the infusion stopped until symptoms resolve. If symptoms persist after stopping the infusion, appropriate treatment should be initiated. In case of an anaphylactic shock reaction (anaphylactic shock with severe drop in blood pressure), treatment with the medicine must be stopped immediately and standard medical therapy for shock should be initiated.

Patients with kidney problems and other risk factors
Cases of impaired kidney function and acute kidney failure have been reported in association with the administration of immunoglobulins intravenously. You are at particular risk if you have certain risk factors, such as pre-existing kidney dysfunction (kidney failure), diabetes (diabetes mellitus), or reduced blood volume (hypovolemia). Other conditions considered risk factors include obesity, concomitant use of medicines that are harmful to the kidneys, and/or age over 65 years. In any case, the following precautions should be taken:

• Drink sufficient fluids to ensure adequate hydration before starting therapy.
• Your doctor should monitor urine output and measure kidney function.
• Do not use certain medicines that increase urine production (loop diuretics) at the same time. The infusion rate in your case should be as low as possible, and the immunoglobulin product should be used at the lowest possible concentration. If kidney function impairment occurs, your doctor will consider whether to discontinue immunoglobulin treatment.

Hemolysis (abnormal breakdown of red blood cells)
It is commonly reported that immunoglobulins increase the risk of red blood cell destruction (hemolysis) in both adults and children. If you have received high doses of IVIg in a single day or over several days, and your blood group is A, B, or AB and/or you have an underlying inflammatory disease, you may have an increased risk of red blood cell destruction (hemolysis).
Post-marketing reports indicate that high-dose IVIg indications in children, particularly Kawasaki disease, are associated with a higher reporting rate of hemolytic reactions compared to other pediatric IVIg indications.
Contact your doctor if you develop paleness (pale skin), lethargy (feeling of weakness), dark urine, shortness of breath, or palpitations (rapid heartbeat).
Isolated cases of kidney function impairment/kidney failure related to hemolysis with fatal outcome have occurred.

Infection safety information
When medicines are derived from human blood or plasma, certain measures are taken to prevent transmission of infections to patients. These include:

• careful selection of blood and plasma donors to exclude donors at risk of carrying infections,
• testing of each donation and plasma pool for signs of viruses/infections,
• implementation of manufacturing procedures capable of inactivating or eliminating viruses. Despite these measures, when administering medicines prepared from human blood or plasma, the possibility of transmitting an infection cannot be completely excluded. This also applies to any unknown or emerging viruses or other types of infections.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus. These measures may have limited effectiveness against non-enveloped viruses such as hepatitis A virus and/or parvovirus B19. Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, possibly because the antibodies against these infections contained in the product have a protective effect.

This medicine contains less than 1 mmol of sodium (23 mg) per single dose (up to a maximum of 2 g/kg), i.e., it is essentially “sodium-free”.
It is strongly recommended that each time you receive a dose of this medicine, you record the name and batch number of the product to maintain documentation of the batches used.

Other medicines and Gamunex
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
You should avoid concomitant use of medicines that increase water excretion from the body (loop diuretics) during treatment with Gamunex.
Vaccine effects: Gamunex may reduce the effectiveness of certain types of vaccines (vaccines containing live attenuated viruses). For rubella, mumps, and varicella, an interval of up to 3 months should elapse between administration of this product and administration of these vaccines. For measles, this interval should be extended up to 1 year.

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

Driving and using machines
Dizziness or other reactions may occasionally occur, which could affect your ability to drive or use machinery. If you experience such symptoms, wait until they resolve before driving or using machinery.

3. How to use Gamunex

Gamunex is administered intravenously (IV infusion) by a physician.
The dose administered depends on the disease and body weight, and will be determined by the physician
(see the section “Information for healthcare professionals” at the end of this leaflet).
At the beginning of the infusion, Gamunex will be given slowly. If you feel well, your doctor may gradually increase the infusion rate.
If you interrupt treatment with Gamunex
If treatment with this medicine is discontinued, your clinical condition may worsen. Consult your treating physician if you wish to stop therapy with this medicine prematurely.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Rare and isolated cases of the following side effects have been reported with immunoglobulin preparations. Contact your doctor immediately if you experience any of the following side effects during or after the infusion:

• A sudden drop in blood pressure and, in isolated cases, anaphylactic shock (signs of which include, among others, skin rash, low blood pressure, rapid or irregular heartbeat, wheezing, cough, sneezing, and difficulty breathing), even if you did not show an allergic reaction during previous administrations.
• Cases of transient non-infectious meningitis (signs include headache, fear of or intolerance to light, neck stiffness).
• Cases of temporary reduction in red blood cells in the blood (hemolytic anemia / reversible hemolysis).
• Cases of transient skin reactions.
• Increase in serum creatinine levels (a test measuring kidney function) and/or acute kidney failure (signs include back pain, fatigue, reduced urine output).
• Thromboembolic reactions, such as myocardial infarction (chest tightness with sensation of rapid heartbeat), stroke (facial, arm or leg muscle weakness, difficulty speaking or understanding others when speaking), pulmonary embolism (shortness of breath, chest pain and fatigue), deep vein thrombosis (pain and swelling in a limb).
• Cases of transfusion-related acute lung injury (TRALI), causing hypoxia (lack of oxygen), difficulty breathing, rapid breathing, bluish discoloration of the skin or mucous membranes, fever, and low blood pressure.

The following side effects were observed in clinical studies conducted with Gamunex:
The following side effects were common (may affect up to 1 in 10 infusions):

• headache
• fever

The following side effects were uncommon (may affect up to 1 in 100 infusions):

• dizziness
• urticaria (hives, skin redness, itching)
• itching
• rash
• nausea
• vomiting
• high blood pressure
• sore throat
• cough
• nasal congestion
• wheezing
• joint pain
• back pain
• flu-like malaise
• fatigue
• chills
• asthenia (weakness)
• muscle pain

The following side effects were rare (may affect up to 1 in 1,000 infusions):

• hemolytic anemia (destruction of red blood cells)
• shortness of breath
• sinusitis
• skin peeling
• anxiety
• reduction in hemoglobin
• indigestion
• bruising
• flushing
• musculoskeletal stiffness
• palmar erythema (redness of the palms of the hands)
• aphonia (inability to produce voice sounds)
• reduction in white blood cell count
• dermatitis (skin inflammation) or contact dermatitis
• abdominal pain
• diarrhea
• low blood pressure
• neck pain
• musculoskeletal pain
• chest pain
• malaise
• injection site reaction
• urethritis (pain or difficulty urinating)
• upper respiratory viral infection (illnesses caused by an acute infection affecting the upper respiratory tract, including nose, sinuses, and throat)
• lymphocytosis (increase in a specific type of white blood cells)
• hypersensitivity (allergic reaction)
• light sensitivity of the eyes
• hypertensive crisis (acute increase in blood pressure)
• hyperemia (increased blood flow)
• hemoglobinuria (presence of the oxygen-carrying blood protein at excessively high concentrations in urine)
• increased blood pressure
• presence of free hemoglobin (hemoglobin circulating outside red blood cells)
• increased erythrocyte sedimentation rate (increased rate of red blood cell sedimentation in a test tube)

What measures should be taken if side effects occur?
If side effects occur, the infusion rate should be reduced or the infusion should be suspended until symptoms disappear. If symptoms persist after stopping the infusion, appropriate treatment should be initiated.
In case of a severe hypersensitivity reaction with reduced arterial pressure and dyspnea progressing to a severe generalized allergic reaction (anaphylactic shock), use of this medicine must be stopped immediately and appropriate countermeasures must be taken.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the Italian Medicines Agency (Agenzia Italiana del Farmaco) website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gamunex

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial.
The shelf life is 3 years.
Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the vial in the outer packaging.
The medicine may be stored outside the refrigerator, in its original outer packaging, for a single period of up to 6 months at room temperature (not above 25°C). In this case, the expiry date of the medicine will be 6 months from the date it was first removed from refrigeration, regardless of the original expiry date. The new expiry date must be clearly indicated on the outer packaging. In no case should the new expiry date extend beyond the printed expiry date. Re-refrigeration is not permitted.
Once the vial has been opened, the contents should be used immediately. Any unused portion must be discarded. Further storage is not allowed, even in the refrigerator, due to the risk of microbial contamination.

6. Package contents and other information

What Gamunex contains
The active substance is human normal immunoglobulin (IVIg). One ml of this medicinal product contains
100 mg of protein, with at least 98% IgG, in water for injections.
A 10 ml vial contains: 1 g of human normal immunoglobulin
A 50 ml vial contains: 5 g of human normal immunoglobulin
A 100 ml vial contains: 10 g of human normal immunoglobulin
A 200 ml vial contains: 20 g of human normal immunoglobulin
A 400 ml vial contains: 40 g of human normal immunoglobulin
The percentage distribution of IgG subclasses is approximately: 62.8% (IgG1), 29.7% (IgG2), 4.8% (IgG3),
2.7% (IgG4). The maximum IgA content is 66 micrograms/ml.
The other components are glycine and water for injections.

Description of the appearance of Gamunex and contents of the pack
Gamunex is a solution for infusion. The solution ranges from clear to slightly opalescent and is colourless or pale yellow.
Gamunex is available in pack sizes of 10 ml, 50 ml, 100 ml, 200 ml and 400 ml. The carton contains one glass vial with stopper (chlorobutyl rubber), a tear-off label-tag and a package leaflet.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Grifols Deutschland GmbH
Colmarer Straße 22
60528 Frankfurt
Germany
Tel.: +49 69/660 593 100

Manufacturer:
Instituto Grifols, S.A.
Can Guasc, 2 – Parets del Vallès
08150 Barcelona
Spain

This medicinal product is authorised in the European Economic Area Member States and in the United Kingdom (Northern Ireland) under the following names:
Austria, Belgium, Cyprus, Ireland, Germany, Luxembourg, Netherlands, Poland, Portugal, United Kingdom (Northern Ireland): Gamunex 10% 100 mg/ml
Czech Republic, Denmark, Finland, France, Hungary, Norway, Slovakia, Spain, Sweden: Gamunex 100 mg/ml
Greece: Gaminex 10% 100 mg/ml
Italy: Gamunex

The following information is intended exclusively for healthcare professionals:

Use only clear or slightly opalescent, colourless or pale yellow solutions, free from
particles – do not shake. Before infusion, warm Gamunex to room temperature or body
temperature (preferably in a water bath at a temperature not exceeding 37°C).
The vials are equipped with a label-hook (Fig. 1). After inserting the infusion set
(Fig. 2), invert the vial and fold back the loop portion of the label (Fig. 3). Press
firmly with fingers to create a crease on each side where the loop portion joins the rest
of the label (Fig. 4). Hang the vial on the infusion stand using the resulting loop (Fig. 5).

Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5
Posology and method of administration
The dose and dosing regimen depend on the indication.
Dose individualization may be necessary for each patient based on clinical response. Weight-based dosing may require adjustment in underweight or overweight patients. The dosing regimens below are provided as a guideline.
The recommended dosage is summarized in the following table

Route of administration
For intravenous use.
Normal human immunoglobulin must be infused intravenously at an initial rate of
0.6 - 1.2 ml/kg/hour for 0.5 hours. In case of an adverse reaction, the infusion rate should be reduced or the infusion stopped. If well tolerated, the infusion rate may be gradually increased up to a maximum of 4.8 - 8.4 ml/kg/hour.
Paediatric population
Since the dosage for each indication is based on body weight and adjusted according to the clinical response in the above-mentioned conditions, the dosage in children and adolescents (0-18 years) is not different from that in adults.
Gamunex must not be mixed with other infusion solutions or medicinal products. If dilution is required prior to infusion, a 50 mg/ml glucose solution may be used for this purpose. Do not dilute with saline solutions.
Concomitant administration of Gamunex and heparin via a single-lumen administration device must be avoided.
Gamunex infusion lines may be flushed with 50 mg/ml glucose solution or sodium chloride solution (9 mg/ml), but not with heparin.
The heparin lock through which Gamunex has been administered must be flushed with 50 mg/ml glucose solution or sodium chloride solution (9 mg/ml), but not with heparin.