IQYMUNE

Package leaflet: Information for the user

IQYMUNE 100 mg/mL solution for infusion

Normal human immunoglobulin (IVIg)
Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, 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, pharmacist, or nurse. See section 4. Contents of this leaflet:
  1. What IQYMUNE is and what it is used for
  2. What you need to know before using IQYMUNE
  3. How to use IQYMUNE
  4. Possible side effects
  5. How to store IQYMUNE
  6. Contents of the pack and other information

1. What IQYMUNE is and what it is used for

What IQYMUNE is
This medicine contains human antibodies, produced by our immune system. It belongs to a class of
medicines called immunoglobulins.
How IQYMUNE works

• The human antibodies contained in this medicine help the body to fight infections or to maintain the immune system in balance.
• If you do not have enough antibodies, the antibodies provided by this medicine can replace the missing ones. Since they are isolated from human plasma, the antibodies in IQYMUNE act exactly as if they were your own antibodies.
• This type of medicine can also be used when your immune system is unbalanced and you need additional antibodies in certain inflammatory diseases (autoimmune diseases). The medicine provides you with these antibodies.
  What IQYMUNE is used for This medicine is used for:

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

1. Patients with congenital antibody synthesis deficiency (primary immunodeficiency syndromes).
2. Patients with acquired antibody deficiency (secondary immunodeficiency) due to specific diseases and/or treatments and who are prone to severe or recurrent infections.

Treatment of patients with certain inflammatory diseases (immunomodulation). There are five groups:

1. Patients who do not have enough platelets (primary immune thrombocytopenia, ITP) and who are at high risk of bleeding or who will shortly undergo surgery.
2. Patients with a disease associated with widespread inflammation of nerves throughout the body (Guillain-Barré syndrome).
3. Patients with a disease causing widespread inflammation in multiple organs of the body (Kawasaki disease). IQYMUNE must be administered in combination with acetylsalicylic acid.
4. Patients suffering from inflammation of the peripheral nerves causing muscle weakness and/or numbness, primarily in the arms and legs (chronic inflammatory demyelinating polyneuropathy, CIDP).
5. Patients suffering from a rare disease characterized by slowly progressive and asymmetric muscle weakness in the arms and legs, without loss of sensation (multifocal motor neuropathy, MMN).

2. What you need to know before using IQYMUNE

Do not use IQYMUNE

• If you are allergic to immunoglobulins or to any of the other ingredients of this medicine (listed in section 6).
• If you have immunoglobulin A (IgA) deficiency, you may have antibodies against IgA in your blood. Since this medicine contains small amounts of immunoglobulin A, an allergic reaction may occur.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using IQYMUNE.
Adverse reactions may occur more frequently:

• if the infusion rate is high,
• if you are receiving IQYMUNE for the first time or if a long time has passed since your last infusion. In these cases, you will be closely monitored for up to 1 hour after the infusion to detect potential side effects.

To avoid the risk of a reaction, your doctor will monitor and adjust the infusion rate according to your individual needs. During the infusion, your doctor will perform clinical monitoring to detect any signs of allergy or other reactions.
Allergic reactions are rare. If an allergic reaction occurs, early signs may include dizziness, facial/leg swelling, shortness of breath, skin rash and/or itching. Inform your doctor or nurse immediately if you notice any of these reactions during or after IQYMUNE infusion.
Depending on your adverse reaction, your doctor may decide to reduce the infusion rate or stop the infusion. They may also initiate treatment for the adverse event, if deemed necessary. If you have any doubts, do not hesitate to consult your doctor or nurse.

Patients with pre-existing risk factors
Very rarely, this medicine may cause or worsen kidney disease (acute renal failure), heart and/or blood vessel disease (myocardial infarction, cerebrovascular accident including stroke, pulmonary embolism, or deep vein thrombosis). Patients who already have certain diseases or risk factors should use this medicine with caution.
Inform your doctor about all medicines you have taken and any diseases you have or have had. Your doctor will monitor you closely if:

• you already have kidney disease (renal insufficiency),
• you are taking certain medicines that may be harmful to the kidneys,
• you have high blood sugar levels (diabetes),
• you have insufficient blood volume (hypovolemia),
• you are overweight (obesity),
• you are over 65 years old,
• you already have heart or blood vessel disease,
• you have high blood pressure (arterial hypertension),
• you are at risk of prolonged immobilization,
• you have a disease causing increased blood viscosity (hematological hyperviscosity).

White blood cells
A temporary reduction in the number of certain white blood cells (leukopenia/neutropenia) is common. It usually occurs within hours or days after infusion and resolves spontaneously within 7–14 days.
Before using this medicine, inform your doctor if you know:

• you have a low number of white blood cells, or
• you are taking a medicine that may reduce white blood cell count.

Aseptic meningitis syndrome
Cases of aseptic meningitis syndrome (reversible and non-infectious) have been reported during treatment with immunoglobulins, such as IQYMUNE. This typically begins within several hours to two days after treatment and may present with symptoms such as fever, headache, neck stiffness, nausea, and vomiting.
If you experience these symptoms, inform your doctor, who will perform a thorough neurological examination to rule out other causes of meningitis.

Hemolytic anemia/hemolysis
Following immunoglobulin therapy such as IQYMUNE, hemolytic anemia (a transient decrease in red blood cells due to their destruction) may occur, particularly if you have blood group A, B, or AB. Reversible hemolytic anemia may be characterized by symptoms such as pallor, fatigue, weakness, yellowing of the skin or eyes (jaundice), and dark urine. During administration of immunoglobulins such as IQYMUNE, you will be monitored for clinical signs and symptoms of hemolysis.

Transfusion-related acute lung injury (TRALI)
Rare cases of transfusion-related acute lung injury (TRALI) have been reported in patients receiving immunoglobulins such as IQYMUNE. This condition is characterized by low oxygen levels in the blood (hypoxemia), difficulty breathing (dyspnea), increased respiratory rate (tachypnea), bluish discoloration of the skin (cyanosis), fever, and low blood pressure (hypotension). Symptoms of transfusion-related acute lung injury usually appear during or within 6 hours after immunoglobulin infusion, often within 1 or 2 hours. Therefore, if you notice such reactions during IQYMUNE infusion, inform your doctor immediately, who will decide whether to reduce the infusion rate or stop the infusion.

Viral safety information
When medicines are manufactured from human blood or plasma, several safety measures are implemented to prevent transmission of infections to patients. These include:

• careful selection of blood and plasma donors to exclude potential carriers of infections,
• testing of each donation and plasma pool for the presence of viruses and infections,
• inclusion of manufacturing steps that can inactivate or remove viruses.
  Despite these measures, the possibility of transmitting an infection cannot be completely ruled out whenever medicines derived from human blood or plasma are administered. This also applies to unknown or emerging viruses and other types of infections. The measures taken are considered effective against viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, hepatitis A virus, and parvovirus B19. No association has been observed between immunoglobulins and hepatitis A or parvovirus B19 infections, likely due to the protective role of antibodies against these infections present in the product. It is strongly recommended that the name and batch number of each IQYMUNE dose administered to you be recorded to maintain documentation of the batches used.

Children and adolescents
There are no specific or additional warnings or precautions for children and adolescents.

Other medicines and IQYMUNE
Inform your doctor or pharmacist if you are currently using, have recently used, or might use any other medicines.

Effects on vaccines
The use of immunoglobulins such as IQYMUNE may reduce the effectiveness of vaccines against measles, rubella, mumps, and/or varicella for up to 3 months. It is recommended to wait at least 3 months between the last administration of immunoglobulins and vaccination with these vaccines. For the measles vaccine, a waiting period of 1 year after the last immunoglobulin administration may be necessary. Before vaccination, inform your doctor that you are being treated with IQYMUNE.

Loop diuretics
Avoid concomitant use of loop diuretics with IQYMUNE.

Effects on blood tests
Some antibodies contained in IQYMUNE may interfere with the results of certain blood tests (serological tests). Inform your doctor or the person drawing your blood sample that you have received IQYMUNE before undergoing any blood test.

Pregnancy, breastfeeding, and fertility

• If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
• Reproduction studies with IQYMUNE have not been conducted in animals, and experience in pregnant women is limited. Although no harmful effects on the fetus have been reported, IQYMUNE should not be administered to pregnant women unless the need for treatment has been clearly established.
• The antibodies contained in IQYMUNE are excreted in breast milk and may help protect the infant against certain infections.

Driving and using machines
During treatment with IQYMUNE, patients may experience reactions (e.g., dizziness or nausea) that could affect their ability to drive or operate machinery. In such cases, do not drive or use machinery until these effects have resolved.

IQYMUNE contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially "sodium-free".

3. How to use IQYMUNE

This medicine must be administered intravenously (infusion into a vein).
It is administered by your doctor or a nurse.
The dose and frequency of infusion depend on your general health and body weight.
At the beginning of the infusion, IQYMUNE will be given at a low rate. Depending on how well you tolerate the
administration, your doctor may gradually increase the infusion rate.
Use in children and adolescents
For children and adolescents (age: 0–18 years), the same indications, dose, and infusion frequency as used in adults apply.
If you use more IQYMUNE than you should
Since this medicine is usually administered under medical supervision, overdose is very unlikely. However, if you do receive more IQYMUNE than you should, your blood may become too thick (hyperviscosity). This may particularly occur if you are a patient at risk, for example, if you are elderly or if you have heart or kidney problems. Make sure you drink enough fluids to avoid dehydration, and inform your doctor if you know you have any medical conditions.

4. Possible side effects

Like all medicines, IQYMUNE can cause side effects, although not everybody gets them.
Contact your doctor immediately if you experience any of the side effects listed below.
Depending on the type and severity of the reaction, the doctor will immediately stop treatment with
IQYMUNE and/or start appropriate treatment:

• Allergic reaction: skin rash, itching, hives, shortness of breath, low blood pressure, dizziness, wheezing (as in asthma), rapid heartbeat
• Swelling of the face, throat or mouth with difficulty breathing
• Heart attack: chest pain or shortness of breath
• Stroke: sudden onset of muscle weakness, loss of sensation and/or balance, reduced alertness or difficulty speaking
• Blood clots in the lungs (Pulmonary embolism): chest pain, difficulty breathing or blood in sputum
• Thrombosis/blood clots: pain and swelling in limbs, redness
• Transfusion-related acute lung injury (TRALI): difficulty breathing, shortness of breath, mottled skin, fever and low blood pressure
• Aseptic meningitis: severe headache, fever, neck stiffness, nausea, vomiting, sensitivity to light
• Haemolytic anaemia: paleness, fatigue, weakness, yellowish discoloration of the skin or eyes, reddish urine
• Severe kidney dysfunction: dark-colored urine during or after infusion, difficulty urinating and/or reduced urine output

During clinical studies with IQYMUNE, the following side effects have been reported (in decreasing order of frequency):

The following adverse reactions are common (up to 1 in 10 infusions):

• reduced number of a type of white blood cells (neutropenia). See also “white blood cells” in section 2.
• headache,
• high blood pressure (hypertension),
• fever, tiredness (fatigue), chills.

The following adverse reactions are uncommon (up to 1 in 100 infusions):

• reduced number of other types of white blood cells (leukopenia, lymphopenia, monocytopenia),
• transient decrease in red blood cells (anaemia),
• allergic reaction (anaphylactic reaction),
• dizziness (including sensation of vertigo), migraine,
• gastrointestinal disturbances (nausea), vomiting, abdominal pain, oral pain,
• skin rash, itching, excessive sweating (hyperhidrosis), skin redness (erythema),
• back pain, joint pain, bone pain (arthralgia), limb pain, muscle pain (myalgia),
• reaction at the site of administration, malaise, flu-like illness, swelling (peripheral edema),
• blood tests showing changes in kidney function (decreased creatinine clearance).

The following adverse reactions are rare (up to 1 in 1,000 infusions):

• transient ischaemic attack,
• inflammation of the membranes covering the brain and spinal cord (reversible aseptic meningitis),
• sensation of numbness (paraesthesia),
• inflammation of the eyelids (allergic blepharitis), eye irritation,
• bluish discoloration of the skin (peripheral cyanosis), hot flushes,
• dry throat,
• loose stools (diarrhoea),
• cramps (muscle spasms),
• feeling of discomfort,
• blood tests showing changes in kidney function (increased serum creatinine), increased body temperature, increased fibrin D-dimer,
• infusion-related reaction.

The following adverse events have been reported spontaneously with IQYMUNE:

• anaphylactic shock,
• excessive breakdown of red blood cells (haemolytic anaemia),
• thromboembolic reactions including stroke, heart attack (myocardial infarction), blood clot in the lung (pulmonary embolism), blood clot in a deep vein (deep vein thrombosis),
• acute kidney injury.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system at: 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 IQYMUNE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the outer packaging and on the label of the
vial after Exp. The expiry date refers to the last day of that month.
Do not use this medicine if you notice that the solution is cloudy or contains suspended particles.
Do not store above 25 °C. Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What IQYMUNE contains

• The active substance in IQYMUNE is normal human immunoglobulin.
• 1 mL of IQYMUNE contains 100 mg of human proteins, of which at least 95% are immunoglobulins G.
• The other components are: glycine, polysorbate 80, and water for injections.

Description of the appearance of IQYMUNE and contents of the pack
IQYMUNE is a solution for infusion supplied in vials of 20 mL, 50 mL, 100 mL or 200 mL.
The solution is clear or slightly opalescent, colourless or light brown or light yellow.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Laboratoire Français du Fractionnement et des Biotechnologies
Tour W, 102 Terrasse Boieldieu, 19th Floor, 92800 Puteaux, FRANCE
Tel: +33(0)1 69 82 70 10

Manufacturer:
LFB BIOMEDICAMENTS
59 rue de Trévise
59000 Lille
FRANCE

Concessionaire for sale:
BIOVIIIx srl
Via A. Manzoni, 1
80123 - Napoli
ITALY

This medicinal product is authorised in the European Economic Area countries under the following names:
Austria: IQYMUNE 100 mg/mL Infusionslösung
Belgium and the Netherlands: IQYMUNE 100 mg/mL oplossing voor infusie
Czech Republic: IQYMUNE 100 mg/ml infuzní roztok
Denmark: IQYMUNE 100 mg/mL infusionsvæske, opløsning
Finland: IQYMUNE 100 mg/mL infuusioneste, liuos
Germany: IQYMUNE
Greece: IQYMUNE 100 mg/mL διάλυμα για έγχυση
Hungary: IQYMUNE 100 mg/mL oldatos infúzió
Luxembourg: IQYMUNE 100 mg/mL solution pour perfusion
Spain: IQYMUNE 100 mg/mL solución para perfusión
Sweden: IQYMUNE 100 mg/mL infusionsvätska, lösning

The following information is intended for healthcare professionals only:
Dosage
The recommended doses are summarised in the table below.

Route of administration
For intravenous use only.
Normal human immunoglobulin must be administered intravenously at an initial rate of 0.5 mL/kg/hour for 30 minutes. If well tolerated, the infusion rate may be gradually increased up to a maximum of 6 mL/kg/hour.
Clinical data obtained from a limited number of patients with PID and ITP also indicate that adult and pediatric patients may tolerate an infusion rate of up to 8 mL/kg/hour.
Special precautions

• Certain adverse reactions may be related to the rate of infusion. The recommended infusion rate must be carefully observed. If adverse effects occur, the infusion rate should be reduced or the infusion stopped. In patients at risk of acute renal failure or thromboembolic reactions, IQYMUNE must be administered at the lowest infusion rate and dose.
• It is strongly recommended that each time IQYMUNE is administered to a patient, the product name and batch number be recorded to maintain a traceable link between the patient and the product batch.
  Incompatibilities
  In the absence of compatibility studies, this product must not be mixed with other medicinal products, nor with any other IVIg products.
  Instructions for handling and disposal
  Before administration, the solution should be visually inspected. The solution should be clear or slightly opalescent and colourless, or light brown or light yellow. Do not use turbid solutions or solutions containing deposits.
  Any unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local applicable regulations.