Cuvitru

Package leaflet: Information for the user

Cuvitru, 200 mg/ml, solution for injection
Human normal immunoglobulin
Please read all of this leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Cuvitru is and what it is used for

What Cuvitru is
Cuvitru belongs to a class of medicines called "human normal immunoglobulins".
Immunoglobulins are also known as antibodies and are naturally present in the blood of healthy individuals.
Antibodies are part of the immune system (the body's natural defence mechanism)
and help the body fight infections.

How Cuvitru works
Cuvitru is manufactured from the plasma of healthy donors. It works in exactly the same way as
immunoglobulins naturally present in blood.

What Cuvitru is used for
Cuvitru is used in patients with a weakened immune system who have insufficient levels of antibodies in their blood and who are prone to frequent infections. Regular administration of appropriate doses of Cuvitru can raise abnormally low immunoglobulin levels to a normal range (replacement therapy).

Cuvitru is prescribed:

• to patients with congenital antibody deficiency (primary immunodeficiency syndromes);
• to patients who have severe or recurrent infections due to weakened immunity resulting from other diseases or treatments (secondary immunodeficiency syndromes).

2. Important information before using Cuvitru

When NOT to use Cuvitru:

• If the patient is allergic to immunoglobulins or to any of the other ingredients of this medicine (listed in section 6).
• If the patient has antibodies against immunoglobulin A (IgA) in their blood. This situation may occur in patients with IgA deficiency. Cuvitru contains trace amounts of IgA, which may cause an allergic reaction in such patients.
• Into blood vessels (intravenously) or into muscle (intramuscularly).

Warnings and precautions
Before starting treatment with Cuvitru, discuss this with your doctor, pharmacist, or nurse.
Leaving Cuvitru in syringes coated with silicone polymer for more than two hours may lead to the formation of solid particles. You must strictly follow the detailed instructions provided in section 3, "Instructions for use", of this leaflet.

Allergic reactions
The patient may be allergic to immunoglobulins without knowing it. Allergic reactions, such as sudden drop in blood pressure or anaphylactic shock (rapid drop in blood pressure combined with other symptoms such as throat swelling, breathing difficulties, and skin rash), are rare but may occasionally occur, even if the patient has not previously experienced any problems when taking similar medicines. Patients with IgA deficiency and presence of anti-IgA antibodies have an increased risk of allergic reactions. Inform your doctor or nurse about IgA deficiency before starting treatment. Cuvitru contains residual amounts of IgA, which may increase the risk of an allergic reaction. Subjective and objective symptoms of these rare allergic reactions include:

• Feeling faint, dizzy, or fainting;
• Skin rash and itching, swelling of the mouth or throat, breathing difficulties, wheezing;
• Irregular heartbeat, chest pain, bluish discoloration of lips or fingers and toes;
• Blurred vision.

Your doctor or nurse will start the Cuvitru infusion slowly and will closely monitor you during the first few infusions to detect and immediately treat any possible allergic reactions.
► If any of these symptoms occur during the infusion, inform your doctor or nurse immediately. They will decide whether to reduce the infusion rate or stop the infusion completely.

Monitoring during infusion
Some adverse reactions may occur more frequently in the following situations:

• First-time use of Cuvitru;
• Previous use of another immunoglobulin and switching to Cuvitru;
• A long interval since the last dose of Cuvitru.
  ► In such cases, the patient will be closely monitored during the first infusion and for at least one hour after its completion.

In all other cases, monitoring during the infusion and for at least 20 minutes after administration of Cuvitru is recommended.

Special patient groups
Your doctor will exercise particular caution if the patient has obesity, is elderly, has diabetes, high blood pressure, low blood volume (hypovolemia), or vascular disorders. In these conditions, immunoglobulins may increase the risk of myocardial infarction, stroke, pulmonary embolism, or deep vein thrombosis, although only very rarely.
Your doctor will also exercise particular caution if the patient has or has previously had kidney problems or is receiving medicinal products that may harm the kidneys (nephrotoxic medicinal products), as there is a very high risk of acute kidney failure.

Aseptic meningitis (Aseptic Meningitis Syndrome, AMS)
Infusions of immunoglobulin products, including Cuvitru, may cause meningitis. Discontinuation of immunoglobulin therapy may lead to remission of AMS within a few days. AMS typically occurred within a few hours to 2 days after administration of immunoglobulin.
Contact your doctor if any of the following subjective and objective symptoms occur after receiving Cuvitru: severe headache, neck stiffness, drowsiness, fever, nausea, vomiting, and light sensitivity. Your doctor will decide whether further investigations are needed and whether treatment with Cuvitru should continue.

Destruction of red blood cells (hemolysis)
Cuvitru contains blood group antibodies, which may cause destruction of red blood cells and hemolytic anemia.

Effect on blood test results
Cuvitru contains many different antibodies, some of which may affect blood test results (serological tests).
► Before any blood test, inform your doctor that you are receiving Cuvitru.

Home treatment
Patients self-administering Cuvitru at home and/or their caregivers will be trained to recognize early signs of adverse reactions, especially allergic reactions. During the infusion, the patient or caregiver should monitor for the first signs of adverse reactions (further detailed information is provided in section 4, "Possible side effects").
► If any adverse reactions occur, the patient or caregiver must immediately stop the infusion and contact the doctor.
► In case of a severe adverse reaction, the patient or caregiver must immediately call for emergency medical help.

Information on the source of Cuvitru
Cuvitru is manufactured from human plasma (the liquid part of blood). During the manufacturing of medicines from human blood or plasma, measures are taken to prevent transmission of infections to patients.
These include:

• Careful selection of blood and plasma donors to ensure that donors at risk of infection are excluded;
• Testing each donation and plasma pools for the presence of viruses/infections;
• Including steps in the blood and plasma processing that can inactivate or remove viruses.

Despite these measures, it cannot be completely excluded that administration of medicines derived from human blood or plasma may transmit infection. This also includes unknown or emerging viruses or other types of infections.
The measures used are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and against non-enveloped viruses such as hepatitis A virus and parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, probably because the antibodies against these infections contained in Cuvitru provide protective effects.

It is strongly recommended to record the following information in the treatment diary each time Cuvitru is administered:

• Date of administration,
• Batch number of the medicine,
• Injected volume, infusion rate, number and location of injection sites.

Children and adolescents
The above warnings and precautions apply to both adults and children.

Cuvitru and other medicines
Inform your doctor, pharmacist, or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

Vaccinations
Cuvitru may weaken the effect of certain vaccines containing live viruses, such as vaccines against measles, mumps, rubella, and varicella (live virus vaccines).
Therefore, it may be necessary to wait up to 3 months after receiving Cuvitru before receiving certain vaccines. Before vaccination against measles, it may be necessary to wait up to 1 year after the last dose of Cuvitru.
► Inform the doctor or nurse administering the vaccine that the patient is receiving Cuvitru.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Clinical studies on the use of Cuvitru in pregnant or breastfeeding women have not been conducted. However, clinical experience with immunoglobulins suggests that harmful effects on pregnancy or the unborn child are not expected.
If the patient is breastfeeding and receiving Cuvitru, antibodies from the medicine may also be present in breast milk and may protect the infant against certain infections.
Experience with immunoglobulins suggests that harmful effects on fertility are not expected.

Driving and operating machinery
During treatment with Cuvitru, patients may experience adverse reactions (e.g., dizziness or nausea) that may affect their ability to drive or operate machinery. In such cases, patients should wait until these reactions have subsided.

3. How to use Cuvitru

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your doctor.

Cuvitru must be administered subcutaneously (by subcutaneous infusion).
Administration of Cuvitru will be initiated by a doctor or nurse. However, after receiving several initial infusions under medical supervision and appropriate training, a patient may be authorized to self-administer the medicine at home. The decision whether a patient can use Cuvitru at home (e.g. using an infusion pump or manually using a syringe) is made jointly by the patient and the doctor. Do not begin using Cuvitru at home until you have received complete instruction and training.

Dosage

Your doctor will calculate the appropriate dose based on your body weight, previous treatment, and response to therapy.
Your doctor will determine whether a loading dose (for adults or children) of at least 1.0–2.5 ml/kg body weight, divided over several days, is required. Cuvitru will then be administered at regular intervals, ranging from once daily to once every two weeks. The cumulative monthly dose will be approximately 1.5 to 5 ml/kg body weight (in cases of primary immunodeficiency disorders) or approximately 1.0 to 2.0 ml/kg body weight (in cases of secondary immunodeficiency disorders). Your doctor may also adjust the dose depending on your response to treatment.

Do not change the dose or dosing schedule without consulting your doctor. If you think Cuvitru should be administered less or more frequently, discuss this with your doctor. If you suspect a dose has been missed, inform your doctor as soon as possible.

Starting treatment

Treatment will be initiated by a doctor or nurse experienced in managing patients with impaired immune systems and in training patients for home therapy. You will be closely monitored throughout the entire infusion and for at least 1 hour after completion to assess how well you tolerate the medicine. Initially, the doctor or nurse will use a low infusion rate and gradually increase it during the first and subsequent infusions. Once the appropriate dose and infusion rate have been established by the doctor or nurse, you may be authorized to self-administer Cuvitru at home.

Home treatment

Cuvitru may be self-administered by the patient or caregiver. You will be trained by a doctor or nurse experienced in advising and treating such patients. The doctor or nurse will supervise you during the first few administrations.

You or your caregiver will receive training on:

• aseptic infusion techniques,
• use of the infusion device (if applicable),
• keeping a treatment diary, and
• actions to take in case of severe adverse reactions.

To ensure effective treatment, carefully follow all instructions provided by your doctor regarding dose, infusion rate, and administration schedule for Cuvitru.

Method and route of administration

Selection of infusion sites

Recommended sites for subcutaneous infusion of Cuvitru include the abdomen, thighs, upper arms, or lower back. Cuvitru may be administered at multiple infusion sites. Infusion sites should be at least 10 cm apart. Avoid areas over bones, areas with visible blood vessels, scars, inflamed (irritated) areas, or sites of infection. Rotate infusion sites with each administration as directed by your doctor or nurse.

When using an infusion device:

Multiple subcutaneous infusion sites may be used simultaneously by using a multi-needle set. The volume infused at each site may vary, and doses exceeding 30 ml can be divided according to patient preference.

When administering manually:

Cuvitru may be administered using a syringe at a single site. If administration at additional sites is required, a new sterile needle must be used. The volume infused at each site may vary, and doses exceeding 30 ml can be divided according to patient preference.

Infusion rate

Your doctor will determine the appropriate technique and infusion rate based on your prescribed dose, frequency of administration, and your tolerance to the medicine.

When using an infusion device:

The recommended initial infusion rate is 10 ml per hour per infusion site. If the infusion is well tolerated, the rate may be increased in increments of at least 10-minute intervals up to a maximum of 20 ml per hour per site during the first two infusions. For subsequent infusions, the infusion rate may be increased depending on tolerance.

When administering manually:

Consult your doctor. Begin infusion at a rate that does not cause discomfort. The infusion should never be painful. The recommended maximum infusion rate is approximately 1–2 ml per minute. Larger infusion volumes may be better tolerated at certain sites than others.

If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

Detailed instructions for use are provided below.

Do not use Cuvitru at home before receiving full instruction and training from your doctor or nurse.

Preparing Cuvitru vials:

• Remove Cuvitru from the carton. If the product has been stored in the refrigerator, allow the vials to reach room temperature. This may take up to 90 minutes.
• Do not heat or place in a microwave oven.
• Do not shake the vials.

1. Check the vials: Do not use after the expiry date. Do not use if the protective cap is missing or damaged. Check the solution color: it should be clear and colorless, light yellow, or light brown. Do not use if the solution is cloudy or contains particulate matter.
2. Gather all necessary materials: Gather all required materials: Cuvitru vials, infusion supplies including subcutaneous administration set, infusion device(s), syringes, sterile caps for ends, sterile transparent dressing, adhesive tape, gauze, sharps container, infusion pump (if used), infusion tubing, infusion logbook. Clean the work area. If using an infusion pump: program the infusion pump according to the recommended infusion rate and manufacturer's instructions. Wash hands thoroughly and allow them to dry. Open the required materials using the method demonstrated by your doctor or nurse.
3. Prepare the syringes: Remove the cap from the vial. Disinfect each rubber stopper with a sterile alcohol swab and allow it to dry. Attach a sterile syringe to the transfer needle with vent. Insert the transfer needle with vent into the center of the vial. Invert the vial and pull back the plunger to draw the solution into the syringe. If using multiple vials, repeat these steps to obtain the required dose. Infusion must begin immediately after drawing Cuvitru into the syringe. If administration is expected to take longer than two hours, the required dose should be divided and administered at different infusion sites. Leaving Cuvitru in syringes coated with silicone polymer for more than two hours may lead to formation of particulate matter. In case of using a sterile needle: Attach the sterile syringe to a sterile needle and pull back the plunger to fill the syringe with air equal to the volume of solution to be withdrawn from the vial. Insert the needle into the center of the stopper and inject the air. Pull back the plunger and withdraw the required volume.
4. Prepare for infusion: a. When using an infusion pump: Follow the manufacturer's instructions for filling the tubing and operating the pump. Connect the syringe filled with solution to the administration set. Point the syringe tip upward and gently press the plunger to remove air and fill the administration set up to the hub of the needle. b. For manual administration: follow the instructions provided by your nurse or doctor. Connect the syringe filled with solution to the administration set. Point the syringe tip upward and gently press the plunger to remove air and fill the administration set up to the needle hub.
5. Prepare infusion sites: Determine the number of infusion sites based on total dose volume. Select infusion sites: upper arms, abdomen, thighs, or lower back. Avoid areas over bones, visible blood vessels, scars, or areas with inflammation (irritated skin) or infection. Administer the solution into one or multiple infusion sites simultaneously. Choose sites at least 10 cm apart from each other. Rotate infusion sites with each subsequent infusion. Disinfect infusion sites with a sterile alcohol swab, starting from the center of each site and moving outward in circular motions. Allow the sites to dry (for at least 30 seconds).
6. Insert and secure the subcutaneous needle set: Remove the needle cover. Firmly pinch and hold together at least 2.5 cm of skin between two fingers. Quickly insert the needle straight into the skin at a 90-degree angle. Secure the needle in place with a sterile adhesive tape (included with the transparent dressing). If using multiple sites, repeat these steps. Secure the needle set in place by applying a sterile protective dressing over the infusion sites.
7. Start the infusion: When using an infusion pump: turn on the pump and begin infusion according to the manufacturer's instructions. For manual administration: slowly push the syringe plunger as demonstrated by your doctor or nurse, until all fluid in the syringe has been administered, or as otherwise instructed by your healthcare provider. Check the infusion sites periodically during infusion.
8. After infusion is complete, remove the subcutaneous needles from the infusion sites. Remove the needle set by loosening the tape along all edges. Pull the wings of the needle upward and withdraw the needle. Gently press gauze over the site and cover it with a dressing. Dispose of needles into a sharps container.
9. Document the infusion. Remove the detachable label with product lot number and expiry date from the vial and affix it to the treatment/infusion logbook. Record the date, time, dose, administration sites (to assist in rotating sites), and any reactions after each infusion. Dispose of all single-use materials, vials, and unused solution remnants according to your doctor’s or nurse’s instructions.

Use in children and adolescents
The same indications, dosage, and frequency of infusions as in adult patients apply
to children and adolescents (aged 0 to 18 years).
Administration of a higher than recommended dose of Cuvitru
If an overdose of Cuvitru is suspected, a doctor should be informed as soon as possible.
Missed administration of Cuvitru
Do not administer a double dose of Cuvitru to make up for a missed dose. If a dose of Cuvitru is missed, inform the doctor as soon as possible.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, such as: chills, headache,
dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low
blood pressure, and mild to moderate lower back pain, although not everyone will experience them.
Some adverse reactions, such as headache, chills, or body pain, may be reduced
by slowing the infusion rate.

Serious adverse reactions
Infusions of medicines such as Cuvitru may rarely lead to serious, although uncommon, allergic reactions. A sudden drop in blood pressure may occur, and in isolated cases, anaphylactic shock.
Doctors are aware of the possibility of these adverse reactions and will monitor the patient during and after the initial infusions.
Immediately inform your doctor or nurse if any of the following symptoms occur:

• feeling faint, dizzy, or lightheaded, or fainting;
• skin rash and itching, swelling of the mouth or throat, difficulty breathing, wheezing;
• irregular heartbeat, chest pain, bluish discoloration of lips, hands, or feet;
• blurred vision.

When administering Cuvitru at home, the patient may have an infusion in the presence of a caregiver who can help detect allergic reactions, stop the infusion if necessary, and call for medical help.
Information regarding the risk of allergic reactions and the use of Cuvitru at home can be found in section 2 of this leaflet.

Very common adverse reactions (may affect more than 1 in 10 people):

• headache
• diarrhoea and nausea
• redness and pain at the infusion site
• fatigue

Common adverse reactions (may affect up to 1 in 10 people):

• dizziness, migraine, and drowsiness
• low blood pressure
• abdominal pain
• itching and rash
• muscle pain
• swelling, itching, rash, and bruising at the infusion site
• pain

Uncommon adverse reactions (may affect up to 1 in 100 people):

• burning sensation
• lower abdominal pain
• swelling at the infusion site
• positive blood test for antibodies

Adverse reactions with unknown frequency (frequency cannot be estimated from available data):

• meningitis (aseptic meningitis)

Adverse reactions observed with similar medicines
The following adverse reactions have been observed during subcutaneous infusions of normal human immunoglobulin. Although these adverse reactions have not yet been reported with Cuvitru, they may occur in individuals receiving this medicine.

• Tingling
• Tremor
• Rapid heartbeat
• Shortness of breath
• Voice disorders
• Chest pain
• Hardening and/or sensation of warmth at the infusion site

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: 22 49 21 301
Fax: 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Cuvitru

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton following: EXP.
The expiry date refers to the last day of the stated month.
Do not use this medicine if the solution is cloudy, contains particles, or has changed colour.
Store the vials in the outer packaging to protect from light.
Do not store above 25°C.
Do not freeze.
If the product is stored in a refrigerator, unopened vials must be removed from refrigerated conditions and allowed to reach room temperature for at least 90 minutes before use. Do not use heating devices, including microwave ovens.

6. Contents of the pack and other information

What Cuvitru contains

• The active substance is human normal immunoglobulin.
• 1 ml of Cuvitru contains 200 mg of human protein, of which at least 98% is immunoglobulin G (IgG).
• The other ingredients (excipients) are glycine and water for injections.

What Cuvitru looks like and contents of the pack
Cuvitru is a solution for injection in vials of 5, 10, 20, 40 or 50 ml. The solution is
clear and colourless, pale yellow or pale brown.
Each 5 ml vial contains: 1 g of human normal immunoglobulin.
Each 10 ml vial contains: 2 g of human normal immunoglobulin.
Each 20 ml vial contains: 4 g of human normal immunoglobulin.
Each 40 ml vial contains: 8 g of human normal immunoglobulin.
Each 50 ml vial contains: 10 g of human normal immunoglobulin.
Pack sizes:
1, 10 or 20 vials containing 5 ml of solution for injection
1, 10, 20 or 30 vials containing 10 ml of solution for injection
1, 10, 20 or 30 vials containing 20 ml of solution for injection
1, 5, 10 or 20 vials containing 40 ml of solution for injection
1 vial containing 50 ml of solution for injection.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warszawa
Tel: +48223062447
[email protected]

Manufacturer
Baxalta Belgium Manufacturing SA
Boulevard René Branquart 80
7860 Lessines
Belgium

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Austria: Cuvitru 200 mg/ml Injektionslösung zur subkutanen Anwendung
Belgium, France: Cuvitru 200 mg/ml solution injectable par voie sous-cutanée
Czech Republic, Denmark, Finland, Germany, Greece, Italy, Norway, Poland: Cuvitru
Ireland, United Kingdom: Cuvitru 200 mg/ml solution for subcutaneous injection
Netherlands: Cuvitru 200 mg/ml, oplossing voor subcutane injectie
Slovakia, Sweden: Cuvitru 200 mg/ml
Spain: Cuvitru 200 mg/ml, solución inyectable subcutánea