Cutaquig

Package leaflet: Information for the user

CUTAQUIG, 165 mg/mL, solution for injection

Normal human immunoglobulin (SCIg)
This medicinal product is subject to additional monitoring. This will allow for the rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before 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, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Cutaquig is and what it is used for

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

How Cutaquig works
Cutaquig contains immunoglobulins that have been prepared from the blood of healthy individuals. The medicine works in exactly the same way as the immunoglobulins naturally present in blood.

What Cutaquig is used for
Cutaquig is used in patients whose antibodies are insufficient to fight infections and who, as a result, tend to suffer from frequent infections. Regular administration of adequate doses of Cutaquig can increase abnormally low levels of immunoglobulins in the blood to normal levels (replacement therapy).

Cutaquig is prescribed for adults and children (aged 0 to 18 years) in the following situations:

• Treatment of patients born with a reduced or absent ability to produce antibodies (primary immunodeficiency).
• Patients with acquired antibody deficiency (secondary immunodeficiency) due to specific diseases and/or treatments and who experience severe or recurrent infections.

2. What you need to know before using Cutaquig

Do not use Cutaquig

• if you are allergic to human normal immunoglobulin or to any of the other ingredients of this medicine (listed in section 6). Do not inject Cutaquig into a blood vessel.

Warnings and precautions
Talk to your doctor or pharmacist before using Cutaquig.
You may be allergic (hypersensitive) to immunoglobulins without knowing it.
True allergic reactions, such as sudden drop in blood pressure or anaphylactic shock (a sudden drop in blood pressure associated with other symptoms such as swelling of the throat, breathing difficulties, and skin rash), are rare but may occasionally occur even if you have previously been treated with human immunoglobulins and tolerated them well. These reactions may particularly occur if you do not have sufficient amounts of immunoglobulin A (IgA) in your blood (IgA deficiency) and have antibodies against IgA.

• Inform your doctor or healthcare provider before treatment if you have immunoglobulin A (IgA) deficiency. Cutaquig contains trace amounts of IgA which may cause an allergic reaction. In these rare cases, allergic reactions such as sudden drop in blood pressure or shock may occur (see also section 4). Signs and symptoms of these rare allergic reactions include:
  • dizziness, lightheadedness, or fainting
  • skin rash and itching, swelling of mouth or throat, difficulty breathing, wheezing
  • abnormal heart rate, chest pain, bluish discoloration of lips, fingers, or toes
  • blurred vision
    If you notice any of these signs during Cutaquig infusion, inform your doctor immediately. The doctor will decide whether to reduce the infusion rate or stop the infusion completely.
• Inform your doctor if you have a history of heart or vascular disease or blood clots, if you have thick blood, or if you have been immobile for a prolonged period. These conditions may increase the risk of blood clots after using Cutaquig. Also inform your doctor about any medications you are taking, as certain medicines—such as those containing estrogen hormone (e.g., contraceptive pills)—may increase the risk of developing blood clots. Seek immediate medical attention if you experience symptoms such as shortness of breath, chest pain, pain and swelling in limbs, weakness, or numbness on one side of the body after receiving Cutaquig.
• Talk to your doctor if you experience the following signs and symptoms: severe headache, neck stiffness, drowsiness, fever, sensitivity to light (photophobia), nausea, and vomiting after receiving Cutaquig. These may be signs of aseptic meningitis. Your doctor will decide whether further tests are needed and whether to continue treatment with Cutaquig.
• Cutaquig contains blood group antibodies that may cause destruction of red blood cells and consequently lead to anemia (low number of red blood cells).

The healthcare provider will avoid potential complications by ensuring that you:

• are not sensitive to human normal immunoglobulin. The medicine must be infused slowly at the beginning. The recommended infusion rate stated in section 3 must be strictly followed.
• are closely monitored for any symptoms throughout the entire infusion period, especially if: o you are receiving human normal immunoglobulin for the first time o you have switched from another medicine to Cutaquig o a long interval (more than eight weeks) has passed since your last infusion.
  In these cases, monitoring during the first infusion and for one hour afterwards is recommended.
  If none of the above applies to you, observation for at least 20 minutes after administration is recommended.

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

Other medicines and Cutaquig

• Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicines.
• You must not use Cutaquig with other medicines.
• Before vaccination, inform the doctor administering the vaccine that you are being treated with Cutaquig. Cutaquig (like all normal human immunoglobulin solutions) may interfere with the effect of certain live virus vaccines, such as vaccines against measles, rubella, mumps, or varicella. Therefore, you may need to wait up to 3 months after receiving Cutaquig before being vaccinated with a live attenuated vaccine. For measles vaccination, this interference may last up to one year.
• Blood glucose testing
  Some types of blood glucose monitoring systems (so-called glucometers) falsely recognize maltose contained in Cutaquig as glucose. This may result in falsely elevated blood glucose readings during infusion and for approximately 15 hours after the end of infusion, potentially leading to inappropriate insulin administration and life-threatening hypoglycemia (i.e., low blood sugar levels). Additionally, actual hypoglycemia may be overlooked if low blood sugar is masked by falsely high glucose readings. Therefore, when administering Cutaquig or other products containing maltose, blood glucose levels must be measured using test systems based on a glucose-specific method. Test systems relying on the glucose dehydrogenase-pyrroloquinoline quinone (GDH-PQQ) method or on the colorimetric glucose oxidoreductase method must not be used. Carefully read the product information of the glucose test system, including test strips, to determine whether the system is suitable for use with parenteral products containing maltose. If in doubt, consult your physician to determine whether the glucose test system you are using is appropriate for use with parenteral products containing maltose.

Cutaquig with food, drinks, and alcohol
No effects have been observed.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine. This product should be used during pregnancy or breastfeeding only after consulting your doctor or pharmacist.
No clinical studies have been conducted with Cutaquig in pregnant women. However, medicines containing immunoglobulins have been used for years in pregnant and breastfeeding women without harmful effects on pregnancy or the child being observed.
If you are breastfeeding and receive Cutaquig, immunoglobulins from the medicine may also be present in breast milk. Therefore, it is possible that your baby may be protected against certain infections.
Experience with immunoglobulins suggests that harmful effects on fertility are not expected.

Driving and using machines
The ability to drive vehicles and operate machinery may be impaired by certain adverse reactions associated with Cutaquig. Patients who experience adverse reactions during treatment should wait until symptoms resolve before driving or operating machinery.

Cutaquig contains sodium
This medicine contains 33.1 mg of sodium (the main component of table salt) per 48 mL vial and 13.8 mg per 20 mL vial. This corresponds to 1.7% and 0.7% of the maximum daily recommended dietary intake for an adult, respectively.

Information on the ingredients of Cutaquig
Cutaquig is made from human blood plasma (i.e., the liquid part of blood). When medicines are made from human blood or plasma, certain measures are taken to prevent transmission of infections to patients. These measures include:

• careful selection of blood and plasma donors to exclude those at risk of carrying infections,
• testing each donation and plasma pool for signs of viruses/infections,
• inclusion of steps in the blood or plasma processing that inactivate or remove 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 or other types of infections.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV, the virus that causes AIDS), hepatitis B virus, and hepatitis C virus.

The measures taken may have limited effectiveness against non-enveloped viruses such as hepatitis A virus and parvovirus B19.
Immunoglobulins have not been associated with transmission of hepatitis A virus or parvovirus B19, possibly because antibodies against these infections contained in the product are protective.

It is strongly recommended to record the name and batch number of the product each time a dose of Cutaquig is administered, in order to maintain a record of batches used (see Annex I: Administration Guide).

3. How to use Cutaquig

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Cutaquig must be infused under the skin (subcutaneous administration or s.c.).
Treatment will be initiated by your doctor or by a nurse experienced in managing patients with a
weakened immune system.
Once your doctor or nurse has determined the correct dose and infusion rate for you and after the
first infusions have been administered under supervision, you may be allowed to self-administer the
treatment at home, or have it administered by a caregiver who has been trained in the necessary procedures. The doctor or nurse experienced in training patients for home therapy will ensure that you or your caregiver receives proper training and information on:

• aseptic (germ-free) infusion technique
• use of the infusion device (if necessary)
• how to keep a treatment diary
• what actions to take in case of serious adverse reactions (see also section 4). Once you are able to self-administer the treatment and have not experienced any adverse reactions during treatment, your doctor may allow you to continue treatment at home.

Dosage
Your individual dose and infusion rate will be determined by your doctor, who will adjust the dose specifically for you based on your body weight, any previous treatments you may have received, and your response to therapy. Always follow your doctor’s instructions.
Replacement therapy in primary immunodeficiency syndromes:
Your doctor will determine whether you require a loading dose (for adults and children) of at least
1.2–3.0 mL/kg body weight, divided over several days. Subsequently, Cutaquig will be administered regularly at intervals ranging from daily administration to administration every other week. The monthly cumulative dose will be between approximately
2.4 and 4.8 mL/kg body weight. Your healthcare provider may adjust the dose based on your response to treatment.
Replacement therapy in secondary immunodeficiencies:
The recommended dose of Cutaquig is a cumulative monthly dose of 1.2–2.4 mL/kg administered at repeated intervals (approximately once a week). It may be necessary to administer each individual dose at different anatomical sites. Your healthcare provider may adjust the dose based on your response to treatment.
Do not change the dose or administration interval without contacting your doctor. If you think you should administer Cutaquig more or less frequently, consult your doctor. If you think you have missed a dose, contact your doctor as soon as possible.
Method and route of administration
Selection of infusion site(s)
Recommended sites for subcutaneous infusion of Cutaquig include the abdomen, thighs, upper arms, or upper leg/hip area. Multiple infusion sites may be used simultaneously. There is no limit to the number of infusion sites, but they should be at least 5 cm apart. Rotate infusion sites with each administration as advised by your doctor or nurse.
The volume infused per site may vary, but it is recommended to divide large infusion volumes (greater than 30 mL) and administer them across multiple infusion sites. In neonates and children, infusion sites may be changed every 5–15 mL.
Infusion rate
Your doctor will determine the appropriate infusion rate for you, taking into account your individual dose, administration frequency, and product tolerability.
The recommended initial infusion rate is 15 mL/hour/site if you have not previously been treated with SCIG. If you are already receiving SCIG therapy and are switching to Cutaquig, the previously used infusion rates for initial infusions are recommended. For subsequent infusions, if well tolerated, the infusion rate may be gradually increased by approximately
10 mL/hour/site every 2–4 weeks in adults (≥40 kg) and up to 10 mL/hour/site every 4 weeks in pediatric patients (<40 kg).
Subsequently, if you tolerate initial infusions at the full dose per site and at maximum rate, further increases in infusion rate may be considered for subsequent infusions, up to a maximum rate of 67.5 mL/hour/site for adults (≥40 kg) and 25 mL/hour/site for pediatric patients (<40 kg).
Detailed instructions for use are provided below.
Cutaquig must be administered only subcutaneously (under the skin). Do not inject Cutaquig into a blood vessel.
Use Cutaquig at home only after receiving proper instructions and training from a healthcare professional.
Follow the administration guide at the end of this leaflet (Annex I) step by step, and use an aseptic/sterile technique when administering Cutaquig.
Wear gloves during infusion preparation if specifically instructed to do so.
Use in children and adolescents
The same indications, dosage, and infusion frequency as for adults apply to children and adolescents (aged 0 to 18 years).
If you use more Cutaquig than you should
If you think you have infused too much Cutaquig, contact your healthcare provider as soon as possible.
If you forget to use Cutaquig
If you think you have missed a dose, consult your doctor or healthcare provider as soon as possible. Do not infuse a double dose of Cutaquig to make up for a missed dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects such as chills, headache,
dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood
pressure, and moderate lower back pain, although not everyone will experience them.
Some side effects such as headache, chills, or body pain may be reduced
by slowing the rate of infusion.
No severe adverse drug reactions have been observed in subjects treated with Cutaquig
during clinical studies evaluating its safety.
You may be allergic (hypersensitive) to immunoglobulins and allergic reactions may occur,
such as a sudden drop in blood pressure and, in isolated cases, shock. Physicians are
aware of these possible side effects and will monitor you during and after initial
infusions.
Inform your doctor immediately if you experience any of the following signs:

• feeling faint, dizzy, or fainting,
• skin rash and itching, swelling of the mouth or throat, difficulty breathing, wheezing,
• abnormal heart rate, chest pain, bluish discoloration of the lips, fingers, or toes,
• blurred vision.

If you use Cutaquig at home, you may perform the infusion in the presence of a caregiver who will help you watch for signs of an allergic reaction. If any symptoms of an allergic reaction occur, stop the infusion and seek medical assistance if necessary. Also refer to section 2 of this leaflet regarding the risk of allergic reactions.

The following side effects are very common (may occur in more than 1 infusion out of 10):

• Reactions at the injection site such as redness, swelling, itching, and discomfort.

The following side effects are uncommon (may occur in more than 1 infusion out of 1,000 and in
less than 1 infusion out of 100):

• Headache
• Nausea
• Fatigue

The following side effects are rare (may occur in more than 1 infusion out of 10,000):

• Dizziness
• Abdominal pain
• Abdominal distension
• Vomiting
• Nausea
• Muscle pain
• Joint pain
• Fever
• Chills
• Chest discomfort
• Flu-like illness
• Pain
• General feeling of malaise
• Positive blood test for antibodies
• Abnormal blood test results showing destruction of red blood cells
• Increased hemoglobin
• Increased blood creatinine
• Skin rash
• Skin reactions
• Elevated levels of certain liver enzymes called transaminases

Other side effects not observed in clinical studies but reported include:

• Hypersensitivity (e.g. erythema, urticaria)
• Increased blood pressure
• Problems due to blood clot formation in blood vessels (e.g. deep vein thrombosis, stroke)
• Blood clots in blood vessels (see also section 2 “Warnings and precautions”)
• Itching
• Back pain

Side effects observed with similar medicines
The following additional side effects have been observed with subcutaneous infusion of
normal human immunoglobulin. It is possible that someone using Cutaquig may
experience them.

• chills
• pallor
• diarrhea
• pain at injection site
• rapid redness of the neck/face area
• feeling of warmth
• feeling of cold
• weakness
• sensation of throat tightness
• breathing difficulties
• asthma-like symptoms
• cough
• facial swelling
• a condition called aseptic meningitis (see also section 2 “Warnings and precautions”)

Inform your doctor immediately if you experience any of the following symptoms. They may be
signs of a serious problem.

• Severe headache associated with nausea, vomiting, neck stiffness, fever, and sensitivity to light. These may be signs of a temporary, reversible, non-infectious swelling of the membranes surrounding the brain and spinal cord (meningitis).
• Pain, swelling, warmth, redness, or a lump in the arms or legs, unexplained shortness of breath, chest pain or discomfort that worsens with deep breathing, unexplained rapid pulse, numbness or weakness in part of the body, sudden confusion, or difficulty speaking. These may be signs of blood clot formation.

Such side effects may occur even if you have previously been treated with
human immunoglobulin and tolerated it well.
For additional details on circumstances that increase the risk of side effects, consult
section 2.

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 national reporting system:
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 Cutaquig
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 after
"Exp". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the vial in the outer
packaging to protect the medicine from light.
Within the shelf life, the product may be stored at room temperature (do not store
above 25°C) for up to 9 months without the need for further refrigeration during this period; if not used after this time, the product must be discarded.
After first opening, the product must be used immediately.
Do not use Cutaquig if the solution is cloudy or contains particles.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Cutaquig contains
The active substance is human normal immunoglobulin 165 mg/mL (at least 95% is
immunoglobulin G)

• IgG ……….. 71%
• IgG ……….. 25%
• IgG ………... 3%
• IgG ………… 2%

The other excipients are maltose, polysorbate 80, and water for injections.
The maximum IgA content is 300 micrograms/mL.
Cutaquig contains less than or equal to 30 mmol/L of sodium.

Description of the appearance of Cutaquig and contents of the pack
Cutaquig is an injectable solution.
The solution is clear and colourless.
During storage, the solution may develop a slightly opalescent and pale yellow appearance.
Cutaquig is available as:
6, 10, 12, 20, 24 or 48 mL solution in a vial (Type I glass) with a bromobutyl rubber stopper; pack sizes of 1, 10 or 20.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Octapharma Italy S.p.A.
Via Cisanello, 145
56100 Pisa
Italy

Manufacturers:
Octapharma Pharmazeutika Produktionsges.m.b.H.
Oberlaaer Strasse 235
1100 Vienna
Austria
Octapharma AB
Lars Forssells gata 23
112 75 Stockholm
Sweden

This medicinal product is authorised in the European Economic Area countries with the
following trade names:
Austria, Belgium, Bulgaria, Croatia, Denmark, Estonia, Finland,
France, Germany, Ireland, Iceland, Italy, Latvia, Lithuania, Cutaquig®
Luxembourg, Malta, Norway, the Netherlands, Poland, Portugal,
United Kingdom (Northern Ireland), Czech Republic, Slovak Republic, Romania, Slovenia, Spain, Sweden, Hungary:

Annex I - Administration Guide

1. Prepare the required number of Cutaquig vials

• If stored in the refrigerator, allow the vials to reach room temperature for at least 90 minutes before infusion.
• Do not heat the vials or place them in a microwave oven.
• Do not shake the vials to avoid foaming.

2. Preparation for infusion

• Select and prepare a clean work surface using antiseptic wipes or a disinfectant solution (Figure 1).

Figure 1

• Gather all materials needed for infusion:
  • Infusion pump (optional) and compatible syringe(s)
  • Needle (to draw product from the vial)
  • Infusion set
  • Infusion cannula and Y-connector (if required)
  • Alcohol and alcohol-impregnated wipes/aseptic wipes
  • Gauze or transparent dressing and tape
  • Sharps and biohazard waste container
  • Treatment diary and pen
• Wash hands thoroughly and allow them to dry (Figure 2). Use hand disinfectant gel as demonstrated during the practical training session.

Figure 2

• If required, program the pump according to the instructions manual and as shown by the healthcare professional during the practical demonstration.

3. Inspection and opening of the vial

• Carefully inspect each vial for:
  • confirmation that the label corresponds to the prescribed medication,
  • assessment of the solution appearance (it should be clear and colourless to pale yellow or light brown),
• check that the protective closure cap is not broken or missing,
• verify the expiry date and batch number,
• do not use the solution if it is cloudy or contains particles.
  • Remove the protective closure cap.
  • Disinfect the rubber stopper with an antiseptic wipe and allow it to dry (Figure 3).

Figure 3

4. Preparation and filling of the syringe

• Open the sterile syringe and needle.
• Attach the needle to the syringe by rotating it.
• Pull back the plunger to fill the syringe with air equal to approximately the volume of solution to be drawn up from the vial.
• Insert the needle into the vial and turn the vial upside down. Inject the air, making sure that the tip of the needle is not in the solution to avoid foaming.
• Then draw up Cutaquig, taking care that the needle tip remains immersed in the solution at all times (Figure 4).

Figure 4

• Remove the needle from the vial.
• This procedure may need to be repeated if multiple vials are required for the calculated dose.
• Once the procedure is complete, remove the needle and dispose of it in a sharps and puncture-resistant waste container.
• Proceed immediately to the next step, as the IgG solution must be used promptly.

5. Preparation of the infusion pump and infusion set (optional)

• Follow the manufacturer's instructions to prepare the infusion pump.
• To prepare the administration set, attach the syringe to the infusion set and gently push the plunger to fill it with Cutaquig and remove air. (Figure 5).

Figure 5

6. Selection of infusion sites and insertion of the needle(s)

• Cutaquig can be infused at the following sites: abdomen, thigh, upper arm, and/or upper leg/hip area (Figure 6).

Figure 6

• The distance between infusion sites should be at least 5 cm.
• Use different infusion sites from those used for the previous administration.
• Avoid inserting the needle into scars, tattoos, stretch marks, or damaged/inflamed/irritated skin areas.
• Clean the selected infusion site(s) with antiseptic skin wipes and allow to dry.
• Pinch the skin around the infusion site between thumb and index finger (Figure 7), then carefully remove the needle protector and insert the needle into the skin (Figure 8). The angle of insertion will depend on the type of infusion set used.

Figure 7 Figure 8

7. Infusion Control

• The solution must not be infused into a blood vessel.
• Secure the needle in place by applying a sterile gauze and adhesive tape or a transparent dressing (Figure 9).

8. Starting the Infusion Figure 9
   • Start the infusion. If using an infusion pump for administration, follow the manufacturer's instructions.

9. Recording the infusion

• Each Cutaquig vial has an attached removable adhesive label containing the batch number details. Affix the label to the treatment diary or infusion record. Record the dose details, date, time, infusion site location, and any infections, adverse reactions, or other comments related to this infusion.

10. After completion of the infusion

• Gently remove the needle or needles and dispose of them in the sharps container.
• If necessary, apply pressure to the injection site with a small piece of gauze and cover with a dressing.
• Discard all single-use materials together with any unused product and empty vial(s) as recommended by the healthcare provider and in accordance with local requirements.
• Tidy up and store all reusable materials (e.g., pump) safely until the next infusion.