Keycute

PACKAGE LEAFLET: INFORMATION FOR THE USER

Keycute 160 mg/ml Solution for subcutaneous infusion

Normal human immunoglobulin (SCIg) for subcutaneous use
This medicinal product is subject to additional monitoring. This will allow for 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 all of 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, ask your doctor.
• This medicine has been prescribed for you. 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 effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Keycute is and what it is used for

Keycute is a normal human immunoglobulin solution for subcutaneous use.
Immunoglobulins are human antibodies also present in blood.
Keycute is used:

• to restore antibody levels to normal (replacement therapy) in adult patients who have a reduced or completely absent congenital ability to produce antibodies (primary immunodeficiencies).
• in the treatment of blood cancers leading to severely reduced antibody levels (hypogammaglobulinemia) and recurrent bacterial infections:
  • in patients with chronic lymphocytic leukemia (CLL) who have not responded to antibiotic prophylaxis or in whom such prophylaxis is contraindicated.
  • in patients with multiple myeloma (MM).
• in patients with severely reduced antibody levels (hypogammaglobulinemia) who are about to undergo or have undergone allogeneic hematopoietic stem cell transplantation (HSCT).

2. What you need to know before using Keycute

Do not use Keycute
If you are allergic to human immunoglobulins or to any of the other ingredients of this
medicinal product (listed in section 6).
If you have antibodies in your blood directed against IgA-type immunoglobulins. This is
very rare and may occur if you do not have IgA-type immunoglobulins in your blood.
Into a blood vessel.

Warnings and precautions
Talk to your doctor before using Keycute.
Your doctor or another healthcare professional will closely monitor you and observe you carefully
throughout the infusion and for 20 minutes after the infusion with Keycute to check for any reactions.
After the first infusion, you will be asked to remain under observation for one hour following the
infusion to ensure no reactions occur.
Adverse reactions may occur more frequently if you are receiving normal human immunoglobulins
for the first time, or rarely, if you have previously been treated with another medicinal product
containing normal human immunoglobulins, or when a long interval has passed since the previous
infusion.
In certain conditions, immunoglobulins may increase the risk of myocardial infarction, stroke,
pulmonary embolism, or deep vein thrombosis, as they can increase blood viscosity.
Therefore, your doctor will exercise particular caution in the following circumstances:

• if you are elderly,
• if you have diabetes,
• if you have high blood pressure (hypertension),
• if your blood volume is too low (hypovolemia),
• if you have or have had blood vessel problems (vascular diseases),
• if you have an increased tendency for blood clotting (hereditary or acquired thrombophilic disorders),
• if you suffer from thrombotic episodes,
• if you have diseases that increase blood thickness (viscosity),
• if you have had a prolonged period of immobility.

If you experience symptoms such as shortness of breath, pain and swelling in the limbs, loss of movement or sensation in part of the body (focal neurological deficits), or chest pain, you must contact your doctor immediately, as you may be experiencing a thrombotic event.
If you develop a severe headache, neck stiffness, drowsiness, fever, photophobia (light sensitivity), nausea, and vomiting, you may have Aseptic Meningitis Syndrome (AMS); contact your doctor immediately.
You may be allergic (hypersensitive) to immunoglobulins (antibodies) without knowing it.
This can happen even if you have previously received human immunoglobulins and tolerated prior administrations. This may occur particularly if you lack sufficient IgA-type immunoglobulins (IgA deficiency with anti-IgA antibodies). In these rare cases, allergic (hypersensitivity) reactions such as a drop in blood pressure or shock may occur. If you have anti-IgA antibodies and subcutaneous IgG treatment remains the only therapeutic option, treatment with Keycute must be administered under strict medical supervision.
In case of an adverse reaction, your doctor will decide whether to reduce the rate of administration or discontinue the infusion. The necessary treatment will be determined based on the nature and severity of the side effect.
Keycute is for subcutaneous use only. If Keycute is accidentally administered into a blood vessel, you may go into shock.
In case of shock, your doctor must administer standard treatment for shock.
Inform your doctor if you suffer from any of the conditions described above; your doctor will exercise particular caution when prescribing and administering Keycute to you.

Viral safety
Medicinal products prepared from human blood or plasma are subject to a number of safety measures to prevent the transmission of infections to patients. These measures include careful selection of blood or plasma donors to ensure potentially infected donors are excluded, and testing of each donation and plasma pool to detect the possible presence of viruses. Manufacturers of these medicinal products also incorporate steps in the processing of blood or plasma capable of inactivating or removing pathogens.
Despite these measures, when administering medicinal products prepared from human blood or plasma, the possibility of transmitting an infection cannot be completely ruled out. This also applies to emerging or unknown viruses or other types of infectious agents.
The measures taken are considered effective against lipid-enveloped viruses such as the human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and against the non-lipid-enveloped hepatitis A virus (HAV). The measures taken have limited effectiveness against non-lipid-enveloped viruses such as parvovirus B19. Immunoglobulins have not been associated with hepatitis A (HAV) or parvovirus B19 infections; this may be due to the protective capacity of the antibodies against these infections contained in the product.
It is strongly recommended that each time you receive a dose of Keycute, the name and batch number of the product be recorded, in order to maintain traceability of the batch used.

Blood tests
Keycute may interfere with certain blood tests.

Children
The safety and efficacy of Keycute in children have not yet been established.

Elderly
The safety and efficacy of Keycute in the elderly have not yet been established.

Other medicines and Keycute
Inform your doctor if you are taking or have recently taken any other medicines, including those without a prescription.
Normal human immunoglobulins for subcutaneous use must not be mixed with other medicinal products.

Live attenuated virus vaccines
Administration of immunoglobulin may alter the effectiveness of live attenuated virus vaccines, such as those for measles, rubella, mumps, and varicella, for a period of at least 6 weeks and up to 3 months. After administration of this product, an interval of three months must pass before vaccination with live attenuated virus vaccines. In the case of measles, this reduction in immune response may last up to one year. Therefore, in patients receiving the measles vaccine, antibody levels should be monitored.

Paediatric population
No specific interaction data are available in the paediatric population.

Pregnancy, breastfeeding, and fertility

• If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before using this medicinal product. Your doctor will decide whether it is appropriate to use Keycute during pregnancy and breastfeeding.
• Clinical studies with Keycute have not been conducted in pregnant women. It has been shown that human immunoglobulin products cross the placenta increasingly during the third trimester. However, antibody-containing medicines have been used for years in pregnant women, and no harmful effects on the course of pregnancy, the fetus, or the newborn are expected.
• If you are breastfeeding while being treated with Keycute, the antibodies contained in the product may pass into breast milk and may contribute to protecting your baby from potential infections.
• Clinical experience with immunoglobulins suggests that no harmful effects on fertility are expected.

Driving and using machines
Your ability to drive or use machines may be affected by some adverse reactions associated with Keycute. If you experience any adverse reactions to the medicine during treatment, wait until they have resolved before driving or operating machinery.

Keycute contains sodium
This medicinal product contains up to a maximum of 39 mg of sodium (a main component of table salt) per 10 ml vial and 98 mg of sodium per 25 ml vial.
These amounts correspond, respectively for the 10 ml and 25 ml vials, to 1.95% and 4.9% of the maximum daily dietary intake recommended for an adult.

3. How to use Keycute

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.

This medicine must be administered exclusively by subcutaneous infusion.

Subcutaneous infusion for home treatment must initially be performed and monitored by a physician experienced in the treatment of immunodeficiency and in training patients for home therapy.

You must be trained in the use of the infusion pump, infusion techniques, completion of a treatment diary, and measures to take in case of serious adverse reactions.

If you administer the infusion yourself, always use Keycute exactly as described in the section “Instructions for correct use”. If in doubt, consult your doctor.

The dosing regimen should aim to achieve a trough level of IgG (measured just before the next infusion) of at least 5 g/l.

The dose and treatment schedule depend on the indication.

Your doctor will calculate the correct dose for you, taking into account your body weight and response to treatment.

Keycute can be infused at sites such as the abdomen and thigh. Doses exceeding 30 ml may be divided across multiple sites according to your preference. There is no limit to the number of infusion sites.

At the beginning of treatment, you will receive Keycute at a low infusion rate, which may be gradually increased by your doctor if well tolerated.

Use in children and adolescents
The safety and efficacy of Keycute in children have not yet been established.

Further information on dosage and duration of therapy is provided at the end of this leaflet in the section intended for physicians or healthcare professionals.

If you use more Keycute than you should
Effects of overdose are not known.

If you forget to use Keycute
If you think you have missed a dose, contact your doctor as soon as possible.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
If you notice any of the following side effects, contact your doctor immediately:

• sudden drop in blood pressure
• allergic or hypersensitivity reactions (anaphylactic shock), even if the patient has not previously shown hypersensitivity to earlier administrations.

During treatment with Keycute, the following side effects may also occur:

• headache (cephalalgia)
• diarrhoea
• chills
• fever (pyrexia)
• joint pain (arthralgia)
• back pain
• moderate low back pain
• ear pain (otalgia)
• dizziness
• vertigo
• nausea
• vomiting
• panic attacks

Infections of various types may also occur, affecting the gastrointestinal system (gastroenteritis), respiratory tract (nasopharyngitis, pharyngitis, rhinitis, sinusitis, bronchitis), and the female genitourinary system (e.g. fungal infections of the vulva and vagina caused by Candida species, cystitis).
At the infusion site, the following side effects may frequently occur: swelling, hardening, skin redness (erythema), itching, pain, warmth, urticaria, bruising, skin rashes.
If you notice the onset or worsening of any of the above-mentioned side effects, consult your doctor, pharmacist, or nurse.

Additional side effects in children
This product is indicated for use in adult patients.
The safety and efficacy of Keycute in children have not yet been established.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. You may also report side effects directly via the national reporting system at the following 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.

For information on viral safety, see section 2 “What you need to know before using Keycute”.

5. How to Store Keycute

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 outer packaging after "Exp.". The expiry date refers to the last day of the month.
Store in a refrigerator (2°C - 8°C).
Before use and within the expiry date, only the 10 ml vial may be stored at room temperature, not exceeding 25°C, for a maximum of 6 consecutive months.
After this period, the product must be disposed of. In any case, the product must not be returned to the refrigerator if it has been stored at room temperature.
Record the date of the start of room temperature storage on the outer carton.
The 25 ml vial must be stored exclusively in the refrigerator (2°C - 8°C).
Once the infusion container has been opened, the contents must be used immediately.
Keep the vial in the outer packaging.
Do not freeze.
Do not use this medicine if you notice that the solution is highly turbid, contains deposits, or shows any colour change.
Do not dispose of any medicine 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 Keycute contains
The active substance is human normal immunoglobulin.
One ml of solution contains 160 mg of human normal immunoglobulins.
The solution contains human proteins at a concentration of 160 mg/ml, of which at least 95% consists of immunoglobulin G (IgG).
The subclasses of immunoglobulin G (IgG) have the following distribution:
IgG1 61.6%
IgG2 34.2%
IgG3 3.3%
IgG4 0.9%
The maximum IgA content is 50 micrograms/ml.
Produced from human donor plasma.
The other components are glycine, sodium chloride, and water for injections.

Description of the appearance of Keycute and package contents
Keycute is a clear, colorless solution, or slightly yellowish to light brown in color; slight cloudiness or a small amount of suspended particles may appear during storage. Do not use this medicine if you notice that the solution is markedly cloudy, contains deposits, or shows changes in color.
Keycute 1.6 g/10 ml solution for subcutaneous infusion, 10 ml vial
Keycute 4 g/25 ml solution for subcutaneous infusion, 25 ml vial

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Kedrion S.p.A. - Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca) - ITALY.
Manufacturer:
Kedrion S.p.A. - S.S. 7 bis Km 19.5, S. Antimo (Naples).

The following information is intended exclusively for physicians or healthcare professionals:
Instructions for proper use

• Before administration, bring the product to room or body temperature.
• Before administration, visually inspect the product for particulate matter or discoloration. Do not use solutions that are markedly cloudy or contain deposits. Keycute must be administered by subcutaneous infusion at an initial rate of 10 ml/h/site. If well tolerated, the infusion rate may be gradually increased with each subsequent infusion up to a recommended maximum infusion rate of 22 ml/h/site. More than one pump may be used simultaneously. The volume infused at a particular site may vary. In adults, doses exceeding 30 ml may be divided across multiple sites according to patient preference. There is no limit to the number of infusion sites.

Special precautions
Potential complications can often be avoided by:

• starting treatment with a slow infusion rate (10 ml/h/site),
• ensuring patients are closely monitored for any symptoms during the infusion period. In particular, patients receiving human normal immunoglobulin for the first time, patients previously treated with another immunoglobulin product, and patients who have had a long interval since their last infusion should be monitored during and for the first hour after the first infusion to detect potential signs of adverse reactions. All other patients should be observed for at least 20 minutes after administration. If an adverse reaction occurs, the infusion rate should be reduced or the infusion stopped. The required treatment depends on the nature and severity of the adverse effect. In the event of accidental intravascular administration, patients may go into shock. In case of shock, standard medical treatment for shock must be initiated.

Thromboembolism
Clinical evidence shows an association between immunoglobulin administration and thromboembolic events such as myocardial infarction, cerebrovascular accident (including stroke), pulmonary embolism, and deep vein thrombosis. Caution should be exercised when prescribing and administering immunoglobulins to patients with pre-existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus, history of vascular disease or thrombotic episodes, patients with inherited or acquired thrombophilic disorders, patients who are immobilized for prolonged periods, severely hypovolemic patients, or patients with conditions that increase blood viscosity). Patients should be informed about early symptoms of thromboembolic events, such as dyspnea, pain and swelling in limbs, focal neurological deficits, and chest pain; they should be advised to contact their physician immediately upon onset of such symptoms. Patients should be adequately hydrated prior to the use of immunoglobulins.

Aseptic Meningitis Syndrome (AMS)
Aseptic meningitis syndrome may occur in association with subcutaneous immunoglobulin therapy; symptoms typically appear within several hours up to 2 days after treatment.
Discontinuation of immunoglobulin therapy leads to resolution of AMS within a few days, without sequelae.
Patients should be informed about possible symptoms, including severe headache, neck stiffness, drowsiness, fever, photophobia, nausea, and vomiting.

Dosing recommendations
The dosing regimen should aim to achieve a trough level of IgG (measured just before the next infusion) of at least 5–6 g/l, in order to remain within the age-related reference range for serum IgG levels. A loading dose of at least 0.2–0.5 g/kg (1.25–3.125 ml/kg) body weight may be required, which may need to be divided over several days with a maximum daily dose of 0.1–0.15 g/kg. After achieving stable IgG levels, maintenance doses should be administered at regular intervals (approximately once a week) to achieve a cumulative monthly dose of 0.4–0.8 g/kg body weight. It may be necessary to administer each individual dose at different anatomical sites.
Trough levels should be measured and evaluated together with the incidence of infections.
It may be necessary to increase the dose and achieve higher trough levels to reduce the frequency of infections.

Blood tests
Keycute may interfere with certain blood tests due to the temporary increase in various antibodies that are passively transferred into the bloodstream following immunoglobulin infusion; this increase in antibodies may lead to blood test results that may not be accurate. The passive transfer of antibodies against erythrocyte antigens, e.g., A, B, D (determining blood group), may interfere with certain serological tests for red blood cell antibodies, for example, the direct antiglobulin test (DAT, direct Coombs test).