KEYCUTE 160 mg /Ml Infusion Solution

Зміст інструкції

1. Keycute 160 mg/ml Solution for subcutaneous infusion
   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. Content of the pack and other information

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 the rapid identification
of new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before 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.
• 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 any side effects occur, including those not listed in this leaflet, tell 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 that are also present in the blood.
Keycute is used:

• to restore normal levels (replacement therapy) of antibodies in the blood of adult patients who have a reduced or total congenital inability to produce antibodies (primary immunodeficiencies).
• in the treatment of blood cancers that lead to severely reduced levels of antibodies (hypogammaglobulinemia) and recurrent bacterial infections:
• in patients with chronic lymphocytic leukemia (CLL) who have not responded to antibiotic prophylaxis or in whom the latter is contraindicated.
• in patients with multiple myeloma (MM).
• in patients with severely reduced levels of antibodies (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 medicine (listed in section 6).
If you have antibodies directed against IgA-type immunoglobulins in your blood. This is a very rare occurrence 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.
The doctor or another healthcare professional will monitor you closely and observe you carefully throughout the entire period and for 20 minutes after the infusion with Keycute to verify that there are no reactions.
Only with the first infusion will you be asked to remain under observation for one hour after the infusion to verify that there are no reactions.
Some adverse reactions may occur more frequently if you receive normal human immunoglobulins for the first time or rarely if you have previously been treated with another medicinal product based on normal human immunoglobulins, or when a long interval of time has passed since the previous infusion.
In certain conditions, immunoglobulins may increase the risk of myocardial infarction, stroke, pulmonary embolism, or deep vein thrombosis because they increase blood viscosity.
Therefore, the doctor will pay particular attention in the following circumstances:

• if you are elderly,
• if you suffer from diabetes,
• if you have high blood pressure (hypertension),
• if the blood volume is too low (hypovolemia),
• if you have or have had problems with blood vessels (vascular diseases),
• if you have an increased tendency to blood clotting (inherited or acquired thrombophilic disorders),
• if you suffer from thrombotic episodes,
• if you suffer from diseases that increase blood density (viscosity),
• if you have had a prolonged period of immobility,

If symptoms such as shortness of breath, pain and swelling in the limbs, loss of movement or sensation in a part of the body (focal neurological deficits) and chest pain should occur, you should immediately contact your doctor, you may have an ongoing thrombotic event.
If you experience severe headache, stiff neck, drowsiness, fever, photophobia (sensitivity to light), nausea and vomiting, you may be affected by 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 already received human immunoglobulins in the past and have tolerated previous administrations. This is particularly likely to occur if you do not have enough 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 treatment with IgG for subcutaneous use remains the only therapeutic option, treatment with Keycute must be carried out under strict medical supervision.
In case of an adverse reaction, the doctor will decide whether to reduce the administration rate or to stop the infusion. The necessary treatment will be decided based on the nature and severity of the side effect.
Keycute is exclusively for subcutaneous use. In case of accidental administration of Keycute into a blood vessel, you may go into shock.
In case of shock, the doctor must perform the standard treatment for shock.
Inform the doctor if you suffer from any of the conditions described above, the doctor will use particular caution in prescribing and administering Keycute to you.
Viral safety
Medicines that are prepared from human blood or plasma are subjected 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 that potentially infected donors are excluded and testing of each donation and plasma pool for the presence of viruses. Manufacturers of these medicines also introduce some steps in the processing of blood or plasma capable of inactivating or removing pathogens.
Despite these measures, the possibility of transmitting an infection cannot be completely excluded when administering medicinal specialties prepared from human blood or plasma. This also applies to viruses, or other types of infectious agents, emerging or unknown.
The measures taken are considered effective against enveloped viruses such as the human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and against the non-enveloped hepatitis A virus (HAV). The measures taken have a limited value against non-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 fact that the antibodies against these infections, which are contained in the product, have a protective capacity.
It is strongly recommended that each time you receive a dose of Keycute, the name and batch number of the product are recorded, in order to maintain the traceability of the batch used
Blood tests
Keycute may interfere with some 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
Tell your doctor if you are taking or have recently taken any other medicines, including those available without a prescription.
Normal human immunoglobulins for subcutaneous use must not be mixed with other medicinal products.
Live attenuated virus vaccines
The administration of immunoglobulin may alter for a period of at least 6 weeks and up to 3 months the effectiveness of live attenuated virus vaccines such as those for measles, rubella, mumps and varicella. After the administration of this product, an interval of three months must elapse before vaccination with live attenuated virus vaccines. In the case of measles, this weakening of the response can last up to a year. Therefore, in patients receiving the measles vaccine, the level of antibodies must be checked.
Paediatric population
No specific data on interactions are available in the paediatric population.

Pregnancy, breastfeeding and fertility

• If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are breastfeeding, ask your doctor for advice before using this medicine. The 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. Products containing human immunoglobulins have been shown to cross the placenta in increasing amounts during the third trimester. However, medicines containing antibodies have been used for years in pregnant women and have been shown not to be expected to have harmful effects on the course of pregnancy, the fetus and the newborn.
• If you are breastfeeding and are being treated with Keycute, the antibodies contained in the product may pass into breast milk and may contribute to the protection of your baby from any infections.
• Clinical experience with immunoglobulins suggests that there are no expected adverse effects on fertility.

Driving and using machines
The ability to drive vehicles and use machines may be affected by some adverse reactions associated with Keycute. If you experience adverse reactions to the medicine during treatment, wait for them to resolve before driving or using machines.

Keycute contains sodium
This medicine contains up to a maximum of 39 mg of sodium (the main component of table salt) per 10 ml vial and 98 mg of sodium per 25 ml vial.
These, respectively for the 10 ml and 25 ml vials, are equivalent to 1.95% and 4.9% of the recommended maximum daily intake with the diet of an adult.

3. How to use Keycute

Use this medicine following the instructions of your doctor exactly. If you have any doubts, consult your
doctor.
The medicine must be administered exclusively by subcutaneous route.
Subcutaneous infusion for home treatment must be performed and monitored
initially by a doctor experienced in the treatment of immunodeficiency and in guiding patients
in home therapy.
You must be instructed on the use of the infusion pump, on infusion techniques, on
compiling a therapeutic diary and on the measures to be taken in case of serious adverse reactions.
If you perform the product infusion yourself, always use Keycute following the
instructions exactly as reported in the “Instructions for correct use” paragraph. If you have any doubts, consult your
doctor.
The dosage regimen should induce the achievement of a baseline IgG level (measured before the
next infusion) of at least 5 g/l.
The dose and treatment regimen depend on the indication.
The doctor will calculate the correct dose for you, taking into consideration your weight and the response to
treatment.
Keycute can be injected into sites such as the abdomen and thigh. Doses greater than 30 ml can be
divided into multiple sites according to your preferences. There is no limit to the number of infusion sites.
At the beginning of treatment, you will receive Keycute with a low infusion rate, which may be
gradually increased by the doctor if well tolerated.

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

Further information regarding dosage and duration of therapy is included at the end
If you use more Keycute than you should
No effects of overdose are known.

If you forget to use Keycute
If you believe you have forgotten a dose, contact your doctor as soon as possible.
If you have any doubts 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 gets them.

If you notice any of the following side effects, contact your doctor immediately:

• a sudden drop in blood pressure. Allergic or hypersensitivity reactions (anaphylactic shock) even when the patient has not shown hypersensitivity to previous administrations.

During the use of Keycute, the following side effects may also occur:

• headache
• diarrhoea
• chills
• fever (pyrexia)
• joint pain (arthralgia)
• back pain
• moderate intensity lower back pain
• ear pain (otalgia)
• dizziness
• lightheadedness
• nausea
• vomiting
• panic attacks

Infections of various kinds affecting the gastrointestinal system (gastroenteritis), the airways (nasopharyngitis, pharyngitis, rhinitis, sinusitis, bronchitis) and the female genitourinary system (e.g. infections of the vulva and vagina caused by fungi of the Candida genus and cystitis) cannot be ruled out.
Near the infusion site, the appearance of side effects such as: swelling, hardening, skin redness (erythema), itching, pain, heat, hives, bruises, skin rashes can be frequently noticed.
If you notice the appearance or worsening of any of the side effects listed above, consult your doctor, pharmacist or nurse.

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

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report side effects directly through 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.
For information on viral safety see section 2 “What you need to know before you use Keycute”.

Keycute.

5. How to Store Keycute

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and the 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 can be
stored at room temperature, not exceeding 25°C, for a maximum of 6 consecutive months.
After this period, the product must be discarded. In any case, the product can no longer be
returned to the refrigerator if stored at room temperature.
Record the date of commencement of storage at room temperature on the outer box.
The 25 ml vial must be stored exclusively in a 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 very cloudy or contains deposits or shows
a change in color.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Keycute contains
The active ingredient is normal human immunoglobulin.
One ml of solution contains 160 mg of normal human immunoglobulins.
The solution contains human proteins in an amount of 160 mg/ml, of which at least 95% is
constituted by immunoglobulin G (IgG).
The subclasses of immunoglobulin of type G (IgG) have the following distribution:
IgG 61.6 %
IgG 34.2 %
IgG 3.3 %
IgG 0.9 %
The maximum content of IgA is 50 micrograms/ml.
Produced from plasma of human donors.
The other components are glycine, sodium chloride and water for injections.

Description of the appearance of Keycute and content of the pack
Keycute is a clear and colorless solution, or of pale yellow or light brown color; during
storage, slight turbidity or a small amount of particles in suspension may occur. Do not use this medicine if you notice that the solution is very cloudy or contains deposits
or presents a color change.
Keycute 1.6 g/10 ml solution for subcutaneous infusion, vial of 10 ml
Keycute 4 g/25 ml solution for subcutaneous infusion, vial of 25 ml

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 (Napoli).

The following information is intended exclusively for doctors or healthcare professionals:
Instructions for correct use

• Before administration, bring the product to room or body temperature.
• Before administration, visually inspect the product for particles or chromatic alterations. Do not use solutions that are very cloudy or that contain deposits. Keycute must be infused subcutaneously at an initial rate of 10 ml/h/site. If well tolerated, the infusion rate can be gradually increased with each subsequent infusion up to a recommended maximum infusion rate of 22 ml/h/site. More than one pump can be used simultaneously. The amount of product infused in a particular site may vary. In adults, doses greater than 30 ml may be divided into multiple sites according to patient preference. There is no limit to the number of infusion sites.

Particular precautions
Potential complications can often be avoided:

• by starting treatment with a slow infusion (10 ml/h/site)
• by ensuring that patients are carefully monitored for any symptoms during the infusion period. In particular, patients receiving normal human immunoglobulin for the first time, patients previously treated with another immunoglobulin product, and patients for whom a long interval has elapsed since the previous infusion, must be monitored during the first infusion and for the first hour after the first infusion, to identify potential signs of adverse reactions. All other patients should be observed for at least 20 minutes after administration. In case of an adverse reaction, the administration rate should be reduced or the infusion should be stopped. The necessary treatment depends on the nature and severity of the undesirable effect. In case of accidental administration into a blood vessel, patients may go into shock. In case of shock, standard medical treatment for shock should be performed.

Thromboembolism
There is clinical evidence demonstrating a relationship between the administration of
immunoglobulins and thromboembolic events such as myocardial infarction, stroke
(including stroke), pulmonary embolism and deep vein thrombosis. Caution should be exercised in
prescribing and infusing immunoglobulins in patients with pre-existing risk factors for
thrombotic events (such as advanced age, hypertension, diabetes mellitus and a history of vascular
disease or thrombotic episodes, patients with hereditary or acquired thrombophilic disorders, patients immobilized
for a prolonged period, patients severely hypovolemic, patients with diseases that increase
blood viscosity). Patients should be informed about the first symptoms that may occur
in case of thromboembolic events such as dyspnea, pain and swelling of the limbs, focal neurological deficits and
chest pain; in these cases, it should be recommended to contact their doctor immediately at the onset
of the symptoms themselves. Patients should be adequately hydrated before
use of Immunoglobulins.
Aseptic Meningitis Syndrome (AMS)
Aseptic meningitis syndrome may occur in combination with subcutaneous immunoglobulin therapy; generally symptoms may occur within a period
of time ranging from several hours to 2 days from treatment.
Discontinuation of immunoglobulin therapy leads to remission of AMS within a few
days, without consequences.
Patients should be informed about the symptoms that may appear and include severe headache, neck stiffness, drowsiness, fever, photophobia, nausea and vomiting.

Recommendations for dosage
The dosage regimen should induce the achievement of a baseline IgG level (measured before the
next infusion) of at least 5-6 g/l in order to remain, according to age, within the reference serum
range for IgG. A loading dose of at least 0.2 - 0.5 g/kg (1.25
to 3.125 ml/kg) of body weight may be necessary, which may need to be divided over several days with a maximum daily dose allowed of 0.1 - 0.15 g/kg. After reaching stable IgG levels
administer maintenance doses at repeated intervals (approximately once a
week), to achieve a monthly cumulative dose of approximately 0.4 - 0.8 g/kg of body
weight. Each single dose may need to be injected into different anatomical sites.
Baseline levels should be measured and evaluated together with the incidence of infections.
The dose may need to be increased and higher baseline levels achieved to reduce
the frequency of infections.
Blood tests
Keycute may interfere with some blood tests due to the temporary increase in various
antibodies that are passively transferred into the blood after immunoglobulin infusion; this
increase in antibodies may cause some blood tests to have a result that may not
be correct. Passive transmission of antibodies against red blood cell antigens, e.g. A, B, D
(determining the blood group), may interfere with some serological tests for red blood cell antibodies, for example the direct antiglobulin test (DAT, direct Coombs test).