GRAFALON 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Grafalon 20 mg/ml concentrate for solution for infusion

Human anti-T-lymphocyte immunoglobulin of rabbit origin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of thepackage leaflet:

1. What is Grafalon and what is it used for
2. What you need to know before you use Grafalon
3. How to use Grafalon
4. Possible side effects

5 Storage of Grafalon

1. Package contents and further information

1. What is Grafalon and what is it used for

Grafalon belongs to a class of medicines called immunosuppressants.

You will be prescribed Grafalon if you have had or are going to have a kidney transplant.The function of the medicine is to prevent your immune system from rejecting the new organ. Grafalon will help you prevent or stop the rejection response by blocking the development of certain cells that would normally attack the transplanted organ.

You may also receive Grafalon before a stem cell transplant(e.g. a peripheral blood or bone marrow transplant) to prevent a disorder known as "graft-versus-host disease". This is a serious complication that can occur after a stem cell transplant when the donated cells react against the patient's own tissues.

Grafalon is used as part of an immunosuppressive treatmentin combination with other immunosuppressive medicines.

2. Before you use Grafalon

Do not use Grafalon

• if you are allergicto the active substance of Grafalon (human anti-T-lymphocyte immunoglobulin of rabbit origin) or to any of the other components of this medicine (listed in section 6)
• if you have an infectionand the treatment you are receiving is not working
• if you have problems stopping a bleeddue to a low platelet count (blood cells responsible for blood clotting)
• if you have a tumor, unless you are going to have a stem cell transplant

Warnings and precautions

Talk to your doctor or pharmacist before starting treatment with Grafalon, especially if you have had any of the following problems. You may be prescribed Grafalon, but you will need to discuss it with your doctor first.

• if you have previously had allergic reactions to these medicines (immunosuppressants) or to rabbit proteins
• if you have liver disease
• if you have heart problems

You will have blood tests to measure your platelet count (blood cells responsible for blood clotting) and other coagulation parameters, as the administration of Grafalon may increase the risk of bleeding.

Infections with Grafalon

Grafalon reduces your body's defense system and therefore your body will not be as effective as usual in fighting infections. Your doctor will treat these infections properly. In patients treated for the prevention of graft-versus-host disease, infections can be fatal.

There is no data on the use of Grafalon after allogeneic stem cell transplantation from umbilical cord blood.

Using Grafalon with other medicines

Tell your doctor if you are taking, have recently taken, or might take other medicines, including those obtained without a prescription.

These medicines may interfere with the effect of Grafalon.

• Grafalon is used in combination with other immunosuppressive medicines. If you take Grafalon at the same time as these other immunosuppressants, you will increase the risk of infection, abnormal bleeding, and anemia (a blood disorder).

• Live vaccinesare contraindicated because you are receiving immunosuppressive treatment. Inactivated vaccinesmay not work if administered at the same time as Grafalon. If you are given a vaccine, inform your doctor about your treatment.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine. If it is necessary for you to take Grafalon, your doctor will discuss the risks and benefits of taking this medicine during pregnancy.

Tell your doctor if you are breastfeeding. Grafalon may pass into breast milk.

Driving and using machines

Not applicable.

Important information about the manufacture of Grafalon

In the production of Grafalon, human components (e.g. red blood cells) are used. Therefore, a series of measures are necessary to prevent the transmission of infectious agents to patients. These include careful selection of donors to ensure that those who may transmit infections are excluded, as well as analysis of each donation to detect the presence of viruses/infections. The manufacturing process also includes a series of stages for processing human components that can inactivate or eliminate viruses. Despite these measures, when medicines for which human components have been used are administered, the transmission of infections cannot be completely excluded. This also applies to unknown viruses and new or emerging viruses, or other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as for non-enveloped viruses such as hepatitis A virus and parvovirus B19.

3. How to use Grafalon

Follow the instructions for administration of this medicine exactly as prescribed by your doctor. If you are unsure, consult your doctor or pharmacist again.

Treatment with Grafalon has been prescribed by a qualified doctor with experience in immunosuppressive treatment.

Grafalon will be administered to you in a hospital. Grafalon will be administered by intravenous infusion. Before administering the infusion, the medicine will be diluted in a sodium chloride solution.

One of the following doses may be administered to adults and children, based on their weight and condition:

If you are going to receivea kidney transplant:

Your doctor will decide which of the following doses will be administered to you:

If you have receiveda kidney transplant:

The recommended daily dose will be 3-5 mg/kg body weight. Your treatment cycle will last from 5 to 14 days.

Adults who are going to undergoa stem cell transplant

The recommended daily dose is 20 mg per kg body weight, usually starting from day -3 to day -1 before the stem cell transplant.

Use in children and adolescents

Available information indicates that pediatric patients do not require a different dosage from adult patients.

Elderly patients

Experience in patients over 65 years of age is limited. There is no data on the prevention of graft-versus-host disease in patients 65 years of age or older.

If you use more Grafalon than you should

Treatment with Grafalon will be stopped immediately and the rest of the immunosuppressive treatments will be modified. Your immune system may be weakened if you have exceeded the use of Grafalon, so you may be given medicines to prevent the onset of infections.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately if you notice any of the following serious side effects of allergic reactions and anaphylactic shock:

Allergic reactionsare frequent side effects following treatment with Grafalon. Less than 1 in 10 patients is likely to experience them:

• chest pain
• wheezing
• muscle pain
• skin redness

In 3 out of more than 240 patients, allergic reactions evolved into anaphylactic shock. It is a serious and potentially life-threatening condition in which the patient may experience the following symptoms:

• high fever
• skin rash
• swelling
• difficulty breathing
• low blood pressure

Tell your doctorif you notice any of the following side effects:

Very common side effects(may affect more than 1 in 10 people):

• fever
• chills
• headache
• shaking
• vomiting
• nausea
• diarrhea
• abdominal pain
• difficulty breathing
• shortness of breath
• increased risk of infection
• low red blood cell count (anemia)

Common side effects(may affect up to 1 in 10 people):

• thrombocytopenia, leukopenia, pancytopenia (blood disorder)
• mucosal inflammation
• swelling
• feeling tired
• chest pain
• joint and muscle pain
• back pain
• muscle stiffness
• low or high blood pressure
• tingling, numbness, or prickling sensation of the skin
• rapid heartbeat (tachycardia)
• increased sensitivity to light (photophobia)
• increased laboratory parameters
• increased bilirubin in the blood
• blood in the urine
• cough
• nosebleed
• skin redness
• itching
• skin rash
• renal tubular necrosis (kidney failure)
• lymphoproliferative disorder (a type of cancer that originates from certain white blood cells)
• veno-occlusive disease (small veins in the liver blocked)
• bacterial sepsis, pneumonia, pyelonephritis, herpes infection, influenza, candidiasis, bronchitis, rhinitis, sinusitis, nasopharyngitis, skin infection

Uncommon side effects(may affect up to 1 in 100 people):

• indigestion (dyspepsia)
• inflammation of the mucous membranes caused by reflux of gastric secretion into the esophagus
• increased liver enzymes (laboratory parameters for the liver)
• increased cholesterol
• veno-occlusive disease (small veins in the liver blocked)
• shock related to blood vessels (dilation of blood vessels)

• increased red blood cell count (polycythemia)
• abnormal accumulation of lymph
• water retention
• infection at the catheter site, Epstein-Barr virus infection, gastrointestinal infection, erysipelas, wound infection

Rare but medically important side effects(may affect up to 1 in 1,000 people):

• Hemolysis (abnormal breakdown of red blood cells)

In rare cases, especially if the medicine is administered over a prolonged period, serum sickness may develop, which is a type of allergic reaction to a foreign protein and is characterized by symptoms such as fever, muscle and joint pain, and skin rash with itching.

Additional side effects in children and adolescents

Available information indicates that the side effects of Grafalon in children and adolescents are not fundamentally different from those observed in adults.

Tell your doctor immediately if you think any of the side effects you are experiencing are serious or if you notice any side effect not mentioned in this leaflet.

Some side effects may occur several months after administration of Grafalon, these late effects include an increased risk of infections and certain types of cancer.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Grafalon

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month shown.

Store in a refrigerator (between 2°C and 8°C). Store the vial in the outer packaging to protect it from light.

Do not use Grafalon if the solution is cloudy.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

Your doctor will be responsible for disposing of unused medicines.

The extraction of the medicine from the vials and the preparation of the solution for infusion should not be performed with siliconized syringes.

Not suitable for multiple withdrawals.

6. Package contents and further information

Composition ofGrafalon

The active substanceis 20 mg/ml of human anti-T-lymphocyte immunoglobulin of rabbit origin.

The other ingredients are sodium dihydrogen phosphate dihydrate, phosphoric acid (85%), and water for injections.

Appearance and package contents

Grafalon is a clear to slightly opalescent, colorless to pale yellow solution, in glass vials.

The smallest vial, 5 ml, contains 100 mg of Grafalon, while the largest vial, 10 ml, contains 200 mg of Grafalon.

Grafalon is supplied in a carton containing 1 vial or 10 vials.

Marketing authorization holder and manufacturer

Neovii Biotech GmbH

Am Haag 6+7

82166 Gräfelfing

Germany

Date of last revision of this leaflet: September 2024

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es/.