Prospecto: information for the user

Grafalon 20 mg/ml concentrate for solution for infusion

Human anti-T lymphocyte immunoglobulin from rabbit

Read this prospect carefully before starting to use this medicine, because it contains important information for you

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

Content of theprospect:

1.What Grafalon is and for what it is used

2.What you need to know before using Grafalon

3.How to use Grafalon

4.Possible adverse effects

5Storage of Grafalon

6. Contents of the container and additional information

Grafalonbelongs to a class of medications called immunosuppressants.

You will be prescribedGrafalonif you have undergone or are about to undergo arenal transplant.The purpose of the medication is to prevent your immune system from rejecting the new organ.Grafalonwill help you prevent or stop the rejection response by blocking the development of special cells that would normally attack the transplanted organ.

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

Grafalonis used as part of animmunosuppressive treatmentin combination with other immunosuppressive medications.

No use Grafalon

• if you areallergicto the active ingredient of Grafalon (human anti-thymocyte globulin from rabbit) or to any of the other components of this medication(listed in section 6)
• if you have aninfectionand the treatment you are receiving is not working
• if you have difficulty stoppingbleedingdue to a low platelet count (blood cells responsible for blood coagulation)
• if you have atumor, except if you are to undergo a hematopoietic stem cell transplant

Warnings and precautions

Consult your doctor or pharmacist before starting to use Grafalon and especially if you have had any of the following problems. You may be prescribed Grafalon, but you will first need to consult with your doctor.

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

Blood tests will be performed to measure your platelet count (blood cells responsible for blood coagulation) 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 offinfections. Your doctor will treat these infections properly. In patients treated for the prevention of GvHD, infections can be fatal.

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

Use of Grafalon with other medications

Inform your doctor if you are taking, have recently taken, or may need to take other medications, including those obtained without a prescription.

These medications may interfere with the effect of Grafalon.

• Grafalon is used in combination with other immunosuppressants. 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).

• Livevaccinesare contraindicated because you are receiving immunosuppressive treatment. Inactivatedvaccinesmay not work if administered at the same time as Grafalon. If you are administered a vaccine, inform your doctor about your treatment.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.If you need to take Grafalon, your doctor will discuss with you the risks and benefits of taking this medication during pregnancy.

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

Driving and operating machinery

Not applicable.

Important information about the manufacture of Grafalon

Human components (e.g., red blood cells) are used in the production of Grafalon. Therefore, a series of measures are necessary to prevent the transmission of infectious agents to patients. These include the careful selection of donors to ensure that those who may transmit infections are excluded, as well as the analysis of each donation to detect the presence of viruses/infections. The manufacturing process also includes a series of steps in the processing of human components that may inactivate or eliminate viruses. Despite these measures, when administering medications for which human components have been used, it cannot be entirely ruled out that infectious agents may be transmitted. This may also apply to unknown viruses and emerging viruses or other types of infections.

The measures taken are considered effective for viruses with a coat such as HIV, hepatitis B virus, and hepatitis C virus, as well as for viruses without a coat such as hepatitis A virus and parvovirus B19.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Grafalon has been prescribed to you by a qualified and experienced doctor in immunosuppressive treatment.

Grafalon will be administered to you in a hospital. Grafalon will be administered to you through a venous infusion. Before administering the infusion, the medication will be diluted in a sodium chloride solution.

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

Ifyou are to receivea kidney transplant:

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

Ifyou have receiveda kidney transplant:

The recommended daily dose will be 3-5 mg/kg of body weight. Your treatment cycle will last from5 to14 days.

Adults whoare to undergoa bone marrow transplant

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

Use in children and adolescents

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

Older patients

Experience in older patients (?65years) is limited. There are no data on the prevention of EICH in patients 65 years or older.

If you use more Grafalon than you should

Treatment with Grafalon will be stopped immediately and other immunosuppressive treatments will be modified. Your immune system may be weakened if you have used too much Grafalon, so you may be given medications to prevent the development of infections.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Inform your doctor immediately if you notice any allergic reactions and anaphylactic shock indicated below:

Reactions to allergensare frequent side effects, following treatment with Grafalon.Less than 1 in 10 patients is likely to experience:

• chest pain
• whistling when breathing
• muscle pain
• skin redness

In 3 out of more than 240 patients, allergic reactions evolved intoanaphylactic shock, a serious and potentially life-threatening condition in which the patient may present the following symptoms:

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

Inform your doctorif you notice any side effects indicated below:

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

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

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

• thrombocytopenia, leucopenia, pancitopenia (blood disorder)
• inflammation of mucous membranes
• swelling
• sensation of fatigue
• chest pain
• joint and muscle pain
• back pain
• muscle stiffness
• low or high blood pressure
• sensation of tingling, pinching, or numbness of the skin
• rapid heart rate (tachycardia)
• sensitivity to light (photophobia)
• increased laboratory parameters
• increased bilirubin in the blood
• blood in the urine
• cough
• epistaxis (nosebleed)
• skin redness
• itching
• skin rash
• renal tubular necrosis (kidney function impairment)
• lymphoproliferative disorder (type of cancer originating from certain white blood cells)
• veno-occlusive disease (small liver veins blocked)
• bacterial sepsis, pneumonia, pyelonephritis, herpes infection, influenza, candidiasis, bronchitis, rhinitis, sinusitis, nasopharyngitis, skin infection

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

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

• increased red blood cell count (polycythemia)
• abnormal lymphatic accumulation
• 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 drug is administered over a prolonged period, a serum disease may develop, which is a type of allergic reaction to a foreign protein and manifests with symptoms such as fever, muscle and joint pain, and skin rash with itching.

Additional side effects in children and adolescents

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

Inform your doctor immediately if you consider that any of the side effects you are experiencing is severe or if you notice any side effect not mentioned in this prospectus.

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C). Store the vial without opening in the outer packaging to protect it from light.

Do not use Grafalon if the solution is cloudy.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and unused medications. This will help protect the environment.

Your doctor will be responsible for disposing of unused medications.

The extraction of the medication from vials and the preparation of the perfusion solution should not be performed with siliconized syringes.

Not suitable for multiple extractions.

Composition ofGrafalon

Theactive principleis 20 mg/ml ofhuman anti-T lymphocyte immunoglobulin from rabbit.

The other components are dihydrogen phosphate monohydrate, phosphoric acid (85%) and water for injection preparations.

Appearance of the product and contents of the packaging

Grafalonis a transparent 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.

Grafalonis supplied in a box containing 1vial or 10vials.

Marketing authorization holder and manufacturer responsible

Neovii Biotech GmbH

Am Haag 6+7

82166 Gräfelfing

Germany

Last review date of this leaflet: September 2024

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/.