Reblozyl 25 mg polvo para solucion inyectable

Patient Information Leaflet

Reblozyl 25 mg powder for injection

Reblozyl 75 mg powder for injection

luspatercept

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this leaflet carefully before receiving this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this leaflet. See section 4.

1.What Reblozyl is and what it is used for

2.What you need to know before receiving Reblozyl

3.How to administer Reblozyl

4.Possible side effects

5.Storage of Reblozyl

6.Contents of the pack and additional information

Reblozyl contains the active ingredient luspatercept. It is used for the following:

Mylodysplastic syndromes

Mylodysplastic syndromes (MDS) are a group of diverse blood and bone marrow disorders.

• Red blood cells show alterations and do not develop correctly.

• Patients may present several signs and symptoms, including few red blood cells (anemia) and may require red blood cell transfusions.

Reblozyl is used in adults with anemia caused by MDS who require red blood cell transfusions. It is used in adults who have already received other treatments with erythropoietin or who cannot receive them.

Beta-thalassemia

Beta-thalassemia is a hereditary blood disorder.

• Affects the production of hemoglobin.
• Patients may present several signs and symptoms, including few red blood cells (anemia) and may require red blood cell transfusions.

Reblozyl is used for the treatment of anemia in adults with beta-thalassemia who may or may not require regular red blood cell transfusions.

How Reblozyl works

Reblozyl improves the body's ability to produce red blood cells. Red blood cells contain hemoglobin, a protein that transports oxygen throughout the body. When the body produces more red blood cells, the level of hemoglobin increases.

For patients with MDS and beta-thalassemia who require regular blood transfusions

The treatment with Reblozyl may prevent or reduce the need for red blood cell transfusions.

• Red blood cell transfusions can elevate iron concentrations in the blood and different organs of the body. This can be harmful in the long term.

For patients with beta-thalasemia who do not require regular blood transfusions

The treatment with Reblozyl may improve anemia by increasing the level of hemoglobin.

Do not use Reblozyl

• If you are allergic to luspatercept or any of the other components of this medication (listed in section6)
• If you are pregnant (see section on pregnancy)
• If you need treatment for the control of masses that produce blood cells outside of the bone marrow (extramedullary hematopoietic masses, HEM)

Warnings and precautions

Consult your doctor before starting treatment with this medication if:

• You haveβ‑thalassemia and have had your spleen removed. You may have a higher risk of forming a blood clot. Your doctor will discuss with you other possible factors that may increase this risk, such as:
• • hormone replacement therapy or
  • a previous blood clot

Your doctor may use preventive measures or medications to reduce the possibility of a blood clot.

• You have intense back pain that does not go away, numbness or weakness, or loss of voluntary movement in your legs, hands, or arms, fecal and urinary incontinence. These may be symptoms of HEM and spinal cord compression.
• You have had high blood pressure (because Reblozyl may increase it). Your blood pressure will be monitored before receiving Reblozyl and during treatment. Reblozyl will only be administered if your blood pressure is controlled.
• You have a condition that affects the strength and health of your bones (osteopenia and osteoporosis). You may be at risk of breaking your bones more easily.

Periodic analysis

You will have a blood test before each administration of this medication. This is because your doctor needs to verify that the hemoglobin concentration is adequate for treatment.

If you have kidney problems, your doctor may perform other tests.

Children and adolescents

This medication is not recommended for use in children and adolescents under 18years.

Other medications and Reblozyl

Inform your doctor if you are taking, have taken recently, or may need to take any other medication.

Pregnancy

• Do not use this medication during pregnancy or at least 3months before conception. Reblozyl may cause harm to the fetus.
• Your doctor will perform a pregnancy test before starting treatment.
• If you think you may be pregnant or plan to become pregnant, consult your doctor before using this medication.

Breastfeeding

• You should not breastfeed during treatment with this medication or for 3months after the last administration. It is not known if this medication passes into breast milk.

Contraception

• You should use an effective contraceptive method during treatment with Reblozyl and for 3months after receiving your last dose.

Discuss contraceptive methods with your doctor that may be suitable for you during treatment with this medication.

Fertility

If you are a woman, this medication may cause fertility problems. That is, it may affect your ability to have a baby. Consult your doctor before starting treatment.

Driving and operating machinery

You may feel tired, dizzy, or faint during treatment with Reblozyl. If you experience these effects, do not drive or operate tools or machinery and contact your doctor immediately.

Reblozyl contains sodium

This medication contains less than 1mmol of sodium (23mg) per dose; that is, it is essentially “sodium-free”.

Before receiving this medication, your doctor will have had you undergo a blood test and decided if you need Reblozyl.

Reblozyl will be administered via a subcutaneous injection (under the skin).

Amount to be Administered

The dose is based on your body weight in kilograms. The injection will be administered by a doctor, nurse, or other healthcare professional.

• The recommended initial dose is 1.0 mg per kilogram of body weight.
• This dose should be administered once every three weeks.
• Your doctor will monitor your progress and adjust the dose as necessary.

During treatment with Reblozyl, your doctor will monitor your blood pressure.

Myleodysplastic Syndromes

The maximum single dose is 1.75 mg per kilogram of body weight.

Beta-Thalassemia

The maximum single dose is 1.25 mg per kilogram of body weight.

Missed Dose

If you miss a Reblozyl injection or delay a medical appointment, you will receive a Reblozyl injection as soon as possible. Your dose will then continue as prescribed (with a minimum of 3 weeks between injections).

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

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

Severe side effects

Inform your doctor immediatelyif you experience any of the following side effects:

• difficulty walking or speaking, dizziness, loss of balance and coordination, numbness or paralysis in the face, arm, or leg (often on one side of the body) or blurred vision. These effects may be symptoms of a stroke

• painful swelling and pressure in the leg or arm (blood clots)
• intense back pain that does not go away, numbness or weakness or loss of voluntary movement in legs, hands, or arms, fecal and urinary incontinence. They may be symptoms of extramedullary hematopoietic masses (HEM masses) and spinal cord compression
• swelling around the eyes, face, lips, mouth, tongue, or throat
• allergic reactions
• hives

Other side effects:

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

• chest infection
• cough
• difficulty breathing or shortness of breath
• high blood pressure without symptoms or associated with headache
• urinary tract infection
• upper respiratory tract infection
• flu or flu-like symptoms

• dizziness, headache
• diarrhea, nausea (urge to vomit)
• stomach pain
• back, bone, or joint pain
• sense of fatigue or weakness
• difficulty sleeping or staying asleep
• changes in blood test results (elevated liver enzymes, elevated blood creatinine). These may be signs of liver and kidney problems.

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

• fainting, feeling like everything is spinning
• broken bones due to trauma
• nosebleed
• intense headache on one side of the head
• redness, burning, and pain at the injection site (injection site reactions) or swelling, itching (erythema at the injection site)
• high levels of uric acid in the blood (detected in clinical tests)
• foamy urine. This may be a sign of excessive protein in the urine (proteinuria and albuminuria)

Reporting side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directlythrough the national notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information about 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 box and vial after EXP. The expiration date is the last day of the month indicated.

Unopened vials: Store in refrigerator (between 2°C and 8°C). Do not freeze. Store in the original packaging to protect it from light.

After the first opening and reconstitution, Reblozyl must be used immediately. If not used immediately, the reconstituted medication can be stored for a maximum of 8 hours at room temperature (≤25°C) or for a maximum of 24 hours between 2°C and 8°C.

Do not freeze the reconstituted solution.

Do not dispose of medications through drains or trash. Ask your pharmacist how to dispose of empty containers and unused medications. This will help protect the environment.

Composition of Reblozyl

• The active ingredient is luspatercept. Each vial contains 25mg or 75mg of luspatercept. After reconstitution, each milliliter of the solution contains 50mg of luspatercept.
• The other excipients are citric acid monohydrate (E330), sodium citrate (E331), polisorbate 80, sucrose, hydrochloric acid (to adjust the pH) and sodium hydroxide (to adjust the pH).

Appearance of the product and contents of the package

Reblozyl is a white to off-white powder for injectable solution. Reblozyl is supplied in glass vials containing 25mg or 75mg of luspatercept.

Each package contains 1vial.

Marketing Authorization Holder

Bristol‑MyersSquibbPharmaEEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Responsible for manufacturing

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BD Utrecht

Netherlands

Last review date of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.

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This information is intended only for healthcare professionals:

Traceability

In order to improve the traceability of biological medicines, the name and batch number of the administered medicine must be clearly recorded.

Incompatibilities

This medicine should not be mixed with others, except those mentioned in section6.

Storage of the medicine

Unopened vial

Store in refrigerator (between 2°C and 8°C). Do not freeze. Store in the original packaging to protect it from light.

Reconstituted solution

When stored in the original packaging, the physical and chemical stability of the reconstituted medicine during use has been demonstrated for a maximum of 8hours at room temperature (≤25°C) or for a maximum of 24hoursbetween 2°Cand8°C.

From a microbiological point of view, the medicine should be used immediately. If not used immediately, the storage periods during use and the storage conditions before use are the responsibility of the user and should not exceed 24hoursa temperatures between 2°Cand8°C.

Do not freeze the reconstituted solution.

Dose calculation

The total dose, according to the patient's weight (kg), is calculated as follows:

Total dose (mg) = dose level (mg/kg)×patient weight (kg), every three weeks.

Instructions for reconstitution

Reblozyl is supplied as a lyophilized powder for reconstitution with water for injection (API). A graduated syringe should be used during reconstitution to ensure the accuracy of the dose. See Table1.

Table1. Reconstitution table of Reblozyl

1.Remove the colored cap from the vial and clean the top with an alcohol wipe.

2.Add API to the vial using a graduated syringe with a needle, directing the flow towards the lyophilized powder. Let it rest for one minute.

3.Discard the syringe and needle used for reconstitution. Do not use them for subcutaneous injection.

4.Gently move the vial in a circular motion for 30seconds. Stop moving and let the vial stand upright for 30seconds.

5.Inspect the vial to verify that there is no undissolved powder in the solution. If undissolved powder is observed, repeat step4 until it is completely dissolved.

6.Invert the vial and gently move it in an inverted position for 30seconds. Place the vial back in the upright position and let it rest for 30seconds.

7.Repeat step6 seven times to ensure complete reconstitution of the material located on the sides of the vial.

8.Visually inspect the reconstituted solution before administration. If properly mixed, the reconstituted solution of Reblozyl is a colorless to yellowish, transparent to slightly opalescent solution in which no foreign particles are observed. Do not use if foreign particles or undissolved medicine are observed.

9.If the reconstituted solution is not used immediately, see the previous section,Storage of the medicine.

Administration form

If the reconstituted solution of Reblozyl has been refrigerated, it should be removed 15-30minutes before injection to reach room temperature. This will make the injection more comfortable.

The maximum recommended volume of the medicine per injection site is 1.2ml. If more than 1.2ml is needed, the total volume of Reblozyl should be divided into injections of similar volume and administered in separate areas in the same anatomical location, but on opposite sides of the body. Reconstitute the number of Reblozyl vials necessary to achieve the desired dose.

Inject Reblozyl subcutaneously in the arm, thigh, or abdomen.

If multiple injections are needed, use a new syringe and needle for each subcutaneous injection. Discard the unused content. Do not administer more than one dose from the same vial.

Elimination

The elimination of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.