REBLOZYL 75 mg POWDER FOR INJECTABLE SOLUTION

2. What you need to know before you are given Reblozyl

Do not use Reblozyl

• if you are allergic to luspatercept or any of the other ingredients of this medicine (listed in section 6)
• if you are pregnant (see section on pregnancy)
• if you need treatment to control the production of blood cells outside the bone marrow (extramedullary hematopoietic masses, HEM masses)

Warnings and precautions

Talk to your doctor before starting treatment with this medicine if:

• You have beta-thalassemia and have had your spleen removed. You may have a higher risk of forming a blood clot. Your doctor will discuss 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 likelihood of a blood clot.

• You have severe back pain that does not go away, numbness or weakness or loss of voluntary movement in your legs, arms, or hands, fecal and urinary incontinence. These may be symptoms of extramedullary hematopoietic masses (HEM masses) and spinal cord compression.
• You have ever had high blood pressure (because Reblozyl may increase it). Your blood pressure will be checked before you receive Reblozyl and during treatment. You will only be given Reblozyl if your blood pressure is under control.
• 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.

Regular tests

You will have a blood test before each administration of this medicine. The reason is that your doctor needs to check that your hemoglobin level is suitable for treatment.

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

Children and adolescents

This medicine is not recommended for use in children and adolescents under 18 years of age.

Other medicines and Reblozyl

Tell your doctor if you are taking, have recently taken, or might take any other medicines.

Pregnancy

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

Breast-feeding

• Do not breast-feed during treatment with this medicine or for 3 months after the last administration. It is not known if this medicine passes into breast milk.

Contraception

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

Talk to your doctor about the contraceptive methods that may be suitable for you during treatment with this medicine.

Fertility

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

Driving and using machines

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

Reblozyl contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially "sodium-free".

3. How Reblozyl is given

Before you are given this medicine, your doctor will have done a blood test and decided if you need Reblozyl.

Reblozyl will be given by subcutaneous injection (under the skin).

Amount to be given

The dose is based on your body weight in kilograms. The injection will be given 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 given once every three weeks.
• Your doctor will check your progress and change the dose if necessary.

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

Myelodysplastic 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.

If you miss a dose

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

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

4. Possible side effects

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

Serious side effects

Tell your doctor immediatelyif you get any of the following side effects:

• difficulty walking or talking, dizziness, unsteadiness, and lack of 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

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

Other side effects:

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

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

• dizziness, headache
• diarrhea, nausea (feeling sick)
• stomach pain
• back pain, bone pain, or joint pain
• feeling tired or weak
• difficulty sleeping or staying asleep
• changes in blood test results (increased liver enzymes, increased creatinine in blood). 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 injury
• nosebleeds
• severe headache on one side of the head
• redness, burning, and pain at the injection site (injection site reactions) or swelling, itching of the skin (erythema at the injection site)
• high levels of uric acid in the blood (detected in laboratory tests)
• foamy urine. This may be a sign of excess protein in the urine (proteinuria and albuminuria)

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Reblozyl

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 and on the vial after EXP. The expiry date is the last day of the month stated.

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

After first opening and reconstitution, Reblozyl should be used immediately. If not used immediately, when stored in the original packaging, the reconstituted medicinal product 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.

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.

6. Contents of the pack and other information

Composition of Reblozyl

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

Appearance and pack contents

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

Each pack contains 1 vial.

Marketing authorisation holder

Bristol-Myers Squibb Pharma EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Manufacturer

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BD Utrecht

Netherlands

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: 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 medicinal products, the name and batch number of the administered product should be clearly recorded.

Incompatibilities

This medicine must not be mixed with other medicines except those mentioned in section 6.

Storage of the medicine

Unopened vial

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

Reconstituted solution

When stored in the original carton, the physicochemical stability of the reconstituted medicinal product has been demonstrated for a maximum of 8 hours at room temperature (≤25°C) or for a maximum of 24 hours between 2°C and 8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and should not exceed 24 hours at 2°C to 8°C.

Do not freeze the reconstituted solution.

Dose calculation

The total dose, based on 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 injections (API). A graduated syringe should be used during reconstitution to ensure dose accuracy. See Table 1.

Table1. Reblozyl reconstitution table

1. Remove the color cap from the vial and clean the top with an alcohol swab.
2. Add API to the vial using a properly graduated syringe with a needle, directing the flow towards the lyophilized powder. Let it stand for 1 minute.
3. Discard the needle and syringe used for reconstitution. Do not use them for subcutaneous injection.
4. Gently move the vial in a circular motion for 30 seconds. Stop moving and let the vial stand upright for 30 seconds.
5. Inspect the vial to ensure that there is no undissolved powder in the solution. If undissolved powder is observed, repeat step 4 until it is completely dissolved.
6. Invert the vial and gently move it upside down for 30 seconds. Place the vial upright again and let it stand for 30 seconds.
7. Repeat step 6 seven more times to ensure complete reconstitution of the material on the sides of the vial.
8. Visually inspect the reconstituted solution before administration. If mixed correctly, the reconstituted Reblozyl solution is a colorless to yellowish, clear to slightly opalescent solution, in which no foreign particles are visible. 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.

Method of administration

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

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

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

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

Disposal

Disposal of unused medicine and all materials that have come into contact with it should be done in accordance with local regulations.