Reblozyl

Package leaflet: Information for the patient

Reblozyl 25 mg powder for injectable solution, 75 mg powder for injectable solution

luspatercept
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you get any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

1. What Reblozyl is and what it is used for
2. What you need to know before receiving Reblozyl
3. How Reblozyl is administered
4. Possible side effects
5. How to store Reblozyl
6. Contents of the pack and other information

1. What Reblozyl is and what it is used for

Reblozyl contains the active substance luspatercept. It is used for:
Myelodysplastic syndromes
Myelodysplastic syndromes (MDS) are a group of several different disorders affecting the blood and bone marrow.

• Red blood cells become abnormal and do not develop properly.
• Patients may experience various signs and symptoms, including low red blood cell count (anaemia), and may require red blood cell transfusions.

Reblozyl is used in adults with anaemia due to MDS who require red blood cell transfusions.
Beta-thalassaemia
Beta-thalassaemia is a genetic blood disorder.

• It affects the production of haemoglobin.
• Patients may experience various signs and symptoms, including low red blood cell count (anaemia), and may require red blood cell transfusions.

Reblozyl is used to treat anaemia in adults with beta-thalassaemia, whether or not they require regular red blood cell transfusions.
How Reblozyl works
Reblozyl improves the body's ability to produce red blood cells, which contain haemoglobin—a protein that carries oxygen throughout the body. As the body produces more red blood cells, haemoglobin levels increase.
For patients with MDS and beta-thalassaemia who require regular blood transfusions
Taking Reblozyl may prevent or reduce the need for red blood cell transfusions.

• Red blood cell transfusions can lead to excessively high levels of iron in the blood and in various organs of the body. This can become harmful over time.

For patients with beta-thalassaemia who do not require regular blood transfusions
Taking Reblozyl may improve anaemia by increasing haemoglobin levels.

2. What you should know before receiving Reblozyl

Do not use Reblozyl

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

Warnings and precautions
Talk to your doctor before you are given this medicine if:

• you are a patient with β-thalassemia and have had your spleen removed. There may be an increased risk of blood clots. Your doctor will explain other possible factors that may increase the risk, including:
  • hormone replacement therapy or
  • a history of blood clots;
• you are a patient with MDS and have had a stroke or have heart or circulatory problems. There may be an increased risk of blood clots. Your doctor may use preventive measures or medications to reduce the possibility of you developing a blood clot;
• you have severe back pain that does not go away, numbness, weakness, or loss of voluntary movement in your legs, hands, or arms, or loss of control of your bowel or bladder (incontinence). These may be symptoms of extramedullary hematopoietic masses (EMH masses) and spinal cord compression;
• you have ever had high blood pressure; this is because Reblozyl may increase it. Your blood pressure will be monitored before each administration of Reblozyl and throughout the treatment period. Reblozyl will only be administered if your blood pressure is under control;
• you have a condition affecting bone strength and health (osteopenia and osteoporosis). You may have an increased risk of bone fractures.

Routine tests
You will undergo a blood test before each administration of this medicine. This is because your doctor needs to ensure that your hemoglobin level is appropriate for treatment administration.
If you have kidney problems, your doctor may carry out additional tests.

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

Other medicines and Reblozyl
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

Pregnancy

• This medicine must not be used during pregnancy and for at least 3 months before starting a pregnancy. Reblozyl may cause harm to the unborn baby.
• Your doctor will perform a pregnancy test before starting treatment and will provide you with a Patient Alert Card.
• If you suspect you may become pregnant or are planning a pregnancy, consult your doctor before using this medicine.

Breast-feeding

• Do not breast-feed while using this medicine and for 3 months after the last dose. It is not known whether the medicine passes into breast milk.

Contraception

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

Talk to your doctor about contraceptive methods that may be suitable while taking this medicine.

Fertility
If you are a woman, this medicine may cause fertility problems. This may affect your ability to have a child. Talk to your doctor before using this medicine.

Driving and using machines
You may feel tired, dizzy, or faint while using Reblozyl. If this happens, do not drive or operate tools or machinery and contact your doctor immediately.

Reblozyl contains sodium and polysorbate 80
Sodium: This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially ‘sodium-free’.
Polysorbate 80: This medicine contains 0.1 mg of polysorbate 80 in each 25 mg vial or 0.3 mg of polysorbate 80 in each 75 mg vial, equivalent to 0.2 mg/mL. Polysorbates may cause allergic reactions. Consult your doctor if you have known allergies.

3. How Reblozyl is administered

Before you are given this medicine, your doctor will have carried out blood tests and decided whether you need Reblozyl.
Reblozyl will be administered by injection under the skin (subcutaneous route).

How much medicine you will be given
The dose is based on body weight in kilograms. Injections will be given by a doctor, nurse, or other healthcare professional.

• The recommended starting dose is 1 mg per kilogram of body weight.
• This dose should be given once every three weeks.
• Your doctor will monitor your progress and, if necessary, may adjust the dose.

Your doctor will monitor your blood pressure while you are using Reblozyl.

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 an appointment is delayed, you will receive a Reblozyl injection as soon as possible. Then your dosing will continue as prescribed, with at least 3 weeks between doses.

If you have any doubts about how to use this medicine, consult 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 immediately if you notice any of the following:

• difficulty walking or speaking, dizziness, loss of balance and coordination, numbness or paralysis of the face, arms or legs (often on one side of the body), blurred vision. These may all be symptoms of a stroke.
• swelling and painful tightness in the leg or arm (blood clots).
• severe back pain that does not go away, numbness, weakness or loss of voluntary movement in the legs, hands or arms, loss of bowel or bladder control (incontinence). These may be symptoms of extramedullary haematopoiesis masses (EMH masses) and spinal cord compression.
• swelling around the eyes, face, lips, mouth, tongue or throat.
• allergic reactions.
• skin rashes.

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

• cough.
• breathing difficulties or shortness of breath.
• swelling of the legs or hands.
• high blood pressure without symptoms or associated with headache.
• upper respiratory tract infection.
• flu or flu-like symptoms.
• dizziness, headache.
• diarrhoea, feeling unwell (nausea).
• stomach ache.
• back pain, bone 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 or kidney problems.
• cramps, dizziness, irregular heartbeat, mental confusion. These may be symptoms of excess or deficiency of certain minerals in the body (electrolyte abnormalities).

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

• chest infection.
• fainting, vertigo, feeling confused.
• reduced appetite.
• stomach ache.
• bone fracture due to trauma.
• muscle pain.
• chest pain.
• reduced muscle strength.
• small round red/purple spots.
• easy bruising, nosebleeds or bleeding from gums.
• severe headache on one side.
• fast heartbeat (tachycardia).
• redness, burning sensation, pain at the injection site (injection site reactions) or swelling, itching (injection site erythema).
• impaired kidney function.
• excessive sweating.
• high level of uric acid in the blood (detected in tests).
• insufficient fluid levels in the body (dehydration).
• urinary tract infection.
• foamy urine. This may be a sign of excess protein in the urine (proteinuria and albuminuria).
• shortness of breath during physical activity or when lying down. This may be a sign of heart failure.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or nurse.
You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Reblozyl

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging and vial after “Exp.” The expiry date refers to the last day of that month.
Unopened vials: store in a refrigerator (2°C – 8°C). Do not freeze. Keep in the original packaging to protect the medicine from light.
After first opening and reconstitution, Reblozyl must be used immediately. If not used immediately, the reconstituted medicine, when stored in the original packaging, may be kept for up to 8 hours at room temperature (≤ 25°C) or up to 24 hours at 2°C – 8°C.
Do not freeze the reconstituted solution.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Reblozyl contains

• The active substance is luspatercept. Each vial contains 25 mg or 75 mg of luspatercept. After reconstitution, each mL of solution contains 50 mg of luspatercept.
• The other components are monohydrate citric acid (E330), sodium citrate (E331), polysorbate 80 (E433), sucrose, hydrochloric acid (for pH adjustment) and

sodium hydroxide (for pH adjustment). See section 2 - Reblozyl contains
sodium and polysorbate 80.
Description of the appearance of Reblozyl and contents of the pack
Reblozyl is a white to off-white powder for injectable solution (powder for injection). 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
The Netherlands
For further information about this medicinal product, contact the local representative of the Marketing Authorisation Holder:
Belgique/België/Belgien Lietuva
N.V. Bristol-Myers Squibb Belgium S.A. Swixx Biopharma UAB
Tél/Tel: + 32 2 352 76 11 Tel: + 370 52 369140
[email protected] [email protected]
България Luxembourg/Luxemburg
Swixx Biopharma EOOD N.V. Bristol-Myers Squibb Belgium S.A.
Teл.: + 359 2 4942 480 Tél/Tel: + 32 2 352 76 11
[email protected] [email protected]
Česká republika Magyarország
Bristol-Myers Squibb spol. s r.o. Bristol-Myers Squibb Kft.
Tel: + 420 221 016 111 Tel.: + 36 1 301 9797
[email protected] [email protected]
Danmark Malta
Bristol-Myers Squibb Denmark A.M. Mangion Ltd
Tlf: + 45 45 93 05 06 Tel: + 356 23976333
[email protected] [email protected]
Deutschland Nederland
Bristol-Myers Squibb GmbH & Co. KGaA Bristol-Myers Squibb B.V.
Tel: 0800 0752002 (+ 49 89 121 42 350) Tel: + 31 (0)30 300 2222
[email protected] [email protected]
Eesti Norge
Swixx Biopharma OÜ Bristol-Myers Squibb Norway AS
Tel: + 372 640 1030 Tlf: + 47 67 55 53 50
[email protected] [email protected]
Ελλάδα Österreich
Bristol-Myers Squibb A.E. Bristol-Myers Squibb GesmbH
Τηλ: + 30 210 6074300 Tel: + 43 1 60 14 30
[email protected] [email protected]
España Polska
Bristol-Myers Squibb, S.A. Bristol-Myers Squibb Polska Sp. z o.o.
Tel: + 34 91 456 53 00 Tel.: + 48 22 2606400
[email protected] [email protected]
France Portugal
Bristol-Myers Squibb SAS Bristol-Myers Squibb Farmacêutica Portuguesa, S.A.
Tél: + 33 (0)1 58 83 84 96 Tel: + 351 21 440 70 00
[email protected] [email protected]
Hrvatska România
Swixx Biopharma d.o.o. Bristol-Myers Squibb Marketing Services S.R.L.
Tel: + 385 1 2078 500 Tel: + 40 (0)21 272 16 19
[email protected] [email protected]
Ireland Slovenija
Bristol-Myers Squibb Pharmaceuticals uc Swixx Biopharma d.o.o.
Tel: 1 800 749 749 (+ 353 (0)1 483 3625) Tel: + 386 1 2355 100
[email protected] [email protected]
Ísland Slovenská republika
Vistor hf. Swixx Biopharma s.r.o.
Sími: + 354 535 7000 Tel: + 421 2 20833 600
[email protected] [email protected]
[email protected]
Italia Suomi/Finland
Bristol-Myers Squibb S.r.l. Oy Bristol-Myers Squibb (Finland) Ab
Tel: + 39 06 50 39 61 Puh/Tel: + 358 9 251 21 230
[email protected] [email protected]
Κύπρος Sverige
Bristol-Myers Squibb A.E. Bristol-Myers Squibb Aktiebolag
Τηλ: 800 92666 (+ 30 210 6074300) Tel: + 46 8 704 71 00
[email protected] [email protected]
Latvija
Swixx Biopharma SIA
Tel: + 371 66164750
[email protected]
Other sources of information
More detailed information about this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu/ . In addition, links to other websites on rare diseases and related therapeutic treatments are provided.

The following information is intended exclusively for healthcare professionals:

Traceability
In order to improve the traceability of biological medicinal products, the name and batch number of the administered medicinal product must be clearly recorded.

Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.

Storage of the product
Unopened vial
Store in a refrigerator (2°C – 8°C). Do not freeze. Keep in the original packaging to protect from light.
Reconstituted solution
When stored in the original container, the chemical and physical stability during use of the reconstituted medicinal product has been demonstrated for up to 8 hours at room temperature (≤ 25°C) or up to 24 hours at 2°C – 8°C.
From a microbiological point of view, the medicinal product should be used immediately.
If not used immediately, the times and conditions of storage during use and conditions prior to use are the responsibility of the user and must not exceed 24 hours at 2°C – 8°C.
Do not freeze the reconstituted solution.

Dose calculation
The total dose, based on the patient's body weight (kg), can be calculated as follows:
Total dose (mg) = dose level (mg/kg) × patient's body weight (kg) every three weeks.

Instructions for reconstitution
Reblozyl is supplied as a lyophilized powder to be reconstituted with water for injections (WFI). A graduated syringe must be used for reconstitution to ensure accurate dosing. See Table 1.
Table 1: Reblozyl reconstitution table

1. Remove the colored cap from the vial and clean with a cotton ball soaked in alcohol.
2. Add the WFI to the vial using a specially graduated syringe equipped with a needle, directing the flow onto the lyophilized powder. Let it stand for one minute.
3. Discard the needle and syringe used for reconstitution. Do not use them for subcutaneous injection.
4. Gently swirl the vial in a circular motion for 30 seconds. Stop swirling and leave the vial in an upright position for 30 seconds.
5. Inspect the vial to ensure there is no undissolved powder in the solution. If undissolved powder is observed, repeat step 4 until the powder is completely dissolved.
6. Invert the vial and gently swirl for 30 seconds in the inverted position. Return the vial to an upright position and let it stand for 30 seconds.
7. Repeat step 6 an additional seven times to ensure complete reconstitution of material on the vial walls.
8. Visually inspect the reconstituted solution before administration. When properly mixed, the reconstituted Reblozyl solution is a colorless to slightly yellow solution, clear to slightly opalescent, free of visible foreign particles. Do not use if undissolved product or foreign particles are visible.
9. If the reconstituted solution is not used immediately, refer to the section Storage of the product above.

Method of administration
If the Reblozyl solution has been refrigerated after reconstitution, remove it from the refrigerator 15–30 minutes before injection to allow the product to reach room temperature. This will make the injection more comfortable.
The maximum recommended volume of medication per injection site is 1.2 mL. If more than 1.2 mL is required, the total volume of Reblozyl must be divided into separate injections of equal volume and administered at separate sites, using the same anatomical area but on opposite sides of the body. Reconstitute an appropriate number of Reblozyl vials to achieve the desired dose.
Inject Reblozyl subcutaneously in the arm, thigh, or abdomen.
If multiple injections are required, use a new syringe and a new needle for each subcutaneous injection. Discard any unused portion. Do not administer more than one dose from a single vial.

Disposal
Dispose of unused medicine and waste materials derived from this medicine in accordance with local regulations.