Sarclisa

Package leaflet: Information for the patient

Sarclisa 20 mg/mL concentrate for solution for infusion

isatuximab
Please 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 questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Sarclisa is and what it is used for

What Sarclisa is
Sarclisa is an anticancer medicine that contains the active substance isatuximab. It belongs to a
group of medicines called "monoclonal antibodies".
Monoclonal antibodies, such as Sarclisa, are proteins designed to recognise and bind to a specific target substance. In the case of Sarclisa, the target is a substance called CD38 found on multiple myeloma cells, a cancer of the bone marrow. By binding to multiple myeloma cells, the medicine helps the body's natural defences (the immune system) to identify and destroy them.
What Sarclisa is used for
Sarclisa is used to treat multiple myeloma.
It is used in combination with two other medicines in patients who have previously received treatment for multiple myeloma:

• pomalidomide and dexamethasone, or
• carfilzomib and dexamethasone.

It is used in combination with three other medicines in patients with newly diagnosed multiple myeloma:

• bortezomib, lenalidomide and dexamethasone. If you have any questions about how Sarclisa works or about treatment with Sarclisa, speak to your doctor.

2. What you need to know before using Sarclisa

Do not use Sarclisa if:

• you are allergic to isatuximab or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or nurse before using Sarclisa and follow all instructions carefully.
Infusion-related reactions
Tell your doctor or nurse immediately if you experience signs of infusion-related reactions
during or after the infusion of Sarclisa – see section 4 “Possible side effects” for a list of signs of “Infusion-related reactions”.

• Before starting an infusion of Sarclisa, you may be given medicines to reduce the risk of infusion-related reactions (see section 3 “How to use Sarclisa”).
• Infusion-related reactions can occur during or after the infusion of Sarclisa and may be serious. These reactions are reversible. Healthcare staff will closely monitor you during treatment. If you experience an infusion-related reaction, your doctor or nurse may give you additional medicines to treat symptoms and prevent complications. They may also temporarily interrupt, slow down, or permanently stop the infusion of Sarclisa.

Fever and low white blood cell count
Tell your doctor or nurse immediately if you develop fever, as this could be a sign of infection. Sarclisa may reduce the number of white blood cells, which are important for fighting infections.
Your doctor or nurse will monitor your blood cell counts during treatment with Sarclisa.
Your doctor may prescribe an antibiotic or antiviral medicine (for example, for herpes zoster [shingles]) to help prevent infections, or a medicine to increase your white blood cell count during treatment with Sarclisa.

Heart problems
Talk to your doctor or nurse before using Sarclisa in combination with carfilzomib and dexamethasone if you have heart problems or if you have previously taken a heart medication. Contact your doctor or nurse immediately if you experience difficulty breathing, cough, or swelling in your legs.

Risk of new cancers
New cancers have occurred in patients treated with Sarclisa when administered in combination with pomalidomide and dexamethasone, or with carfilzomib and dexamethasone, or with bortezomib, lenalidomide and dexamethasone. Your doctor or nurse will monitor you for the possible development of new cancers during treatment.

Tumour lysis syndrome
A rapid breakdown of tumour cells (tumour lysis syndrome) may occur. Symptoms may include irregular heartbeat, seizures (epileptic fits), confusion, muscle cramps, or reduced urine production. Contact your doctor immediately if you experience any of these symptoms.

Blood transfusion
If you need a blood transfusion, a blood test will first be performed to determine your blood group.
Inform the person performing the blood test that you are being treated with Sarclisa. This is because this may affect the results of the blood test for at least 6 months after your last dose of Sarclisa.

Children and adolescents
Sarclisa is not recommended for use in children and adolescents under 18 years of age. This is because the efficacy of Sarclisa has not been established in paediatric patients.

Other medicines and Sarclisa
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines. This includes medicines you can obtain without a prescription and herbal medicines.
Tell your doctor or nurse before taking Sarclisa if you have previously taken a medicine for the heart.
Sarclisa is used together with two or three other medicines in the treatment of multiple myeloma:

• pomalidomide and dexamethasone, or
• carfilzomib and dexamethasone, or
• bortezomib, lenalidomide and dexamethasone. For information about the other medicines used with Sarclisa, refer to their respective package leaflets.

Pregnancy
Ask your doctor, pharmacist, or nurse for advice before using Sarclisa.
The use of Sarclisa is not recommended during pregnancy. If you are pregnant or planning to become pregnant, inform your doctor about the use of Sarclisa.
For information on the use of other medicines taken with Sarclisa during pregnancy, consult the package leaflet of those medicines.

Breast-feeding
Ask your doctor, pharmacist, or nurse for advice before using Sarclisa.

• This is because Sarclisa may pass into breast milk. It is not known how it might affect the baby.
• You and your doctor will decide whether the benefit of breast-feeding is greater than the risk to your baby.

Contraception
Women of childbearing potential who are using Sarclisa must use effective contraceptive measures. Ask your doctor for advice on which contraceptive method to use during this period. Use contraception during treatment and for 5 months after the last dose of Sarclisa.

Driving and using machines
It is unlikely that Sarclisa will affect your ability to drive or use machines. However, Sarclisa is used with other medicines that may impair your ability to drive or use machines. Please consult the package leaflet of the other medicines you are taking concurrently with Sarclisa.

Sarclisa.

Sarclisa contains polysorbate 80
This medicine contains 0.2 mg of polysorbate 80 in each mL of isatuximab concentrate for infusion solution, equivalent to 0.1 mg/kg of body weight.
Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How Sarclisa is administered

How much Sarclisa is administered
The amount of Sarclisa you will be given is based on your body weight. The recommended dose is
10 mg of Sarclisa per kilogramm of body weight.

How Sarclisa is administered
Your doctor or nurse will administer Sarclisa to you as an intravenous infusion (a drip into a vein).

How often Sarclisa is administered
When Sarclisa is used in combination with two other medicines, pomalidomide and dexamethasone or carfilzomib
and dexamethasone, treatment cycles last 28 days (4 weeks).

• In cycle 1: Sarclisa is administered once a week on days 1, 8, 15, and 22.
• In cycle 2 and beyond: Sarclisa is administered every 2 weeks, on days 1 and 15.

When Sarclisa is used in combination with three other medicines, bortezomib, lenalidomide, and dexamethasone:

• For patients not eligible for autologous bone marrow transplantation (own stem cells): Treatment cycles last 42 days (6 weeks) from cycle 1 to cycle 4, and 28 days (4 weeks) from cycle 5 onwards.
  • In cycle 1: Sarclisa is administered on days 1, 8, 15, 22, and 29.
  • From cycle 2 to cycle 4: Sarclisa is administered every 2 weeks, on days 1, 15, and 29.
  • From cycle 5 to cycle 17: Sarclisa is administered every 2 weeks, on days 1 and 15.
  • From cycle 18 onwards: Sarclisa is administered every 4 weeks, on day 1.
• For patients eligible for autologous bone marrow transplantation (own stem cells): Treatment cycles last 42 days (6 weeks) from cycle 1 to cycle 3.
  • In cycle 1: Sarclisa is administered on days 1, 8, 15, 22, and 29.
  • From cycle 2 to cycle 3: Sarclisa is administered every 2 weeks, on days 1, 15, and 29.

Your doctor will continue treating you with Sarclisa for as long as you benefit from it and side effects
remain manageable.

Medicines administered before Sarclisa
Before the Sarclisa infusion, you will be given the following medicines to help reduce the likelihood of infusion-related reactions:

• Medicines to reduce allergic reactions (antihistamines)
• Medicines to reduce inflammation (corticosteroids)
• Medicines to reduce pain and fever.

If you miss a dose of Sarclisa
It is very important to attend all your appointments to ensure you receive treatment at the correct time for it to work properly. If you miss any appointment, contact your doctor or nurse as soon as possible to reschedule.
Your doctor or nurse will decide how your treatment should continue.

If you are given more Sarclisa than you should receive
Sarclisa will be administered to you by your doctor or nurse. If you are accidentally given too much (overdose), your doctor will treat and monitor any side effects.

If you stop treatment with Sarclisa
Do not stop treatment with Sarclisa without first discussing it with your doctor.
If you have any questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Your doctor will inform you about the side effects of Sarclisa and explain the possible risks and benefits of treatment with Sarclisa.
Hospital staff will closely monitor your condition during treatment. Inform them immediately if you notice any of the side effects listed below.

Infusion-related reactions – very common (may affect more than 1 in 10 people).
Inform your doctor or nurse immediately if you feel unwell during or after
infusion of Sarclisa.
Severe signs of infusion-related reactions include:

• high blood pressure (hypertension)
• feeling short of breath
• severe allergic reaction (anaphylactic reaction affecting up to 1 in 100 people) with difficulty breathing and swelling of the face, mouth, throat, lips or tongue.

More common signs of infusion-related reactions include:

• feeling short of breath
• cough
• chills
• nausea

You may also experience other side effects during the infusion. Your doctor or nurse may decide to temporarily interrupt, slow down, or permanently discontinue the infusion of Sarclisa. They may also administer additional medicines to treat symptoms and prevent complications.
Inform your doctor or nurse immediately if you feel unwell during or after the infusion of Sarclisa.

Other side effects
If you experience any of the side effects listed below, contact your doctor, pharmacist, or nurse immediately:

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

• lower number of certain white blood cells (neutrophils), which are important for fighting infections
• lower number of platelets (thrombocytopenia) – inform your doctor or nurse if you develop unusual bruising or bleeding
• lung infection (pneumonia)
• airway infection (such as nose, sinuses, or throat)
• diarrhoea
• bronchitis
• shortness of breath
• nausea
• vomiting
• high blood pressure (hypertension)
• cough
• fatigue (tiredness)
• reduced appetite
• Covid-19
• blurred vision (cataract)

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

• heart problems, which may present as difficulty breathing, cough, or swelling of the legs when Sarclisa is given with carfilzomib and dexamethasone
• fever with a severe decrease in certain white blood cells (febrile neutropenia) (see section 2 “What you need to know before using Sarclisa” for further details)
• lower number of red blood cells (anaemia)
• weight loss
• irregular heartbeat (atrial fibrillation)
• herpes zoster (shingles)
• lower number of certain white blood cells (lymphocytes) important in fighting infections

If any of the above conditions apply to you or if you have any doubts, contact your doctor, pharmacist, or nurse immediately.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, 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 Sarclisa

Sarclisa will be stored at the hospital or clinic.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Store in the original packaging to protect the medicine from light.
Medicines must not be disposed of via wastewater. Your doctor, pharmacist, or nurse will dispose of any unused medicines for you. This will help protect the environment.

6. Package contents and other information

What Sarclisa contains

• The active substance in Sarclisa is isatuximab.
• One mL of concentrate contains 20 mg of isatuximab.
• Each vial of concentrate contains either 100 mg of isatuximab in 5 mL of concentrate or 500 mg of isatuximab in 25 mL of concentrate.
• The other ingredients (excipients) are sucrose, monohydrate histidine hydrochloride, histidine, polysorbate 80, and water for injections (see sections 2 and 4.4).

Description of the appearance of Sarclisa and contents of the pack
Sarclisa is a concentrate for solution for infusion. It is a colourless to slightly yellow liquid, essentially free from visible particles.
Pack sizes:
100 mg of isatuximab in 5 mL of concentrate (100 mg/5 mL): each box contains 1 or 3 vials.
500 mg of isatuximab in 25 mL of concentrate (500 mg/25 mL): each box contains 1 vial.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sanofi Winthrop Industrie
82 avenue Raspail
94250 Gentilly
France

Manufacturer
Sanofi-Aventis Deutschland GmbH
Industriepark Hoechst Brueningstrasse 50
65926 Frankfurt am Main
Germany

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sanofi Belgium Swixx Biopharma UAB
Tél/Tel: +32 (0)2 710 54 00 Tel: +370 5 236 91 40

България Luxembourg/Luxemburg
Swixx Biopharma EOOD Sanofi Belgium
Тел.: +359 (0)2 4942 480 Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Repubblica ceca Magyarország
Sanofi s.r.o. SANOFI-AVENTIS Zrt.
Tel: +420 233 086 111 Tel: +36 1 505 0050

Danmark Malta
Sanofi A/S Sanofi S.r.l.
Tlf: +45 45 16 70 00 Tel: +39 02 39394275

Sanofi-Aventis Deutschland GmbH Nederland
Tel: 0800 04 36 996 Sanofi B.V.
Tel. aus dem Ausland: +49 69 305 70 13 Tel: +31 20 245 4000

Eesti Norge
Swixx Biopharma OÜ sanofi-aventis Norge AS
Tel: +372 640 10 30 Tlf: +47 67 10 71 00

Ελλάδα Österreich
Sanofi-Aventis Μονοπρόσωπη ΑΕΒΕ sanofi-aventis GmbH
Τηλ: +30 210 900 16 00 Tel: +43 1 80 185 – 0

España Polska
sanofi-aventis, S.A. Sanofi Sp. z o.o.
Tel: +34 93 485 94 00 Tel: +48 22 280 00 00

France Portugal
Sanofi Winthrop Industrie Sanofi - Produtos Farmacêuticos, Lda.
Tél: 0 800 222 555 Tel: +351 21 35 89 400
Appel depuis l’étranger: +33 1 57 63 23 23

Hrvatska România
Swixx Biopharma d.o.o. Sanofi Romania SRL
Tel: +385 1 2078 500 Tel: +40 (0) 21 317 31 36

Ireland Slovenija
sanofi-aventis Ireland Ltd. T/A SANOFI Swixx Biopharma d.o.o.
Tel: +353 (0) 1 403 56 00 Tel: +386 1 235 51 00

Ísland Slovenská republika
Vistor hf. Swixx Biopharma s.r.o.
Sími: +354 535 7000 Tel: +421 2 208 33 600

Italia Suomi/Finland
Sanofi S.r.l. Sanofi Oy
Tel: 800 536 389 Puh/Tel: +358 (0) 201 200 300

Κύπρος Sverige
C.A. Papaellinas Ltd. Sanofi AB
Τηλ: +357 22 741741 Tel: +46 (0)8 634 50 00

Latvija United Kingdom (Northern Ireland)
Swixx Biopharma SIA sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +371 6 616 47 50 Tel: +44 (0) 800 035 2525

More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu. Links to other websites on rare diseases and their treatments are also provided.
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

The following information is intended exclusively for healthcare professionals:

SARCLISA vials are for single use only. The infusion solution must be prepared under aseptic conditions and administered by a healthcare professional in a setting where resuscitation facilities are available.
Preparation and administration of SARCLISA

• Calculate the required dose (mg) of SARCLISA concentrate and determine the number of vials required for the 10 mg/kg dose based on the patient's body weight. More than one vial may be needed.
• Visually inspect the SARCLISA concentrate before dilution to ensure it is free from particulate matter and discoloration.
• Remove a volume of diluent equal to the required volume of SARCLISA concentrate from an infusion bag containing 250 mL of 9 mg/mL (0.9%) sodium chloride injection or 5% dextrose solution.
• Withdraw the appropriate volume of SARCLISA concentrate from the SARCLISA vial and dilute it into a 250 mL infusion bag of 9 mg/mL (0.9%) sodium chloride injection or 5% dextrose solution.
• The infusion bag must be composed of polyolefin (PO), polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC) with di-(2-ethylhexyl) phthalate (DEHP), or ethylene vinyl acetate (EVA).
• Gently invert the bag to mix the diluted solution. Do not shake.
• Administer the infusion solution intravenously using an intravenous infusion set (made of PE, PVC with or without DEHP, polybutadiene (PBD), or polyurethane (PU)) with an in-line 0.22 micron filter (made of polyethersulfone (PES), polysulfone, or nylon).
• Administer the infusion solution over a period of time depending on the infusion rate (see section 4.2 of the SmPC, “Dosage and administration”).
• Use the prepared SARCLISA infusion solution immediately. If not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2 °C to 8 °C, unless the dilution was performed under validated and controlled aseptic conditions.
• No light protection is required for the prepared infusion bag when handled under standard artificial light conditions.
• Do not infuse SARCLISA solution together with other agents in the same intravenous line. Discard all unused portions of the solution. All materials used for dilution and administration must be disposed of according to standard procedures.