Nivolumab BMS - patient leaflet, side effects, dosage

1. What Nivolumab BMS is and what it is used for

Nivolumab BMS is a medicine used to treat advanced non-small cell lung cancer (a type of lung cancer) in adults. It contains the active substance nivolumab, which is a monoclonal antibody, a type of protein designed to recognise and attach to a specific target substance in the body.

Nivolumab attaches to a target protein called programmed death-1 receptor (PD-1) that can switch off the activity of T cells (a type of white blood cell that forms part of the immune system, the body’s natural defences). By attaching to PD-1, nivolumab blocks its action and prevents it from switching off your T cells. This helps increase their activity against the lung cancer cells.

2. What you need to know before you use Nivolumab BMS

You should not be given Nivolumab BMS

• ■ if you are allergic to nivolumab or any of the other ingredients of this medicine (listed in

section 6 „Contents of the pack and other information“). Talk to your doctor if you are not sure.

Warnings and precautions

Talk to your doctor before using Nivolumab BMS as it may cause:

Problems with your lungs such as breathing difficulties or cough. These may be signs of inflammation of the lungs (pneumonitis or interstitial lung disease).

Diarrhoea (watery, loose or soft stools) or any symptoms of inflammation of the intestines (colitis), such as stomach pain and mucus or blood in stool.

Inflammation of the liver (hepatitis). Signs and symptoms of hepatitis may include abnormal liver function tests, eye or skin yellowing (jaundice), pain on the right side of your stomach area, or tiredness.

Inflammation or problems with your kidneys. Signs and symptoms may include abnormal kidney function tests, or decreased volume of urine.

Problems with your hormone producing glands (including the pituitary, the thyroid and adrenal glands) that may affect how these glands work. Signs and symptoms that these glands are not working properly may include fatigue (extreme tiredness), weight change or headache and visual disturbances.

Diabetes (symptoms include excessive thirst, the passing of a greatly increased amount of urine, increase in appetite with a loss of weight, feeling tired, drowsy, weak, depressed, irritable and generally unwell) or diabetic ketoacidosis (acid in the blood produced from diabetes).

Inflammation of the skin that can lead to rash and itching.

Tell your doctor immediately if you have any of these signs or symptoms or if they get worse. Do not try to treat your symptoms with other medicines on your own. Your doctor may

give you other medicines in order to prevent complications and reduce your symptoms, withhold the next dose of Nivolumab BMS, or stop your treatment with Nivolumab BMS altogether.

Please note that these signs and symptoms are sometimes delayed , and may develop week after your last dose. Before treatment, your doctor will check your general health. You will also have blood tests during your treatment.

Check with your doctor or nurse before you are given Nivolumab BMS if:

you have been told that your cancer has spread to your brain

you have an autoimmune disease (a condition where the body attacks its own cells);

you have any history of inflammation of the lungs ;

you have been taken medicines to suppress your immune system.

Children and adolescents

Nivolumab BMS should not be used in children and adolescents below 18 years of age.

Other medicines and Nivolumab BMS

Before you are given Nivolumab BMS, tell your doctor if you are taking any medicines that suppress your immune system, such as corticosteroids, since these medicines may interfere with the effect of Nivolumab BMS. However, once you are treated with Nivolumab BMS, your doctor may give you corticosteroids to reduce any possible side-effects that you may have during your treatment and this will not impact the effect of the medicine.

Tell your doctor if you are taking or have recently taken any other medicines. Do not take any other medicines during your treatment without talking to your doctor first.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant or think you might be, if you are planning to become pregnant, or if you are breast-feeding.

Do not use Nivolumab BMS if you are pregnant unless your doctor specifically tells you to. The effects of Nivolumab BMS in pregnant women are not known, but it is possible that the active substance, nivolumab, could harm an unborn baby.

• ■ You must use effective contraception while you are being treated with Nivolumab BMS and for at least 5 months following the last dose of Nivolumab BMS, if you are a woman who could become pregnant.

• ■ If you become pregnant while using Nivolumab BMS tell your doctor.

It is not known whether nivolumab gets into breast milk. A risk to the breast-fed infant cannot be excluded. Ask your doctor if you can breast-feed during or after treatment with Nivolumab BMS.

Driving and using machines

Nivolumab is unlikely to affect your ability to drive or use machines; however, use caution when performing these activities until you are sure that nivolumab does not adversely affect you.

Nivolumab BMS contains sodium

Tell your doctor if you are on a low-sodium (low-salt) diet before you are given Nivolumab BMS.

This medicine contains 2.5 mg sodium per mL of concentrate.

You will also find this information in the Patient Alert Card you have been given by your doctor. It is important that you keep this Alert Card and show it to your partner or caregivers.

3. How to use Nivolumab BMS

How much Nivolumab BMS is given

The amount of Nivolumab BMS you will be given will be calculated based on your body weight. The recommended dose is 3 mg of nivolumab per kilogram of your body weight.

Depending on your dose, the appropriate amount of Nivolumab BMS will be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 50 mg/mL (5%) solution for injection before use. More than one vial of Nivolumab BMS may be necessary to obtain the required dose.

How Nivolumab BMS is given

You will receive treatment with Nivolumab BMS in a hospital or clinic, under experienced doctor.

Nivolumab BMS will be given to you as an infusion (a drip) into a vein (intravenously) over a period of 60 minutes, every 2 weeks. Your doctor will continue giving you Nivolumab BMS for as long as you keep benefitting from it or until you no longer tolerate the t

If you miss a dose of Nivolumab BMS

It is very important for you to keep all your appointments to receive Nivolumab BMS. If you miss an appointment, ask your doctor when to schedule your next dose.

If you stop using Nivolumab BMS

Stopping your treatment may stop the effect of the medicine. Do not stop treatment with

Nivolumab BMS unless you have discussed this with your doctor.

If you have any further questions about your treatment or on the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Your doctor will discuss these with you and will explain the risks and benefits of your treatment.

Be aware of important symptoms of inflammation. Nivolumab BMS acts on your immune system and may cause inflammation in parts of your body. Inflammation may cause serious damage to your body and some inflammatory conditions may be life-threatening and need treatment or withdrawal of nivolumab.

The following side effects have been reported in clinical trials with nivolumab:

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

• ■ Decreased appetite

• ■ Nausea

• ■ Feeling tired or weak

Common (may affect up to 1 in 10 people)

• ■ Underactive thyroid gland which can cause tiredness or weight gain

• ■ Inflammation of the nerves causing numbness, weakness, tingling or burning pain of the arms and legs, headache, dizziness

Inflammation of the lungs (pneumonitis), characterised by coughing and difficulty breathing, shortness of breath (dyspnoea), cough

Diarrhoea (watery, loose or soft stools), mouth ulcers and cold sores (stomatitis), vomiting, stomach pain, constipation, dry mouth

Skin rash, itching

Pain in the muscles, bones and joints

Fever, oedema (swelling)

Bronchitis, infections of the upper respiratory tract

A disease causing the inflammation or enlargement of a lymph node (Kikuchi lymphadenitis) Allergic reaction, reactions related to the administration of the medicine

Adrenal glands not working properly, inflammation of the thyroid gland

A condition in which the muscles become weak and tire easily (myasthenic syndrome), damage to the nerves in different parts of the body that can cause decreased feeling or affect movement Fast heart rate

Inflammation of blood vessels

Fluid in the lungs

Inflammation of the intestines (colitis), ulcer of the small intestines

Hives (itchy, bumpy rash)

Inflammation of muscles causing pain or stiffness

Kidney disease, kidney failure.

Tell your doctor immediately if you get any of the side effects listed above. Do not try to treat your symptoms with other medicines on your own.

Changes in test results

Nivolumab BMS may cause changes in the results of tests carried out by your doctor. These include:

• ■ A decreased number of red blood cells (which carry oxygen), white blood cells (which are important in fighting infection) or platelets (cells which help the blood to clot)

• ■ Abnormal liver function tests (increased amounts of the liver enzymes aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase in your blood, higher blood

levels of bilirubin)

• ■ Abnormal kidney function tests (increased amounts of creatinine in your blood)

• ■ Abnormal levels of calcium, potassium, magnesium, or sodium in your blood

• ■ An increased level of the enzyme that breaks down lipids and of the enzyme that breaks down starch.

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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. How to store Nivolumab BMS

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 the vial label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C to 8°C).

Do not freeze.

Store in the original package in order to protect from light.

Do not store any unused portion of the infusion solution for reuse. Any unused medicine or waste material should be disposed of in accordance with local requirements.

6. Contents of the pack and other information

What Nivolumab BMS contains

• ■ The active substance is nivolumab.

Each mL of concentrate for solution for infusion contains 10 mg of nivolumab.

Each vial contains either 40 mg (in 4 mL) or 100 mg (in 10 mL) of nivolumab.

The other ingredients are sodium citrate dihydrate, sodium chloride (see section 2 " Nivolumab BMS contains sodium"), mannitol (E421), pentetic acid, polysorbate 80, sodi hydroxide, hydrochloric acid and water for injections.

What Nivolumab BMS looks like and contents of the pack

Nivolumab BMS concentrate for solution for infusion (sterile concentrate) is a clear to opalescent, colourless to pale yellow liquid that may contain few light particles.

It is available in packs containing either 1 vial of 4 mL or 1 vial of 10 mL.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Bristol-Myers Squibb Pharma EEIG

Uxbridge Business Park

Sanderson Road

Uxbridge UB8 1DH United Kingdom

Manufacturer

Bristol-Myers Squibb S.r.l.

Loc. Fontana del Ceraso 03012 Anagni (FR) Italy

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

Lietuva

Bristol-Myers Squibb Gyógyszerkeres­kedelmi Kft.

Tel: + 370 5 2790 762

Luxembourg/Lu­xemburg

ers Squibb Gyógyszerkeres­kedelmi Kft. N.V. Bristol-Myers Squibb Belgium S.A.

Tél/Tel: + 32 2 352 76 11

Magyarország

Bristol-Myers Squibb Gyógyszerkeres­kedelmi Kft.

Tel.: + 36 1 301 9700

Malta

BRISTOL-MYERS SQUIBB S.R.L.

Tel: + 39 06 50 39 61

Deutschland

Bristol-Myers Squibb GmbH & Co. KGaA

Tel: + 49 89 121 42–0

Eesti Norge

Bristol-Myers Squibb Gyógyszerkeres­kedelmi Kft. Bristol-Myers Squibb Norway Ltd

Tel: + 372 6827 400 Tlf: + 47 67 55 53 50

Österreich

Bristol-Myers Squibb GesmbH

Tel: + 43 1 60 14 30

Polska

BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O.

Tel.: + 48 22 5796666

Portugal

Bristol-Myers Squibb Farmacêutica Portuguesa, S.A.

Tel: + 351 21 440 70 00

România

Bristol-Myers Squibb Gyógyszerkeres­kedelmi Kft.

Tel: + 40 (0)21 272 16 00

Slovenija

Bristol-Myers Squibb spol. s r.o.

Tel: + 386 1 236 47 00

Latvija United Kingdom

Bristol-Myers Squibb Gyógyszerkeres­kedelmi Kft. Bristol-Myers Squibb Pharmaceuticals Ltd

Tel: + 44 (0800) 731 1736

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

The following information is intended for healthcare professionals only:

Preparation and administration of Nivolumab BMS

Preparation should be performed by trained personnel in accordance with good practices rules, especially with respect to asepsis.

Calculating the dose

The prescribed dose for the patient is given in mg/kg. Based on this prescribed dose, calculate the total dose to be given. More than one vial of Nivolumab BMS concentrate may be needed to give the total dose for the patient.

• ■ The total nivolumab dose in mg = the patient’s weight in kg x the prescribed dose in mg/kg.

• ■ The volume of Nivolumab BMS concentrate to prepare the dose (mL) = the total dose in. mg,

divided by 10 (the Nivolumab BMS concentrate strength is 10 mg/mL).

Preparing the infusion

Take care to ensure aseptic handling when you prepare the infusion. The infusion should be prepared in a laminar flow hood or safety cabinet using standard precautions for the safe handling of intravenous agents.

Nivolumab BMS can be used for intravenous administration either:

without dilution, after transfer to an infusion container using an appropriate sterile syringe; or

after diluting to concentrations as low as 1 mg/mL. The final infusion concentration should range between 1 and 10 mg/mL. Nivolumab BMS concentrate may be diluted with either:

sodium chloride 9 mg/mL (0.9%) solution for injection; or 50 mg/mL (5%) glucose solution for injection.

STEP 1

Inspect the Nivolumab BMS concentrate for particulate matter or discoloration. Do not shake the vial. Nivolumab BMS concentrate is a clear to opalescent, colourless to pale yellow liquid

that may contain few light particles.

Withdraw the required volume of Nivolumab BMS concentrate using an appropriate sterile

syringe.

STEP 2

• ■ Transfer the concentrate into a sterile, evacuated glass bottle or intravenous container (PVC or polyolefin).

• ■ If applicable, dilute with the required volume of sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) glucose solution for injection. Gently mix the infusion by manual rotation. Do not shake.

Administration

Nivolumab BMS infusion must not be administered as an intravenous push or bolus injection.

Administer the Nivolumab BMS infusion intravenously over a period of 60 minutes.

Nivolumab BMS infusion should not be infused at the same time in the same intravenous line with other agents. Use a separate infusion line for the infusion.

Use an infusion set and an in-line, sterile, non-pyrogenic, low protein binding filter (pore size of 0.2 gm to 1.2 gm).

Nivolumab BMS infusion is compatible with:

• ■ PVC containers

• ■ Polyolefin containers

• ■ Glass bottles

• ■ PVC infusion sets

• ■ In-line filters with polyethersulfone membranes with pore sizes of 0.2 ^m to 1.2 ^m.