This medicine contains the active substance carfilzomib.

Carfilzomib SPC 60 mg for injection works by blocking the proteasome. The proteasome is a system within the cells that breaks down proteins when they are damaged or no longer needed. By preventing the breakdown of proteins in cancer cells, which are more likely to contain more abnormal proteins, Carfilzomib SPC 60 mg for injection causes the death of cancer cells.

Carfilzomib SPC 60 mg for injection is used to treat adult patients with multiple myeloma who have had at least one previous treatment for this disease. Multiple myeloma is a cancer of plasma cells (a type of white blood cell).

Carfilzomib SPC 60 mg for injection will be given to you together with lenalidomide and dexamethasone, or only with dexamethasone. Lenalidomide and dexamethasone are other medicines used to treat multiple myeloma

Your doctor will examine you and review your full medical history. You will be monitored closely during treatment. Before starting Carfilzomib SPC 60 mg for injection and during treatment, you will undergo blood testing. This is to check that you have enough blood cells and your liver and kidneys are working properly. Your doctor or nurse will check if you are getting enough fluids.

You must read the package leaflet of all medicines that you take in combination with Carfilzomib SPC 60 mg for injection so that you understand the information related to those medicines.

Do not use Carfilzomib SPC 60 mg for injection if you are allergic to carfilzomib or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or nurse before using Carfilzomib SPC 60 mg for injection if you have any of the conditions listed below.

You may need extra tests to check that your heart, kidneys and liver are working properly.

•       Heart problems, including a history of chest pain (angina), heart attack, irregular heartbeat, high blood pressure or if you have ever taken a medicine for your heart

•       Lung problems, including a history of shortness of breath at rest or with activity (dyspnea)

•       Kidney problems, including kidney failure or if you have ever received dialysis

•       Liver problems, including a history of hepatitis, fatty liver, or if you have ever been told your liver is not working properly

•       Unusual bleeding, including easy bruising, bleeding from an injury, such as a cut, that takes longer than expected to stop, or internal bleeding such as coughing up blood, vomiting up blood, dark tarry stools, or bright red blood in your stools; or bleeding in the brain leading to sudden numbness or paralysis on one side of the face, legs or arms, sudden severe headache or trouble seeing or difficulty speaking or swallowing. This can indicate you have low numbers of platelets (cells that help the blood to clot)

•       A history of blood clots in your veins

•       Leg or arm pain or swelling (which could be a symptom of blood clots in the deep veins of the leg or arm), chest pain or shortness of breath (which may be a symptom of blood clots in the lungs)

•       Any other major disease for which you were hospitalized or received any medicine.

Conditions you need to look out for

You must look out for certain symptoms while you are taking Carfilzomib SPC 60 mg for injection to reduce the risk of any problems. Carfilzomib SPC 60 mg for injection can make some conditions worse or cause serious side effects, which may be fatal, such as heart problems, lung problems, kidney problems, tumour lysis syndrome (a life-threatening condition that occurs when cancer cells break and release their content to the bloodstream), reactions to the Carfilzomib SPC 60 mg for injection, unusual bruising or bleeding, (including internal bleeding), blood clots in your veins, liver problems, certain blood conditions, or a neurological condition known as PRES. See section 4.

Other medicines and Carfilzomib SPC 60 mg for injection

Tell your doctor if you are taking, have recently taken or might take any other medicines. This includes any medicines obtained without a prescription, such as vitamins or herbal remedies. Tell your doctor or nurse if you are taking medicines used to prevent pregnancy such as oral contraceptives or other hormonal contraceptives, as these may not be suitable for use with Carfilzomib SPC 60 mg for injection.

Pregnancy and breast-feeding

For women taking Carfilzomib SPC 60 mg for injection

Do not take Carfilzomib SPC 60 mg for injection if you are pregnant, think you may be pregnant or are planning to have a baby. Treatment with Carfilzomib SPC 60 mg for injection has not been evaluated in pregnant women. While taking Carfilzomib SPC 60 mg for injection, and for 30 days after stopping treatment you should use a suitable method of contraception to ensure you do not become pregnant. You should talk to your doctor or nurse about suitable methods of contraception.

If you become pregnant while taking Carfilzomib SPC 60 mg for injection, notify your doctor or nurse immediately.

Do not take Carfilzomib SPC 60 mg for injection if you are breast-feeding. It is not known if Carfilzomib SPC 60 mg for injection passes into breast milk in humans.

Lenalidomide is expected to be harmful to the unborn child. As Carfilzomib SPC 60 mg is given in combination with lenalidomide, you must follow the Pregnancy Prevention Programme (see package leaflet for lenalidomide for information on pregnancy prevention and discuss with your doctor, pharmacist or nurse).

For men taking Carfilzomib SPC 60 mg for injection

While taking Carfilzomib SPC 60 mg for injection and for 90 days after stopping treatment, you should use a condom

even if your partner is pregnant.

If your partner becomes pregnant whilst you are taking Carfilzomib SPC 60 mg for injection or within 90 days after stopping treatment, notify your doctor or nurse immediately.

Driving and using machines

While you are being treated with Carfilzomib SPC 60 mg for injection you may experience fatigue, dizziness, fainting, and/or a drop-in blood pressure. This may impair your ability to drive or operate machines. Do not drive a car or operate machines if you have these symptoms.

Carfilzomib SPC 60 mg for injection contains sodium

This medicinal product contains 210 mg sodium per vial, equivalent to 10.5 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Carfilzomib SPC 60 mg for injection will be given to you by a doctor or nurse. The dose will be calculated based on your height and weight (body surface area). Your doctor or nurse will determine the dose of Carfilzomib SPC 60 mg for injection that you receive.

Carfilzomib SPC 60 mg for injection will be given as an infusion into a vein. The infusion may last up to 30 minutes. Carfilzomib SPC 60 mg for injection is given once weekly or twice weekly.

Once weekly

Carfilzomib SPC 60 mg for injection is administered once weekly for three weeks followed by a 13-day rest period. Each 28-day period is considered one treatment cycle. This means that Carfilzomib SPC 60 mg for injection will be given to you on days 1, 8 and 15 of each 28-day cycle.

Twice weekly

Carfilzomib SPC 60 mg for injection is administered twice weekly for 2 days in a row each week, for 3 weeks, followed by one week without treatment.

Each 28-day period is one treatment cycle. This means that Carfilzomib SPC 60 mg for injection will be given to you on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. The doses on day 8 and 9 of each cycle will not be given from cycle 13 onwards if you are treated with Carfilzomib SPC 60 mg for injection in combination with lenalidomide and dexamethasone.

Most patients will receive treatment for as long as their disease improves or remains stable. However, Carfilzomib SPC 60 mg for injection treatment may also be stopped if you experience side effects that cannot be managed.

Together with Carfilzomib SPC 60 mg for injection you will also be given either lenalidomide and dexamethasone, or only dexamethasone. You may also be given other medicines.

If you are given too much Carfilzomib SPC 60 mg for injection

As this medicine is being given by a doctor or nurse, it is unlikely that you will be given too much. However, if you are given too much Carfilzomib SPC 60 mg for injection your doctor will monitor you for side effects.

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

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

Some side effects could be serious. Tell your doctor straight away if you get notice any of the following symptoms:

•       Chest pains, shortness of breath, or if there is swelling of your feet, which may be symptoms of heart problems

•       Difficulty breathing, including shortness of breath at rest or with activity or a cough (dyspnea), rapid breathing, feeling like you can't breathe in enough air, wheezing, or cough, which can be signs of lung toxicity

•       Very high blood pressure, severe chest pain, severe headache, confusion, blurred vision, nausea and vomiting, or severe anxiety, which may be signs of a condition known as hypertensive crisis

•       Shortness of breath with everyday activities or at rest, irregular heartbeat, racing pulse, tiredness, dizziness, and fainting spells, which can be signs of a condition known as pulmonary hypertension

•       Swollen ankles, feet or hands, loss of appetite, passing less urine, or abnormal blood test results, which may be symptoms of kidney problems or kidney failure

•       A side effect called tumour lysis syndrome, which can be caused by the rapid breakdown of tumour cells and may cause irregular heartbeat, kidney failure or abnormal blood test results

•       Fever, chills or shaking, joint pain, muscle pain, facial flushing or swelling, weakness, shortness of breath, low blood pressure, fainting, chest tightness, or chest pain can occur as a reaction to the infusion

•       Unusual bruising or bleeding, such as a cut, that takes longer than usual to stop bleeding; or internal bleeding such as coughing up blood, vomiting up blood, dark tarry stools, or bright red blood in your stools; or bleeding in the brain leading to sudden numbness or paralysis on one

•       Leg or arm pain or swelling (which could be a symptom of blood clots in the deep veins of the leg or arm), chest pain or shortness of breath (which may be a symptom of blood clots in the lungs)

•       Yellowing of your skin and eyes (jaundice), abdominal pain or swelling, nausea or vomiting, which could be symptoms of liver problems including liver failure

•       Bleeding, bruising, weakness, confusion, fever, nausea, vomiting and diarrhea, and acute kidney failure, which may be signs of a blood condition known as thrombotic microangiopathy

•       Headaches, confusion, seizures (fits), visual loss, and high blood pressure (hypertension), which may be symptoms of a neurologic condition known as posterior reversible encephalopathy syndrome (PRES).

Other possible side effects

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

•       Serious lung infection (pneumonia)

•       Blood clots in the veins (deep vein thrombosis)

•       Respiratory tract infection (infection of the airways)

•       Low platelets, which may cause easy bruising or bleeding (thrombocytopenia)

•       Low white blood cell count, which may decrease your ability to fight infection and may be associated with fever

•       Low red blood cell count (anemia) which may cause tiredness and fatigue

•       Changes to blood tests (decreased blood levels of potassium, increased blood levels of sugar and/or creatinine)

•       Decreased appetite

•       Difficulty sleeping (insomnia)

•       Headache

•       Numbness, tingling, or decreased sensation in hands and/or feet

•       Dizziness

•       High blood pressure (hypertension)

•       Shortness of breath

•       Cough

•       Diarrhea

•       Nausea

•       Constipation

•       Vomiting

•       Stomach pain

•       Back pain

•       Joint pain

•       Pain in limbs, hands or feet

•       Muscle spasms

•       Fever

•       Chills

•       Swelling of the hands, feet or ankles

•       Feeling weak

•       Tiredness (fatigue)

•       Feeling too hot

•       Lung infection

•       Cough which could include chest tightness or pain, nasal congestion (bronchitis)

•       Changes to blood tests (decreased blood levels of sodium, magnesium, protein, calcium or phosphate, increased blood levels of calcium, uric acid, potassium, bilirubin or c-reactive protein)

•       Indigestion

•       Rash

•       Pain

•       Pain, swelling, irritation or discomfort where you received the injection into your vein

•       A general feeling of illness or discomfort

•       Infusion reaction

•       Heart failure and heart problems including rapid, strong or irregular heartbeat

•       Heart attack

•       Kidney problems, including kidney failure

•       Bleeding in the lungs

•       Blood clot in the lungs

•       Fluid in the lungs

•       Wheezing

•       Liver problems including an increase in liver enzymes in the blood

•       Serious infection including infection in the blood (sepsis)

•       Flu-like symptoms (influenza)

•       Reactivation of the chicken pox virus (shingles) that can cause a skin rash and pain (herpes zoster)

•       Urinary tract infection (infection of structures that carry urine)

•       Sore throat

•       Inflammation of the nose and throat

•       Runny nose, nasal congestion or sneezing

•       Viral infection

•       Infection of the stomach and intestine (gastroenteritis)

•       Bleeding in the stomach and bowels

•       Dehydration

•       Anxiety

•       Feeling confused

•       Blurred vision

•       Cataract

•       Low blood pressure (hypotension)

•       Nose bleed

•       Change in voice or hoarseness

•       Toothache

•       Bone pain, muscle pain, chest pain

•       Muscle weakness

•       Aching muscles

•       Itchy skin

•       Redness of the skin

•       Increased sweating

•       Ringing in the ears (tinnitus)

Other less common side effects

•        Inflammation of the colon caused by a bacteria called Clostridium difficile

•        Allergic reaction to Carfilzomib

•        Multi-organ failure

•        Reduced blood flow to the heart

•        Bleeding in the brain

•        Stroke

•        Difficulty breathing, rapid breathing and/or fingertips and lips looking slightly blue (acute respiratory distress syndrome)

•        Swelling of the lining of the heart (pericarditis), symptoms include pain behind the breast bone, sometimes spreading across to the neck and shoulders, sometimes with a fever

•        Fluid build-up in the lining of the heart (pericardial effusion), symptoms include chest pain or pressure and shortness of breath

•        A blockage in the flow of bile from the liver (cholestasis), which can cause itchy skin, yellow skin, very dark urine and very pale stools Perforation of the digestive system

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the local reporting system. By reporting side affects you can help provide more information on the safety of this medicine.

Keep this medicine out of the sight and reach of children.

Do not use Carfilzomib SPC 60 mg for injection after the expiry date printed on the vial and the carton. The expiry date refers to the last day of that month.

Unopened vials: Stored in a refrigerator (2°C to 8°C). Store in original package in order to protect from light.

The reconstituted product should be a clear colorless solution and should not be administered if any discoloration or particulate matter is observed.

Carfilzomib SPC 60 mg for injection is for single use only.

Any unused product or waste material should be disposed of in accordance with local requirements.