KYPROLIS 60 mg Powder For Intravenous Infusion Solution

Зміст інструкції

1. Kyprolis 10 mg powder for solution for infusion, 30 mg powder for solution for infusion, 60 mg powder for solution for infusion
   1. What is Kyprolis and what is it used for
   2. What you need to know before using Kyprolis
   3. How to use Kyprolis
   4. Possible side effects
   5. How to store Kyprolis
   6. Package contents and other information

Kyprolis 10 mg powder for solution for infusion, 30 mg powder for solution for infusion, 60 mg powder for solution for infusion

carfilzomib

Read this leaflet carefully before you start to use this medicine as 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, even those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What is Kyprolis and what is it used for

Kyprolis is a medicine that contains the active substance carfilzomib.
Carfilzomib works by blocking the proteasome. The proteasome is a system within cells that
destroys proteins when they are damaged or no longer needed. By preventing the destruction of
proteins in cancer cells, which tend to contain a higher amount of abnormal proteins, Kyprolis causes
the death of cancer cells.
Kyprolis is used to treat adult patients with multiple myeloma who have already undergone at least one
previous treatment for this disease. Multiple myeloma is a cancer that affects
plasma cells (a type of white blood cell).
Kyprolis will be administered to you together with daratumumab and dexamethasone, together with lenalidomide and
dexamethasone or with dexamethasone alone. Daratumumab, lenalidomide and dexamethasone are other
medicines used to treat multiple myeloma.

2. What you need to know before using Kyprolis

The doctor will review and evaluate your entire medical history. During treatment, you will be subjected to
careful monitoring. Before starting the administration of Kyprolis, and during treatment,
you will undergo blood tests. This is done to verify that there are sufficient
blood cells and that the liver and kidneys are functioning correctly. The doctor or nurse
will check that you are drinking enough fluids
in order to understand the information relating to these medicines.

Do not use Kyprolis if you are allergicto carfilzomib or to any of the other components of this
medicinal product (listed in paragraph 6).

Warnings and precautions
Before using Kyprolis, talk to your doctor or nurse if you have any of the
conditions listed below.You may need to undergo additional tests to verify the correct
functioning of the heart, kidneys and liver.

• Heart problems, including a history of chest pain (angina), heart attack, irregular heartbeat, high blood pressure or if you have ever taken medicines for the heart
• Lung problems, including a history of shortness of breath at rest or during physical activity (dyspnea)
• Kidney problems, including kidney failure, or if you have ever undergone dialysis
• Liver problems, including a history of hepatitis, fatty liver, or if you have been told that the liver is not functioning correctly
• Unusual bleeding, including a predisposition to bruising, bleeding of wounds, such as a cut that takes longer than expected to stop bleeding, internal bleeding such as coughing up blood, vomiting blood, dark tarry stools, or bright red blood in the stool, or bleeding in the brain leading to sudden numbness or paralysis of one side of the face, legs or arms, severe sudden headache or vision problems or difficulty speaking or swallowing. This may indicate that you have a low number of platelets (cells that help blood clotting)
• History of blood clots in the veins
• Pain or swelling in the legs or arms (which may be a symptom of blood clots in the deep veins of the legs or arms), chest pain or shortness of breath (which may be a symptom of blood clots in the lungs)
• Any other significant illness for which you have been hospitalized or for which you have received a medicine.

Conditions to watch out for
Pay attention to the appearance of certain symptoms while taking Kyprolis to reduce the
risk of problems. Kyprolis may worsen certain conditions or cause serious side effects,
which may be fatal, including heart problems, lung problems, kidney problems, tumor lysis syndrome (a potentially fatal condition that occurs when cancer cells
break down and release their contents into the bloodstream), reactions to Kyprolis infusion,
unusual bruising or bleeding (including internal bleeding), blood clots in the
veins, liver problems, certain blood diseases or a neurological disease known as
reversible posterior encephalopathy syndrome (PRES). See “Conditions to watch out for”
in paragraph 4.
Tell your doctor if you have ever had a hepatitis B virus infection or may have one currently,
because this medicine may reactivate the hepatitis B virus. The doctor will check
for any signs of this infection before, during and for a period of time after
treatment with this medicine. Immediately inform your doctor if your state of
fatigue worsens or if you experience yellowing of the skin or the whites of your eyes.
At any time, during or after treatment, immediately inform your doctor or nurse
if you experience blurred vision, loss of vision or double vision, difficulty speaking,
weakness in one arm or leg, a change in the way you walk or problems with balance,
persistent numbness, reduced or loss of sensation, memory loss or confusion.
These could all be symptoms of a serious and potentially fatal brain condition
called Progressive Multifocal Leukoencephalopathy (PML). If you had these symptoms before
treatment with carfilzomib, inform your doctor about any changes in these symptoms.

Other medicines and Kyprolis
Tell your doctor if you are taking, have recently taken or may take any other
medicines, including over-the-counter medicines such as vitamin supplements and 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 they may not be compatible for use
with Kyprolis.

Pregnancy and breastfeeding
For women taking Kyprolis
Do not take Kyprolis if you are pregnant, if you suspect you are pregnant or are planning to become
pregnant. Treatment with Kyprolis in pregnant women has not been evaluated. During use of
Kyprolis and for 30 days after stopping treatment, you must use a suitable contraceptive
method to avoid pregnancy. You should talk to your doctor or nurse about suitable methods of
contraception.
If you become pregnant during treatment with Kyprolis, inform your doctor or
nurse immediately.
Do not take Kyprolis if you are breastfeeding. It is not known whether Kyprolis passes into breast milk in humans.
Lenalidomide may be harmful to the fetus. When Kyprolis is administered in combination
with lenalidomide, you must adhere to the pregnancy prevention program (see the leaflet
for lenalidomide for information on pregnancy prevention and discuss with your
doctor, pharmacist or nurse).

Driving and using machines
During treatment with Kyprolis you may experience fatigue, dizziness, fainting and/or a
lowering of blood pressure. These conditions may impair your ability to
drive or use machines. Do not drive a vehicle and do not use machines if you experience
any of these symptoms.

Kyprolis contains sodium
This medicine contains 37 mg of sodium per 10 mg vial equivalent to 1.9%
of the recommended daily intake by the WHO which corresponds to 2 g of sodium for an
adult.
This medicine contains 109 mg of sodium per 30 mg vial equivalent to 5.5%
of the recommended daily intake by the WHO which corresponds to 2 g of sodium for an
adult.
This medicine contains 216 mg of sodium per 60 mg vial equivalent to 11%
of the recommended daily intake by the WHO which corresponds to 2 g of sodium for an
adult.

Kyprolis contains cyclodextrin
This medicine contains 500 mg of cyclodextrin (sodium sulfobutylether beta-cyclodextrin) per
10 mg vial equivalent to 88 mg/kg for an adult weighing 70 kg.
This medicine contains 1,500 mg of cyclodextrin (sodium sulfobutylether beta-cyclodextrin) per
30 mg vial equivalent to 88 mg/kg for an adult weighing 70 kg.
This medicine contains 3,000 mg of cyclodextrin (sodium sulfobutylether beta-cyclodextrin) per
60 mg vial equivalent to 88 mg/kg for an adult weighing 70 kg.

3. How to use Kyprolis

The administration of Kyprolis will be performed by a doctor or a nurse. The dose will be calculated
based on your height and weight (body surface area). The doctor or nurse will calculate the dose
of Kyprolis that you will receive.
Kyprolis will be administered as an intravenous infusion. The infusion may last up to 30 minutes.
Kyprolis is administered for 2 consecutive days each week for 3 weeks, followed by a
week without treatment.
Each 28-day period is a treatment cycle. This means that Kyprolis will be administered to you
on days 1, 2, 8, 9, 15 and 16 of each 28-day cycle. The doses administered on day 8 and day
9 of each cycle will no longer be administered starting from cycle 13 if you are treated with
Kyprolis in combination with lenalidomide and dexamethasone.
Most patients will continue to receive treatment until the disease improves or remains stable. However, treatment with Kyprolis may also be discontinued if you experience side effects that cannot be managed.
Along with Kyprolis, you will also be administered lenalidomide and dexamethasone, daratumumab and
dexamethasone, or dexamethasone alone. You may also be given other medicines.

If you are given too much Kyprolis
Because this medicine is administered by a doctor or a nurse, it is unlikely that you
will receive too much of it. However, if this were to happen, the doctor will monitor you for any side effects.
If you have any doubts 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.

Conditions to watch out for
Some side effects can be serious. Tell your doctor immediatelyif you notice any of the
following symptoms:

• Chest pain, shortness of breath, or swelling of the feet, as possible symptoms of heart problems
• Difficulty breathing, including shortness of breath at rest or during activity, or cough (dyspnea), rapid breathing, feeling of not getting 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 can be signs of a condition known as hypertensive crisis
• Shortness of breath with daily activities or at rest, irregular heartbeat, rapid heartbeat, fatigue, dizziness and fainting, which can be signs of a condition known as pulmonary hypertension
• Swelling of the ankles, feet, or hands, loss of appetite, decreased amount of urine, or abnormalities in blood test results, which can be symptoms of kidney problems or kidney failure
• A side effect called tumor lysis syndrome, which can be caused by the rapid destruction of cancer cells and can lead to irregular heartbeat, kidney failure, or abnormalities in blood test results
• Fever, chills, or tremors, joint pain, muscle pain, flushing of the face, or swelling of the face, lips, tongue and/or throat, which can cause difficulty breathing or swallowing (angioedema), weakness, shortness of breath, low blood pressure, fainting, slowing of the heart rate, feeling of tightness in the chest or chest pain may occur as an infusion reaction
• Unusual bruising or bleeding, such as a cut that takes longer than usual to stop bleeding, internal bleeding such as coughing up blood, vomiting blood, dark tarry stools, or bright red blood in the stool, or bleeding in the brain leading to sudden numbness or paralysis of one side of the face, legs, or arms, sudden severe headache, or problems with seeing or difficulty speaking or swallowing
• Pain or swelling in legs or arms (which can be a symptom of blood clots in the deep veins of legs or arms), chest pain or shortness of breath (which can be a symptom of blood clots in the lungs)
• Yellowing of the skin and eyes (jaundice), abdominal pain or swelling, nausea or vomiting which can be symptoms of liver problems, including liver failure. If you have ever had hepatitis B virus infection, treatment with this medicine may cause reactivation of hepatitis B virus infection
• Bleeding, bruising, weakness, confusion, fever, nausea, vomiting and diarrhea, and acute kidney failure, which can be possible signs of a blood condition known as thrombotic microangiopathy
• Headache, confusion, seizures, decreased vision, and high blood pressure (hypertension), which can be possible symptoms of a neurological condition known as reversible posterior encephalopathy syndrome (PRES).

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

• Severe lung infection (pneumonia)
• Respiratory tract infection (airway infection)
• Low number of platelets, which can cause a greater tendency to bruise or bleed (thrombocytopenia)
• Low number of white blood cells, which can reduce the body's ability to fight infections and may be accompanied by fever
• Low number of red blood cells (anemia), which can cause fatigue and tiredness
• Changes in blood test results (low potassium levels in the blood, increased creatinine levels in the blood)
• Decreased appetite
• Difficulty sleeping (insomnia)
• Headache
• Numbness, tingling, or decreased sensation in the 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 hands, feet or ankles
• Feeling weak
• Fatigue (tiredness)

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

• Infusion reaction
• Heart failure and heart problems, including a fast, strong, or irregular heartbeat
• Heart attack
• Kidney problems, including kidney failure
• Blood clots in the veins (deep vein thrombosis)
• Feeling of excessive heat
• Blood clots in the lungs
• Fluid in the lungs
• Wheezing
• Severe infection, including a blood infection (sepsis)
• Lung infection
• Liver problems, including increased liver enzymes in the blood
• Flu-like symptoms (influenza)
• Reactivation of the chickenpox virus which can cause a skin reaction and pain (herpes zoster)
• Urinary tract infection (infection of the tubes that carry urine)
• Cough which can also include tightness in the chest or pain, nasal congestion (bronchitis)
• Sore throat
• Inflammation of the nose and throat
• Runny nose, nasal congestion or sneezing
• Viral infection
• Stomach and intestinal infection (gastroenteritis)
• Bleeding in the stomach and intestines
• Changes in blood test results (decreased levels of sodium, magnesium, proteins, calcium or phosphate in the blood, increased levels of calcium, uric acid, potassium, bilirubin, C-reactive protein or sugars in the blood)
• Dehydration
• Anxiety
• Feeling confused
• Blurred vision
• Cataract
• Low blood pressure (hypotension)
• Nosebleed
• Change in voice or hoarseness
• Digestive difficulties
• Tooth pain
• Skin rash
• Pain in bones, muscles, chest
• Muscle weakness
• Sore muscles
• Itchy skin
• Redness of the skin
• Increased sweating
• Pain
• Pain, swelling, irritation or discomfort at the site where you received the injection in the vein
• Ringing in the ears (tinnitus)
• A general feeling of being unwell or discomfort

Uncommon side effects (may affect up to 1 in 100 people)

• Bleeding in the lungs
• Inflammation of the colon caused by a bacterium called Clostridium difficile
• Allergic reaction to Kyprolis
• Multi-organ failure
• Reduced blood flow to the heart
• Bleeding in the brain
• Stroke
• Difficulty breathing, rapid breathing and/or slightly bluish fingertips and lips (acute respiratory distress syndrome)
• Swelling of the membrane around the heart (pericarditis), symptoms include pain behind the breastbone, which sometimes spreads to the neck and shoulders, sometimes with fever
• Fluid buildup in the membrane lining 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 itching, yellowing of the skin, very dark urine and very pale stools
• Bleeding in the stomach and intestines
• Cytomegalovirus infection
• Reactivation of hepatitis B virus infection (viral inflammation of the liver)
• Inflammation of the pancreas

Reporting of side effects
If you get any side effects, even those not listed in this leaflet,tell your
doctor, pharmacist or nurse. You can also report side effects directly through 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 Kyprolis

Kyprolis will be stored at the pharmacy.
Keep this medicine out of sight and reach of children.
Do not use Kyprolis after the expiry date which is stated on the vial and the packaging. 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.
The reconstituted product must be clear, from colourless to slightly yellowish and must not be
administered if any colour change or particles are observed.
Kyprolis is for single use only. Unused medicine and waste medicine must be disposed of in
accordance with current local regulations.

6. Package contents and other information

What Kyprolis contains

• The active substance is carfilzomib. Each vial contains 10 mg, 30 mg or 60 mg of carfilzomib. After reconstitution, 1 mL of solution contains 2 mg of carfilzomib.
• The other ingredients are sodium sulfobutylether beta-cyclodextrin, anhydrous citric acid (E330) and sodium hydroxide (see section 2 “Kyprolis contains sodium”).

Description of Kyprolis and package contents
Kyprolis is supplied in a glass vial as a powder for solution for infusion, ranging in color from
white to off-white, to be reconstituted (dissolved) before use. The reconstituted solution is a
clear, colorless to slightly yellowish solution.
Each pack contains 1 vial.

Marketing authorisation holder and manufacturer
Amgen Europe B.V.
Minervum 7061,
4817 ZK Breda,
Netherlands

Marketing authorisation holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
Netherlands

Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Dublin
Ireland

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium
For further information on this medicine, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
s.a. Amgen n.v.
Tel/Tél: +32 (0)2 7752711

Lietuva
Amgen Switzerland AG Vilniaus filialas
Tel: +370 5 219 7474

България
Амджен България ЕООД
Тел.: +359 (0)2 424 7440

Luxembourg/Luxemburg
s.a. Amgen
Belgique/Belgien
Tel/Tél: +32 (0)2 7752711

Česká republika
Amgen s.r.o.
Tel: +420 221 773 500

Magyarország
Amgen Kft.
Tel.: +36 1 35 44 700

Danmark
Amgen, filial af Amgen AB, Sverige
Tlf: +45 39617500

Malta
Amgen B.V.
The Netherlands
Tel: +31 (0)76 5732500

Deutschland
AMGEN GmbH
Tel.: +49 89 1490960

Nederland
Amgen B.V.
Tel: +31 (0)76 5732500

Eesti
Amgen Switzerland AG Vilniaus filialas
Tel: +372 586 09553

Norge
Amgen AB
Tel: +47 23308000

Ελλάδα
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε.
Τηλ.: +30 210 3447000

Österreich
Amgen GmbH
Tel: +43 (0)1 50 217

España
Amgen S.A.
Tel: +34 93 600 18 60

Polska
Amgen Biotechnologia Sp. z o.o.
Tel.: +48 22 581 3000

France
Amgen S.A.S.
Tél: +33 (0)9 69 363 363

Portugal
Amgen Biofarmacêutica, Lda.
Tel: +351 21 4220606

Hrvatska
Amgen d.o.o.
Tel: +385 (0)1 562 57 20

România
Amgen România SRL
Tel: +4021 527 3000

Ireland
Amgen Ireland Limited
Tel: +353 1 8527400

Slovenija
AMGEN zdravila d.o.o.
Tel: +386 (0)1 585 1767

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Amgen Slovakia s.r.o.
Tel: +421 2 321 114 49

Italia
Amgen S.r.l.
Tel: +39 02 6241121

Suomi/Finland
Amgen AB, sivuliike Suomessa/Amgen AB, filial
i Finland
Puh/Tel: +358 (0)9 54900500

Kύπρος
C.A. Papaellinas Ltd
Τηλ.: +357 22741 741

Sverige
Amgen AB
Tel: +46 (0)8 6951100

Latvija
Amgen Switzerland AG Rīgas filiāle
Tel: +371 257 25888

United Kingdom (Northern Ireland)
Amgen Limited
Tel: +44 (0)1223 420305

Other sources of information
More detailed information on this medicine is available on the website of the European
Agency http://www.agenziafarmaco.gov.it/
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:
Instructions for reconstitution and preparation of Kyprolis powder for solution for infusion
for intravenous administration
Carfilzomib is a cytotoxic agent. Therefore, caution should be exercised during handling and
preparation of Kyprolis. The use of gloves and other protective devices is recommended.
Kyprolis vials do not contain antimicrobial preservatives and are for single use only. Adequate
aseptic technique must be used.
The reconstituted solution contains carfilzomib at a concentration of 2 mg/mL. Read the detailed
instructions for preparation before reconstitution:

• 1. Calculate the dose (mg/m²) and the number of Kyprolis vials needed using the patient’s baseline body surface area (BSA). Patients with a BSA greater than 2.2 m² should receive a dose calculated based on a BSA of 2.2 m². No dose adjustments are necessary for weight changes ≤ 20%.
• 2. Remove the vial from the refrigerator immediately before use.
• 3. Use only a 21 gauge or larger needle (needle outer diameter of 0.8 mm or less) to reconstitute each vial using aseptic technique by slowly injecting 5 mL (for the 10 mg vial), 15 mL (for the 30 mg vial) or 29 mL (for the 60 mg vial) of sterile water for injection through the stopper and directing the solution stream towards the INNER WALL OF THE VIAL to minimize foam formation.
• 4. Gently rotate and/or invert the vial slowly for approximately 1 minute or until complete dissolution. DO NOT SHAKE. If foam forms, allow the solution inside the vial to rest until the foam dissolves (approximately 5 minutes) and the solution returns to being clear.
• 5. Visually inspect for particulate matter and color change prior to administration. The reconstituted product should be clear, from colorless to slightly yellowish and should not be used if discoloration or particulate matter is observed.
• 6. Discard any remaining solution inside the vial.
• 7. Kyprolis can be administered directly by intravenous infusion or alternatively, it can be administered using an intravenous infusion bag. Do not administer by rapid intravenous push or bolus.
• 8. If administering with an intravenous infusion bag, use only a 21 gauge or larger needle (needle outer diameter of 0.8 mm or less) to withdraw the calculated dose from the vial and dilute it in a 50 mL or 100 mL intravenous infusion bag containing 5% dextrose injection.

From a microbiological point of view, the product should be used immediately. Otherwise, the
storage times and conditions during use are the responsibility of the user and should not exceed 24
hours at a temperature of 2°C – 8°C.
Unused medicine or waste material derived from such medicine should be disposed of in accordance
with local regulations.