KLEDER

Package leaflet: Information for the patient

Kleder, 5 mg, hard capsules
Kleder, 10 mg, hard capsules
Kleder, 15 mg, hard capsules
Kleder, 20 mg, hard capsules
Kleder, 25 mg, hard capsules
Lenalidomide
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• Ask your doctor or pharmacist if you have any questions.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any side effects, including any possible side effects not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Kleder is and what it is used for
2. Important information before taking Kleder
3. How to take Kleder
4. Possible side effects
5. How to store Kleder
6. Contents of the pack and other information

1. What Kleder is and what it is used for

What Kleder is
Kleder contains the active substance lenalidomide. This medicine belongs to a group of medicines that affect the function of the immune system.
What Kleder is used for
Kleder is used in adults to treat:

• multiple myeloma,
• myelodysplastic syndromes,
• mantle cell lymphoma,
• follicular lymphoma.

Multiple myeloma
Multiple myeloma is a type of cancer that affects a certain type of white blood cells called plasma cells. These cells accumulate in the bone marrow and divide uncontrollably. This may lead to damage of bones and kidneys.
Multiple myeloma is generally incurable, but it is possible to achieve a temporary significant reduction or elimination of signs and symptoms of the disease. This is called a “response”.
Newly diagnosed multiple myeloma in patients after bone marrow transplant
In this indication, Kleder is used as monotherapy for maintenance treatment after achieving an adequate response following transplantation.
Newly diagnosed multiple myeloma – in patients who cannot be treated with bone marrow transplantation
Kleder is taken in combination with other medicines. These may include:

• a chemotherapy medicine called “bortezomib”;
• an anti-inflammatory medicine called “dexamethasone”;
• a chemotherapy medicine called “melphalan”; and
• an immunosuppressive medicine called “prednisone”. The patient starts treatment with additional medicines and then continues with Kleder alone.

If the patient is 75 years of age or older, or has moderate to severe kidney impairment, the doctor will perform thorough assessments before starting treatment.
Multiple myeloma – in previously treated patients
Kleder is taken in combination with an anti-inflammatory medicine called “dexamethasone”.
Kleder may stop the progression of signs and symptoms of multiple myeloma. It has also been shown to delay the recurrence of multiple myeloma after treatment.
Myelodysplastic syndromes (MDS)
Myelodysplastic syndromes (MDS) are a group of different blood and bone marrow disorders. Abnormal blood cells are present, which do not function properly. Patients may experience various subjective and objective symptoms, including low red blood cell count (anaemia), need for blood transfusions, and risk of infection.
Kleder as monotherapy is used to treat adult patients diagnosed with MDS, if all of the following conditions are met:

• the patient requires regular blood transfusions due to low red blood cell count (“transfusion-dependent anaemia”);
• the patient has an abnormality in bone marrow cells called “isolated cytogenetic abnormality with deletion 5q”. This means the patient’s body does not produce enough healthy blood cells;
• the patient has previously been treated with other therapies that were inappropriate or insufficiently effective.

Taking Kleder may lead to an increase in the number of healthy blood cells produced by the body by reducing the number of abnormal cells:

• this may lead to a reduction in the number of required blood transfusions. It may even become possible to discontinue transfusions altogether.

Mantle cell lymphoma (MCL)
MCL is a cancer affecting part of the immune system (lymphatic tissue). It attacks a type of white blood cells called B-lymphocytes or B-cells. Mantle cell lymphoma is a disease characterised by uncontrolled growth of B-lymphocytes, leading to their accumulation in lymphatic tissue, bone marrow, or blood.
Kleder as monotherapy is used to treat adult patients who have been previously treated with other medicines.
Follicular lymphoma (FL)
Follicular lymphoma (FL) is a slowly growing malignant tumour that attacks B-lymphocytes. These are a type of white blood cells that help the body fight infections. In patients with FL, excessive numbers of B-lymphocytes may accumulate in the blood, bone marrow, lymph nodes, and spleen.
Kleder is taken together with another medicine called “rituximab” in the treatment of adult patients with previously treated follicular lymphoma.
How Kleder works
Kleder works by affecting the function of the immune system and directly attacking cancer cells. The medicine works in several different ways:

• by inhibiting the growth of cancer cells,
• by inhibiting the development of blood vessels in the tumour,
• by stimulating part of the immune system to attack cancer cells.

2. Important information before taking Kleder
Before starting treatment with Kleder, carefully read the leaflets of all medicinal products taken in combination with Kleder.
When not to use Kleder:

• If the patient is pregnant, suspects she is pregnant, or plans to become pregnant, because Kleder is expected to be harmful to the unborn child (see section 2 “Pregnancy, breastfeeding and contraception – information for women and men”).
• If the patient may become pregnant, unless she uses all required contraceptive measures (see section 2 “Pregnancy, breastfeeding and contraception – information for women and men”). If the patient may become pregnant, the doctor will always document that necessary measures have been taken and ensure the patient is aware of them.
• If the patient is allergic to lenalidomide or any of the other ingredients of this medicine listed in section 6. If allergy is suspected, consult your doctor for advice.

If any of these points apply to the patient, do not use Kleder. If in doubt, consult your doctor.
Warnings and precautions
Before starting to take Kleder, consult your doctor, pharmacist, or nurse if:

• the patient has previously had blood clots – this means an increased risk of developing blood clots in veins and arteries during treatment;
• the patient has any signs of infection, such as cough or fever;
• the patient currently has or has previously had a viral infection, particularly hepatitis B virus, varicella-zoster virus (chickenpox and shingles), or HIV. If in doubt, consult your doctor. Treatment with Kleder may cause reactivation of the virus in patients who are carriers. This leads to recurrence of infection. The doctor will check whether the patient has previously had hepatitis B;
• the patient has kidney problems – the doctor may adjust the dose of Kleder;
• the patient has had a heart attack (infarction), has previously had a blood clot, smokes, has high blood pressure, or high cholesterol levels;
• the patient experienced allergic reactions while taking thalidomide (another medicine used to treat multiple myeloma), such as rash, itching, swelling, dizziness, or difficulty breathing;
• the patient previously experienced a combination of any of the following symptoms: widespread rash, skin redness, high fever, flu-like symptoms, increased liver enzyme activity, blood abnormalities (eosinophilia), enlarged lymph nodes – these are symptoms of a severe skin reaction called drug rash with eosinophilia and systemic symptoms, also known as “DRESS” or “drug hypersensitivity syndrome” (see also section 4 “Possible side effects”).

If any of the above apply to the patient, consult your doctor, pharmacist, or nurse.
If at any time during or after treatment the patient experiences:

• vision disturbances, loss of vision or double vision, difficulty speaking, weakness in the arm or leg, change in walking pattern or balance disturbances, persistent numbness, reduced sensation or loss of sensation, memory loss or disorientation, immediately inform your doctor or nurse. These may be symptoms of a severe and potentially fatal brain disease called progressive multifocal leukoencephalopathy (PML). If the patient had such symptoms before treatment with lenalidomide, inform the doctor of any changes in these symptoms.
• shortness of breath, fatigue, dizziness, chest pain, rapid heartbeat, or swelling of the legs or ankles. These may be symptoms of a serious condition known as pulmonary hypertension (see section 4).

Tests and examinations
Before and during treatment with Kleder, regular blood tests will be performed. This is because Kleder may cause a decrease in the number of blood cells involved in fighting infections (white blood cells) and blood clotting (platelets).
Your doctor will ask you to have blood tests:

• before treatment;
• weekly for the first 8 weeks of treatment;
• then at least once a month.

Before starting lenalidomide treatment and during treatment, the patient may be evaluated for cardiovascular and respiratory diseases.
Patients with MDS taking Kleder
If the patient has myelodysplastic syndromes, there is an increased chance of developing a serious disease called acute myeloid leukaemia. In addition, it is not known how Kleder affects the likelihood of developing acute myeloid leukaemia. Therefore, the doctor may perform tests and check for signs that help better predict the risk of acute myeloid leukaemia during treatment with Kleder.
Patients with MCL taking Kleder
The doctor will ask for blood tests:

• before treatment;
• weekly for the first 8 weeks (2 cycles) of treatment;
• then every 2 weeks during cycles 3 and 4 (more information in section 3 “Treatment cycle”);
• then at the beginning of each cycle, and
• at least once a month.

Patients with FL taking Kleder
The doctor will ask for blood tests:

• before treatment;
• weekly for the first 3 weeks (1 cycle) of treatment;
• then every 2 weeks during cycles 2 to 4 (more information in section 3 “Treatment cycle”);
• then at the beginning of each cycle, and
• at least once a month.

The doctor may perform a test to determine whether the patient has a large amount of tumour tissue in the body, including in the bone marrow. This may lead to a situation where tumour tissue begins to die and causes an abnormal increase in the concentration of various substances in the blood, which may lead to kidney failure (a condition called tumour lysis syndrome).
The doctor may examine the patient to check for skin changes, such as red spots or rash.
The doctor may change the dose of Kleder or discontinue treatment based on the patient’s blood test results and general condition. If the disease has been recently diagnosed, the doctor may also assess treatment based on the patient’s age and other pre-existing conditions.
Blood donation
During treatment and for at least 7 days after treatment ends, the patient must not donate blood.
Children and adolescents
Kleder is not recommended for use in children and adolescents under 18 years of age.
Elderly patients and patients with kidney problems
If the patient is 75 years of age or older, or has moderate to severe kidney impairment, the doctor will perform thorough assessments before starting treatment.
Kleder and other medicines
Tell your doctor or nurse about all medicines you are currently taking or have recently taken. This is necessary because Kleder may affect the action of other medicines. Likewise, some other medicines may affect how Kleder works.
In particular, inform your doctor or nurse if the patient is taking the following medicines:

• certain contraceptives, such as oral contraceptives, because they may stop working;
• certain medicines used for heart problems – such as digoxin;
• certain medicines used to thin the blood – such as warfarin.

Pregnancy, breastfeeding and contraception – information for women and men
Pregnancy
Applies to women taking Kleder

• Do not use Kleder if the patient is pregnant, because it is expected to be harmful to the unborn child.
• Women must not become pregnant while taking Kleder.
• For this reason, women who may become pregnant must use an effective method of contraception (see “Contraception”).
• If the patient becomes pregnant while taking Kleder, she must immediately stop treatment and inform her doctor.

Applies to men taking Kleder

• If the partner of a man undergoing treatment with Kleder becomes pregnant, she should immediately inform the doctor. The patient’s partner should seek medical advice.
• Men must also use an effective method of contraception (see “Contraception”).

Breastfeeding
Do not breastfeed while taking Kleder, because it is not known whether Kleder passes into human milk.
Contraception
Applies to women taking Kleder
Before starting treatment, ask your doctor about the possibility of becoming pregnant, even if the patient considers it unlikely.
Women who may become pregnant:

• will undergo pregnancy tests performed under medical supervision (before each treatment cycle, at least every 4 weeks during treatment, and at least 4 weeks after treatment ends), except in cases where the fallopian tubes have been cut and sealed to prevent the egg from reaching the uterus (tubal sterilisation)
  AND

• must use effective methods of contraception for at least 4 weeks before starting treatment, during treatment, and for at least 4 weeks after treatment ends. The doctor will advise the patient on appropriate contraceptive methods.

Applies to men taking Kleder
Kleder passes into human semen. If a woman is pregnant or may become pregnant and is not using an effective contraceptive method, her partner must use a condom during treatment and for at least 7 days after treatment ends. This applies also to men who have had a vasectomy. During treatment and for at least 7 days after treatment ends, the patient must not donate semen.
Driving and operating machinery
Do not drive or operate machinery if the patient experiences dizziness, fatigue, drowsiness, balance disturbances due to vertigo, or blurred vision after taking Kleder.
Kleder contains lactose and sodium.
Kleder contains lactose. If the patient has previously been diagnosed with intolerance to certain sugars, the patient should contact the doctor before taking this medicine.
The medicine contains less than 1 mmol (23 mg) of sodium per capsule, meaning the medicine is considered “sodium-free”.

3. How to take Kleder

Kleder must be administered by medical professionals experienced in the treatment of multiple myeloma, MDS, MCL, or FL.

• When Kleder is used to treat multiple myeloma in patients who are not eligible for bone marrow transplantation or who have previously received other treatment, the medicine is given in combination with other drugs (see section 1 "Why Kleder is used").
• When Kleder is used to treat multiple myeloma in patients after bone marrow transplantation, or in patients with MDS or MCL, the medicine is used as monotherapy.
• When Kleder is used to treat follicular lymphoma, it is taken together with another medicine called "rituximab".

Kleder should always be used exactly as prescribed by the doctor. In case of doubt, consult the doctor or pharmacist.
If the patient is taking Kleder together with other medicines, they should read the package leaflet included with those medicines to obtain information about their use and effects.

Treatment cycle
Kleder is taken on specific days within a period of three weeks (21 days).

• Each 21-day period is referred to as a treatment cycle.

• Depending on the day of the cycle, the patient will take one or more medicines. However, on some days, the patient will not take any medicines.

• After completing each 21-day cycle, the patient should start a new 21-day cycle.
  OR
  Kleder is taken on specific days within a period of four weeks (28 days).

• Each 28-day period is referred to as a treatment cycle.

• Depending on the day of the cycle, the patient will take one or more medicines. However, on some days, the patient will not take any medicines.

• After completing each 28-day cycle, the patient should start a new 28-day cycle.

What dose of Kleder should be taken
Before starting treatment, the doctor will inform the patient:

• how much Kleder should be taken;
• how many other medicines should be taken in combination with Kleder, if applicable;
• on which days of the cycle each medicine should be taken.

How and when to take Kleder

• Swallow the capsule whole, preferably with water.
• Do not crush, open, or chew the capsules. If the powder from a damaged Kleder capsule comes into contact with the skin, wash the skin immediately and thoroughly with soap and water.
• Healthcare professionals, caregivers, and family members should wear disposable gloves when handling the blister pack or capsules. Gloves should be carefully removed to avoid skin exposure, placed in a sealable polyethylene plastic bag, and disposed of according to local regulations. Hands should then be washed thoroughly with soap and water. Pregnant women or women who suspect they may be pregnant should not handle the blister pack or capsules.
• Capsules may be taken with or without food.
• Kleder should be taken at approximately the same time each day on which dosing is scheduled.

How to take Kleder
To remove a capsule from the blister:

• press only on one side of the capsule to push it through the foil;
• do not press on the center of the capsule, as this may damage it.

Duration of treatment with Kleder
Kleder is administered in treatment cycles; each cycle lasts 21 or 28 days (see above, "Treatment cycle"). Treatment cycles should continue until the doctor decides to discontinue treatment.

Taking more Kleder than prescribed
If a patient takes more Kleder than prescribed, they should contact their doctor immediately.

Missed dose of Kleder
If a dose of Kleder has been missed:

• if less than 12 hours have passed since the scheduled time: take the capsule immediately;
• if more than 12 hours have passed since the scheduled time: do not take the missed capsule. Take the next capsule at the scheduled time on the following day.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following severe adverse reactions occur, stop taking Kleder and seek immediate medical advice – immediate treatment may be required:

• hives, rash, swelling of the eyes, lips or face, breathing difficulties or itching, which may be symptoms of severe allergic reactions known as angioedema and anaphylactic reaction;
• severe allergic reaction possibly starting as a rash in one area, spreading over the entire body and associated with significant skin peeling (Stevens-Johnson syndrome and/or toxic epidermal necrolysis);
• widespread rash, high fever, increased liver enzyme activity, blood abnormalities (eosinophilia), swollen lymph nodes and involvement of other organs (drug rash with eosinophilia and systemic symptoms, also known as “DRESS” or “drug hypersensitivity syndrome”). See also section 2.

Immediately inform your doctor if any of the following severe adverse reactions occur:

• fever, chills, sore throat, cough, mouth ulcers or any other signs of infection (including blood infections (sepsis));
• bleeding or bruising without injury;
• chest pain or leg pain;
• shortness of breath;
• bone pain, muscle weakness, confusion or fatigue, which may result from high calcium levels in the blood.

Kleder may reduce the number of white blood cells that fight infection, as well as blood cells that help blood clot (platelets), which may lead to bleeding disorders, such as nosebleeds and bruising. Kleder may also cause blood clots in veins (thrombosis).
Other adverse reactions
Note that in a small number of patients, development of other types of tumours may occur, and it is possible that this risk may increase due to treatment with Kleder.
Therefore, your doctor should carefully evaluate the benefits and risks before prescribing Kleder.
Very common adverse reactions (may affect more than 1 in 10 people):

• reduced number of red blood cells, which may cause anaemia leading to tiredness and weakness;
• rashes, itching;
• muscle cramps, muscle weakness, muscle pain, tenderness in muscles, bone pain, joint pain, back pain, limb pain;
• generalised swelling, including swelling of hands and feet;
• weakness, fatigue;
• fever and flu-like symptoms, including fever, muscle pain, headache, ear pain, cough and chills;
• numbness, tingling or burning sensation in the skin, pain in hands or feet, dizziness, tremor;
• decreased appetite, altered taste sensation;
• increased pain, enlargement or redness around a tumour;
• weight loss;
• constipation, diarrhoea, nausea, vomiting, abdominal pain, heartburn;
• low blood levels of potassium, calcium and/or sodium;
• underactive thyroid gland;
• leg pain (which may be a sign of thrombosis), chest pain or shortness of breath (which may be symptoms of blood clots in the lungs, known as pulmonary embolism);
• all types of infections, including sinus infection, lung infection and upper respiratory tract infections;
• shortness of breath;
• blurred vision;
• cloudy vision (cataract);
• kidney problems, including abnormal kidney function or inability to maintain normal kidney function;
• abnormal liver test results;
• increased liver function test values;
• changes in blood proteins, leading to inflammation of arteries (vasculitis);
• increased blood sugar levels (diabetes);
• decreased blood sugar levels;
• headache;
• nosebleeds;
• dry skin;
• depression, mood changes, sleep problems;
• cough;
• low blood pressure;
• vague feeling of physical discomfort, malaise;
• painful inflammation of the mouth, dry mouth;
• dehydration.

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

• breakdown of red blood cells (haemolytic anaemia);
• certain types of skin tumours;
• bleeding from gums, stomach or intestines;
• increased blood pressure, slow, fast or irregular heartbeat;
• increased levels of substances resulting from normal and abnormal breakdown of red blood cells;
• increased blood level of a protein indicating inflammation in the body;
• darkening of the skin, skin discolouration due to bleeding under the skin, usually caused by bruising; blood-filled skin swelling, bruising;
• increased blood uric acid levels;
• skin eruptions, skin redness, skin cracking, peeling or flaking, hives;
• excessive sweating, night sweats;
• difficulty swallowing, sore throat, problems with voice quality or voice changes;
• nasal inflammation (rhinitis);
• passing significantly more or less urine than normal, or inability to control urination;
• blood in the urine;
• shortness of breath, especially when lying down (which may be a sign of heart failure);
• erectile problems;
• stroke, fainting, dizziness (inner ear disorders causing a sensation that everything is spinning), transient loss of consciousness;
• chest pain spreading to arms, neck, jaw, back or abdomen, sweating, shortness of breath, nausea or vomiting, which may be symptoms of a heart attack (myocardial infarction);
• muscle weakness, lack of energy;
• neck pain, chest pain;
• chills;
• joint swelling;
• slowing or blockage of bile flow from the liver;
• low blood levels of phosphates or magnesium;
• speech difficulties;
• liver damage;
• balance disorders, difficulty moving;
• deafness, tinnitus (ringing in the ears);
• nerve pain, unpleasant abnormal sensations, especially in response to touch;
• excess iron in the body;
• thirst;
• confusion;
• toothache;
• falls that may lead to injury.

Uncommon adverse reactions (may affect up to 1 in 100 people):

• bleeding inside the skull;
• circulatory problems;
• loss of vision;
• loss of sex drive (libido);
• passing large amounts of urine, accompanied by bone pain and weakness, which may be symptoms of kidney disease (Fanconi syndrome);
• yellowing of the skin, mucous membranes or eyes (jaundice), pale-coloured stools, dark-coloured urine, itchy skin, rash, abdominal pain or swelling – may be symptoms of liver damage (liver failure);
• abdominal pain, bloating or diarrhoea, which may be symptoms of inflammation of the large intestine (so-called colitis or typhlitis);
• kidney cell damage (known as tubular necrosis);
• skin colour changes, sensitivity to sunlight;
• tumour lysis syndrome – metabolic complications that may occur during cancer treatment, and sometimes even without treatment. These complications are caused by products released from dying tumour cells and may include: changes in blood chemistry; high levels of potassium, phosphate and uric acid, and low calcium levels, leading to kidney dysfunction, irregular heart rhythm, seizures, and sometimes death;
• high blood pressure in the blood vessels leading to the lungs (pulmonary hypertension).

Unknown frequency adverse reactions (frequency cannot be estimated from available data)

• sudden or mild but progressively worsening pain in the upper abdomen and/or back, lasting for several days, usually accompanied by nausea, vomiting, fever and rapid heartbeat – these symptoms may occur in association with pancreatitis;
• wheezing, shortness of breath or dry cough, possibly due to inflammation of lung tissue;
• rare cases of muscle breakdown (muscle pain, weakness or swelling) leading to kidney problems (rhabdomyolysis) have been observed, some occurring when Kleder was administered concomitantly with a statin (a type of medicine that lowers blood cholesterol);
• skin disease caused by inflammation of small blood vessels, associated with joint pain and fever (leucocytoclastic vasculitis);
• perforation of the stomach or intestinal wall; this may lead to a very serious infection. Inform your doctor if you experience severe stomach pain, fever, nausea, vomiting, blood in stool or changes in bowel habits;
• viral infections, including shingles (a viral disease causing a painful skin rash with blisters) and reactivation of hepatitis B virus infection (which may cause yellowing of the skin and eyes, dark brown urine, abdominal pain on the right side, fever, nausea and vomiting);
• rejection of solid organ transplant (e.g. kidney, heart).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website:
https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the responsible entity.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Kleder

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack and the cardboard
carton after the word "EXP". The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Do not use this medicine if you notice any damage or signs of tampering with the packaging.
Medicines should not be disposed of via wastewater or household waste. Unused medicines should be returned to a pharmacy, which will accept them. This will help protect the environment.

6. Contents of the packaging and other information

What Kleder contains
Kleder 5 mg, hard capsules:

• The active substance is lenalidomide. Each capsule contains 5 mg of lenalidomide.
• The other ingredients are:
  • capsule content: lactose (see section 2), microcrystalline cellulose, sodium croscarmellose, and magnesium stearate;
  • capsule shell: brilliant blue FCF (E 133), iron oxide red (E 172), iron oxide yellow (E 172), titanium dioxide (E 171), and gelatin;
  • printing ink: shellac, iron oxide black (E 172), propylene glycol, and potassium hydroxide.

Kleder 10 mg, hard capsules:

• The active substance is lenalidomide. Each capsule contains 10 mg of lenalidomide.
• The other ingredients are:
  • capsule content: lactose (see section 2), microcrystalline cellul游戏副本