TALIDOMIDE BMS 50 mg HARD CAPSULES

Introduction

Patient Information Leaflet

Thalidomide Celgene 50 mg hard capsules

thalidomide

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.

• If you have any further questions, ask your doctor, pharmacist, or nurse.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Thalidomide Celgene and what is it used for
2. What you need to know before you take Thalidomide Celgene
3. How to take Thalidomide Celgene
4. Possible side effects

1. Storage of Thalidomide Celgene
2. Contents of the pack and other information

1. What is Thalidomide Celgene and what is it used for

What is Thalidomide Celgene

Thalidomide Celgene contains an active substance called thalidomide, which belongs to a group of medicines that affect the way your immune system works.

What is Thalidomide Celgene used for

Thalidomide Celgene is used with two other medicines called melphalan and prednisone to treat adults with a type of cancer called multiple myeloma. It is used in people 65 years of age or older who have been newly diagnosed and have not previously used any medicine for multiple myeloma, or in people under 65 years of age who cannot be treated with high-dose chemotherapy because it may be difficult for the body to tolerate.

What is multiple myeloma

Multiple myeloma is a type of cancer that affects a type of white blood cell called plasma cells. These cells are produced in the bone marrow and divide out of control. This can damage the bones and kidneys. Multiple myeloma usually has no cure. However, the signs and symptoms can decrease greatly or disappear for a period of time. This is called "remission".

How Thalidomide Celgene works

Thalidomide Celgene works by helping the body's immune system and directly attacking the cancer. It works in different ways:

• slowing the growth of cancer cells;

• slowing the growth of blood vessels in the cancer;

• stimulating part of the immune system to attack cancer cells.

2. What you need to know before you take Thalidomide Celgene

You must receive specific instructions from your doctor, particularly about the effects of thalidomide on the fetus (which are explained in the Thalidomide Celgene Pregnancy Prevention Program). You must receive a patient information leaflet from your doctor. Read it carefully and follow the instructions.

If you do not fully understand these instructions, ask your doctor to explain them again before taking thalidomide. You can find more information in this section in the "Warnings and precautions" and "Pregnancy and breastfeeding" sections.

Do not take Thalidomide Celgene

• if you are pregnant, think you may be pregnant, or plan to become pregnant, since Thalidomide Celgene causes birth defects and fetal death.

• if you can become pregnant unless you are able to follow or comply with the required contraceptive measures to avoid becoming pregnant (see section 2 "Warnings and precautions" and "Pregnancy and breastfeeding").

• if you can become pregnant, your doctor will register with each prescription that the necessary measures have been taken and will provide you with this confirmation.

• if you are allergic to thalidomide or any of the other components of this medicine listed in section 6 "Contents of the pack and other information".

Do not take Thalidomide Celgene if any of the above points apply to you. If you are not sure, consult your doctor or pharmacist before starting to take Thalidomide Celgene.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take this medicine in the following cases:

For womentaking Thalidomide Celgene

Before starting treatment, you must consult with your doctor if there is a possibility that you may become pregnant, even if you think this is unlikely. Even if you do not have menstrual bleeding after cancer treatment, you can still become pregnant. If you can become pregnant:

• Your doctor will ensure that you have pregnancy tests

• before treatment
• • every 4 weeks during treatment

• 4 weeks after the end of treatment

• You must use an effective method of contraception:

• for at least 4 weeks before starting treatment
• during treatment

• until at least 4 weeks after the end of treatment. Your doctor will tell you which contraceptive method to use.

If you can become pregnant, your doctor will register with each prescription that the necessary measures have been taken, as described above.

For mentaking Thalidomide Celgene

Thalidomide passes into semen. Therefore, do not have unprotected sex, even if you have had a vasectomy.

• You must avoid pregnancy and any exposure during pregnancy. Always use a condom:
• • during treatment
  • for at least 7 days after the end of treatment

• You must not donate semen:
• • during treatment
  • for at least 7 days after the end of treatment

For all patients

Before taking Thalidomide Celgene, consult your doctor if:

• you do not understand the instructions on contraception given by your doctor or do not think you can follow them;

• you have had a heart attack, have ever had a blood clot, or if you smoke, or have high blood pressure or high cholesterol levels. During treatment with Thalidomide Celgene, you have a higher risk of developing blood clots in the veins and arteries (see also section 4 "Possible side effects");

• you have had or have neuropathy, i.e., nerve damage that causes tingling, abnormal coordination, or pain in the hands or feet (see also section 4 "Possible side effects");

• you have had or have a slow heart rate (which can be a symptom of bradycardia);

• you have high blood pressure in the arteries that come out of the lungs (see also section 4 "Possible side effects");

Children and adolescents

Thalidomide Celgene is not recommended for use in children and adolescents under 18 years of age.

Other medicines and Thalidomide Celgene

Tell your doctor or pharmacist if you are using or have recently used any other medicines, including those obtained without a prescription and herbal preparations.

Make sure to inform your doctor if you are taking any medicine that:

• causes drowsiness, as thalidomide may increase this effect. These medicines include sedatives (such as anxiolytics, hypnotics, antipsychotics, antihistamines H1, opioids, and barbiturates);

• slows down the heart rate (induces bradycardia, such as anticholinesterases and beta-blockers);

• is used for heart problems (such as digoxin) or to thin the blood (such as warfarin);

• is associated with neuropathy, such as other cancer treatments;

• is used for contraception.

Taking Thalidomide Celgene with food, drinks, and alcohol

Do not drink alcohol if you are taking Thalidomide Celgene. The reason is that alcohol will make you drowsy and Thalidomide Celgene may make you even drowsier.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

Thalidomide causes severe birth defects and fetal death.

• The fact that a pregnant woman takes even a small dose, such as one capsule, can cause the baby to be born with severe birth defects.

• These defects can include shorter arms or legs, deformities in hands or feet,

eye, ear, or internal organ problems.

If you are pregnant, do not take Thalidomide Celgene. Also, do not become pregnant if you are taking Thalidomide Celgene.

Women who can become pregnant must use an effective method of contraception (see section 2, "What you need to know before you take Thalidomide Celgene").

You must stop treatment and inform your doctor immediately if:

• You do not have a period or think you have not had a period, in case of unusual menstrual bleeding or if you suspect you may be pregnant.

• You have unprotected heterosexual sex without using an effective contraceptive method.

If you become pregnant during treatment with thalidomide, you must stop treatment and inform your doctor immediately.

Men who take Thalidomide Celgene and have a partner who can become pregnant must read section 2 "What you need to know before you take Thalidomide Celgene". If your partner becomes pregnant while you are taking thalidomide, you must inform your doctor immediately.

Breastfeeding

Do not breastfeed when taking Thalidomide Celgene, as it is not known whether thalidomide passes into human breast milk.

Driving and using machines

Do not drive or use tools or machines if you experience side effects such as dizziness, fatigue, drowsiness, or blurred vision.

3. How to take Thalidomide Celgene

Follow exactly the instructions for taking Thalidomide Celgene given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

How much to take

The recommended dose is 200 mg (4 capsules of 50 mg) per day in adults 75 years of age or younger or 100 mg (2 capsules of 50 mg) per day in adults over 75 years of age. However, your doctor will choose the most suitable dose for you, monitor your progress, and may adjust the dose. Your doctor will tell you how to take Thalidomide Celgene and for how long you will need to take it (see section 2, "What you need to know before you take Thalidomide Celgene").

Thalidomide Celgene is taken every day in treatment cycles, each lasting 6 weeks, in combination with melphalan and prednisone, which are taken on days 1 to 4 of each 6-week cycle.

How to take Thalidomide Celgene

• Do not break, open, or chew the capsules. If the powder from a broken Thalidomide Celgene capsule comes into contact with the skin, wash the skin immediately and carefully with water and soap.

• Healthcare professionals, caregivers, and family members must wear disposable gloves when handling the blister or capsule. Then, carefully remove the gloves to avoid skin exposure, place them in a sealable polyethylene plastic bag, and dispose of them according to local requirements. After that, wash your hands well with water and soap. Pregnant women or those who suspect they may be pregnant must not handle the blister or capsule.

• Take this medicine by mouth.

• Swallow the capsules whole with a full glass of water.

• Do not crush or chew them.

• Take the capsules as a single dose before going to bed. This will make you feel less drowsy at other times.

To remove the capsule from the blister, press only one end of the capsule to make it come out through the foil. Do not press in the center of the capsule as it may break.

If you take more Thalidomide Celgene than you should

If you take more Thalidomide Celgene than prescribed, consult a doctor or go directly to a hospital. If possible, take the medicine pack and this leaflet with you.

If you forget to take Thalidomide Celgene

If you forget to take Thalidomide Celgene at the usual time and

• less than 12 hours have passed: take the capsules immediately.

• more than 12 hours have passed: do not take the capsules. Take the next capsules at the usual time the next day.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

This medicine may cause the following adverse effects:

Stop taking Thalidomide Celgene and consult a doctor immediately if you notice the following serious adverse effects – you may need urgent medical treatment:

• Extremely intense and severe skin reactions. The adverse skin reaction may appear as rashes with or without blisters. Skin irritation, ulcers, or swelling in the mouth, throat, eyes, nose, and around the genitals, edema, and fever, and flu-like symptoms may occur. These symptoms can be signs of rare and severe skin reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome.

• Allergic reactions such as localized or generalized pruritic exanthema, angioedema, and anaphylactic reaction (severe types of allergic reactions that can manifest as hives, skin rashes, eye, mouth, or facial inflammation, difficulty breathing, or itching).

Consult your doctor immediately if you notice any of the following serious adverse effects:

• Numbness, tingling, abnormal coordination, or pain in the hands and feet.

This may be due to nerve damage (peripheral neuropathy), which is a very frequent adverse effect. It can become very severe, painful, and disabling. If you experience these symptoms, consult your doctor immediately, who may reduce the dose or interrupt treatment. This adverse effect usually occurs after taking this medicine for several months, but it can happen before. It can also occur sometime after the end of treatment. It may not disappear or may disappear slowly.

• Sudden chest pain or difficulty breathing.

This may be due to blood clots in the arteries that go to the lungs (pulmonary embolism), which is a frequent adverse effect. It can occur during treatment or after treatment has ended.

• Pain or inflammation in the legs, especially in the lower part or in the calves. This may be due to blood clots in the veins of the legs (deep vein thrombosis), which is a frequent adverse effect. It can occur during treatment or after treatment has ended.

• Chest pain that spreads to the arms, neck, jaw, back, or stomach, sweating, and shortness of breath, nausea, or vomiting.

These can be symptoms of a heart attack/myocardial infarction (which can be due to blood clots in the heart arteries).

• Temporary difficulty seeing or speaking.

These can be symptoms of a stroke (which can be due to a blood clot in a brain artery).

• Fever, chills, sore throat, cough, mouth ulcers, or any other symptom of infection.

• Bleeding or bruising without injury.

Other adverse effects include:

It is essential to note that a small number of patients with multiple myeloma may develop other types of cancer, especially malignant hematological neoplasms, and it is possible that this risk increases with treatment with Thalidomide Celgene; therefore, your doctor must carefully evaluate the benefits and risks when prescribing Thalidomide Celgene.

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

• Constipation.

• Dizziness.

• Somnolence, fatigue.

• Tremors.

• Decreased sensations or abnormal sensations (dysesthesia).

• Inflammation of hands and feet.

• Low blood cell counts, which could mean a higher likelihood of developing infections. Your doctor may monitor your blood cell counts during treatment with Thalidomide Celgene.

Common(may affect up to 1 in 10 people)

• Indigestion, nausea, vomiting, dry mouth.

• Rash, dry skin.

• Decrease in the number of white blood cells (neutropenia) accompanied by fever and infection.

• Decrease in the number of red blood cells, white blood cells, and platelets at the same time (pancytopenia).

• Weakness, fainting, or instability, lack of energy or strength, low blood pressure.

• Fever, general malaise.

• Seizures.

• Sensation that the head is spinning, making it difficult to stand and move normally.

• Blurred vision.

• Pneumonia, lung disease.

• Slow heart rate, heart failure.

• Depression, confusion, mood changes, anxiety.

• Decreased hearing or deafness.

• Kidney disease (kidney failure).

Uncommon(may affect up to 1 in 100 people)

• Inflammation and swelling of the pulmonary tubes (bronchitis).

• Inflammation of the stomach wall.

• Perforation of the large intestine (colon), which can cause infection.

• Intestinal obstruction.

• Decrease in blood pressure when standing, which can cause fainting.

• Irregular heartbeat (heart block or atrial fibrillation), sensation of loss of consciousness or fainting.

Frequency not known(cannot be estimated from the available data):

• Underactive thyroid (hypothyroidism).

• Sexual dysfunction, for example, impotence.

• Severe blood infection (septicemia) accompanied by fever, chills, and severe tremors, and possibly complicated by low blood pressure and confusion (septic shock).

• Tumor lysis syndrome – metabolic complications that can occur during cancer treatment and sometimes even without treatment. These complications are due to the breakdown products of dying cancer cells and can include changes in blood biochemistry; high levels of potassium, phosphorus, uric acid, and low levels of calcium, which can result in changes in kidney function, heartbeat, seizures, and sometimes death.

• Liver damage (liver disorder) including abnormal liver function test results.

• Bleeding in the stomach or intestines (gastrointestinal bleeding).

• Worsening of Parkinson's disease symptoms (such as tremors, depression, or confusion).

• Pain in the upper abdomen and/or back, which can be intense and last for several days, possibly accompanied by nausea, vomiting, fever, and rapid pulse – these symptoms can be due to pancreatitis (inflammation of the pancreas).

• Increased blood pressure in the blood vessels that supply blood to the lungs, which can lead to difficulty breathing, fatigue, dizziness, chest pain, faster heartbeat, or swelling of the legs or ankles (pulmonary hypertension).

• Viral infections, including herpes zoster (also called "shingles", a viral disease that causes a painful rash with blisters) and recurrence of hepatitis B infection (which can cause the skin and eyes to turn yellow, dark urine, stomach pain on the right side, fever, nausea, or vomiting).

• A brain disease with symptoms such as changes in vision, headache, seizures, and confusion, with or without high blood pressure (posterior reversible encephalopathy syndrome or PRES).

• A disease that affects the skin caused by inflammation of small blood vessels, accompanied by joint pain and fever (leukocytoclastic vasculitis).

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Thalidomide Celgene

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

Do not use this medicine after the expiry date stated on the packaging and on the blister, after CAD/EXP. The expiry date is the last day of the month indicated.

Do not use this medicine if you notice deterioration or signs of tampering with the guarantee seal.

No special storage conditions are required.

At the end of your treatment, you must return all unused capsules to the pharmacist or doctor to prevent misuse.

6. Package contents and additional information

Composition of Thalidomide Celgene:

• The active ingredient is thalidomide. Each capsule contains 50 mg of thalidomide.

• The other excipients are:

• The capsule contains pregelatinized starch and magnesium stearate.
• The capsule shell contains gelatin and titanium dioxide (E171).

• The printing ink is composed of shellac, black iron oxide (E172), and propylene glycol.

Appearance of the product and package contents

The hard capsules of Thalidomide Celgene are white and marked with "Thalidomide Celgene 50 mg". The capsules are supplied in a package that contains 28 capsules (2 blisters of 14 capsules each).

Marketing authorization holder

Celgene Europe B.V.

Winthontlaan 6 N

3526 KV Utrecht

Netherlands

Manufacturer

Celgene Distribution B.V.

Winthontlaan 6 N

3526 KV Utrecht

Netherlands

Date of the last revision of this leaflet

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.