Thalidomide BMS

Package leaflet: Information for the patient

Talidomide BMS 50 mg hard capsules

thalidomide
WARNING
Thalidomide causes birth defects and fetal death. Do not take thalidomide if you are pregnant
or could become pregnant. You must follow your doctor’s advice on contraceptive methods.
Read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be dangerous.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

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

What Talidomide BMS is
Talidomide BMS contains an active substance called “thalidomide”. It belongs to a group of
medicines that affect the way the immune system works.
What Talidomide BMS is used for
Talidomide BMS is used in combination with two other medicines, called “melphalan” and “prednisone”, for the
treatment of adults with a type of cancer known as multiple myeloma. It is used in patients who have been recently diagnosed and who have never been prescribed other medicines for multiple myeloma, either aged 65 or older, or under 65 years of age who cannot be treated with high-dose chemotherapy, which can be very difficult for the body to tolerate.
What is multiple myeloma
Multiple myeloma is a type of cancer that affects a certain kind of white blood cells called
plasma cells. These cells accumulate in the bone marrow and divide uncontrollably. This
can damage bones and kidneys. Multiple myeloma is generally incurable. However, signs and symptoms can be significantly reduced or disappear for a certain period of time, known as “remission”.
How Talidomide BMS works
Talidomide BMS works by helping the body's immune system and by directly attacking the
tumour. It acts in several different ways:

• by stopping the development of tumour cells
• by stopping the growth of blood vessels within the tumour
• by stimulating part of the immune system to attack tumour cells.

2. What you need to know before taking Talidomide BMS

Your doctor will have provided you with specific information, particularly regarding the effects of talidomide on the fetus (described in the Talidomide BMS Pregnancy Prevention Programme).
Your doctor will have given you patient information material. Please read this material carefully and follow the instructions provided.
If you do not fully understand these instructions, ask your doctor for further clarification before taking talidomide. For additional information, refer to the sections “Warnings and precautions” and “Pregnancy and breastfeeding” in this paragraph.
Do not take Talidomide BMS

• if you are pregnant, think you might be pregnant, or are planning a pregnancy, because Talidomide BMS causes birth defects and fetal death
• if you are of childbearing potential, unless you are able to comply with the required contraceptive measures to prevent pregnancy (see section 2 “Warnings and precautions” and “Pregnancy and breastfeeding”)
• if you are of childbearing potential, your doctor will document at each prescription that the necessary precautions have been taken and will provide you with this confirmation
• if you are allergic to talidomide or to any of the other ingredients of this medicine (listed in section 6 “Contents of the pack and other information”).

Do not take Talidomide BMS if any of these conditions apply to you. If you have any doubts, consult your doctor or pharmacist before taking Talidomide BMS.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking this medicine in the following situations:
For women taking Talidomide BMS
Before starting treatment, you must ask your doctor whether there is any possibility that you could become pregnant, even if you think it unlikely. Even if you do not have menstrual bleeding after anti-tumour therapy, you may still become pregnant.
If you are of childbearing potential:

• Your doctor will ensure that pregnancy tests are performed: either before treatment, every 4 weeks during treatment, or 4 weeks after treatment ends
• You must use an effective method of contraception: either for at least 4 weeks before starting treatment, during treatment, and for at least 4 weeks after treatment ends. Your doctor will advise you on which contraceptive method to use.

If you are of childbearing potential, your doctor must document at each talidomide prescription that the necessary contraceptive measures described above have been taken.
For men taking Talidomide BMS
Talidomide is present in seminal fluid. Therefore, you must not have unprotected sexual intercourse, even if you have had a vasectomy.

• Avoiding pregnancy and any exposure to the drug during pregnancy is essential. You must always use a condom: either during treatment or for at least 7 days after treatment ends
• You must not donate semen: either during treatment or for at least 7 days after treatment ends

For all patients
Talk to your doctor before taking Talidomide BMS if

• you do not understand the contraceptive advice given by your doctor or feel unable to comply with it
• you have had a heart attack, previously had a blood clot, or if you smoke, have high blood pressure, or high cholesterol levels. The risk of developing blood clots (thrombi) in veins and arteries increases during treatment with Talidomide BMS (see also section 4 “Possible side effects”)
• you have or have previously had neuropathy, i.e. nerve damage causing tingling, coordination problems, or pain in hands or feet (see also section 4 “Possible side effects”)
• you have or have previously had a slow heart rate (which may be a sign of bradycardia)
• you have high blood pressure in the lung arteries (pulmonary hypertension) (see also section 4 “Possible side effects”)
• you have or have previously had a low white blood cell count (neutropenia) accompanied by fever and infection
• you have a low platelet count. You will be more prone to bleeding and bruising
• you have or have previously had liver damage (hepatic disorders), including abnormal liver function test results
• you have or have previously had severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms (also known as DRESS or drug hypersensitivity syndrome). (For a description of symptoms, see section 4 “Possible side effects”)
• you have had an allergic reaction during treatment with Talidomide BMS, such as rash, itching, swelling, dizziness, or difficulty breathing
• you have experienced drowsiness
• you have had fever, chills, and severe shivering, possibly complicated by low blood pressure and confusion (which may be signs of serious infections)
• you have or have previously had a viral infection, particularly chickenpox, hepatitis B virus infection, or HIV. If in doubt, consult your doctor. Treatment with Talidomide BMS may reactivate the virus in carriers, leading to recurrence of infection. Your doctor should check whether you have ever had hepatitis B virus infection.
• you have kidney or liver problems (see also section 4 “Possible side effects”)

Before taking talidomide, you may be required to have your thyroid function checked and monitored during treatment.
At any time during or after treatment, inform your doctor or nurse immediately if you experience blurred vision, loss of vision, double vision, difficulty speaking, weakness in one arm or leg, changes in walking or balance problems, persistent numbness, reduced sensation, or loss of sensation, memory loss, or confusion. These may be symptoms of a serious brain disease that can be fatal, known as progressive multifocal leukoencephalopathy (PML). If you had these symptoms before treatment with Talidomide BMS, inform your doctor of any changes in these symptoms.
Your doctor may assess whether you have a high tumour burden throughout the body, including in the bone marrow. This may lead to a condition in which tumours break down and cause abnormally high levels of certain chemicals in the body, potentially leading to kidney failure (this condition is called tumour lysis syndrome) (see also section 4 “Possible side effects”).
Your doctor should evaluate whether you develop other types of blood cancers (called acute myeloid leukaemia and myelodysplastic syndromes) during treatment with Talidomide BMS (see also section 4 “Possible side effects”).
You must not donate blood during treatment with Talidomide BMS and for at least 7 days after treatment ends.
If you are unsure whether any of the above conditions apply to you, consult your doctor before taking Talidomide BMS.
Children and adolescents
The use of Talidomide BMS is not recommended in children and adolescents under 18 years of age.
Other medicines and Talidomide BMS
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription, as well as herbal products.
Make sure to inform your doctor if you are taking other medicines that:

• cause drowsiness, as talidomide may increase these effects. These include sedatives (such as anxiolytics, hypnotics, antipsychotics, H-\antihistamines, opioids, and barbiturates)
• reduce heart rate (cause bradycardia), such as anticholinesterases and beta-blockers
• are used for heart problems or complications (such as digoxin) or to thin the blood (such as warfarin)
• are associated with neuropathy, such as other anti-cancer treatments
• are used for contraception.

Talidomide BMS with food, drinks, and alcohol
Do not consume alcohol during treatment with Talidomide BMS, as alcohol may cause drowsiness, which can be worsened by Talidomide BMS.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Talidomide causes severe birth defects or fetal death.

• Taking just one capsule during pregnancy is sufficient to cause severe congenital malformations in the newborn.
• These defects may include shortened arms or legs, malformed hands or feet, eye or ear abnormalities, and internal organ problems. If you are pregnant, you must not take Talidomide BMS. Furthermore, if you are taking Talidomide BMS, you must avoid becoming pregnant.

If you are a woman of childbearing potential, you must use an effective method of contraception (see section 2 “What you need to know before taking Talidomide BMS”).
You must stop treatment and inform your doctor immediately if:

• You miss a menstrual period or think you may have missed one, notice unusual menstrual bleeding, or suspect you are pregnant.
• You are sexually active without using an effective contraceptive method. If you become pregnant while taking talidomide, stop treatment immediately and inform your doctor.

For men taking Talidomide BMS whose partner is of childbearing potential, see section 2 “What you need to know before taking Talidomide BMS”. If your partner becomes pregnant while you are taking talidomide, inform your doctor immediately.
Breastfeeding
Do not breastfeed while taking Talidomide BMS, as it has not been established whether talidomide passes into breast milk.
Driving and using machines
Do not drive or operate tools or machinery if you experience side effects such as dizziness, fatigue, drowsiness, or blurred vision.

3. How to take Talidomide BMS

Take this medicine exactly as prescribed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
How much medicine to take
The recommended dose is 200 mg (4 capsules x 50 mg) per day for adults aged 75 years and younger, while it is 100 mg (2 capsules x 50 mg) per day for adults older than 75 years. However, your doctor will determine your dose, monitor your progress, and may adjust the dose as needed. Your doctor will instruct you on how to take Talidomide BMS and for how long you should take it (see section 2 “What you need to know before taking Talidomide BMS”).
Talidomide BMS is taken daily in treatment cycles of 6 weeks each, in combination with melphalan and prednisone (taken on day 1 and day 4 of each 6-week cycle).
How to take this medicine

• Do not break, open, or chew the capsules. If the powder from a broken Talidomide BMS capsule comes into contact with the skin, wash the skin immediately and thoroughly with soap and water.
• Healthcare providers, caregivers, and family members should wear disposable gloves when handling the blister pack or capsule. Gloves should then be carefully removed to avoid skin exposure, placed in a sealed polyethylene bag, and disposed of according to local regulations. Hands should then be thoroughly washed with soap and water. Pregnant women, or those who suspect they might be pregnant, must not handle the blister pack or capsule.
• Take this medicine by mouth.
• Swallow the capsules whole with a full glass of water.
• Do not crush or chew the capsule.
• Take the single daily dose at bedtime. This will make it less likely that drowsiness will interfere with daytime activities.

To remove the capsule from the blister pack, press on one side of the capsule, pushing it through the aluminium foil. Do not press on the center of the capsule, as this may cause it to break.

If you take more Talidomide BMS than you should
If you take more Talidomide BMS than prescribed, contact your doctor or go to hospital immediately. If possible, bring the medicine package and this leaflet with you.
If you forget to take Talidomide BMS
If you forget to take Talidomide BMS at your usual time and

• less than 12 hours have passed: take the missed dose immediately.
• more than 12 hours have passed: do not take the missed dose. Take the next dose at your usual time the following day.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

This medicine may cause the following side effects:

Stop taking Talidomide BMS and consult your doctor immediately if you notice any of the following serious side effects. You may require urgent medical treatment:

• Severe and intense skin reactions. Adverse skin reactions may present as rashes with or without blisters. Skin irritation, ulcers or swelling in the mouth, throat, eyes, nose and genital area, oedema, fever and flu-like symptoms may occur. These symptoms may be signs of rare and serious skin reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis or DRESS syndrome.
• Allergic reactions, such as localized or generalized rash with itching, angioedema and anaphylactic reaction (types of severe allergic reactions that may present as hives, skin rashes, swelling of the eyes, mouth or face, difficulty breathing or itching).

If you notice any of the following serious side effects, inform your doctor immediately:

• Numbness, tingling, coordination problems or pain in the hands and feet. These may be caused by nerve damage (“peripheral neuropathy”), a very common side effect. It can become severe, painful and disabling. If you experience these symptoms, contact your doctor immediately, as the dose may need to be reduced or treatment stopped. This side effect usually occurs when the medicine is taken for many months, but may also occur after shorter periods. It may also develop some time after stopping treatment. It may not resolve or may resolve slowly.
• Sudden chest pain or difficulty breathing. This may be caused by blood clots in the arteries supplying blood to the lungs (“pulmonary embolism”), a common side effect. Blood clots may form during or after treatment.
• Pain or swelling in the legs, especially in the lower legs or calves. This may be caused by blood clots in the deep veins of the legs (“deep vein thrombosis”), a common side effect. Blood clots may form during or after treatment.
• Chest pain spreading to the arms, neck, jaw, back or stomach, accompanied by sweating, shortness of breath, feeling unwell or vomiting. These may be symptoms of a heart attack/myocardial infarction (which may be caused by blood clots in the heart arteries).
• Temporary difficulty seeing or speaking.

These may be symptoms of a stroke (which may be caused by a blood clot in a cerebral artery).

• Fever, chills, sore throat, cough, mouth ulcers or any other sign of infection.
• Bleeding or bruising without injury.

Other side effects are listed below:
Please note that a small number of patients with multiple myeloma may develop other types of cancer, particularly blood cancers, and this risk may possibly increase with treatment with Talidomide BMS; therefore, your doctor must carefully evaluate the benefit and risk when prescribing Talidomide BMS to you.

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

• Constipation.
• Dizziness.
• Drowsiness, feeling of tiredness.
• Tremor (trembling).
• Reduced or abnormal sensation (dysaesthesia).
• Swelling of the hands and feet.
• Reduced blood cell counts. This may mean you are more likely to develop infections. During treatment with Talidomide BMS, your doctor may monitor your blood cell counts.

Common (may affect up to 1 in 10 people)

• Indigestion, feeling unwell (nausea), feeling of illness (vomiting), dry mouth.
• Erythema, dry skin.
• A reduction in white blood cell count (neutropenia) accompanied by fever and infection.
• A simultaneous reduction in red blood cells, white blood cells and platelets (pancytopenia).
• Feeling of weakness, fainting or instability, lack of energy or strength, low blood pressure.
• Fever, feeling of general malaise.
• Seizures.
• Dizziness, making it difficult to stand upright and move normally.
• Blurred vision.
• Chest infection (pneumonia), lung disease.
• Low heart rate, heart failure.
• Depression, confusion, mood changes, anxiety.
• Hearing loss or deafness.
• Kidney disease (renal failure).

Uncommon (may affect up to 1 in 100 people)

• Inflammation and swelling of the lung ducts (bronchitis).
• Inflammation of the cells lining the stomach wall.
• Perforation of a part of the large intestine (colon) which may cause infection.
• Bowel obstruction.
• Drop in blood pressure when standing up, which may lead to fainting.
• Irregular heartbeat (heart block or atrial fibrillation), feeling faint or fainting.

Not known (frequency cannot be estimated from the available data)

• Underactive thyroid gland (hypothyroidism).
• Sexual dysfunction, for example impotence.
• Severe blood infection (sepsis), accompanied by fever, chills and severe shaking, possibly complicated by low blood pressure and confusion (septic shock).
• Tumour lysis syndrome – metabolic complications that may occur during cancer treatment and sometimes even without treatment. These complications are caused by the breakdown products of dying tumour cells and may include the following: changes in blood chemistry; high levels of potassium, phosphate and uric acid; and low calcium levels, leading to changes in kidney function, heartbeat, seizures and, sometimes, death.
• Liver damage (hepatic disorders), including changes in liver function tests.
• Bleeding from the stomach or intestine (gastrointestinal haemorrhage).
• Worsening of symptoms of Parkinson’s disease (such as tremor, depression or confusion).
• Pain in the upper abdomen and/or back, which may be severe and last for several days, possibly accompanied by nausea, vomiting, fever and rapid pulse: these symptoms may be due to inflammation of the pancreas (pancreatitis).
• Increased pressure in the blood vessels supplying the lungs, which may cause shortness of breath, fatigue, dizziness, chest pain, rapid heartbeat or swelling in the legs or ankles (pulmonary hypertension).
• Viral infections, including herpes zoster (also known as “shingles”, a viral disease causing a painful rash with blisters) and reactivation of hepatitis B infection (which may cause yellowing of the skin and eyes, dark brown urine, stomach pain on the right side, fever and feeling of nausea or illness).
• A brain condition with symptoms including vision changes, headache, seizures and confusion, with or without high blood pressure (reversible posterior encephalopathy syndrome or PRES).
• A condition affecting the skin, caused by inflammation of small blood vessels, with joint pain and fever (leucocytoclastic vasculitis).

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via 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 Talidomide BMS

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the wallet pack and on the blister after Exp./EXP. The expiry date refers to the last day of that month.
Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.
This medicine does not require any special storage conditions.
At the end of treatment, return all unused capsules to the pharmacist or doctor. These measures prevent misuse.

6. Package contents and other information

What Talidomide BMS contains

• The active substance is thalidomide. Each capsule contains 50 mg of thalidomide.
• The other components are:
  o The capsule core contains pregelatinized starch and magnesium stearate.
  o The capsule shell contains gelatin and titanium dioxide (E171).
  o Printing ink consists of shellac, black iron oxide (E172), and propylene glycol.

Description of the appearance of Talidomide BMS and package contents
Talidomide BMS is presented as white, hard capsules marked with the inscription "Thalidomide BMS 50 mg". The capsules are supplied in wallet packs containing 28 capsules (2 blisters with 14 capsules each).

Marketing Authorization Holder
Bristol-Myers Squibb Pharma EEIG
Plaza 254
Blanchardstown Corporate Park 2
Dublin 15, D15 T867
Ireland

Manufacturer
Celgene Distribution B.V.
Orteliuslaan 1000
3528 BD Utrecht
The Netherlands

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. Links to other websites on rare diseases and their therapeutic treatments are also provided.