Thalidomide: package leaflet

What Thalidomide BMS is
Thalidomide BMS contains an active substance called thalidomide. This belongs to a group of medicines which affect how your immune system works.

What Thalidomide BMS is used for
Thalidomide BMS 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 who have recently been diagnosed and who have not been prescribed another medicine for their multiple myeloma before who are aged 65 years and over, or aged less than 65 years who cannot be treated with high dose chemotherapy, which can be very difficult for the body to handle.

What is multiple myeloma
Multiple myeloma is a type of cancer which affects a certain type of white blood cell, called the plasma cell. These cells collect in the bone marrow and divide out of control. This can damage the bone and kidneys. Multiple myeloma generally cannot be cured. However, the signs and symptoms can be greatly reduced or disappear for a period of time. This is called a ‘remission’.

How Thalidomide BMS works
Thalidomide BMS works by helping the body’s immune system and directly attacking the cancer. It works in a number of different ways:
- by stopping the cancer cells developing
- by stopping blood vessels growing in the cancer
- by stimulating part of the immune system to attack the cancer cells.

You will have been given specific instructions by your doctor, particularly on the effects of thalidomide on unborn babies (outlined in the Thalidomide BMS Pregnancy Prevention Programme).

You will have been given an educational brochure for patient by your doctor. Read it carefully and follow the related instructions.

If you do not fully understand these instructions, please ask your doctor to explain them again before you take thalidomide. See also further information in this section under “Warnings and precautions” and “Pregnancy and breast-feeding”.

Do not take Thalidomide BMS
- if you are pregnant or think you may be pregnant or are planning to become pregnant, as Thalidomide BMS causes birth defects and foetal death.
- if you are able to become pregnant, unless you are able to follow or comply with the required contraceptive measures to prevent you from becoming pregnant (see section 2 “Warnings and precautions” and “Pregnancy and breast-feeding”).
- if you are able to become pregnant, your doctor will record 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 ingredients of this medicine listed in section 6 “Contents of the pack and other information”.

Do not take Thalidomide BMS if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before taking Thalidomide BMS.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking this medicine in the following situations:

For women taking Thalidomide BMS
Before starting the treatment, you should ask your doctor if you are able to become pregnant, even if you think this is unlikely. Even if you do not have a menstrual bleeding following cancer therapy, you may become pregnant.
If you are able to become pregnant:
- Your doctor will make sure that you have pregnancy tests o before treatment o every 4 weeks during treatment o 4 weeks after stopping treatment
- You must use one effective method of contraception:
o for at least 4 weeks before starting treatment o during treatment o until at least 4 weeks after stopping treatment Your doctor will tell you what method of contraception to use.

If you are able to become pregnant, your doctor will record with each prescription that the necessary measures, as outlined above, have been taken

For men taking Thalidomide BMS
Thalidomide passes into semen. Therefore, do not have unprotected intercourse, even if you had a vasectomy.
- Pregnancy and any exposure during pregnancy must be avoided. Always use a condom:
o during treatment o for at least 7 days after stopping treatment
- You must not donate semen:
o during treatment o for at least 7 days after stopping treatment

For all patients
Talk to your doctor before taking Thalidomide BMS if
- you do not understand the contraception advice given to you by your doctor or if you do not feel able to follow this advice.
- you have had a heart attack, have ever had a blood clot in the past, or if you smoke, have high blood pressure or high cholesterol levels. During the treatment with Thalidomide BMS you have an increased risk of developing blood clots in the veins and arteries (see also section 4 “Possible side effects”).
- you have experienced or have existing neuropathy i.e. nerve damage causing tingling, abnormal co-ordination or pain in your hands or feet (see also section 4 “Possible side effects”).
- you experienced or have existing slow heart rate (this may be a symptom of bradycardia).
- you have high blood pressure in the arteries of the lungs (see also section 4 “Possible side effects”).
- you have a fall in the number of white blood cells (neutropenia) accompanied by fever and infection.
- you have a fall in the number of platelets. You will be more prone to bleeding and bruising.
- you have or have had injury to the liver (hepatic disorders) including abnormal liver test results.
- you experience or have experienced in the past severe skin reactions called Stevens-Johnson syndrome, toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms (which is also known as DRESS or drug hypersensitivity syndrome). (For description of symptoms see section 4 “Possible side effects”).
- you have had an allergic reaction whilst taking Thalidomide BMS such as rash, itching, swelling, dizziness or trouble breathing.
- you have experienced sleepiness.
- you have experienced fever, chills and severe shaking, and possibly complicated by low blood pressure and confusion (these may be symptoms of severe infections).
- you have or have ever had previous viral infection, particularly varicella zoster, hepatitis B infection, or HIV. If you are in doubt, talk to your doctor. Treatment with Thalidomide BMS may cause a virus to become active again in patients who carry it, resulting in a recurrence of the infection. Your doctor should check whether you have ever had hepatitis B infection.
- you have kidney or liver problems (see also section 4 “Possible side effects”).

Your thyroid function may be checked before you take thalidomide and monitored during treatment.

At any time during or after your treatment, tell your doctor or nurse immediately if you experience:
blurred, loss of or double vision, difficulty speaking, weakness in an arm or a leg, a change in the way you walk or problems with your balance, persistent numbness, decreased sensation or loss of sensation, memory loss or confusion. These may all be symptoms of a serious and potentially fatal brain condition known as progressive multifocal leukoencephalopathy (PML). If you had these symptoms prior to treatment with Thalidomide BMS, tell your doctor about any change in these symptoms.

Your doctor may check if you have a high total amount of tumour throughout the body, including your bone marrow. This could lead to a condition where the tumours break down and cause unusual levels of chemicals in the body which can lead to kidneys failure (this condition is called Tumour Lysis Syndrome) (see also section 4 “Possible side effects”).

Your doctor should evaluate if you develop additional types of haematological malignancies (called acute myeloid leukaemia and myelodysplastic syndromes) during your treatment with Thalidomide BMS (see also section 4 “Possible side effects”).

You must not donate blood during Thalidomide BMS treatment and for at least 7 days after stopping treatment.

If you are not sure if any of the above apply to you, talk to your doctor before taking Thalidomide BMS.

Children and adolescents
Thalidomide BMS is not recommended for use in children and young people under 18 years.

Other medicines and Thalidomide BMS
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription, including herbal medicines.

Make sure you tell your doctor if you are taking any medicines which:
- cause sleepiness as thalidomide may increase their effects. This includes sedatives (such as anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opiate derivatives and barbiturates).
- slow the heart rate (induce bradycardia, such as anticholinesterases and beta blockers).
- are used for heart problems and complications (such as digoxin), or for thinning the blood (such as warfarin).
- are associated with neuropathy such as other treatments for cancer.
- are used for contraception.

Thalidomide BMS with food, drink and alcohol
Do not drink alcohol while you are taking Thalidomide BMS. This is because alcohol can make you sleepy and Thalidomide BMS can make you even sleepier.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
Thalidomide causes severe birth defects or death to an unborn baby.
- As little as one capsule taken by a pregnant woman can cause a baby to have serious birth defects.
- These defects can include shortened arms or legs, malformed hands or feet, eye or ear defects, and problems with internal organs.
If you are pregnant, you must not take Thalidomide BMS. In addition, you must not become pregnant while taking Thalidomide BMS.

You must use one effective method of contraception if you are a woman who is able to become pregnant (see section 2, “What you need to know before you take Thalidomide BMS”).

You must stop treatment and inform your doctor straight away if:
- You miss or think you have missed a period, or you have unusual menstrual bleeding, or suspect you are pregnant.
- You have heterosexual intercourse without using an effective method of contraception.
If you do become pregnant during the treatment with thalidomide, you must stop the treatment and inform your doctor immediately.

For men taking Thalidomide BMS who have a female partner who is able to become pregnant, please see section 2 “What you need to know before you take Thalidomide BMS”. If your partner becomes pregnant whilst you are taking thalidomide, you should inform your doctor immediately.

Breast-feeding
Do not breastfeed when taking Thalidomide BMS as it is not known if thalidomide is passed into human breast milk.

Driving and using machines
Do not drive or use any tools or machines if you experience side effects, such as dizziness, tiredness, sleepiness or blurred vision.

Always take Thalidomide BMS exactly as your doctor or pharmacist has told you to. Check with your doctor or pharmacist if you are not sure.

How much to take
The recommended dose is 200 mg (4 x 50 mg capsules) a day for adults aged 75 years and under or 100 mg (2 x 50 mg capsules) a day for adults aged over 75 years. However, your doctor will choose the dose for you, monitor your progress and may adjust your dose. Your doctor will tell you how to take Thalidomide BMS and for how long you will need to take it (see section 2, “What you need to know before you take Thalidomide BMS”).

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

Taking this medicine
- Do not break, open or chew the capsules. If powder from a broken Thalidomide BMS capsule makes 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 or capsule. Gloves should then be removed carefully to prevent skin exposure, placed in a sealable plastic polyethylene bag and disposed of in accordance with local requirements. Hands should then be washed thoroughly with soap and water. Women who are pregnant or suspect they may be pregnant should 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.
- Take the capsules as a single dose before going to bed. This will make you less likely to feel sleepy at other times.

To remove the capsule from the blister, press only one end of the capsule out to push it through the foil. Do not apply pressure on the centre of the capsule as this can cause it to break.

If you take more Thalidomide BMS than you should
If you take more Thalidomide BMS than you should, talk to a doctor or go to a hospital straightaway.
If possible, take the medicine pack and this leaflet with you.

If you forget to take Thalidomide BMS
If you forget to take Thalidomide BMS at your regular time and
- less than 12 hours have passed: take your capsules immediately.
- more than 12 hours have passed: do not take your capsules. Take your next capsules at the usual time the next day.

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

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

The following side effects may happen with this medicine:

Stop taking Thalidomide BMS and see a doctor straight away if you notice the following serious side effects – you may need urgent medical treatment:
- Extremely intense and serious skin reactions. The adverse reaction of the skin may appear as rashes with or without blisters. Skin irritation, sores or swelling in the mouth, throat, eyes, nose and around the genitals, oedema and fever and flulike symptoms may occur. These symptoms may be signs of the rare and serious skin reactions Stevens-Johnson syndrome, toxic epidermal necrolysis or DRESS syndrome.
- Allergic reactions such as a localised or generalised pruritic rash, angioedema and anaphylactic reaction (serious types of allergic reaction that may be manifested as hives, rashes, swelling of eyes, mouth or face, difficulty of breathing, or itching).

Tell your doctor straight away if you notice any of the following serious side effects:
- Numbness, tingling, abnormal coordination or pain in your hands and feet.
This may be due to nerve damage (called ‘peripheral neuropathy’), which is a very common side effect. It may become very severe, painful and disabling. If you experience such symptoms, speak to your doctor straight away, who may reduce the dose or discontinue the treatment. This side effect usually happens after you have been taking this medicine for several months but can happen sooner than this. It can also happen sometime after treatment has stopped. It may not go away, or may go away slowly.
- Sudden pain in your chest or difficulty in breathing.
This may be due to blood clots in the arteries leading to your lungs (called ‘pulmonary embolism’), which is a common side effect. These can happen during treatment, or after treatment has stopped.
- Pain or swelling in your legs, especially in your lower leg or calves.
This may be due to blood clots in the veins of your leg (deep vein thrombosis), which is a common side effect. These can happen during treatment, or after treatment has stopped.
- Chest pain spreading to the arms, neck, jaw, back or stomach, feeling sweaty and breathless, feeling sick or vomiting.
These may be symptoms of a heart attack/myocardial infarction (which may be due to blood clots in the arteries of your heart).
- Having difficulty in seeing or speaking, which is temporary.
These may be symptoms of a stroke (which may be due to a clot in an artery in your brain).
- Fever, chills, sore throat, cough, mouth ulcers or any other symptoms of infection.
- Bleeding or bruising in the absence of injury.

Other side effects include:
It is important to note that a small number of patients with multiple myeloma may develop additional types of cancer, especially haematological malignancies, and it is possible that this risk may be increased with Thalidomide BMS treatment; therefore your doctor should carefully evaluate the benefit and risk when you are prescribed Thalidomide BMS.

Very common (may affect more than 1 in 10 people)
- Constipation.
- Feeling dizzy.
- Sleepiness, feeling tired.
- Shaking (tremor).
- Decreased or abnormal sensation (dysaesthesia).

• Swelling of hands and feet.
• Low blood cell counts. This may mean that you are more likely to develop infections. Your doctor may monitor your blood cell counts during treatment with Thalidomide BMS.

Common (may affect up to 1 in 10 people)
- Indigestion, feeling sick (nausea), being sick (vomiting), dry mouth.
- Rash, dryness of the skin.
- A fall in the number of white blood cells (neutropenia) accompanied by fever and infection.
- A fall in the number of red and white blood cells and platelets at the same time (pancytopenia).
- Feeling weak, faint or unsteady, lack of energy or strength, low blood pressure.
- Fever, feeling generally unwell.
- Convulsions.
- A spinning feeling in your head, making it difficult to stand up and move normally.
- Blurred vision.
- Chest infection (pneumonia), lung disease.
- A slow heart rate, heart failure.
- Depression, confusion, mood changes, anxiety.
- Hearing decreased or deafness.
- Kidney disease (renal failure).

Uncommon (may affect up to 1 in 100 people)
- Inflammation and swelling of the tubes in your lungs (bronchitis).
- Inflammation of the cells lining your stomach wall.
- A hole in part of your large bowel (colon) which can cause infection.
- Bowel obstruction.
- Fall of blood pressure on standing which may lead to fainting.
- Irregularities of the heartbeat (heart block or atrial fibrillation), feeling faint or fainting.

Not known (frequency cannot be estimated from the available data):
- Underactive thyroid (hypothyroidism).
- Sexual dysfunction, for example impotence.
- Severe blood infection (sepsis) accompanied by fever, chills and severe shaking, and possibly complicated by low blood pressure and confusion (septic shock).
- Tumour Lysis Syndrome - metabolic complications that can occur during the treatment of cancer and sometimes even without treatment. These complications are caused by the break- down products of dying cancer cells and may include the following: changes to blood chemistry; high potassium, phosphorus, uric acid, and low calcium consequently leading to changes in kidney function, heart beat, seizures, and sometimes death.
- Injury to the liver (hepatic disorder) including abnormal liver test results.
- Bleeding from the stomach or bowels (gastrointestinal haemorrhage).
- Worsening of Parkinson’s disease symptoms (such as tremor, depression or confusion).
- Pain in the upper abdomen and/or back, which may be severe and which remains for a few days, possibly accompanied by nausea, vomiting, fever and a rapid pulse – these symptoms may be due to the inflammation of the pancreas (pancreatitis).
- Increase in blood pressure within blood vessels that supply the lungs which can lead to shortness of breath, tiredness, dizziness, pain in the chest, a faster heartbeat, or swelling in the legs or ankles (pulmonary hypertension).
- Viral infections, including herpes zoster (also known as ‘shingles’, a viral disease that causes a painful skin rash with blisters) and recurrence of hepatitis B infection (which can cause yellowing of the skin and eyes, dark brown-coloured urine, right-sided stomach pain, fever and feeling nauseous or being sick).
- A brain condition with symptoms including vision changes, headache, seizures, and confusion, with or without high blood pressure (Posterior Reversible Encephalopathy Syndrome or PRES).
- A condition affecting the skin caused by inflammation of small blood vessels, along with pain in the joints and fever (leukocytoclastic vasculitis).

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

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

Do not use this medicine after the expiry date which is stated on the wallet card and the blister after EXP. The expiry date refers to the last day of that month.

Do not use if you notice any damage or signs of tampering.

This medicine does not require any special storage conditions.

At the end of your treatment you should return all unused capsules to the pharmacist or doctor. These measures will prevent misuse.

What Thalidomide BMS contains
- The active substance is thalidomide. Each capsule contains 50 mg of thalidomide.
- The other excipients are:
o
The capsule content contains pregelatinised starch and magnesium stearate.
o
The capsule shell contains gelatin and titanium dioxide (E171).
o
The printing ink is composed of shellac, black iron oxide (E172) and propylene glycol.

What Thalidomide BMS looks like and contents of the pack
Thalidomide BMS are white hard capsules marked “Thalidomide BMS 50 mg”. The capsules are supplied in a wallet card containing 28 capsules (2 blisters of 14 capsules each).

Marketing Authorisation 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
Netherlands

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgique/België/Belgien
N.V. Bristol-Myers Squibb Belgium S.A.
Tél/Tel: + 32 2 352 76 11 medicalinfo.belgium@bms.com
Lietuva
Swixx Biopharma UAB
Tel: + 370 52 369140 medinfo.lithuania@swixxbiopharma.com

България
Swixx Biopharma EOOD
Teл.: + 359 2 4942 480 medinfo.bulgaria@swixxbiopharma.com
Luxembourg/Luxemburg
N.V. Bristol-Myers Squibb Belgium S.A.
Tél/Tel: + 32 2 352 76 11 medicalinfo.belgium@bms.com
Česká republika
Bristol-Myers Squibb spol. s r.o.
Tel: + 420 221 016 111 medinfo.czech@bms.com
Magyarország
Bristol-Myers Squibb Kft.
Tel.: + 36 1 301 9797
Medinfo.hungary@bms.com
Danmark
Bristol-Myers Squibb Denmark
Tlf: + 45 45 93 05 06 medinfo.denmark@bms.com
Malta
A.M. Mangion Ltd
Tel: + 356 23976333 pv@ammangion.com
Deutschland
Bristol-Myers Squibb GmbH & Co. KGaA
Tel: 0800 0752002 (+ 49 89 121 42 350) medwiss.info@bms.com
Nederland
Bristol-Myers Squibb B.V.
Tel: + 31 (0)30 300 2222 medischeafdeling@bms.com
Eesti
Swixx Biopharma OÜ
Tel: + 372 640 1030 medinfo.estonia@swixxbiopharma.com
Norge
Bristol-Myers Squibb Norway AS
Tlf: + 47 67 55 53 50 medinfo.norway@bms.com
Ελλάδα
Bristol-Myers Squibb A.E.
Τηλ: + 30 210 6074300 medinfo.greece@bms.com
Österreich
Bristol-Myers Squibb GesmbH
Tel: + 43 1 60 14 30 medinfo.austria@bms.com
España
Bristol-Myers Squibb, S.A.
Tel: + 34 91 456 53 00 informacion.medica@bms.com
Polska
Bristol-Myers Squibb Polska Sp. z o.o.
Tel.: + 48 22 2606400 informacja.medyczna@bms.com
France
Bristol-Myers Squibb SAS
Tél: + 33 (0)1 58 83 84 96 infomed@bms.com
Portugal
Bristol-Myers Squibb Farmacêutica Portuguesa,
S.A.
Tel: + 351 21 440 70 00 portugal.medinfo@bms.com
Hrvatska
Swixx Biopharma d.o.o.
Tel: + 385 1 2078 500 medinfo.croatia@swixxbiopharma.com
România
Bristol-Myers Squibb Marketing Services S.R.L.
Tel: + 40 (0)21 272 16 19 medinfo.romania@bms.com
Ireland
Bristol-Myers Squibb Pharmaceuticals uc
Tel: 1 800 749 749 (+ 353 (0)1 483 3625) medical.information@bms.com
Slovenija
Swixx Biopharma d.o.o.
Tel: + 386 1 2355 100 medinfo.slovenia@swixxbiopharma.com
Ísland
Vistor hf.
Sími: + 354 535 7000 vistor@vistor.is medical.information@bms.com
Slovenská republika
Swixx Biopharma s.r.o.
Tel: + 421 2 20833 600 medinfo.slovakia@swixxbiopharma.com

Italia
Bristol-Myers Squibb S.r.l.
Tel: + 39 06 50 39 61 medicalinformation.italia@bms.com
Suomi/Finland
Oy Bristol-Myers Squibb (Finland) Ab
Puh/Tel: + 358 9 251 21 230 medinfo.finland@bms.com
Κύπρος
Bristol-Myers Squibb A.E.
Τηλ: 800 92666 (+ 30 210 6074300) medinfo.greece@bms.com
Sverige
Bristol-Myers Squibb Aktiebolag
Tel: + 46 8 704 71 00 medinfo.sweden@bms.com
Latvija
Swixx Biopharma SIA
Tel: + 371 66164750 medinfo.latvia@swixxbiopharma.com

This leaflet was last revised in

Other sources of information

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

What Thalidomide Lipomed is
Thalidomide Lipomed contains an active substance called thalidomide. This belongs to a group of medicines which affect how your immune system works.

What Thalidomide Lipomed is used for
Thalidomide Lipomed 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 who have recently been diagnosed and who have not been prescribed another medicine for their multiple myeloma before who are aged 65 years and over, or aged less than 65 years who cannot be treated with high dose chemotherapy, which can be very difficult for the body to handle.

What is multiple myeloma
Multiple myeloma is a type of cancer which affects a certain type of white blood cell, called the plasma cell. These cells collect in the bone marrow and divide out of control. This can damage the bone and kidneys. Multiple myeloma generally cannot be cured. However, the signs and symptoms can be greatly reduced or disappear for a period of time. This is called a ‘remission’.

How Thalidomide Lipomed works
Thalidomide Lipomed works by helping the body’s immune system and directly attacking the cancer.
It works in a number of different ways:
- by stopping the cancer cells developing,
- by stopping blood vessels growing in the cancer,
- by stimulating part of the immune system to attack the cancer cells.

You will have been given specific instructions by your doctor, particularly on the effects of thalidomide on unborn babies (outlined in the Thalidomide Lipomed Pregnancy Prevention Programme).

You will have been given an educational brochure for patients by your doctor. Read it carefully and follow the related instructions.

If you do not fully understand these instructions, please ask your doctor to explain them again before you take thalidomide. See also further information in this section under “Warnings and precautions” and “Pregnancy and breast-feeding”.

Do not take Thalidomide Lipomed
- if you are pregnant or think you may be pregnant or are planning to become pregnant, as Thalidomide Lipomed causes birth defects and foetal death,
- if you are able to become pregnant, unless you are able to follow or comply with the required contraceptive measures to prevent you from becoming pregnant (see section 2 “Warnings and precautions” and “Pregnancy and breast-feeding”),
- if you are able to become pregnant, your doctor will record 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 ingredients of this medicine listed in section 6 “Contents of the pack and other information”.

Do not take Thalidomide Lipomed if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before taking Thalidomide Lipomed.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking this medicine in the following situations:

For women taking Thalidomide Lipomed
Before starting the treatment, you should ask your doctor if you are able to become pregnant, even if you think this is unlikely. Even if you do not have a menstrual bleeding following cancer therapy, you may become pregnant.
If you are able to become pregnant:
- Your doctor will make sure that you have pregnancy tests o before treatment, o every 4 weeks during treatment, o 4 weeks after stopping treatment.
- You must use one effective method of contraception:
o for at least 4 weeks before starting treatment, o during treatment, o until at least 4 weeks after stopping treatment.
Your doctor will tell you what method of contraception to use.

If you are able to become pregnant, your doctor will record with each prescription that the necessary measures, as outlined above, have been taken.

For men taking Thalidomide Lipomed
Thalidomide passes into semen. Therefore, do not have unprotected intercourse, even if you had a vasectomy.
- Pregnancy and any exposure during pregnancy must be avoided. Always use a condom o during treatment, o for at least 7 days after stopping treatment.

• You must not donate semen o during treatment, o for at least 7 days after stopping treatment.

For all patients
Talk to your doctor before taking Thalidomide Lipomed if any of the following apply to you:
- You do not understand the contraception advice given to you by your doctor or if you do not feel able to follow this advice.
- You have had a heart attack, have ever had a blood clot in the past, or if you smoke, have high blood pressure or high cholesterol levels. During the treatment with Thalidomide Lipomed you have an increased risk of developing blood clots in the veins and arteries (see also section 4 “Possible side effects”).
- You have experienced or have existing neuropathy, i.e. nerve damage causing tingling, abnormal co-ordination or pain in your hands or feet (see also section 4 “Possible side effects”).
- You experienced or have existing slow heart rate (this may be a symptom of bradycardia).
- You have high blood pressure in the arteries of the lungs (see also section 4 “Possible side effects”).
- You have a fall in the number of white blood cells (neutropenia) accompanied by fever and infection.
- You have a fall in the number of platelets. You will be more prone to bleeding and bruising.
- You have or have had injury to the liver (hepatic disorders) including abnormal liver test results.
- You experience or have experienced in the past severe skin reactions called Stevens-Johnson syndrome, toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms (which is also known as DRESS or drug hypersensitivity syndrome) (for description of symptoms see section 4 “Possible side effects”).
- You have had an allergic reaction whilst taking Thalidomide Lipomed such as rash, itching, swelling, dizziness or trouble breathing.
- You have experienced sleepiness.
- You have experienced fever, chills and severe shaking, and possibly complicated by low blood pressure and confusion (these may be symptoms of severe infections).
- You have or have ever had previous viral infection, particularly varicella zoster, hepatitis B infection, or HIV. If you are in doubt, talk to your doctor. Treatment with Thalidomide Lipomed may cause a virus to become active again in patients who carry it, resulting in a recurrence of the infection. Your doctor should check whether you have ever had hepatitis B infection.
- You have kidney or liver problems (see also section 4 “Possible side effects”).

Your thyroid function may be checked before you take thalidomide and monitored during treatment.

At any time during or after your treatment, tell your doctor or nurse immediately if you experience:
blurred, loss of or double vision, difficulty speaking, weakness in an arm or a leg, a change in the way you walk or problems with your balance, persistent numbness, decreased sensation or loss of sensation, memory loss or confusion. These may all be symptoms of a serious and potentially fatal brain condition known as progressive multifocal leukoencephalopathy (PML). If you had these symptoms prior to treatment with Thalidomide Lipomed, tell your doctor about any change in these symptoms.

Your doctor may check if you have a high total amount of tumour throughout the body, including your bone marrow. This could lead to a condition where the tumours break down and cause unusual levels of chemicals in the body which can lead to kidney failure (this condition is called Tumour Lysis Syndrome) (see also section 4 “Possible side effects”).

Your doctor should evaluate if you develop additional types of haematological malignancies (called acute myeloid leukaemia and myelodysplastic syndromes) during your treatment with Thalidomide Lipomed (see also section 4 “Possible side effects”).

You must not donate blood during treatment with Thalidomide Lipomed and for at least 7 days after stopping treatment.

If you are not sure if any of the above apply to you, talk to your doctor before taking Thalidomide Lipomed.

Children and adolescents
Thalidomide Lipomed is not recommended for use in children and young people under 18 years.

Other medicines and Thalidomide Lipomed
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription, including herbal medicines.
Make sure you tell your doctor if you are taking any of the following medicines:
- Medicines which cause sleepiness as thalidomide may increase their effects. This includes sedatives (such as anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opiate derivatives and barbiturates).
- Medicines which slow the heart rate (induce bradycardia, such as anticholinesterases and beta blockers).
- Medicines which are used for heart problems and complications (such as digoxin), or for thinning the blood (such as warfarin).
- Medicines which are associated with neuropathy such as other treatments for cancer.
- Medicines which are used for contraception.

Thalidomide Lipomed with food, drink and alcohol
Do not drink alcohol while you are taking Thalidomide Lipomed. This is because alcohol can make you sleepy and Thalidomide Lipomed can make you even sleepier.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
Thalidomide causes severe birth defects or death to an unborn baby.
- As little as one coated tablet taken by a pregnant woman can cause a baby to have serious birth defects.
- These defects can include shortened arms or legs, malformed hands or feet, eye or ear defects, and problems with internal organs.
If you are pregnant, you must not take Thalidomide Lipomed. In addition, you must not become pregnant while taking Thalidomide Lipomed.

You must use one effective method of contraception if you are a woman who is able to become pregnant (see section 2 “What you need to know before you take Thalidomide Lipomed”).

You must stop treatment and inform your doctor straight away if
- you miss or think you have missed a period, or you have unusual menstrual bleeding, or suspect you are pregnant,
- you have heterosexual intercourse without using an effective method of contraception.
If you do become pregnant during the treatment with thalidomide, you must stop the treatment and inform your doctor immediately.

For men taking Thalidomide Lipomed who have a female partner who is able to become pregnant, please see section 2 “What you need to know before you take Thalidomide Lipomed”. If your partner becomes pregnant whilst you are taking thalidomide, you should inform your doctor immediately.

Breast-feeding
Do not breastfeed when taking Thalidomide Lipomed as it is not known if thalidomide is passed into human breast milk.

Driving and using machines
Do not drive or use any tools or machines if you experience side effects, such as dizziness, tiredness, sleepiness or blurred vision.

Thalidomide Lipomed coated tablets contain lactose and sucrose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Always take Thalidomide Lipomed exactly as your doctor or pharmacist has told you to. Check with your doctor or pharmacist if you are not sure.

How much to take
The recommended dose is 200 mg (2 x 100 mg coated tablet) a day for adults aged 75 years and under or 100 mg (1 x 100 mg coated tablet) a day for adults aged over 75 years. However, your doctor will choose the dose for you, monitor your progress and may adjust your dose. Your doctor will tell you how to take Thalidomide Lipomed and for how long you will need to take it (see section 2 “What you need to know before you take Thalidomide Lipomed”).

Thalidomide Lipomed is taken daily in treatment cycles, each cycle lasting 6 weeks, in combination with melphalan and prednisone which are taken on Days 1 to 4 of each 6-week cycle.

Taking this medicine
- Do not break or chew the coated tablets. If powder from a broken Thalidomide Lipomed coated tablet makes 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 blisters or coated tablets. Gloves should then be removed carefully to prevent skin exposure, placed in a sealable plastic polyethylene bag and disposed of in accordance with local requirements. Hands should then be washed thoroughly with soap and water. Women who are pregnant or suspect they may be pregnant should not handle the blisters or coated tablets.
- Take this medicine by mouth.
- Swallow the coated tablets whole with a full glass of water.
- Do not crush or chew the coated tablets.
- Take the coated tablets as a single dose before going to bed. This will make you less likely to feel sleepy at other times.

If you take more Thalidomide Lipomed than you should
If you take more Thalidomide Lipomed than you should, talk to a doctor or go to a hospital straightaway. If possible, take the medicine pack and this leaflet with you.

If you forget to take Thalidomide Lipomed
If you forget to take Thalidomide Lipomed at your regular time
- and less than 12 hours have passed: take your coated tablets immediately;
- more than 12 hours have passed: do not take your coated tablets. Take your next coated tablets at the usual time the next day.

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

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

The following side effects may happen with this medicine:

Stop taking Thalidomide Lipomed and see a doctor straight away if you notice the following serious side effects – you may need urgent medical treatment:
- Extremely intense and serious skin reactions. The adverse reaction of the skin may appear as rashes with or without blisters. Skin irritation, sores or swelling in the mouth, throat, eyes, nose and around the genitals, oedema and fever and flulike symptoms may occur. These symptoms may be signs of the rare and serious skin reactions Stevens-Johnson syndrome, toxic epidermal necrolysis or DRESS syndrome.
- Allergic reactions such as localised or generalised pruritic rash, angioedema and anaphylactic reaction (serious types of allergic reaction that may be manifested as hives, rashes, swelling of eyes, mouth or face, difficulty of breathing, or itching).

Tell your doctor straight away if you notice any of the following serious side effects:
- Numbness, tingling, abnormal coordination or pain in your hands and feet.
This may be due to nerve damage (called ‘peripheral neuropathy’), which is a very common side effect. It may become very severe, painful and disabling. If you experience such symptoms, speak to your doctor straight away, who may reduce the dose or discontinue the treatment. This side effect usually happens after you have been taking this medicine for several months but can happen sooner than this. It can also happen sometime after treatment has stopped. It may not go away, or may go away slowly.
- Sudden pain in your chest or difficulty in breathing.
This may be due to blood clots in the arteries leading to your lungs (called ‘pulmonary embolism’), which is a common side effect. These can happen during treatment, or after treatment has stopped.
- Pain or swelling in your legs, especially in your lower leg or calves.
This may be due to blood clots in the veins of your leg (deep vein thrombosis), which is a common side effect. These can happen during treatment, or after treatment has stopped.
- Chest pain spreading to the arms, neck, jaw, back or stomach, feeling sweaty and breathless, feeling sick or vomiting.
These may be symptoms of a heart attack/myocardial infarction (which may be due to blood clots in the arteries of your heart).
- Having difficulty in seeing or speaking, which is temporary.
These may be symptoms of a stroke (which may be due to a clot in an artery in your brain).
- Fever, chills, sore throat, cough, mouth ulcers or any other symptoms of infection.
- Bleeding or bruising in the absence of injury.

Other side effects include:

It is important to note that a small number of patients with multiple myeloma may develop additional types of cancer, especially haematological malignancies, and it is possible that this risk may be increased with Thalidomide Lipomed treatment; therefore, your doctor should carefully evaluate the benefit and risk when you are prescribed Thalidomide Lipomed.

Very common (may affect more than 1 in 10 people)
- Constipation.
- Feeling dizzy.
- Sleepiness, feeling tired.
- Shaking (tremor).
- Decreased or abnormal sensation (dysaesthesia).
- Swelling of hands and feet.
- Low blood cell counts. This may mean that you are more likely to develop infections. Your doctor may monitor your blood cell counts during treatment with Thalidomide Lipomed.

Common (may affect up to 1 in 10 people)
- Indigestion, feeling sick (nausea), being sick (vomiting), dry mouth.
- Rash, dryness of the skin.

• A fall in the number of white blood cells (neutropenia) accompanied by fever and infection.
• A fall in the number of red and white blood cells and platelets at the same time (pancytopenia).
• Feeling weak, faint or unsteady, lack of energy or strength, low blood pressure.
• Fever, feeling generally unwell.
• Convulsions.
• A spinning feeling in your head, making it difficult to stand up and move normally.
• Blurred vision.
• Chest infection (pneumonia), lung disease.
• A slow heart rate, heart failure.
• Depression, confusion, mood changes, anxiety.
• Hearing decreased or deafness.
• Kidney disease (renal failure).

Uncommon (may affect up to 1 in 100 people)
- Inflammation and swelling of the tubes in your lungs (bronchitis).
- Inflammation of the cells lining your stomach wall.
- A hole in part of your large bowel (colon) which can cause infection.
- Bowel obstruction.
- Fall of blood pressure on standing which may lead to fainting.
- Irregularities of the heartbeat (heart block or atrial fibrillation), feeling faint or fainting.

Not known (frequency cannot be estimated from the available data)
- Underactive thyroid (hypothyroidism).
- Sexual dysfunction, for example impotence.
- Severe blood infection (sepsis) accompanied by fever, chills and severe shaking, and possibly complicated by low blood pressure and confusion (septic shock).
- Tumour Lysis Syndrome – metabolic complications that can occur during the treatment of cancer and sometimes even without treatment. These complications are caused by the break- down products of dying cancer cells and may include the following: changes to blood chemistry; high potassium, phosphorus, uric acid, and low calcium consequently leading to changes in kidney function, heartbeat, seizures, and sometimes death.
- Injury to the liver (hepatic disorder) including abnormal liver test results.
- Bleeding from the stomach or bowels (gastrointestinal haemorrhage).
- Worsening of Parkinson’s disease symptoms (such as tremor, depression or confusion).
- Pain in the upper abdomen and/or back, which may be severe and which remains for a few days, possibly accompanied by nausea, vomiting, fever and a rapid pulse – these symptoms may be due to the inflammation of the pancreas (pancreatitis).
- Increase in blood pressure within blood vessels that supply the lungs which can lead to shortness of breath, tiredness, dizziness, pain in the chest, a faster heartbeat, or swelling in the legs or ankles (pulmonary hypertension).
- Viral infections, including herpes zoster (also known as ‘shingles’, a viral disease that causes a painful skin rash with blisters) and recurrence of hepatitis B infection (which can cause yellowing of the skin and eyes, dark brown-coloured urine, right-sided stomach pain, fever and feeling nauseous or being sick).
- A brain condition with symptoms including vision changes, headache, seizures, and confusion, with or without high blood pressure (Posterior Reversible Encephalopathy Syndrome or PRES).
- A condition affecting the skin caused by inflammation of small blood vessels, along with pain in the joints and fever (leukocytoclastic vasculitis).

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

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

Do not use this medicine after the expiry date which is stated on the carton and on the blister after EXP. The expiry date refers to the last day of that month.

Do not use if you notice any damage or signs of tampering.

This medicine does not require any special storage conditions.

At the end of your treatment you should return all unused coated tablets to the pharmacist or doctor.
These measures will prevent misuse.

What Thalidomide Lipomed contains
- The active substance is thalidomide. Each coated tablet contains 100 mg of thalidomide.
- The other ingredients are lactose monohydrate (see section 2 “What you need to know before you take Thalidomide Lipomed”), copovidone (E 1208), talc (E 553b), magnesium stearate (E 470b), microcrystalline cellulose [E 460(i)], heavy kaolin (E 559), sucrose (see section 2 “What you need to know before you take Thalidomide Lipomed”), acacia (E 414), calcium carbonate (E 170), titanium dioxide (E 171).

What Thalidomide Lipomed looks like and contents of the pack
Thalidomide Lipomed 100 mg coated tablets are white sugar-coated tablets. The coated tablets are supplied in a carton containing 30 coated tablets (3 blisters of 10 coated tablets each).

Marketing Authorisation Holder and Manufacturer
Lipomed GmbH
Hegenheimer Strasse 2
79576 Weil am Rhein
Germany

This leaflet was last revised in .

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.