Thalidomide Accord

Patient Information Leaflet

Talidomide Accord 50 mg Hard Capsules

Generic Medicine
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 others, even if they have the same symptoms as yours, because it could be harmful.
• 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 Accord is and what it is used for
2. What you need to know before taking Talidomide Accord
3. How to take Talidomide Accord
4. Possible side effects
5. How to store Talidomide Accord
6. Contents of the pack and other information

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

What Talidomide Accord is
Talidomide Accord contains an active substance called "thalidomide". It belongs to a group of
medicines that affect the way the immune system works.
What Talidomide Accord is used for
Talidomide Accord 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 people who have been recently diagnosed and who have never been prescribed other medicines for multiple myeloma, either aged 65 years 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 type of white blood cells called plasma cells. These cells accumulate in the bone marrow and divide uncontrollably. This can damage the bones and kidneys. Multiple myeloma is usually incurable. However, signs and symptoms may be significantly reduced or disappear for a certain period, known as "remission".
How Talidomide Accord works
Talidomide Accord works by helping the body's immune system and by directly attacking the tumour. It acts in several different ways:

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

2. What you should know before taking Talidomide Accord

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

Do not take Talidomide Accord

• if you are pregnant, think you may be pregnant, or are planning a pregnancy, because Talidomide Accord causes congenital malformations 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 measures have been taken and will provide you with this confirmation.
• if you are allergic to thalidomide 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 Accord if any of these conditions apply to you. If you have any doubts, consult your doctor or pharmacist before taking Talidomide Accord.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before taking this medicine if you are in any of the following situations:

For women taking Talidomide Accord

Before starting treatment, you must ask your doctor whether there is any possibility that you could become pregnant, even if you think this is 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 until 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 prescription that the necessary contraceptive measures described above have been taken.

For men taking Talidomide Accord

Thalidomide is present in seminal fluid. Therefore, you must not have unprotected sexual intercourse, even if you have had a vasectomy.

• To avoid pregnancy and any exposure to the drug during pregnancy, you must always use a condom:
  • during treatment
  • for at least 7 days after treatment ends
• You must not donate semen:
  • during treatment
  • for at least 7 days after treatment ends

For all patients

Talk to your doctor before taking Talidomide Accord if:

• you do not understand the advice given by your doctor regarding contraceptive measures or feel unable to comply with it.
• you have had a heart attack, have had a blood clot in the past, 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 Accord (see also section 4 “Possible side effects”).
• you have or have had neuropathy (nerve damage), which causes tingling, coordination problems, or pain in hands or feet (see also section 4 “Possible side effects”).
• you have or have had a slow heart rate (which may be a sign of bradycardia).
• you have high blood pressure in the arteries of the lungs (see also section 4 “Possible side effects”).
• you have or have had low white blood cell count (neutropenia) accompanied by fever and infection.
• you have or have had a low platelet count. You will be more prone to bleeding and bruising.
• you have or have had liver problems, including abnormal liver function test results.
• you have or have 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 thalidomide, 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 had a viral infection, particularly chickenpox, hepatitis B virus infection, or HIV. If in doubt, consult your doctor. Treatment with Talidomide Accord 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”).

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, 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 starting treatment with Talidomide Accord, 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 abnormal levels of 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 monitor you for the development of other types of blood cancers (called acute myeloid leukaemia and myelodysplastic syndromes) during treatment with Talidomide Accord (see also section 4 “Possible side effects”).

You must not donate blood during treatment with Talidomide Accord and for at least 7 days after treatment ends.

Before taking thalidomide, you may be required to have your thyroid function tested and monitored during treatment.

If you are unsure whether any of the above conditions apply to you, consult your doctor before taking Talidomide Accord.

Children and adolescents

The use of Talidomide Accord is not recommended in children and adolescents under 18 years of age.

Other medicines and Talidomide Accord

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription, as well as herbal products.

Be sure to inform your doctor if you are taking other medicines that:

• cause drowsiness, as thalidomide may increase these effects. These include sedatives (such as anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opioid derivatives, and barbiturates).
• reduce heart rate (cause bradycardia), such as anticholinesterases and beta-blockers.
• are used for heart problems and 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 Accord with food, drinks, and alcohol

Do not consume alcohol during treatment with Talidomide Accord, as alcohol may cause drowsiness, which may be worsened by Talidomide Accord.

Pregnancy and breastfeeding

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

Pregnancy

Thalidomide causes severe congenital malformations or fetal death.

• Taking just one capsule during pregnancy is sufficient to cause severe birth defects in the newborn.
• These defects may include shortened arms or legs, malformations of hands or feet, eye or ear defects, and internal organ problems.

If you are pregnant, you must not take Talidomide Accord. Furthermore, if you are taking Talidomide Accord, 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 should know before taking Talidomide Accord”).

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

For men taking Talidomide Accord whose partner is of childbearing potential, see section 2 “What you should know before taking Talidomide Accord”. If your partner becomes pregnant while you are taking thalidomide, you must inform your doctor immediately.

Breastfeeding

Do not breastfeed while taking Talidomide Accord, as it is not known whether thalidomide 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.

Talidomide Accord contains Isomalt

If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per capsule, i.e., essentially “sodium-free”.

3. How to take Talidomide Accord

Take Talidomide Accord exactly as directed 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) daily for adults aged 75 years and younger,
while it is 100 mg (2 capsules x 50 mg) daily 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 Accord and for how long (see section 2 “What you should know before taking Talidomide Accord”).
Talidomide Accord is taken daily in treatment cycles of 6 weeks each, in
combination with melphalan and prednisone, which are 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 Accord capsule comes into contact with the skin, wash the skin immediately and thoroughly with soap and water.
• Healthcare providers, caregivers, and family members must wear disposable gloves when handling the blister pack or capsule. Gloves should then be removed carefully to avoid skin exposure, placed in a sealed polyethylene bag, and disposed of according to local regulations. Hands should then be washed thoroughly 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 dose capsule before going to bed. This is to reduce the likelihood of drowsiness occurring at other times.

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

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

• less than 12 hours have passed: take the missed capsules immediately.
• more than 12 hours have passed: do not take the missed capsules. 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 everybody gets them.
The use of this medicine may cause the following side effects:
Stop taking Talidomide Accord and contact your doctor immediately if you notice any of the
following serious side effects. You may need urgent medical treatment:

• Extremely severe and serious skin reactions. The adverse skin reaction may appear as a rash with or without blisters. Skin irritation, ulcers or swelling in the mouth, throat, eyes, nose and genital area may occur, along with oedema, fever and flu-like symptoms. 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 widespread rash with itching, angioedema and anaphylactic reaction (types of serious 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. This may 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 taking this medicine 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 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 and shortness of breath, nausea 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 include:
Please note that a small number of patients with multiple myeloma may develop other types of cancer, particularly blood cancers, and this risk may increase with treatment with Talidomide Accord; therefore, your doctor must carefully evaluate the benefits and risks before prescribing Talidomide Accord to you.
Very common (may affect more than 1 in 10 people)

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

Common (may affect up to 1 in 10 people)

• Indigestion, nausea, vomiting, dry mouth.
• Rash, dry skin.
• A decrease 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 unsteadiness, lack of energy or strength, low blood pressure.
• Fever, feeling of general malaise.
• Seizures.
• Dizziness, making it difficult to stand 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 (impaired kidney function).

Uncommon (may affect up to 1 in 100 people)

• Inflammation and swelling of the lung airways (bronchitis).
• Inflammation of the cells lining the stomach wall.
• Perforation of part of the large intestine (colon), which may cause infection.
• Intestinal obstruction.
• Drop in blood pressure upon standing, which may lead to fainting.
• Irregular heartbeat (heart block or atrial fibrillation), feeling of fainting 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 consequently to changes in kidney function, heart rhythm, seizures and sometimes death.
• Liver injury (liver disorder), including abnormal 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 nausea or vomiting).
• A brain condition with symptoms including visual 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 experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Talidomide Accord

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/or
on the box and bottle after Exp.. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any damage or signs of tampering.
Do not store above 30°C.
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 Accord contains

• The active substance is thalidomide. Each capsule contains 50 mg of thalidomide.
• The other ingredients are: isomalt (E953), sodium croscarmellose, and sodium stearyl fumarate. The capsule coating contains gelatin and titanium dioxide (E171).

Description of the appearance of Talidomide Accord and package contents
Talidomide Accord is white, opaque, hard gelatin capsules of size number 4. The capsule filling is a white powder.
PVC/PCTFE/Aluminum blisters containing 14 capsules. Packs containing 28 capsules (2 blisters) are packaged in a wallet-style carton.
Unit dose PVC/PCTFE/Aluminum blisters containing 1 x 7 capsules. Packs containing 1 x 28 capsules (4 blisters) are packaged in a cardboard box.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center,
Moll de Barcelona,
s/n, Edifici Est 6ª planta,
08039 Barcelona,
Spain

Manufacturer
Ardena Pamplona, S.L.
Pol Mocholi C/ Noáin, 1
31110 Noáin, Navarra
Spain
or
Medichem S.A.
Narcis Monturiol, 41A
08970 Sant Joan Despí – Barcelona
Spain
or
Bluepharma – Indústria Farmacêutica, S.A.
Eiras, Rua Adriano Lucas
Coimbra, 3020-430
Portugal
or
Bluepharma – Indústria Farmacêutica, S.A.
S. Martinho do Bispo
Coimbra, 3045-016
Portugal