MAVENCLAD 10 mg Tabletki

Treść ulotki

1. MAVENCLAD 10 mg tablets
   1. What is MAVENCLAD and what is it used for
   2. What you need to know before you take MAVENCLAD
   3. How to take MAVENCLAD
   4. Possible side effects
   5. How to store MAVENCLAD
   6. Package Contents and Other Information

MAVENCLAD 10 mg tablets

cladribine

Read this leaflet carefully before you start taking this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours because it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is MAVENCLAD and what is it used for

MAVENCLAD contains the active substance cladribine, a cytotoxic substance (which kills cells)
that acts predominantly on lymphocytes, cells of the immune system that are involved in the
inflammatory process of multiple sclerosis.
MAVENCLAD is a medicine used in the treatment of multiple sclerosis (MS)in adults.
MS is a disease characterized by inflammation that predominantly destroys the protective
sheath of the nerves.
Treatment with MAVENCLAD has been shown to reduce disease relapses and
slow the progression of disability.

2. What you need to know before you take MAVENCLAD

Do not take MAVENCLAD

• if you are allergicto cladribineor to any of the other ingredientsof this medicine (listed in section 6).
• if you are HIV positive, meaning you have a human immunodeficiency virus (HIV) infection.
• if you have active tuberculosis or inflammation of the liver (hepatitis).
• if your immune system is weakeneddue to medical conditions or because you are takingother medicines that weaken the immune system orthat reduce the production of blood cells in the bone marrow. These medicines include:
• cyclosporine, cyclophosphamide and azathioprine (used to suppress the immune system, for example after an organ transplant);
• methotrexate (used to treat diseases such as psoriasis or rheumatoid arthritis);
• corticosteroids given long-term (used to reduce inflammation, for example in the case of asthma). See also “Other medicines and MAVENCLAD”.
• if you have active cancer.
• if you have moderate or severe kidney problems.
• if you are pregnantor breast-feeding(see also “Pregnancy and breast-feeding”).

Do nottake MAVENCLAD and contact your doctor or pharmacist if you are unsure if any of the above conditions apply to you.

Warnings and precautions
Talk to your doctor or pharmacist before taking MAVENCLAD.
Blood tests
Before starting treatment, blood tests will be performed to determine if you can take
MAVENCLAD. Your doctor will also perform blood tests during and after treatment to
verify that you can continue to take MAVENCLAD and that no complications
arise from the treatment.
Infections
Before starting treatment with MAVENCLAD, tests will be performed to determine if you have
any infection. It is important that you contact your doctor if you think you have an infection. It could
be serious and even life-threatening. Symptoms of an infection may include fever,
body aches and muscle pain, headache, general feeling of unwellness, or yellowish discoloration of the eyes. Your doctor may postpone or stop treatment until the infection resolves.

Herpes zoster
If necessary, you will be vaccinated against Herpes zoster before starting treatment. You will need to wait
4 to 6 weeks before the vaccination takes effect. Tell your doctor immediately if you
develop symptoms of Herpes zoster, a common complication of MAVENCLAD (see
section 4), which may require specific treatment.

Progressive multifocal leukoencephalopathy (PML)
If you believe that your MS is worseningor notice new symptoms, such as changes in mood or
behavior, memory loss, difficulty speaking and communicating, see your doctor as
soon as possible. These may be symptoms of a rare brain disease caused by an infection and
called progressive multifocal leukoencephalopathy (PML). PML is a serious disease that can
cause severe disability or death.
Although PML has not been observed with MAVENCLAD, as a precaution, you may be
subjected to an MRI (magnetic resonance imaging ) of the brainbefore starting
treatment.
Cancer
Isolated events of cancer have been observed in clinical studies in patients who received
cladribine. Contact your doctor if you have had cancer. Your doctor will decide which therapeutic
options are most suitable for you. As a precaution, follow the standard recommendations for cancer
screening, as indicated by your doctor.
Liver problems
MAVENCLAD can cause liver problems. Contact your doctor before taking
MAVENCLAD if you have or have ever had liver problems. Tell your doctor immediately if
you develop one or more of the following symptoms:feeling unwell (nausea), vomiting, stomach pain,
fatigue, loss of appetite, yellowing of the skin or eyes (jaundice) or dark urine. These may be symptoms of serious liver problems.
Contraception
Men and women must use effective contraceptive measures during treatment and for at least
6 months after the last dose. This is important because MAVENCLAD can
seriously harm the baby.
See also “Pregnancy and breast-feeding”.
Blood transfusions
If you need a blood transfusion, tell your doctor that you are taking MAVENCLAD. For
preventing complications, the blood may need to be irradiated.
Change of treatment
When switching from other treatments for MS to MAVENCLAD, your doctor will check that the count
of certain blood cells (lymphocytes) is normal before starting treatment.
If you switch from MAVENCLAD to other treatments for MS, contact your doctor. The effects on the immune
system may overlap.

Children and adolescents
The use of MAVENCLAD is not recommended in patients under 18 years of age, because it has not
been studied in this age group.

Other medicines and MAVENCLAD
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.

Do not starttreatment with MAVENCLAD together with medicines that weaken the immune
system or that reduce the production of blood cells in the bone marrow. These medicines
include:

• cyclosporine, cyclophosphamide and azathioprine (used to suppress the immune system, for example after an organ transplant);
• methotrexate (used to treat diseases such as psoriasis or rheumatoid arthritis);
• corticosteroids given long-term (used to reduce inflammation, for example in the case of asthma). Short-term corticosteroids may be used, if prescribed by your doctor.

Do not useMAVENCLAD together with other medicines for MS, unless specifically instructed by your doctor.

Do not takeMAVENCLAD at the same time as any other medicine. Allow at least

3 hoursbetween taking MAVENCLAD and taking other medicines orally.
MAVENCLAD contains hydroxypropyl betadex, which can interact in the stomach with other medicines.

Contact your doctorif you are or have been treated with:

• medicines that can alter blood cells (e.g. carbamazepine, used to treat epilepsy). Your doctor may need to monitor you more closely.
• certain types of vaccines (live and live attenuated vaccines). If you have been vaccinated in the last 4-6 weeks, therapy with MAVENCLAD should be postponed. You should not receive these types of vaccines during treatment with MAVENCLAD. The immune system must have recovered before you can be vaccinated and blood tests will be performed to verify this.
• dilazep, nifedipine, nimodipine, reserpine, cilostazol or sulindac (used to treat heart disease, high blood pressure, vascular diseases or inflammation) or eltrombopag (used to treat diseases associated with bleeding). Your doctor will tell you how to proceed if you need to take these medicines.
• rifampicin (used to treat certain types of infection), St John's wort (used to treat depression) or corticosteroids (used to suppress inflammation). Your doctor will tell you how to proceed if you need to take these medicines.

Pregnancy and breast-feeding
Do nottake MAVENCLAD if you are pregnant or planning a pregnancy. This is
important because MAVENCLAD can be seriously harmful to the baby.
You must use effective contraceptive methodsto avoid pregnancy during treatment with
MAVENCLAD and for 6 months after taking the last dose of MAVENCLAD. If you become
pregnant more than 6 months after taking the last dose in year 1, no safety risk is expected, but you will not be able to receive treatment with MAVENCLAD during
pregnancy.
Men must use effective contraceptive methods to avoid pregnancy of their partner
during treatment with MAVENCLAD and for 6 months after taking the last dose.
Your doctor will inform you about suitable contraceptive methods.

Do nottake MAVENCLAD if you are breast-feeding. If your doctor considers that MAVENCLAD is essential
for you, they will advise you to stop breast-feeding during treatment and for at least one week
after the last dose.

Driving and using machines
MAVENCLAD is not expected to affect your ability to drive and operate machines.

MAVENCLAD contains sorbitol
This medicine contains 64 mg of sorbitol in each tablet.

3. How to take MAVENCLAD

Take this medicine following exactly the instructions of your doctor. If you have any doubts, ask your doctor or pharmacist.

Treatment cycles
MAVENCLAD will be administered to you in two treatment cycles over a total of 2 years.
Each treatment cycle consists of 2 weeksspaced one month apart, at the beginning of each year of treatment.
A treatment weekconsists of 4 or 5 daysduring which you will receive 1 or 2 tablets per day
(see Table 1).

Example:If you start treatment in mid-April, you will take the tablets as indicated here.

Table 1

Before starting a treatment cycle, your doctor will perform a blood test to check if your lymphocytes (a type of white blood cells) are at acceptable levels. If the levels are not acceptable, the treatment will be postponed.
Once the 2 treatment cycles are completed over a total of 2 years, your doctor will continue to observe your health conditions for another 2 years, during which you should not take the medicine.

Dose

• 1. For each week of treatment, you will be prescribed the correct number of tablets based on your body weight, as shown in Table 2.
• 2. You will need one or more packs for the correct number of tablets.
• 3. When you receive the medicine, check that the number of tablets is correct.
• 4. In the left column of the table below, find the row corresponding to your body weight (in kg) and check the number of tablets that should be in the pack or packs for the treatment week you are about to start.
• 5. If the number of tablets in the pack or packs is different from the number indicated for your weight in the table below, contact your doctor.
• 6. Remember that, for some weight ranges, the number of tablets may vary from one treatment week to another.

Example: If you weigh 85 kg and are about to start treatment week 1, you will receive 8 tablets.

Table 2
WeightNumber of tablets to take
Treatment cycle in year 1 Treatment cycle in year 2
Treatment week 2
less than 40 kg The doctor will tell you how many tablets you must take
40 to less than 50 kg 4 4 4 4
50 to less than 60 kg 5 5 5 5
60 to less than 70 kg 6 6 6 6
70 to less than 80 kg 7 7 7 7
80 to less than 90 kg 8 7 8 7
90 to less than 100 kg 9 8 9 8
100 to less than 110 kg 10 9 10 9
110 kg and over 10 10 10 10

How to take the medicine
Take the tablet or tablets each day at approximately the same time. Swallow them with water and without chewing. You do not need to take the tablets with meals. You can take them with or between meals.

Read the “Step-by-step guide” on using the child-resistant pack and taking the tablets contained in the pack at the end of this leaflet.
Important

• Check that your hands are dry before taking the tablet or tablets.
• Press the tablet or tablets through the blister and swallow them immediately.
• Do not leave the tablet or tablets exposed on surfaces, such as a table, and do not handle them for longer than necessary.
• If a tablet has been left exposed on a surface or if it breaks and fragments fall from the blister, the affected area must be washed carefully.
• Wash your hands carefully after handling the tablets.
• If you lose a tablet, ask your doctor for advice.

Duration of a treatment week
Depending on the total number of tablets you have been prescribed, you will need to take them for 4 or 5 days for each treatment week.
Table 3 indicates how many tablets (1 or 2 tablets) you will need to take each day. If your daily dose is 2 tablets, take them together.
Treatment week 1
Treatment week 2
Treatment week 1

Example: If you need to take 8 tablets, you will take 2 tabletson day 1, day 2 and day 3, and then 1 tableton day 4 and day 5.

Table 3

If you take more MAVENCLAD than you should
If you have taken more tablets than you should, contact your doctor immediately, who will decide whether or not to stop treatment.
Experience with MAVENCLAD overdose is limited. It is known that the greater the amount of medicine you take, the lower the number of lymphocytes in your body may be, resulting in lymphopenia (see section 4).

If you forget to take MAVENCLAD

Example:If you forget the dose on day 3 and only remember it on day 4, you should take the dose for day 3 on day 4 and extend the treatment week by 1 day. If you forget 2 consecutive doses (e.g. day 3 and day 4), you should take the forgotten doses over the next 2 days and extend the treatment week by 2 days.
If you have any questions about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Some side effects could be or become serious
Lymphopenia and Herpes zoster(may affect more than 1 in 10 people)
The most important side effect is a reduction in the number of white blood cells called lymphocytes
( lymphopenia), which is very common and can be serious. Lymphopenia may increase the risk of
contracting an infection. An infection that is commonly observed with MAVENCLAD is Herpes
zoster.

Tell your doctor immediately if you develop symptoms of Herpes zostersuch as severe pain and
blisters with a characteristic “band-like” distribution, typically on one side of the upper
body or on the face. Other symptoms include headache, burning, tingling, numbness or
skin itching in the affected area, general feeling of being unwell or fever in the early
stages of the infection.
Herpes zoster may require treatment and it may be necessary to stop MAVENCLAD therapy until the
infection has resolved.

Liver problems(uncommon - may affect up to 1 in 100 people)

Tell your doctor immediately if you develop symptomssuch as feeling unwell (nausea), vomiting, pain
in the stomach, tiredness (fatigue), loss of appetite, yellowing of the skin or eyes
(jaundice) or dark urine. It may be necessary to suspend or stop MAVENCLAD therapy.

Other possible side effects
Common(may affect up to 1 in 10 people)

• Cold sores
• skin rash
• hair loss
• decreased number of certain white blood cells (neutrophils)
• allergic reactions, including itching, hives, rash and swelling of the lips, tongue or face

Very rare(may affect up to 1 in 10,000)

• tuberculosis

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. You can also report side effects directly
through the national reporting system listed in Annex V . By reporting side effects you can help
to provide more information on the safety of this medicine.

5. How to store MAVENCLAD

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 cardboard package and on the
box after Exp. The expiry date refers to the last day of that month.
Store in the original package to protect the medicine from moisture.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What MAVENCLAD contains

• The active ingredient is cladribine. Each tablet contains 10 mg of cladribine.
• The other ingredients are hydroxypropyl betadex, sorbitol and magnesium stearate.

Description of the appearance of MAVENCLAD and package contents
MAVENCLAD tablets are white, round, biconvex, with “C” imprinted on one side and “10”
on the other side. Each pack contains 1, 4, 5, 6, 7 or 8 tablets in a blister sealed in a cardboard
box and attached to a child-resistant box. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
Netherlands

Manufacturer
NerPharMa S.R.L.
Viale Pasteur 10
20014 Nerviano (MI)
Italy
R-Pharm Germany GmbH
Heinrich-Mack-Strasse 35
89257 Illertissen
Germany
Merck S.L.
Polígono Merck
08100 Mollet del Vallés (Barcelona)
Spain

Other sources of information
More detailed information about this medicine is available on the European Medicines Agency website, https://www.ema.europa.eu/ .

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“Step-by-step guide” for taking MAVENCLAD 10 mg tablets
MAVENCLAD is presented in a reclosable child-resistant box and must be kept out of the sight and
reach of children. See below the “step-by-step guide” for handling the pack and taking MAVENCLAD tablets. Check how many

• 1. Prepare a glass of water and make sure your hands are clean and dry before taking the tablet or tablets.

• 2. Take the box holding it with the opening instructions facing upwards.

• 3. (1) Open the tab on the left.
• (2) With your index and thumb, simultaneously press the buttons located on the sides of the box and hold them pressed.
• (3) Pull out the tray until it stops. Caution:do not remove the tray from the box.

including this “step-by-step guide”, and store it in a safe place.

• 5. Lift the blister by inserting a finger into the hole in the tray. Place your hand under the blister and press to drop 1 or 2 tablets into your hand, depending on the prescribed dose.

• 6. Swallow the tablet or tablets with a little water. The tablets must be swallowed whole, without chewing and without letting them dissolve in your mouth. Limit contact with the skin. Avoid touching your nose, eyes and other parts of the body.

• 7. Wash your hands thoroughly with water and soap.

• 8. Push the tray back into the box. Store in the original packaging to protect the medicine from moisture.

Keep the tablets in the blister until the next dose. Do not drop the tablets out of the blister.
Do not store the tablets in a different container.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR THE VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATION/S
Scientific conclusions
Considering the evaluation of the Pharmacovigilance and Risk Assessment Committee (PRAC) of the periodic safety update report (PSUR) for cladribine (multiple sclerosis), the scientific conclusions of the PRAC are as follows:
In light of the available literature data regarding the excretion of cladribine in breast milk, the PRAC considers that the excretion of cladribine in breast milk constitutes at least a reasonable possibility. The PRAC concluded that the product information of medicines containing cladribine (multiple sclerosis) should be amended accordingly.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the related overall conclusions and with the justification for the recommendation.

Justification for the variation of the terms of the marketing authorisation(s)
Based on the scientific conclusions on cladribine (multiple sclerosis) the CHMP considers that the benefit/risk ratio of the medicine(s) containing cladribine (multiple sclerosis) remains unchanged subject to the proposed changes to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation(s).