MAVENCLAD 10 mg TABLETS

Introduction

Package Leaflet: Information for the User

MAVENCLAD 10 mg tablets

cladribine

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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. Storage of 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 (able to kill cells) that acts mainly on lymphocytes, cells of the immune system involved in inflammation.

MAVENCLAD is a medicine used to treat multiple sclerosisin adults. Multiple sclerosis is a disease in which inflammation destroys the protective sheath that surrounds the nerves.

It has been shown that treatment with MAVENCLAD reduces the worsening of symptoms and slows down 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 are infected with the human immunodeficiency virus (HIV).

• if you have active tuberculosis or active hepatitis (liver inflammation).

• if you have a weakened immune systemdue to disease or because you are taking medicines that weaken the immune systemor reduce the production of blood cells in the bone marrow. These include:

• cyclosporin, cyclophosphamide, and azathioprine (used to suppress the immune system, for example, after an organ transplant);
• methotrexate (used to treat conditions such as psoriasis or rheumatoid arthritis);

• corticosteroids for a long time (used to reduce inflammation, for example, in asthma).

Also, see “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 not takeMAVENCLAD and consult your doctor or pharmacist if you are unsure if you are in any of the above situations.

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with MAVENCLAD.

Blood tests

You will have blood tests before starting treatment to check if you can take MAVENCLAD. Your doctor will also have blood tests done during and after treatment to check that you can continue taking MAVENCLAD and that you are not developing any complications from treatment.

Infections

You will have tests to check for infections before starting treatment with MAVENCLAD. It is important that you consult your doctor if you think you have an infection. Infections could be serious and potentially life-threatening. Symptoms of infection may include: fever, pain, muscle aches, headache, general feeling of being unwell, or yellowing of the eyes. Your doctor may delay treatment or interrupt it until the infection goes away.

Herpes zoster

If necessary, you will be vaccinated against herpes zoster before starting treatment. You will have to wait between 4 and 6 weeks for the vaccine to take effect. Tell your doctor immediately if youhave symptoms of herpes zoster, a common complication of MAVENCLAD (see section 4), which may require specific treatment.

Progressive multifocal leukoencephalopathy

If you think that your multiple sclerosis is getting worseor you notice any new symptoms, such as changes in mood or behavior, memory lapses, difficulty speaking or communicating, consult your doctor as soon as possible. These may be symptoms of a rare brain disorder caused by an infection called progressive multifocal leukoencephalopathy. Progressive multifocal leukoencephalopathy is a serious condition that can cause significant disability or death.

Although progressive multifocal leukoencephalopathy has not been observed with MAVENCLAD, as a precautionary measure, you may have a magnetic resonance imaging (MRI) scan of the headbefore starting treatment.

Cancer

Individual cases of cancer have been observed in patients who received cladribine in clinical trials. Consult your doctor if you have had cancer. Your doctor will decide the best treatment options for you. As a precautionary measure, your doctor will advise you to follow standard recommendations for cancer screening.

Liver problems

MAVENCLAD may cause liver problems. Consult your doctor before taking MAVENCLAD if you have or have had liver problems.Tell your doctor immediately if you develop one or more of the following symptoms: nausea, vomiting, stomach pain, fatigue, loss of appetite, yellowing of the skin or eyes (jaundice), or cloudy urine. These may be symptoms of serious liver problems.

Contraception

Men and women must use effective contraceptive methods during treatment and for at least six 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 blood transfusions, tell your doctor that you are taking MAVENCLAD. It may be necessary to irradiate the blood to avoid complications.

Changes in treatment

If you switch from other multiple sclerosis treatments to MAVENCLAD, your doctor will check that your blood cell counts (lymphocytes) are normal before starting treatment.

If you switch from MAVENCLAD to other multiple sclerosis treatments, consult your doctor.

There may be overlaps in the effect on the immune system.

Children and adolescents

MAVENCLAD is not recommended for use in patients under 18 years of age, as 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 startMAVENCLAD with medicines that weaken your immune system or reduce the production of blood cells in your bone marrow. These include:

• cyclosporin, cyclophosphamide, and azathioprine (used to suppress the immune system, for example, after an organ transplant).

• methotrexate (used to treat conditions such as psoriasis or rheumatoid arthritis).

• corticosteroids for a long time (used to reduce inflammation, for example, in asthma). Short-term use of corticosteroids may be used if your doctor advises.

Do not useMAVENCLAD with other multiple sclerosis medicines unless your doctor specifically advises you to do so.

Do not take MAVENCLAD at the same time as any other medicine.Leave an interval of at least three hoursbetween taking MAVENCLAD and taking other medicines by mouth. MAVENCLAD contains hydroxypropylbetadex, which may interact with other medicines in the stomach.

Consult your doctorif you receive or have received treatment with:

• medicines that may affect blood cells (for example, carbamazepine, used to treat epilepsy). Your doctor may need to monitor you more closely.

• certain types of vaccines (live or live attenuated vaccines). If you have been vaccinated in the last 4 to 6 weeks, treatment with MAVENCLAD should be delayed. You should not receive these vaccines during treatment with MAVENCLAD. It is necessary for your immune system to have recovered before you can be vaccinated, and blood tests will be needed to check this.

• dilazep, nifedipine, nimodipine, reserpine, cilostazol, or sulindac (used to treat heart diseases, hypertension, vascular diseases, or inflammatory diseases) or eltrombopag (used to treat diseases associated with bleeding). Your doctor will tell you what to do if you need to take these medicines.

• rifampicin (used to treat some types of infections), St. John's Wort (used to treat depression), or corticosteroids (used to reduce inflammation). Your doctor will tell you what to do if you need to take these medicines.

Pregnancy and breast-feeding

Do not takeMAVENCLAD if you are pregnant or trying to become pregnant. This is important because MAVENCLAD can seriously harm the baby.

You must use effective contraceptive methodsto avoid becoming pregnant during treatment with MAVENCLAD and for at least six months after taking the last dose. If you become pregnant after more than six months after the last dose in year 1, no safety risks are expected, but this means you will not be able to receive treatment with MAVENCLAD while pregnant.

Men must use effective contraceptive methods to avoid getting their partner pregnant while receiving treatment with MAVENCLAD and for six months after the last dose.

Your doctor will advise you on the appropriate contraceptive methods.

Do not takeMAVENCLAD if you are breast-feeding. If your doctor thinks 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 or use machines.

MAVENCLAD contains sorbitol

This medicine contains 64 mg of sorbitol in each tablet.

3. How to take MAVENCLAD

Follow the administration instructions for this medication exactly as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

Treatment courses

You will be given MAVENCLAD in the form of two treatment coursesover two years. Each treatment course consists of two weeks of treatment, separated by a month at the start of each year of treatment.

A treatment weekconsists of four or five dayson which you will receive one or two tabletsper day (see Table 1).

For example:if you start treatment in mid-April, you will take the tablets as indicated below.

Table 1

Before starting each treatment course, your doctor will perform a blood test to check that the levels of lymphocytes (a type of white blood cell) in your body are within acceptable limits. If this is not the case, treatment will be delayed.

Once the two treatment courses have been completed over two years, your doctor will continue to monitor your health for another two years, during which you will not need to take the medication.

Dose

1. You will be prescribed the correct number of tablets for each treatment week, based on your body weight, as indicated in Table 2.
2. You will need one or more packages to provide the correct number of tablets.
3. When you receive the medication supply, check that you have the correct number of tablets.
4. In the left column of the table shown below, find the row that corresponds to your body weight (in kg); then, check the number of tablets that should be in the package(s) for the treatment week you are starting.
5. If the number of tablets in the package(s) is different from the number indicated for your body weight in the table, consult your doctor.
6. Note that, in some weight intervals, the number of tablets may vary from one treatment week to the next.

For example:if you weigh 85 kg and are about to start treatment week 1, you will be given 8 tablets.

Table 2

How to take the medication

Take the tablets at approximately the same time each day. Swallow them with water and without chewing. It is not necessary to take them at meal times. You can take them with meals or between meals.

Read the "Step-by-step guide" at the end of this leaflet on how to handle the child-resistant packaging and how to take the tablets included in the package.

Important

• Make sure your hands are dry before taking the tablet(s).
• Remove the tablet(s) from the blister pack and swallow them immediately.
• Do not leave your tablet(s) exposed on surfaces, for example, on a table, and do not handle the tablet for longer than necessary.
• If you leave a tablet on a surface or if it breaks and the fragments fall out of the blister pack, the area should be cleaned well.
• Wash your hands thoroughly after handling the tablets.
• If you miss a tablet, consult your doctor.

Duration of a treatment week

Depending on the total number of tablets you have been prescribed, you will need to take them over four or five days, in each treatment week.

Table 3 shows how many tablets (one or two tablets) you should take each day. If your daily dose is two tablets, take them at the same time.

For example:if you need to take eight tablets, you would take two tabletson day 1, day 2, and day 3, and then one 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. Your doctor will decide whether or not to interrupt treatment.

There is limited experience with overdose of MAVENCLAD. It is known that the more medication you take, the lower the number of lymphocytes present in your body, which can lead to lymphopenia (see section 4).

If you forget to take MAVENCLAD

For example:If you forgot to take the dose on day 3 and do not remember until day 4, take the dose on day 3 on day 4, and extend the total number of days of the treatment week by one day. If you forget two consecutive doses (for example, the doses on days 3 and 4), take the missed doses on the next two days, and then extend the treatment week by two days.

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Some side effects can be serious or become serious

Lymphopenia and herpes zoster(may affect more than 1 in 10 people)

The most important side effect is a decrease in the number of white blood cells called lymphocytes (lymphopenia), which is very common and can be serious. Lymphopenia can increase the risk of infection. A frequently observed infection with MAVENCLAD is herpes zoster.

Tell your doctor immediately if you experience symptoms of herpes zoster,such as a "band" of intense pain and a skin rash with blisters, usually on one side of the upper body or face. Other symptoms may include headache, itching, tingling, numbness, or prickling sensation on the skin of the affected area, general feeling of discomfort or fever in the initial stages of the infection.

Herpes zoster will require treatment and may need to interrupt treatment with MAVENCLAD until the infection disappears.

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

Tell your doctor immediately if you experience symptomssuch as nausea, vomiting, stomach pain, fatigue, loss of appetite, yellowing of the skin or eyes (jaundice), or cloudy urine. It may be necessary to interrupt or stop treatment with MAVENCLAD.

Other possible side effects

Common(may affect up to 1 in 10 people)

• fever (oral herpes)
• skin rash
• hair loss
• decrease in the number of certain white blood cells (neutrophils)
• allergic reactions, including itching, hives, skin rash, and swelling of the lips, tongue, or face

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

• tuberculosis

Reporting side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Medicines Agency's online reporting system: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of MAVENCLAD

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the carton and on the package after "EXP". The expiration date is the last day of the month indicated.

Store in the original packaging to protect from moisture.

Medications should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package contents and additional information

Composition of MAVENCLAD

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

Appearance of the product and package contents

MAVENCLAD tablets are white, round, biconvex tablets, engraved with "C" on one side and "10" on the other. Each package contains 1, 4, 5, 6, 7, or 8 tablets in a sealed blister pack in a carton and inserted in a child-resistant case. Not all package sizes may be marketed.

Marketing authorization 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

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medication is available on the European Medicines Agency website: http://www.ema.europa.eu.

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Step-by-step guide to taking MAVENCLAD 10 mg tablets

MAVENCLAD is packaged in a child-resistant case and should be kept out of sight and reach of children. See below for the step-by-step guide on how to handle the packaging and how to take the MAVENCLAD tablets. Make sure you know how many tablets are in the package. See the guidelines in the leaflet.

1. Have a glass of water ready and make sure your hands are clean and dry before taking the tablet(s).

1. Take the box with the opening instructions facing up.

1. (1) Open the flap on the left end.

1. Press the tabs on the sides of the box simultaneously with your index finger and thumb, and keep the tabs pressed.
2. Pull the tray out until it stops. Caution:do not remove the tray from the box.

1. Remove the leaflet from the tray. Make sure you have read everything, including this step-by-step guide, and store it in a safe place.

1. Lift the blister pack by putting your finger through the hole in the tray. Place your hand under the blister pack and push one or two tablets into your hand, depending on the prescribed dose.

1. Swallow the tablet(s) with water. The tablets should be swallowed whole and not chewed or allowed to dissolve in the mouth. Skin contact should be limited. Avoid touching your nose, eyes, and other parts of your body.

1. Wash your hands thoroughly with water and soap.

1. Push the tray back into the box. Store in the original packaging to protect from moisture.

Keep the tablets in the blister pack until the next dose. Do not remove the tablets from the blister pack. Do not store the tablets in a different container.