Product Information for the User

MAVENCLAD 10 mg Tablets

cladribina

Read this entire product information carefully before starting to take this medicine, as it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this product information. See section 4.

MAVENCLAD contains the active ingredient cladribina, a cytotoxic substance (capable of killing cells) that primarily acts on lymphocytes, some cells of the immune system involved in inflammation.

MAVENCLAD is a medication used to treatmultiple sclerosisinadults. Multiple sclerosis is a disease in which inflammation destroys the protective sheath surrounding the nerves.

It has been shown that treatment with MAVENCLAD reduces the worsening of symptoms and slows the progression of disability.

Do not take MAVENCLAD

• if you areallergicto cladribina or any of the othercomponentsof this medicine (listed in section 6).

• if you arepositive for HIV, which means you are infected with the human immunodeficiency virus (HIV).

• if you have an activetuberculosisor liver inflammation (hepatitis).

• if you have aweakened immune systemdue to diseases or because you aretakingmedicines that weaken the immune systemor reduce blood cell production in thebone marrow. These include:

• ciclosporina, ciclofosfamida, and azatioprina (used to suppress the immune system, for example, after an organ transplant);
• metotrexato (used to treat conditions such as psoriasis or rheumatoid arthritis);

• corticoesteroides for a prolonged period (used to reduce inflammation, for example, in asthma).

Also see “Other medicines and MAVENCLAD”.

• if you have an activecancer.

• if you havemoderate or severe kidney problems.

• if you arepregnantor breastfeeding (also see “Pregnancy and breastfeeding”).

Do not takeMAVENCLAD and consult your doctor or pharmacist if you are unsure if you are in any of the above circumstances.

Warnings and precautions

Consult your doctor or pharmacist before starting MAVENCLAD.

Blood tests

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

Infections

You will have tests to check if you have infections before starting treatment with MAVENCLAD. It is essential to consult your doctor if you think you have an infection. Infections could be severe and potentially life-threatening. Symptoms of infection may include: fever, pain, muscle aches, headache, general feeling of illness, oryellowing of the eyes.Your doctor may delay treatment or interrupt it until the infection has cleared.

Herpes zóster

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

Leucoencefalopatía multifocal progresiva

If you think yourmultiple sclerosis is worseningornote any new symptoms, such as, for example, 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 and called leucoencefalopatía multifocal progresiva. Leucoencefalopatía multifocal progresiva is a serious condition that can cause significant disability or death.

Although leucoencefalopatía multifocal progresiva has not been observed with MAVENCLAD, as a precaution,you may have a head MRIbefore starting treatment.

Cancer

Cases of cancer have been observed in patients who received cladribina in clinical trials. Consult your doctor if you have had cancer. Your doctor will decide the best treatment options for you. As a precaution, your doctor will advise you to follow standard recommendations for cancer screening tests.

Liver problems

MAVENCLAD may cause liver problems.Consult your doctor before taking MAVENCLAD if you have or have had liver problems.Inform 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 severe 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 essential because MAVENCLAD can severely harm the baby.

Also see “Pregnancy and breastfeeding”.

Blood transfusions

If you need blood transfusions, tell your doctor that you are taking MAVENCLAD. You may need to irradiate the blood to prevent complications.

Changes in treatment

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

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

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

Children and adolescents

MAVENCLAD is not recommended for patients under 18 years old, as it has not been studied in this age group.

Other medicines and MAVENCLAD

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine.

Do not startMAVENCLAD with medicines that weaken your immune system or reduce blood cell production in your bone marrow. These include:

• ciclosporina, ciclofosfamida, and azatioprina (used to suppress the immune system, for example, after an organ transplant).

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

• corticoesteroides for a prolonged period (used to reduce inflammation, for example, in asthma). Corticoesteroides may be used for a short period if your doctor advises it.

Do not useMAVENCLAD with other multiple sclerosis medicines unless your doctor advises it specifically.

Do not take MAVENCLAD at the same time as any other medicine.Leave a gap ofat least three hoursbetween taking MAVENCLAD and other oral medicines. MAVENCLAD contains hydroxypropylbetadex, which may interact with other medicines in the stomach.

Consult your doctorif you receive or have received treatment with:

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

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

• dilazep, nifedipino, nimodipino, reserpina, cilostazol, or sulindaco (used to treat heart disease, hypertension, vascular 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.

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

Pregnancy and breastfeeding

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

You must useeffective contraceptive methodsto avoid becoming pregnant during MAVENCLAD treatment and for at least six months after the last dose. If you become pregnant more than six months after the last dose of year1, there are no safety concerns, but this means you cannot receive MAVENCLAD treatment while pregnant.

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

Your doctor will advise you on suitable contraceptive methods.

Do not takeMAVENCLAD if you are breastfeeding. If your doctor thinks MAVENCLAD is essential for you, they will advise you to stop breastfeeding during treatment and for at least one week after the last dose.

Driving and operating machines

MAVENCLAD is not expected to affect your ability to drive or operate machines.

MAVENCLAD contains sorbitol

This medicine contains 64 mg of sorbitol in each tablet.

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

Treatment Courses

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

Oneweek of treatmentconsists offour or five days in which you will receive one or twotablets per 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 your lymphocyte levels (a type of white blood cell) are within acceptable limits. If this is not the case, treatment will be delayed.

Once the two treatment courses over two years have been completed, 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 week of treatment, 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 week of treatment you will start.
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. Observe that, in some weight intervals, the number of tablets may vary from one week of treatment to the next.

For example:if you weigh 85 kg and are about to start week 1 of treatment, you will be given8 tablets.

Table 2

How to take the medication

Take the tablets approximately at the same time each day. Swallow them with water and do not chew them. It is not necessary to take them with meals. 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 tablets.
• Remove the tablets from the blister pack and swallow them immediately.
• Do not leave your tablets exposed on surfaces, for example, on a table, or handle the tablet for longer than necessary.
• If a tablet is left on a surface or if it breaks and the fragments fall from the blister pack, the area must be thoroughly cleaned.
• Wash your hands thoroughly after handling the tablets.
• If you lose a tablet, consult your doctor.

Duration of a week of treatment

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

The 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 have to take eight tablets, you would taketwo tabletson day 1, day 2, and day 3, and, from then on,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 MAVENCLAD overdose. It is known that the more medication you take, the lower your lymphocyte levels may be, leading to lymphopenia (see section 4).

If you forget to take MAVENCLAD

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

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

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

Some side effects can be serious or life-threatening

Lymphopenia and shingles(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 may increase the risk of infection. A frequently observed infection with MAVENCLAD is theshingles.

Inform your doctor immediately if you experience symptoms of shingles,such as a “band” ofintense pain and a skin rash with blisters, usually on one side of the upper body or face. Other symptoms may be headache, itching, tingling, numbness, or prickling in the affected skin area, general feeling of discomfort or fever in the initial stages of the infection.

Shingles will require treatment and you may need to interrupt treatment with MAVENCLAD until the infection clears up.

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

Inform 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 discontinue treatment with MAVENCLAD.

Other possible side effects

Frequent(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 type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly throughthe Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the carton backing and on the box after “CAD”. The expiration date is the last day of the month indicated.

Store in the original packaging to protect it from moisture.

Medicines should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of MAVENCLAD

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

Appearance of the product and contents of the package

MAVENCLAD tablets are white, round, biconvex, and engraved with “C” on one face and “10” on the other. Each package contains 1, 4, 5, 6, 7, or 8 tablets in a sealed blister pack in a cardboard support and inserted into a child-resistant case. Some package sizes may only be marketed.

Marketing Authorization Holder

Merck Europe B.V.

Gustav Mahlerplein 102

1082 MA Amsterdam

Netherlands

Responsible for manufacturing

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

Last review date of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

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

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

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

1. Take the case with the instructions for opening facing upwards.

1. (1) Open the left flap.

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

1. Take the leaflet out of 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 inserting your finger through the hole in the tray. Place your hand under the blister pack and push one or two tablets towards your hand, as prescribed.

1. Swallow the tablet or tablets 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 case. Store in the original packaging to protect it from moisture.

Store 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.