Mavenclad 10 mg tablets

Patient Information Leaflet

Introduction

Patient Information Leaflet

MAVENCLAD 10 mg tablets

cladribine

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

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

Leaflet Contents

1. What MAVENCLAD is and what it is used for
2. What you need to know before taking 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 MAVENCLAD is and what it is used for

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

MAVENCLAD is a medicine used to treat multiple sclerosis in adults. Multiple sclerosis is a disease in which inflammation damages the protective sheath surrounding the nerves.

Treatment with MAVENCLAD has been shown to reduce the worsening of symptoms and to slow the progression of disability.

2. What you need to know before starting MAVENCLAD

Do not take MAVENCLAD

• if you are allergic to cladribine or any of the other components of 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 liver inflammation (hepatitis).

• if you have a weakened immune system due to diseases or because you are taking medicines that weaken the immune system or reduce blood cell production in the bone marrow. These include:

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

See also “Other medicines and MAVENCLAD”.

• if you have active cancer.

• if you have moderate or severe kidney problems.

• if you are pregnant or breastfeeding (see also “Pregnancy and breastfeeding”).

Do not take MAVENCLAD and consult your doctor or pharmacist if you are unsure whether any of the above conditions apply to you.

Warnings and precautions

Talk to your doctor or pharmacist before starting MAVENCLAD.

Blood tests

You will have blood tests before starting treatment to check whether you can take MAVENCLAD. Your doctor will also perform blood tests during and after treatment to ensure you can continue taking MAVENCLAD and to monitor for any treatment-related complications.

Infections

You will be tested for infections before starting treatment with MAVENCLAD. It is important that you consult your doctor if you suspect 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 or interrupt 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 for the vaccine to take effect. Inform 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

If you think your multiple sclerosis is worsening or you notice any new symptoms, such as changes in mood or behavior, memory lapses, or difficulties 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 lead to severe disability or death.

Although progressive multifocal leukoencephalopathy has not been observed with MAVENCLAD, as a precautionary measure, you may undergo a brain MRI scan before 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 precaution, your doctor will advise you to follow standard cancer screening recommendations.

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 signs of serious liver problems.

Contraception

Women must use effective contraceptive methods during treatment and for at least six months after the last dose. Men must use effective contraceptive methods during treatment and for at least three months after the last dose. This is important because MAVENCLAD can seriously harm the unborn baby.

See also “Pregnancy and breastfeeding”.

Blood transfusions

If you need blood transfusions, inform your doctor that you are taking MAVENCLAD. It may be necessary to irradiate the blood to prevent complications.

Changing treatments

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

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

Overlapping effects on the immune system may occur.

Children and adolescents

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

Other medicines and MAVENCLAD

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

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

• cyclosporine, 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 over a prolonged period (used to reduce inflammation, for example, in asthma). Short-term use of corticosteroids may be permitted if advised by your doctor.

Do not use MAVENCLAD together with other multiple sclerosis medicines unless specifically advised by your doctor.

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

Consult your doctor if you are receiving or have received treatment with:

• medicines that may affect blood cells (e.g., 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 were vaccinated within the last 4 to 6 weeks, treatment with MAVENCLAD should be delayed. You must not receive these vaccines during treatment with MAVENCLAD. The immune system must have recovered before vaccination, and blood tests will be needed to confirm this.

• dipyridamole, nifedipine, nimodipine, reserpine, cilostazol, or sulindac (used to treat heart diseases, hypertension, vascular or inflammatory conditions) or eltrombopag (used to treat bleeding-related disorders). Your doctor will advise you on what to do if you need to take these medicines.

• rifampicin (used to treat certain infections), St. John’s wort (used to treat depression), or corticosteroids (used to reduce inflammation). Your doctor will advise you on what to do if you need to take these medicines.

Pregnancy and breastfeeding

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

You must use effective contraception to prevent pregnancy during treatment with MAVENCLAD and for at least six months after the last dose. If you become pregnant more than six months after the last dose of year 1, no safety risks are expected, but this means you cannot receive MAVENCLAD treatment while pregnant.

Men should use effective contraception while receiving MAVENCLAD and for three months after the last dose.

Your doctor will advise you on appropriate contraceptive methods.

Do not take MAVENCLAD if you are breastfeeding. If your doctor considers MAVENCLAD essential for you, you will be advised to stop breastfeeding 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 operate machinery.

MAVENCLAD contains sorbitol

This medicine contains 64 mg of sorbitol in each tablet.

3. How to take MAVENCLAD

Follow exactly the administration instructions for this medicine given 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 courses over two years. Each treatment course consists of two treatment weeks , separated by one month at the beginning of each treatment year.

A treatment week consists of four or five days during which you will receive one or two tablets per day (see Table 1).

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

Table 1

Year 1	Year 2
1st week of treatment	One or two tablets per day for four or five days, mid-April	1st week of treatment	One or two tablets per day for four or five days, mid-April
2nd week of treatment	One or two tablets per day for four or five days, mid-May	2nd week of treatment	One or two tablets per day for four or five days, mid-May

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

After completing the two treatment courses 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.

Dosage

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 your medication supply, verify that you have the correct number of tablets.
4. In the left column of the table shown below, find the row corresponding 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 about to start.
5. If the number of tablets in the package(s) differs from the number indicated for your body weight in the table, consult your doctor.
6. Note that, for certain weight ranges, the number of tablets may vary from one treatment week to the next.

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

Table 2

Your weight	Number of tablets you should take
	Treatment course year 1	Treatment course year 2
	Week of	Week of	Week of	Week of
	treatment 1	treatment 2	treatment 1	treatment 2
less than 40 kg	Your doctor will tell you the number of tablets you should 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 or more	10	10	10	10

How to take the medicine

Take the tablets at approximately the same time each day. Swallow them with water and do not chew them. It is not necessary to take them with meals. You may 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 contained in the pack.

Important

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

Duration of a week of treatment

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

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 tablets on day 1, day 2, and day 3, and then one tablet on day 4 and day 5.

Table 3

Total number of
tablets per week of	Day 1	Day 2	Day 3	Day 4	Day 5
treatment
4	1	1	1	1	0
5	1	1	1	1	1
6	2	1	1	1	1
7	2	2	1	1	1
8	2	2	2	1	1
9	2	2	2	2	1
10	2	2	2	2	2

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 you need to interrupt treatment.

There is limited experience with overdose of MAVENCLAD. It is known that the more medicine you take, the lower the number of lymphocytes in your body may become, leading to lymphopenia (see section 4).

If you forget to take MAVENCLAD

If you forget to take a dose and remember the	If you forget to take a dose and do not remember until the
same day you were supposed to take it	next day
Take the missed dose that day.	Do not take the missed dose together with the next
	scheduled dose.
	Take the missed dose the next day and extend
	the number of days of that week's treatment.

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone gets them.

Some adverse effects may be serious or become serious

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

The most important adverse 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 developing an infection. A frequently observed infection with MAVENCLAD is herpes zoster.

Inform your doctor immediately if you experience symptoms of herpes zoster, such as a painful "band" of intense pain and a blistering skin rash, usually on one side of the upper body or face. Other symptoms may include headache, burning, tingling, numbness or itching of the skin in the affected area, general feeling of being unwell or fever in the early stages of the infection.

Herpes zoster will require treatment and treatment with MAVENCLAD may need to be interrupted until the infection resolves.

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

Inform your doctor immediately if you experience symptoms such as feeling sick (nausea), vomiting, stomach pain, tiredness (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 adverse effects

Common (may affect up to 1 in 10 people)

• hot flushes (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 of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of MAVENCLAD

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

Do not use this medicine after the expiry date stated on the carton and container after "EXP". The expiry date refers to the last day of the month indicated.

Store in the original packaging to protect it from moisture.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of MAVENCLAD

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

What MAVENCLAD looks like and contents of the pack

MAVENCLAD tablets are white, round, biconvex tablets, engraved with “C” on one side and “10” on the other. Each pack contains 1, 4, 5, 6, 7, or 8 tablets in a sealed blister pack within a cardboard tray, and housed in a child-resistant carton. Only certain pack sizes may be marketed.

Marketing Authorization Holder

Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The 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 the most recent revision of this leaflet:

Other sources of information

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 packaged in a resealable child-resistant carton and must be kept out of sight and reach of children. See below for step-by-step instructions on how to handle the packaging and how to take MAVENCLAD tablets. Make sure you know how many tablets are in the pack. Refer to the instructions in the leaflet.

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

1. Hold the box with the opening instructions facing upwards.

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

2. Press inwards simultaneously on the side latches with your index finger and thumb, and keep the latches pressed.

3. Pull the tray out until it stops. Caution: Do not remove the tray completely from the box.

1. Remove the package leaflet from the tray. Make sure you have read all of it, including this step-by-step guide, and keep 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 into your hand, according to the prescribed dose.

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

1. Wash your hands thoroughly with soap and water.

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. Do not store the tablets in a different container.