Tecfidera

Patient Information Leaflet

Tecfidera 120 mg gastro-resistant hard capsules, 240 mg gastro-resistant hard capsules

dimethyl fumarate
Please read all of 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Tecfidera is and what it is used for

What Tecfidera is
Tecfidera is a medicine that contains the active substance dimethyl fumarate.
What Tecfidera is used for
Tecfidera is used to treat relapsing-remitting multiple sclerosis (MS) in patients aged 13 years and older.
Multiple sclerosis is a chronic disease affecting the central nervous system (CNS), i.e. the brain and spinal cord. Relapsing-remitting multiple sclerosis is characterized by repeated attacks (relapses) of symptoms affecting the nervous system. Symptoms vary from patient to patient but generally include difficulty walking, a sense of imbalance, and vision problems (e.g. blurred or double vision). These symptoms may completely disappear when a relapse resolves, but some problems may persist.
How Tecfidera works
Tecfidera appears to work by preventing the body's immune system from damaging the brain and spinal cord. This may also help delay future worsening of the disease.

2. What you need to know before taking Tecfidera

Do not take Tecfidera

• if you are allergic to dimethyl fumarate or to any of the other ingredients of this medicine (listed in section 6).
• if you are suspected to have a rare brain infection called progressive multifocal leukoencephalopathy (PML) or if the diagnosis of PML has been confirmed.

Warnings and precautions
Tecfidera may affect the number of white blood cells in your blood, your kidneys, and your liver. Before starting Tecfidera, your doctor will perform a blood test to count your white blood cells and check that your kidneys and liver are functioning properly. Your doctor will carry out these tests periodically during treatment. If your white blood cell count decreases during treatment, your doctor may consider further testing or discontinuation of therapy.
Talk to your doctor before taking Tecfidera if you have:

• a serious kidney disease
• a serious liver disease
• a stomach or intestinal disease
• a serious infection (such as pneumonia)

Cases of herpes zoster infection (shingles) may occur during treatment with Tecfidera. In some cases, severe complications have occurred. Contact your doctor immediately if you suspect you may have any symptoms of herpes zoster infection.
If you think your multiple sclerosis (MS) is worsening (for example, if you experience weakness or changes in vision) or if you notice new symptoms, contact your doctor immediately, as these could be symptoms of a rare brain infection called PML. PML is a serious condition that may lead to severe disability or death.
With a medicine containing dimethyl fumarate in combination with other fumaric acid esters, used for the treatment of psoriasis (a skin disease), a rare but serious kidney disorder called Fanconi syndrome has been observed. If you notice that you are urinating more than usual, feel more thirsty and drink more than normal, experience increased muscle weakness, or have bone fractures or just bone pain, contact your doctor as soon as possible so that appropriate investigations can be carried out.
Children and adolescents
Do not give this medicine to children under 10 years of age, as there is no available data in this age group.
Other medicines and Tecfidera
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, especially:

• medicines containing fumaric acid esters (fumarates) used for the treatment of psoriasis
• medicines that affect the immune system, including chemotherapeutic agents, immunosuppressants, or other medicines used to treat MS
• medicines that affect the kidneys, including certain antibiotics (used to treat infections), diuretics, some types of painkillers (such as ibuprofen and other similar anti-inflammatory medicines and over-the-counter medicines), and medicines containing lithium
• taking Tecfidera together with certain types of vaccines ( live vaccines ) could cause you to develop an infection and should therefore be avoided. Your doctor will advise you whether other types of vaccines (non-live vaccines) should be administered.

Tecfidera and alcohol
Consumption of alcoholic beverages with high alcohol content (more than 30% alcohol by volume, e.g., spirits) in amounts greater than a small quantity (more than 50 mL) should be avoided within one hour of taking Tecfidera, as alcohol may interact with this medicine. This could cause stomach inflammation ( gastritis ), particularly in people who are already prone to gastritis.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
There is limited information on the effects of this medicine on the unborn child when used during pregnancy. Do not use Tecfidera during pregnancy unless you have discussed it with your doctor and the medicine is clearly necessary for you.
Breastfeeding
It is not known whether the active ingredient of Tecfidera passes into breast milk. Your doctor will advise you whether you should stop breastfeeding or stop Tecfidera treatment. This decision will involve weighing the benefit of breastfeeding for your child against the benefit of treatment for you.
Driving and using machines
Tecfidera is not expected to affect your ability to drive or use machines.
Tecfidera contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e., essentially ‘sodium-free’.

3. How to take Tecfidera

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor.
Starting dose: 120 mg twice daily.
Take this starting dose for the first 7 days, then switch to the maintenance dose.
Maintenance dose: 240 mg twice daily.
Tecfidera is for oral use.
Swallow each capsule whole with some water. Do not split, crush, dissolve, suck or chew the capsule, as this may increase certain side effects.
Take Tecfidera with food – this may help reduce some of the more common side effects (listed in section 4).
If you take more Tecfidera than you should
If you have taken too many capsules, contact your doctor immediately. You may experience side effects similar to those described in section 4 below.
If you forget to take Tecfidera
If you forget or miss a dose, do not take a double dose to make up for the missed dose.
You may take the missed dose if at least 4 hours remain between doses. Otherwise, wait until your next scheduled dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Tecfidera may reduce levels of lymphocytes (a type of white blood cell). Persistently low levels of white blood cells may increase the risk of infections, including the risk of a rare brain infection called progressive multifocal leukoencephalopathy (PML). PML can cause severe disability or death. PML has occurred after 1–5 years of treatment, so your doctor must continue to monitor your white blood cells throughout the duration of treatment. Be vigilant in carefully observing any potential symptoms of PML, as described below. The risk of PML may be higher if you have previously taken medicines that impair immune system function.
Symptoms of PML may resemble those of a multiple sclerosis relapse. Symptoms may include the onset or worsening of weakness on one side of the body; clumsiness; changes in vision, thinking, or memory; confusion or personality changes; or difficulty speaking and communicating lasting longer than a few days.
Therefore, if you feel that your MS is worsening or if you notice any new symptoms during treatment with Tecfidera, it is very important to contact your doctor as soon as possible. Also, inform your partner or caregiver about your treatment. Symptoms may occur that you might not notice yourself.
If you experience any of these symptoms, call your doctor immediately.
Severe allergic reactions
The frequency of severe allergic reactions cannot be estimated from the available data (not known).
Flushing (redness of the face or body) is a very common side effect. However, if flushing is accompanied by a red rash or hives and you have any of the following symptoms:

• swelling of the face, lips, mouth, or tongue (angioedema)
• shortness of breath, difficulty breathing, or breathlessness (dyspnea, hypoxia)
• dizziness or loss of consciousness (hypotension)

this may indicate a severe allergic reaction (anaphylaxis).
Stop taking Tecfidera and call a doctor immediately.
Other side effects
Very common (may affect more than 1 in 10 people)

• redness of the face or body, sensation of warmth, intense heat, burning, or itching (flushing)
• loose stools (diarrhea)
• feeling of imminent vomiting (nausea)
• stomach ache or stomach cramps

Taking the medicine with food may help reduce the side effects listed above.
The presence of substances called ketones, which are naturally produced by the body, is very commonly detected in urine tests during Tecfidera treatment.
Contact your doctor for advice on how to manage these side effects. Your doctor may reduce your dose. Do not reduce the dose unless your doctor tells you to.
Common (may affect up to 1 in 10 people)

• inflammation of the intestinal lining (gastroenteritis)
• feeling of illness (vomiting)
• indigestion (dyspepsia)
• inflammation of the stomach (gastritis)
• gastrointestinal disorder
• burning sensation
• hot flush, sensation of warmth
• itching
• skin rash
• pink or red spots on the skin (erythema)
• hair loss (alopecia)

Side effects that may be detected in blood or urine tests

• low levels of white blood cells (lymphopenia, leukopenia) in the blood. A reduced number of white blood cells in the blood may indicate that you are unable to fight infections adequately. If you have a serious infection (such as pneumonia), contact your doctor immediately
• protein (albumin) in the urine
• increased levels of liver enzymes (alanine aminotransferase, ALT and aspartate aminotransferase, AST) in the blood

Uncommon (may affect up to 1 in 100 people)

• allergic reactions (hypersensitivity)
• reduction in blood platelets

Rare (may affect up to 1 in 1,000 people)

• inflammation of the liver and increased levels of liver enzymes (ALT or AST in combination with bilirubin)

Not known (frequency cannot be estimated from the available data)

• herpes zoster infection (shingles) with symptoms such as blisters, burning, itching, or skin pain, usually on one side of the torso or face, and other symptoms such as fever and weakness in the early stages of infection, followed by numbness, red or itchy spots with severe pain
• runny nose (rhinorrhea)

Children (aged 13 years and older) and adolescents
The side effects listed above also apply to children and adolescents.
Some side effects have been reported more frequently in children and adolescents than in adults, such as headache, stomach ache or stomach cramps, vomiting, sore throat, cough, and painful menstruation.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, 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 provide more information on the safety of this medicine.

5. How to store Tecfidera

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 blister and the outer carton after
'Exp.'.
The expiry date refers to the last day of that month.
Do not store above 30°C.
Keep blisters in the outer packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Tecfidera contains
The active substance is dimethyl fumarate.
Tecfidera 120 mg: each capsule contains 120 mg of dimethyl fumarate.
Tecfidera 240 mg: each capsule contains 240 mg of dimethyl fumarate.
The other components are microcrystalline cellulose, sodium croscarmellose, talc, anhydrous colloidal silicon dioxide, magnesium stearate, triethyl citrate, methacrylic acid–methyl methacrylate copolymer (1:1), methacrylic acid–ethyl acrylate copolymer (1:1) dispersion 30%, simethicone, sodium lauryl sulfate, polysorbate 80, gelatin, titanium dioxide (E171), Brilliant Blue FCF (E133), iron oxide yellow (E172), shellac, potassium hydroxide and iron oxide black (E172).

Description of the appearance of Tecfidera and pack sizes
Tecfidera 120 mg gastro-resistant hard capsules are green and white, printed with 'BG-12 120 mg', and are available in packs containing 14 capsules.
Tecfidera 240 mg gastro-resistant hard capsules are green, printed with 'BG-12 240 mg', and are available in packs containing 56 or 168 capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Biogen Netherlands B.V.
Prins Mauritslaan 13
1171 LP Badhoevedorp
The Netherlands

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Biogen Belgium NV/SA Biogen Lithuania UAB
Tél/Tel: +32 2 2191218 Tel: +370 5 259 6176

България Luxembourg/Luxemburg
ЕВОФАРМА ЕООД Biogen Belgium NV/SA
Teл: +359 2 962 12 00 Tél/Tel: +32 2 2191218

Česká republika Magyarország
Biogen (Czech Republic) s.r.o. Biogen Hungary Kft.
Tel: +420 255 706 200 Tel: +36 1 899 9883

Danmark Malta
Biogen (Denmark) A/S Pharma. MT Ltd.
Tlf.: +45 77 41 57 57 Tel: +356 21337008

Deutschland Nederland
Biogen GmbH Biogen Netherlands B.V.
Tel: +49 (0) 89 99 6170 Tel: +31 20 542 2000

Eesti Norge
Biogen Estonia OÜ Biogen Norway AS
Tel: +372 618 9551 Tlf: +47 23 40 01 00

Ελλάδα Österreich
Genesis Pharma SA Biogen Austria GmbH
Τηλ: +30 210 8771500 Tel: +43 1 484 46 13

España Polska
Biogen Spain, S.L. Biogen Poland Sp. z o.o.
Tel: +34 91 310 7110 Tel: +48 22 351 51 00

France Portugal
Biogen France SAS Biogen Portugal Sociedade Farmacêutica Unipessoal, Lda.
Tél: +33 (0)1 41 37 95 95 Tel: +351 21 318 8450

Hrvatska România
Biogen Pharma d.o.o. Johnson & Johnson Romania S.R.L.
Tel: +385 (0) 1 775 73 22 Tel: +40 21 207 18 00

Ireland Slovenija
Biogen Idec (Ireland) Ltd. Biogen Pharma d.o.o.
Tel: +353 (0)1 463 7799 Tel: +386 1 511 02 90

Ísland Slovenská republika
Icepharma hf Biogen Slovakia s.r.o.
Sími: +354 540 8000 Tel: +421 2 323 340 08

Italia Suomi/Finland
Biogen Italia s.r.l. Biogen Finland Oy
Tel: +39 02 5849901 Puh/Tel: +358 207 401 200

Κύπρος Sverige
Genesis Pharma Cyprus Ltd Biogen Sweden AB
Τηλ: +3572 2 765715 Tel: +46 8 594 113 60

Latvija
Biogen Latvia SIA
Tel: +371 68 688 158

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