Dimethyl fumarate Neuraxpharm: detailed information

Package leaflet: Information for the patient

Dimetilfumarato Neuraxpharm 120 mg gastro-resistant hard capsules, 240 mg gastro-resistant hard capsules

dimethyl fumarate
Read 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 give it to others, 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, inform your doctor or pharmacist. See section 4.

Contents of this leaflet

What Dimetilfumarato Neuraxpharm is and what it is used for
What you need to know before taking Dimetilfumarato Neuraxpharm
How to take Dimetilfumarato Neuraxpharm
Possible side effects
How to store Dimetilfumarato Neuraxpharm
Contents of the pack and other information

1. What Dimetilfumarato Neuraxpharm is and what it is used for

What Dimetilfumarato Neuraxpharm is
Dimetilfumarato Neuraxpharm is a medicine that contains the active substance dimethyl fumarate.
What Dimetilfumarato Neuraxpharm is used for
Dimetilfumarato Neuraxpharm 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), that is, the brain and spinal cord. Relapsing-remitting multiple sclerosis is characterized by repeated attacks (relapses) of neurological symptoms. Symptoms vary from patient to patient but generally include difficulty walking, feelings of imbalance, and vision problems (e.g., blurred or double vision). These symptoms may completely disappear when a relapse resolves, although some problems may persist.
How Dimetilfumarato Neuraxpharm works
Dimetilfumarato Neuraxpharm 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 should know before taking Dimetilfumarato Neuraxpharm

Do not take Dimetilfumarato Neuraxpharm

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 PML has been confirmed.

Warnings and precautions
Dimetilfumarato Neuraxpharm may affect the number of white blood cells in your blood, your kidneys, and your liver. Before starting Dimetilfumarato Neuraxpharm, your doctor will perform a blood test to count your white blood cells and to 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.
Contact your doctor before taking Dimetilfumarato Neuraxpharm if you have:

a severe kidney disease
a severe liver disease
a disease of the stomach or intestines
a severe infection (such as pneumonia)

Cases of herpes zoster infection (shingles) may occur during treatment with dimethyl fumarate. In some cases, serious complications have occurred. Inform your doctor immediately if you suspect you have any symptoms of herpes zoster infection.
If you think your MS is worsening (for example, if you experience weakness or visual disturbances) or if you notice new symptoms, contact your doctor immediately, as these may 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 increased urination, increased thirst and drinking more than usual, muscle weakness, or bone fractures or 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 data are not available in children under 10 years of age.
Other medicines and Dimetilfumarato Neuraxpharm
Inform 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 for the treatment of 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 medicines purchased without a doctor's prescription), and medicines containing lithium;
taking Dimetilfumarato Neuraxpharm together with certain types of vaccines (live vaccines) may cause you to develop an infection and should therefore be avoided. Your doctor will inform you whether other types of vaccines (non-live vaccines) should be administered.

Dimetilfumarato Neuraxpharm and alcohol
Consumption of alcoholic beverages with high alcohol content (more than 30% alcohol by volume, e.g. spirits) exceeding a small amount (more than 50 ml) should be avoided within one hour of taking Dimetilfumarato Neuraxpharm, as alcohol may interact with this medicine. This may cause inflammation of the stomach (gastritis), particularly in people already prone to gastritis.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, ask your doctor or pharmacist for advice 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 Dimetilfumarato Neuraxpharm during pregnancy unless you have discussed with your doctor that this medicine is clearly necessary for you.
Breastfeeding
It is not known whether the active substance of Dimetilfumarato Neuraxpharm passes into breast milk. Your doctor will advise you whether you should stop breastfeeding or stop treatment with Dimetilfumarato Neuraxpharm. This involves weighing the benefits of breastfeeding for the child against the benefits of treatment for you.
Driving and using machines
Dimetilfumarato Neuraxpharm is not expected to affect your ability to drive or use machines.
Dimetilfumarato Neuraxpharm contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per capsule, i.e. essentially “sodium-free”.

3. How to take Dimethylfumarate Neuraxpharm

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 proceed to the regular dose.
Regular dose: 240 mg twice daily.
Dimethylfumarate Neuraxpharm 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 adverse effects.
Take Dimethylfumarate Neuraxpharm with food – this may help reduce some of the more common side effects (listed in section 4).
If you take more Dimethylfumarate Neuraxpharm than you should
If you have taken too many capsules, contact your doctor immediately. You may experience adverse effects similar to those described in section 4 below.
If you forget to take Dimethylfumarate Neuraxpharm
If you miss or forget 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 will elapse 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

Dimetilfumarato Neuraxpharm may lower 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 to 5 years of treatment, so your doctor must continue to monitor your white blood cell counts throughout the duration of treatment. Be vigilant in 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 think your MS is worsening or if you notice any new symptoms during treatment with dimethyl fumarate, it is very important to contact your doctor as soon as possible. Also, inform your partner or caregiver about your treatment, as symptoms may arise that you might not notice yourself.

→ If you experience any of these symptoms, call your doctor immediately

Serious allergic reactions

The frequency of serious allergic reactions cannot be determined from available data (not known).

Flushing (reddening 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 serious allergic reaction (anaphylaxis).

→ Stop taking Dimetilfumarato Neuraxpharm and call a doctor immediately

Other side effects

Very common (may affect more than 1 in 10 people):

redness of the face or body, feeling 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 above-mentioned side effects

The presence of substances called ketones, which are naturally produced by the body, is very commonly detected in urine tests during treatment with Dimetilfumarato Neuraxpharm.

Contact your doctor for advice on managing these side effects. Your doctor may reduce your dose. Do not reduce the dose unless your doctor tells you to do so.

Common (may affect up to 1 in 10 people):

inflammation of the intestinal lining (gastroenteritis)
feeling unwell (vomiting)
indigestion (dyspepsia)
inflammation of the stomach (gastritis)
gastrointestinal disorder
burning sensation
hot flush, feeling of warmth
itching
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 may mean you are less able to fight infections adequately. If you develop 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)
reduced platelet count in the blood

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

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

Not known (frequency cannot be determined from 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, followed by numbness, red or itchy spots with severe pain
runny nose (rhinorrhea)

Children (aged 13 years and older) and adolescents

The above-mentioned side effects 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 effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Dimethylfumarate Neuraxpharm

Keep this medicine out of the sight and reach of children.
Do not store above 30°C.
Do not use this medicine after the expiry date which is stated on the carton after “Exp”. The expiry
date refers to the last day of that month.
Do not dispose of any medicine via 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 Dimetilfumarato Neuraxpharm contains
The active substance is dimethyl fumarate.
Dimetilfumarato Neuraxpharm 120 mg: each capsule contains 120 mg of dimethyl fumarate.
Dimetilfumarato Neuraxpharm 240 mg: each capsule contains 240 mg of dimethyl fumarate.
The other components are:
Capsule contents: croscarmellose sodium, anhydrous colloidal silica, sodium stearyl fumarate,
methacrylic acid–methyl methacrylate copolymer (1:1), methacrylic acid–ethyl acrylate copolymer (1:1)
30% dispersion, talc, triethyl citrate, glyceryl monostearate 40-55
Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172), Brilliant Blue FCF (E133)
Printing ink on the capsule: shellac, black iron oxide (E172), propylene glycol (E1520),
ammonium hydroxide 28%

Description of the appearance of Dimetilfumarato Neuraxpharm and package contents
Dimetilfumarato Neuraxpharm 120 mg: hard gastro-resistant gelatin capsules, length: 19 mm,
with white body and light green cap, printed on the body “120 mg”, available in packs of 14 or 56 capsules and 14 x 1 capsules in perforated unit dose blisters.
Dimetilfumarato Neuraxpharm 240 mg: hard gastro-resistant gelatin capsules, length: 23 mm,
light green, printed on the body “240 mg”, available in packs of 14, 56, 168 and 196 capsules and 56 x 1 capsules in perforated unit dose blisters.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Neuraxpharm Pharmaceuticals, S.L.
Avda. Barcelona 69
08970 Sant Joan Despí - Barcelona
Spain
Tel: +34 93 475 96 00
E-mail: [email protected]

Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
Poland
Zakłady Farmaceutyczne POLPHARMA S.A.
Production Site in Nowa Dęba
ul. Metalowca 2, 39-460 Nowa Dęba
Poland
Neuraxpharm Pharmaceuticals, S.L.
Avda. Barcelona 69
08970 Sant Joan Despí
Barcelona - Spain
neuraxpharm Arzneimittel GmbH
Elisabeth-Selbert-Straße 23
40764 Langenfeld - Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Neuraxpharm Belgium Neuraxpharm Pharmaceuticals, S.L.
Tél/Tel: +32 (0)2 732 56 95 Tel:+34 93 475 96 00

България Luxembourg/Luxemburg
Neuraxpharm Pharmaceuticals, S.L. Neuraxpharm France
Teл.: +34 93 475 96 00 Tél/Tel: +32 474 62 24 24

Česká republika Magyarország
Neuraxpharm Bohemia s.r.o. Neuraxpharm Hungary Kft.
Tel: +420 739 232 258 Tel.: +3630 464 6834

Danmark Malta
Neuraxpharm Sweden AB Neuraxpharm Pharmaceuticals, S.L.
Tlf: +46 (0)8 30 91 41 Tel.: +34 93 475 96 00
(Sverige)

Deutschland Nederland
neuraxpharm Arzneimittel GmbH Neuraxpharm Netherlands B.V.
Tel: +49 2173 1060 0 Tel.: +31 70 208 5211

Eesti Norge
Neuraxpharm Pharmaceuticals, S.L. Neuraxpharm Sweden AB
Tel: +34 93 475 96 00 Tlf: +46 (0)8 30 91 41
(Sverige)

Ελλάδα Österreich
Brain Therapeutics ΙΚΕ Neuraxpharm Austria GmbH
Τηλ: +302109931458 Tel.: +43 (0)1 208 07 40

España Polska
Neuraxpharm Spain, S.L.U. Neuraxpharm Polska Sp. z.o.o.
Tel: +34 93 475 96 00 Tel.: +48 783 423 453

France Portugal
Neuraxpharm France Neuraxpharm Portugal, Unipessoal Lda
Tél: +33 1.53.62.42.90 Tel: +351 910 259 536

Hrvatska România
Neuraxpharm Pharmaceuticals, S.L. Neuraxpharm Pharmaceuticals, S.L.
T +34 93 475 96 00 Tel: +34 93 475 96 00

Ireland Slovenija
Neuraxpharm Ireland Ltd. Neuraxpharm Pharmaceuticals, S.L.
Tel: +353 (0)1 428 7777 T +34 93 475 96 00

Ísland Slovenská republika
Neuraxpharm Sweden AB Neuraxpharm Slovakia a.s.
Sími: +46 (0)8 30 91 41 Tel: +421 255 425 562
(Svíþjóð)

Italia Suomi/Finland
Neuraxpharm Italy S.p.A. Neuraxpharm Sweden AB
Tel: +39 0736 980619 Puh/Tel: +46 (0)8 30 91 41
(Ruotsi/Sverige)

Κύπρος Sverige
Brain Therapeutics ΙΚΕ Neuraxpharm Sweden AB
Τηλ: +302109931458 Tel: +46 (0)8 30 91 41

Latvija
Neuraxpharm Pharmaceuticals, S.L.
Tel: +34 93 475 96 00

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.