Dimethyl fumarate Accord

Patient Information Leaflet

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

dimethyl fumarate

Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may 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 Dimetilfumarato Accord is and what it is used for
2. What you need to know before taking Dimetilfumarato Accord
3. How to take Dimetilfumarato Accord
4. Possible side effects
5. How to store Dimetilfumarato Accord
6. Contents of the pack and other information

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

What Dimetilfumarato Accord is
Dimetilfumarato Accord is a medicine that contains the active substance dimethyl fumarate.
What Dimetilfumarato Accord is used for
Dimetilfumarato Accord 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, namely 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 walking difficulties, 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 Accord works
Dimetilfumarato Accord 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 Accord

Do not take Dimetilfumarato Accord

• 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 Accord may affect the number of white blood cells in your blood, your kidneys, and your liver. Before starting treatment with Dimetilfumarato Accord, your doctor will perform a blood test to check your white blood cell count and to ensure that your kidneys and liver are functioning properly. Your doctor will carry out regular tests during treatment. If your white blood cell count decreases during treatment, your doctor may consider further investigations or discontinuation of therapy.
Contact your doctor before taking Dimetilfumarato Accord if you have:

• severe disease of the kidneys
• severe disease of the liver
• a disease of the stomach or intestines
• a serious infection (such as pneumonia)

Cases of herpes zoster infection (shingles) may occur during treatment with Dimetilfumarato Accord. In some cases, serious complications have occurred. Inform your doctor immediately if you suspect you may have symptoms of herpes zoster infection.
If you think your multiple sclerosis 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 (Fanconi syndrome) has been observed. If you notice increased urination, increased thirst and fluid intake, muscle weakness, or experience fractures or even pain, contact your doctor as soon as possible so that thorough investigations can be initiated.
Children and adolescents
Do not administer this medicine to children under 10 years of age, as there are no data available for this age group.
Other medicines and Dimetilfumarato Accord
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 multiple sclerosis
• 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, including over-the-counter medicines), and medicines containing lithium
• taking Dimetilfumarato Accord together with certain types of vaccines ( live vaccines ) could cause an infection and should therefore be avoided. Your doctor will advise you whether other types of vaccines ( non-live vaccines ) should be administered.

Dimetilfumarato Accord and alcohol
Consumption of alcoholic beverages with high alcohol content (more than 30% alcohol by volume, e.g. spirits) in amounts exceeding a small quantity (more than 50 mL) should be avoided within one hour of taking Dimetilfumarato Accord, as alcohol may interact with this medicine. This could cause inflammation of the stomach (gastritis), particularly in individuals 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 Dimetilfumarato Accord 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 substance of Dimetilfumarato Accord passes into breast milk. Your doctor will help you decide whether you should stop breastfeeding or stop treatment with Dimetilfumarato Accord. This decision will be based on evaluating the benefit of breastfeeding for the child against the benefit of therapy for you.
Driving and using machines
Dimetilfumarato Accord is not expected to affect the ability to drive or use machinery.
Dimetilfumarato contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially 'sodium-free'.

3. How to take Dimetilfumarato Accord

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
Dimetilfumarato Accord is for oral use.
Swallow each capsule whole with some water. Do not split, crush, dissolve, suck or chew the capsule, as this could increase certain side effects.
Take Dimetilfumarato Accord with food – this may help reduce some of the more common side effects (listed in section 4).
If you take more Dimetilfumarato Accord 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 Dimetilfumarato Accord
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 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

Dimethyl fumarate Accord may reduce levels of lymphocytes (a type of white blood cell). Persistently low levels of white blood cells can 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. Pay close attention to 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 with speech and communication lasting longer than a few days. Therefore, if you feel that your multiple sclerosis is worsening or if you notice any new symptoms during treatment with Dimethyl fumarate Accord, it is very important to contact your doctor as soon as possible. Also, inform your partner or caregiver about your treatment. Symptoms may arise 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 determined from the available data (not known).

Flushing 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 Dimethyl fumarate Accord and call a doctor immediately

Other side effects

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

• flushing of the face or body, feeling of warmth, intense heat, burning, or itching
• 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 Dimethyl fumarate Accord.

Talk to 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 do so.

Common (may affect up to 1 in 10 people)

• inflammation of the intestinal lining (gastroenteritis)
• 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 appear 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 your body is unable 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 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 may 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 Dimethylfumarate Accord

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 carton after
Exp./EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines 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 Accord contains
The active substance is dimethyl fumarate.
Dimetilfumarato Accord 120 mg: each capsule contains 120 mg of dimethyl fumarate.
Dimetilfumarato Accord 240 mg: each capsule contains 240 mg of dimethyl fumarate.
The other components are:
Capsule content (mini-tablets with enteric coating): microcrystalline cellulose, silicified, talc, sodium croscarmellose, anhydrous colloidal silicon dioxide, magnesium stearate, methacrylic acid–methyl methacrylate copolymer (1:1), triethyl citrate, methacrylic acid–ethyl acrylate copolymer (1:1) dispersion 30%.
Capsule shell: gelatin, titanium dioxide (E171), brilliant blue FCF (E133), iron oxide black (E172), iron oxide yellow (E172).
Printing on the capsule (black ink): shellac (E904), iron oxide black (E172), potassium hydroxide (E525).

Description of the appearance of Dimetilfumarato Accord and contents of the pack
Dimetilfumarato Accord 120 mg gastro-resistant hard capsules are hard gelatin capsules of size “0” (approximately 21.3 x 7.5 mm) with a green cap and a white body, printed with “HR1” in black ink on the body of the capsule, containing enteric-coated mini-tablets, white to off-white, round, biconvex, smooth on both sides.
Dimetilfumarato Accord 240 mg gastro-resistant hard capsules are hard gelatin capsules of size “0” (approximately 21.3 x 7.5 mm) with a green cap and green body, printed with “HR2” in black ink on the body of the capsule, containing enteric-coated mini-tablets, white to off-white, round, biconvex, smooth on both sides.

120 mg capsules:
14 capsules in blister packs made of PVC/PE/PVDC-Alu.
14x1 capsules in unit dose perforated blisters made of PVC/PE/PVDC-Alu.

240 mg capsules:
56 or 168 capsules in blister packs made of PVC/PE/PVDC-Alu.
56x1 or 168x1 capsules in unit dose perforated blisters made of PVC/PE/PVDC-Alu.

It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est, 6th Floor,
08039 Barcelona,
Spain

Manufacturer
Accord Healthcare Polska Sp. z.o.o.
ul. Lutomierska 50,
95-200, Pabianice, Poland
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park,
Paola PLA 3000, Malta
Accord Healthcare B.V.
Winthontlaan 200,
3526 KV Utrecht,
The Netherlands
Accord Healthcare single member S.A.
64th Km National Road Athens
Lamia, Schimatari, 32009,
Greece

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
AT / BE / BG / CY / CZ / DE / DK / EE / ES / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT /
NL / NO / PL / PT / RO / SE / SI / SK
Accord Healthcare S.L.U.
Tel: +34 93 301 00 64
EL
Win Medica Α.Ε.
Tel: +30 210 74 88 821

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