DIMETHYL FUMARATE ACCORD 120 mg HARD GASTRO-RESISTANT CAPSULES

Introduction

Package Leaflet: Information for the Patient

Dimethyl Fumarate Accord 120 mg Gastro-Resistant Hard Capsules

Dimethyl Fumarate Accord 240 mg Gastro-Resistant Hard Capsules

dimethyl fumarate

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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What Dimethyl Fumarate Accord is and what it is used for

What Dimethyl Fumarate Accord is

Dimethyl Fumarate Accord is a medicine that contains dimethyl fumarateas the active substance.

What Dimethyl Fumarate Accord is used for

Dimethyl Fumarate Accord is used to treat multiple sclerosis (MS) in patients from 13 years of age and older with relapsing-remitting MS.

MS is a long-term disease that affects the central nervous system (CNS), which includes the brain and spinal cord. Relapsing-remitting MS is characterized by repeated attacks (relapses) of neurological symptoms. The symptoms vary from person to person but often include: difficulty walking, balance problems, and vision problems (e.g., blurred or double vision). These symptoms can disappear completely when the relapse is over, but some problems may remain.

How Dimethyl Fumarate Accord works

Dimethyl Fumarate Accord seems to work by preventing the body's defense system from damaging the brain and spinal cord. This may also help to delay future disability in MS.

2. What you need to know before you take Dimethyl Fumarate Accord

Do not take Dimethyl Fumarate Accord

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

Warnings and precautions

Dimethyl Fumarate Accord may affect your white blood cell count, kidneys, and liver. Before starting Dimethyl Fumarate Accord, your doctor will do a blood test to check your white blood cell count and to make sure your kidneys and liver are working properly. Your doctor will do regular blood tests during treatment. If you have a low white blood cell count during treatment, your doctor may consider additional tests or stop your treatment.

Tell your doctorbefore starting Dimethyl Fumarate Accord if you have:

• severe kidney disease
• severe liver disease
• a stomach or intestine disease
• a severe infection(e.g., pneumonia)

Herpes zoster (shingles) may occur during treatment with Dimethyl Fumarate Accord. In some cases, serious complications have occurred. You must tell your doctor immediatelyif you suspect you have any symptoms of shingles.

If you think your MS is getting worse (e.g., weakness or changes in vision) or you notice any new symptoms, talk to your doctor directly, as they could be symptoms of a rare brain infection called PML. PML is a serious disease that can cause death or severe disability.

A rare but serious kidney disorder called Fanconi syndrome has been reported with a medicine containing dimethyl fumarate in combination with other fumaric acid esters, used to treat psoriasis (a skin disease). If you notice that you are urinating more, are thirstier, and drink more than usual, your muscles seem weaker, you break a bone, or simply have aches and pains, tell your doctor as soon as possible so that this can be investigated further.

Children and adolescents

Do not give this medicine to children under 10 years of age because there is no data available for this age group.

Other medicines and Dimethyl Fumarate Accord

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, in particular:

• medicines that contain fumaric acid esters(fumarates) used to treat psoriasis
• medicines that affect the immune system, including chemotherapy, immunosuppressants, or other medicines used to treat MS
• medicines that affect the kidneys, including some antibiotics(used to treat infections), diuretics(tablets that increase urine production), certain types of painkillers(such as ibuprofen or similar anti-inflammatory medicines, and over-the-counter medicines), and medicines that contain lithium
• The use of Dimethyl Fumarate Accord and the administration of certain types of vaccines(live vaccines) could cause you to get an infection, and therefore should be avoided. Your doctor will tell you if you should receive other types of vaccines (inactivated vaccines).

Taking Dimethyl Fumarate Accord with alcohol

After taking Dimethyl Fumarate Accord, you should avoid consuming more than a small amount (more than 50 ml) of strong alcoholic beverages (with an alcohol content of more than 30%, such as spirits) for the first hour, because alcohol may interact with this medicine. This may cause stomach inflammation (gastritis), especially in people who are prone to this condition.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

There is limited information on the effects of this medicine when used during pregnancy. Do not take Dimethyl Fumarate Accord during pregnancy unless you have discussed it with your doctor and this medicine is clearly necessary.

Breastfeeding

It is not known whether the active substance of Dimethyl Fumarate Accord passes into breast milk. Your doctor will advise you whether you should stop breastfeeding, or stop taking Dimethyl Fumarate Accord. This decision will involve weighing the benefits of breastfeeding for your child and the benefits of treatment for you.

Driving and using machines

Dimethyl Fumarate Accord is not expected to affect your ability to drive or use machines.

Dimethyl Fumarate Accord contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per capsule, which is essentially “sodium-free”.

3. How to take Dimethyl Fumarate Accord

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are unsure, ask your doctor again.

Starting dose:

120 mg twice a day.

Take this starting dose for the first 7 days, then take the usual dose.

Usual dose:

240 mg twice a day.

Dimethyl Fumarate Accord is taken by mouth.

The capsules should be swallowed whole, with some water. Do not split, crush, dissolve, or chew the capsules, as this may increase some side effects.

Take Dimethyl Fumarate Accord with food– this helps to reduce some of the very common side effects (listed in section 4).

If you take more Dimethyl Fumarate Accord than you should

If you take too many capsules, tell your doctor immediately. You may experience side effects similar to those described below in section 4.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, stating the medicine and the amount taken.

If you forget to take Dimethyl Fumarate Accord

Do not take a double doseto make up for forgotten doses.

You may take the forgotten dose if at least 4 hours have passed between doses. Otherwise, wait until the next dose is due.

If you have any further questions on the use of this medicine, ask 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 lower your lymphocyte count (a type of white blood cell). A low white blood cell count can increase the risk of infection, including a rare brain infection called progressive multifocal leukoencephalopathy (PML). PML can cause death or severe disability. PML has occurred after 1 to 5 years of treatment, so your doctor will need to monitor your white blood cells during treatment, and you should be alert to any possible symptoms of PML, as described below. The risk of PML may be higher if you have previously taken a medicine that has weakened your immune system.

The symptoms of PML can be similar to those of an MS relapse. The symptoms can include new or worsening weakness on one side of the body; clumsiness; changes in vision, thinking, or memory; or confusion or changes in personality, or difficulty speaking and communicating that may persist for more than several days. Therefore, it is very important that you talk to your doctor as soon as possible if you think your MS is getting worse or if you notice any new symptoms while taking Dimethyl Fumarate Accord.

In addition, tell your partner or caregivers about your treatment. It is possible that symptoms may arise that you are not aware of yourself.

→ Call your doctor immediately if you have any of these symptoms

Severe allergic reactions

The frequency of severe allergic reactions cannot be estimated from the available data (frequency not known).

Flushing of the face or body (flushing) is a very common side effect. However, if the flushing is accompanied by a red rash or hives andyou have any of the following symptoms:

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

this could be a severe allergic reaction (anaphylaxis).

→ Stop taking Dimethyl Fumarate Accord and call your doctor immediately

Other side effects

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

• flushing of the face or body
• feeling of heat, warmth, or burning sensation (flushing)
• loose stools (diarrhea)
• nausea or vomiting
• stomach pain or cramps

→ Taking the medicine with foodmay help reduce the above side effects

While taking Dimethyl Fumarate Accord, it is common for urine tests to show the presence of ketones, substances that are naturally produced by the body.

Tell your doctorabout these side effects. Your doctor may reduce your dose. Do not reduce the dose unless your doctor tells you to.

Frequent(may affect up to 1 in 10 people)

• inflammation of the intestinal mucosa (gastroenteritis)
• vomiting
• indigestion (dyspepsia)
• inflammation of the stomach mucosa (gastritis)
• gastrointestinal disorders
• burning sensation
• hot flashes, feeling of warmth
• itching of the skin (pruritus)
• rash (exanthema)
• red patches or redness of the skin accompanied by itching (erythema)
• hair loss (alopecia)

Side effects that may appear in blood or urine tests

• low white blood cell count (lymphopenia, leucopenia) in blood. A decrease in white blood cells can make the body less able to fight infections. If you have a severe infection (such as pneumonia), tell your doctor immediately
• proteins (albumin) in urine
• increased liver enzymes (ALT, AST) in blood

Uncommon(may affect up to 1 in 100 people)

• allergic reactions (hypersensitivity)
• reduction of blood platelets

Rare(may affect up to 1 in 1000 people)

• inflammation of the liver and increased liver enzymes (ALT or AST simultaneously with bilirubin)

Frequency not known(cannot be estimated from the available data)

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

Children (13 years of age and older) and adolescents

The side effects described above also apply to children and adolescents.

Some side effects were reported more frequently in children and adolescents than in adults, e.g., headache, stomach pain or cramps, vomiting, sore throat, cough, and painful menstruation.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Dimethyl Fumarate Accord

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

Do not use this medicine after the expiry datestated on the carton and on each blister after “EXP”. The expiry date is the last day of the month stated.

This medicine does not require any special storage conditions.

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

6. Packaging Contents and Additional Information

Composition of Dimethyl Fumarate Accord

• The active ingredientis dimethyl fumarate.

Dimethyl Fumarate Accord 120 mg: each capsule contains 120 mg of dimethyl fumarate.

Dimethyl Fumarate Accord 240 mg: each capsule contains 240 mg of dimethyl fumarate.

• Othercomponents are:

Capsule content (enteric-coated mini-tablets): silicified microcrystalline cellulose, talc, sodium croscarmellose, anhydrous colloidal silica, magnesium stearate, methacrylic acid-methyl methacrylate copolymer (1:1), triethyl citrate, methacrylic acid-ethyl acrylate copolymer (1:1), 30% dispersion,

Coating: gelatin, titanium dioxide (E171), brilliant blue FCF (E133), black iron oxide (E172), and yellow iron oxide (E172).

Capsule printing (black ink): shellac (E904), black iron oxide (E172), potassium hydroxide (E525).

Appearance of the Product and Packaging Contents

Dimethyl Fumarate Accord 120 mg hard gastro-resistant capsules are size "0" (approximately 21.3 x 7.5 mm) hard gelatin capsules, with a green cap and white body, printed with "HR1" in black ink on the capsule body, and containing enteric-coated mini-tablets, round, biconvex, white, smooth on both sides.

Dimethyl Fumarate Accord 240 mg hard gastro-resistant capsules are size "0" (approximately 21.3 x 7.5 mm) hard gelatin capsules, with a green cap and body, printed with "HR2" in black ink on the capsule body, and containing enteric-coated mini-tablets, round, biconvex, white, smooth on both sides.

Capsules of 120 mg:

14 capsules in boxes with PVC/PE/PVDC-Alu blisters.

14x1 capsules in PVC/PE/PVDC-Alu unit-dose perforated blisters.

Capsules of 240 mg:

56 or 168 capsules in boxes with PVC/PE/PVDC-Alu blisters.

56x1 or 168x1 capsules in PVC/PE/PVDC-Alu unit-dose perforated blisters.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n,

Edifici Est, 6a Planta,

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, Netherlands

You can request more information about this medicinal product by contacting the local representative of the marketing authorization 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.

Τηλ: +30 210 74 88 821

Date of the Last Revision of this Leaflet:

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