Dimethyl fumarate Accord 120 mg gastro-resistant hard capsules EFG

Package leaflet: Information for the user

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 the entire 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, 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, talk to your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Fumarate de dimetilo Accord is and what it is used for

What Fumarate de dimetilo Accord is

Fumarate de dimetilo Accord is a medicine that contains dimethyl fumarate as the active substance.

What Fumarate de dimetilo Accord is used for

Fumarate de dimetilo Accord is used to treat relapsing-remitting multiple sclerosis (MS) in patients aged 13 years and older.

MS is a long-term disease affecting the central nervous system (CNS), which includes the brain and spinal cord. Relapsing-remitting MS is characterized by repeated attacks (relapses) of neurological symptoms. Symptoms vary from patient to patient but usually include: difficulty walking, balance disturbances, and visual problems (e.g., blurred or double vision). These symptoms may completely disappear when a relapse ends, although some problems may persist.

How Fumarate de dimetilo Accord works

Fumarate de dimetilo 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 your MS.

2. What you need to know before taking Fumarato de dimetilo Accord

Do not take Fumarato de dimetilo Accord

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

Warnings and precautions

Fumarato de dimetilo Accord may affect your white blood cell count, kidneys, and liver. Before starting Fumarato de dimetilo Accord, your doctor will perform a blood test to determine your white blood cell count and to check that your kidneys and liver are functioning properly. Your doctor will carry out periodic blood tests during treatment. If you experience a decrease in white blood cells during treatment, your doctor may consider additional testing or interrupt your treatment.

Consult your doctor before starting Fumarato de dimetilo Accord if you have:

• severe renal disease
• severe hepatic disease
• a stomach or intestinal disorder
• a serious infection (e.g., pneumonia)

Herpes zoster (shingles) may occur during treatment with Fumarato de dimetilo Accord. In some cases, serious complications have occurred. You must inform your doctor immediately if you suspect you have any symptoms of shingles.

If you think your MS is worsening (e.g., weakness or visual changes) or you notice any new symptoms, speak directly with your doctor, as these could be symptoms of a rare brain infection called PML. PML is a serious condition that can result in 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 condition). If you notice that you are urinating more frequently, feel unusually thirsty and drink more than normal, your muscles seem weaker, you experience a bone fracture, or simply have aches and pains, inform your doctor as soon as possible so this can be further investigated.

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 Fumarato de dimetilo Accord

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

• medicines containing fumaric acid esters (fumarates) used to treat psoriasis
• medicines that affect the body's immune system, including chemotherapy, immunosuppressants, or other medicines used to treat MS
• medicines that affect the kidneys, including certain antibiotics (used to treat infections), "diuretics" (tablets that increase urine output), certain types of painkillers (such as ibuprofen or other similar anti-inflammatory drugs), over-the-counter medications, and medicines containing lithium
• The use of Fumarato de dimetilo Accord together with certain types of vaccines (attenuated vaccines) could cause you to develop an infection and should therefore be avoided. Your doctor will advise you whether other types of vaccines (inactivated vaccines) should be administered.

Taking Fumarato de dimetilo Accord with alcohol

For one hour after taking Fumarato de dimetilo Accord, you should avoid consuming more than a small amount (more than 50 ml) of strong alcoholic drinks (with an alcohol content of more than 30% by volume, such as spirits), as alcohol may interact with this medicine. This may cause stomach inflammation (gastritis), especially in individuals prone to this condition.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

Information on the effects of this medicine on the fetus when used during pregnancy is limited. Do not use Fumarato de dimetilo Accord during pregnancy unless you have discussed it with your doctor and this medicine is clearly necessary.

Breastfeeding

It is unknown whether the active substance of Fumarato de dimetilo Accord passes into breast milk. Your doctor will advise you whether you should stop breastfeeding or stop taking Fumarato de dimetilo Accord. This decision involves weighing the benefits of breastfeeding for your child against the benefits of treatment for you.

Driving and using machines

Fumarato de dimetilo Accord is not expected to affect your ability to drive or use machines.

Fumarato de dimetilo Accord contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per capsule, i.e., essentially "sodium-free".

3. How to take Dimethyl fumarate Accord

Follow exactly the administration instructions for this medicine as given by your doctor. If in doubt, consult your doctor again.

Starting dose:

120 mg twice daily.

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

Maintenance dose:

240 mg twice daily.

Dimethyl fumarate Accord is taken orally.

The capsules must be swallowed whole with some water. Do not split, crush, dissolve, suck, or chew the capsules, as this may increase certain adverse effects.

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

If you take more Dimethyl fumarate Accord than you should

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

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Dimethyl fumarate Accord

Do not take a double dose to make up for missed doses.

You may take the missed dose if there is at least 4 hours until the next dose. Otherwise, wait until the time of your next scheduled dose.

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 will experience them.

Serious adverse effects

Dimethyl fumarate Accord may decrease your lymphocyte count (a type of white blood cell in the blood). A low white blood cell count can increase the risk of infection, including a rare brain infection called progressive multifocal leukoencephalopathy (PML). PML can lead to death or cause severe disability. PML has occurred after 1 to 5 years of treatment; therefore, your doctor must continue to monitor your white blood cells throughout treatment, and you should remain alert for any possible symptoms of PML, as described below. The risk of PML may be higher if you have previously taken a medicine that impaired the function of your immune system.

The symptoms of PML may be similar to those of an MS relapse. Symptoms may include new weakness 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 that may persist for more than several days. Therefore, it is very important that you speak to your doctor as soon as possible if you think your MS is worsening or if you notice any new symptoms while being treated with Dimethyl fumarate Accord.

In addition, inform your partner or caregivers about your treatment. Symptoms may arise that you may not notice yourself.

→ Call your doctor immediately if you experience 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 (rubefaction) is a very common adverse effect. However, if flushing is accompanied by a red rash or hives and you experience 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 loss of consciousness (hypotension)

this could then represent a severe allergic reaction (anaphylaxis).

→ Stop taking Dimethyl fumarate Accord and call your doctor immediately

Other adverse effects

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

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

→ Taking the medicine with food may help reduce the above adverse effects

While being treated with Dimethyl fumarate Accord, urine tests may frequently show the presence of ketones, substances that are naturally produced in the body.

Consult your doctor on how to manage these adverse effects. Your doctor may reduce your dose. Do not reduce the dose unless instructed by your doctor.

Common (may affect up to 1 in 10 people)

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

Adverse effects that may appear in blood or urine tests

• low levels of white blood cells (lymphopenia, leucopenia) in blood. A decrease in white blood cells may reduce the body's ability to fight infections. If you have a serious infection (such as pneumonia), inform 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 in blood platelets

Rare (may affect up to 1 in 1000 people)

• inflammation of the liver and increased levels of 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 skin pain, usually on one side of the upper body or face, and other symptoms such as fever and weakness in the early stages of infection, followed by numbness, itching, or painful red spots
• runny nose (rhinorrhea)

Children (aged 13 years and older) and adolescents

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

Some adverse 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 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 may 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 Dimethyl fumarate Accord

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 on each blister after "EXP". The expiry date refers to the last day of the month indicated.

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 and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Dimethyl fumarate Accord

• The active substance is 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.

• The other components are:

Capsule contents (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,

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

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

Nature of the product and pack sizes

Dimethyl fumarate Accord 120 mg gastro-resistant hard 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 body of the capsule, containing enteric-coated mini-tablets, round, biconvex, white, smooth on both sides.

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

120 mg capsules:

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

14x1 capsules in single-dose perforated PVC/PE/PVDC-Alu blister packs.

240 mg capsules:

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

56x1 or 168x1 capsules in single-dose perforated PVC/PE/PVDC-Alu blister packs.

Only certain pack sizes may be 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

Further information on this medicinal product is available upon request by contacting 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

Date of the most recent revision of this leaflet:

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