DIMETHYL FUMARATE PIRAMAL

Patient Information Leaflet

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

dimethyl fumarate
Generic medicine
Please read this leaflet carefully before taking this medicine, as 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 could be harmful.
• If you experience any side effect, including any not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

Dimetilfumarato Piramal
Dimetilfumarato Piramal is a medicine that contains the active substance dimethyl fumarate.
What Dimetilfumarato Piramal is used for
Dimetilfumarato Piramal 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 symptoms affecting the nervous system. 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, but some problems may persist.
How Dimetilfumarato Piramal works
Dimetilfumarato Piramal 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 Piramal

Do not take Dimetilfumarato Piramal

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

Warnings and precautions
Dimetilfumarato Piramal may affect the number of white blood cells in your blood, your kidneys, and your liver. Before starting Dimetilfumarato Piramal, 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 periodic tests 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 Piramal 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 Dimetilfumarato Piramal. In some cases, severe complications have occurred. Inform your doctor immediately if you suspect you 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 progressive multifocal leukoencephalopathy (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 that you are urinating more than usual, feel more thirsty and drink more than normal, experience muscle weakness, or have a fracture or even just pain, contact your doctor as soon as possible so that appropriate investigations can be carried out.

Children and adolescents
The warnings and precautions listed above also apply to children. Dimetilfumarato Piramal may be used in children and adolescents aged 13 years and older. Data are not available in children under 10 years of age.

Other medicines and Dimetilfumarato Piramal
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 other medicines used for the treatment of multiple sclerosis, such as fingolimod, natalizumab, teriflunomide, alemtuzumab, ocrelizumab or cladribine, or certain treatments commonly used for cancer (rituximab or mitoxantrone)
• 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 Piramal with certain types of vaccines (live vaccines) could 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 Piramal and alcohol
You should avoid consuming alcoholic beverages within two hours of taking this medicine, as alcohol may increase the frequency of gastrointestinal adverse reactions.

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

Pregnancy
Do not use Dimetilfumarato Piramal during pregnancy unless you have discussed this with your doctor.

Breastfeeding
It is not known whether the active substance of Dimetilfumarato Piramal passes into breast milk. Dimetilfumarato Piramal should not be used during breastfeeding. Your doctor will help you decide whether to stop breastfeeding or stop treatment with Dimetilfumarato Piramal. This decision involves weighing the benefit of breastfeeding for your child against the benefit of the therapy for you.

Driving and using machines
The effect of Dimetilfumarato Piramal on the ability to drive or use machines is unknown. Dimetilfumarato Piramal is not expected to affect the ability to drive or use machines.

3. How to take Dimethylfumarate Piramal

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 take the maintenance dose.
Maintenance dose
240 mg twice daily.
Dimethylfumarate Piramal is for oral use.
Swallow each capsule whole with some water. Do not divide, crush, dissolve, suck or chew the capsule, as this could increase certain side effects.
Take Dimethylfumarate Piramal with food – this may help reduce some of the more common side effects (listed in section 4).
If you take more Dimethylfumarate Piramal than you should
If you have taken too many capsules, contact your doctor immediately. You may experience side effects similar to those described below in section 4.
If you forget to take Dimethylfumarate Piramal
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 will pass 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 everyone will experience them.
Serious side effects
Dimethyl fumarate Piramal 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. 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 the immune system function.
The 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 language and communication 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 Piramal, 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 determined 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 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 Piramal and call a doctor immediately
Very common side effects
These 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 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.
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 do so.
Common side effects
These 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 unable to fight infections adequately. If you develop a serious infection (such as pneumonia), contact your doctor immediately
• presence of proteins (albumin) in the urine
• increased levels of liver enzymes (alanine aminotransferase, ALT and aspartate aminotransferase, AST) in the blood

Uncommon side effects
These may affect up to 1 in 100 people:

• allergic reactions (hypersensitivity)
• reduced platelet count in the blood Not known (frequency cannot be estimated from the available data)
• inflammation of the liver and increased levels of liver enzymes (ALT or AST in combination with bilirubin)
• 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, speak to your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Dimethylfumarate Piramal

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.
This medicine does not require any special storage temperature.
Store in the original packaging to protect from light.
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 Piramal contains
The active substance is dimethyl fumarate.
Dimetilfumarato Piramal 120 mg gastro-resistant hard capsules:
each capsule contains 120 mg of dimethyl fumarate.
Dimetilfumarato Piramal 240 mg gastro-resistant hard capsules:
each capsule contains 240 mg of dimethyl fumarate.
The other ingredients are:

• Capsule contents: microcrystalline cellulose, crospovidone type A, talc, povidone K-30, anhydrous colloidal silica, magnesium stearate, triethyl citrate, methacrylic acid/ethyl acrylate copolymer (1:1), hypromellose, titanium dioxide (E 171), triacetin.
• Capsule shell: gelatin, titanium dioxide (E 171), brilliant blue FCF (E 133), yellow iron oxide (E 172).
• Printing ink for capsules: shellac, potassium hydroxide, propylene glycol (E 1520), black iron oxide (E 172), strong ammonia solution.

Description of the appearance of Dimetilfumarato Piramal and package contents
Dimetilfumarato Piramal 120 mg gastro-resistant hard capsules: opaque green cap and opaque white body, capsule shell 21.4 mm long, printed in black ink "DMF 120" on the body, containing white to off-white mini-tablets.
Dimetilfumarato Piramal 240 mg gastro-resistant hard capsules: opaque green cap and body, capsule shell 23.2 mm long, printed in black ink "DMF 240" on the body, containing white to off-white mini-tablets.
Blister OPA/Alu/PVC//Alu or single-dose blister OPA/Alu/PVC//Alu
14 gastro-resistant capsules (7 capsules x 2 blisters)
56 gastro-resistant capsules (7 capsules x 8 blisters)
Not all pack sizes may be marketed.

Marketing Authorization Holder
Piramal Critical Care Italia S.p.A
Via XXIV Maggio 62/A, 37057
San Giovanni Lupatoto (VR)
37057, Italy

Manufacturer
Pharmadox Healthcare Ltd.
Kordin Industrial Park KW20A,
Paola PLA 3000, Malta
Adalvo Limited
Malta Life Sciences Park,
Building 1, Level 4, Sir Temi Zammit Buildings,
San Gwann, SGN 3000 Malta
KeVaRo GROUP Ltd
9 Zaritza Elenora Str., Office 23
Sofia 1618 Bulgaria

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. Links to other websites on rare diseases and related therapeutic treatments are also provided.

This medicinal product is authorized in the Member States of the European Economic Area (EEA) under the following names:
Denmark: Dimethyl Fumarate Piramal 120 mg Magasýruþolið hart hylki
Dimethyl Fumarate Piramal 240 mg Magasýruþolið hart hylki
Germany: Dimethylfumarat Piramal 120 mg magensaftresistente Hartkapseln
Dimethylfumarat Piramal 240 mg magensaftresistente Hartkapseln
Spain: Dimethyl Fumarate Piramal 120 mg cápsulas duras gastrorresistentes EFG
Dimethyl Fumarate Piramal 240 mg cápsulas duras gastrorresistentes EFG
France: Dimethyl Fumarate Zydus 120 mg, gélule gastro-résistante
Dimethyl Fumarate Zydus 240 mg, gélule gastro-résistante
Italy: Dimetilfumarato Piramal