Dimethyl fumarate Zentiva Italia: detailed information

Patient Information Leaflet

Dimetilfumarato Zentiva Italia 120 mg gastro-resistant hard capsules, 240 mg gastro-resistant hard capsules

Generic medicine
Please read all of this leaflet carefully before you start 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 others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is Dimetilfumarato Zentiva Italia and what is it used for

What is Dimetilfumarato Zentiva Italia
Dimetilfumarato Zentiva Italia is a medicine that contains the active substance dimethyl fumarate.
What is Dimetilfumarato Zentiva Italia used for
Dimetilfumarato Zentiva Italia 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), i.e. 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, a sense of imbalance, and vision problems (e.g. blurred or double vision). These symptoms may completely disappear when a relapse resolves, but some issues may persist.
How Dimetilfumarato Zentiva Italia works
Dimetilfumarato Zentiva Italia 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 need to know before taking Dimetilfumarato Zentiva Italia

Do not take Dimetilfumarato Zentiva Italia

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 Zentiva Italia may affect the number of white blood cells in your blood, your kidneys, and your
liver. Before starting treatment with Dimetilfumarato Zentiva Italia, your doctor will perform a blood test to check your white blood cell count and will assess whether your kidneys and liver are functioning properly. Your doctor will repeat these tests periodically during treatment. If your white blood cell count decreases during treatment, your doctor may consider further investigations or discontinuation of therapy.
Talk to your doctor before taking Dimetilfumarato Zentiva Italia if you have:

severe kidney disease
severe liver disease
a stomach or intestinal disorder
a serious infection (such as pneumonia)

Cases of herpes zoster infection (shingles) may occur during treatment with Dimetilfumarato Zentiva Italia. In some cases, serious complications may develop. 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 signs 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 fluid intake, 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 there is no available data in this age group.
Other medicines and Dimetilfumarato Zentiva Italia
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 and over-the-counter medicines), and medicines containing lithium
taking Dimetilfumarato Zentiva Italia together with certain types of vaccines (live vaccines) could cause you to develop an infection and should therefore be avoided. Your doctor will advise you whether other types of vaccines (non-live vaccines) should be administered.

Dimetilfumarato Zentiva Italia 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 Zentiva Italia, as alcohol may interact with this medicine. This could cause stomach inflammation (gastritis), particularly in individuals already predisposed to gastritis.
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
There is limited information on the effects of this medicine on the unborn child when used during pregnancy. Do not use Dimetilfumarato Zentiva Italia if you are pregnant unless you have discussed it with your doctor and the medicine is clearly necessary for you.
Breastfeeding
It is not known whether the active ingredient of this medicine passes into breast milk. Your doctor will advise you whether you should stop breastfeeding or stop treatment with Dimetilfumarato Zentiva Italia. This decision will be based on evaluating the benefits of breastfeeding for your child against the benefits of treatment for you.
Driving and using machines
This medicine is not expected to affect your ability to drive or use machinery.

3. How to take Dimetilfumarato Zentiva Italia

Take this medicine exactly as instructed by your doctor. If you have any doubts, 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.
Dimetilfumarato Zentiva Italia 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 undesirable effects.
Take Dimetilfumarato Zentiva Italia with food – this may help reduce some of the more common side effects (listed in section 4).
If you take more Dimetilfumarato Zentiva Italia 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
Dimetilfumarato Zentiva Italia
If you forget or miss a dose, do not take a double 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 questions 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 Zentiva Italia 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 lead to severe disability or death. PML has occurred after 1 to 5 years of treatment; therefore, your doctor must continue to monitor your white blood cell counts 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 language and communication difficulties lasting longer than a few days.

Therefore, if you think your MS is worsening or if you notice any new symptoms during treatment with Dimetilfumarato Zentiva Italia, it is very important to contact your doctor as soon as possible. Also inform your partner or caregiver about your treatment, as 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 estimated from the 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 skin 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 Dimetilfumarato Zentiva Italia and call a doctor immediately.

Other side effects

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

flushing (reddening of the face or body), sensation of warmth, intense heat, burning, or itching
soft 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 dimethyl fumarate treatment.

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.

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, sensation of warmth
itching
skin 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.
presence of proteins (albumin) in urine
increased levels of liver enzymes (ALT, AST) in the blood

Uncommon (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 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 compared to 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, contact your doctor or pharmacist. You can 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 Dimetilfumarato Zentiva Italia

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and outer carton after 'Exp.'. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Store in the original outer packaging to protect the medicine 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 Zentiva Italia contains
The active substance is dimethyl fumarate.
Dimetilfumarato Zentiva Italia 120 mg gastro-resistant hard capsules
Each gastro-resistant hard capsule contains 120 mg of dimethyl fumarate.
Dimetilfumarato Zentiva Italia 240 mg gastro-resistant hard capsules
Each gastro-resistant hard capsule contains 240 mg of dimethyl fumarate.
The other components are:

Capsule contents: microcrystalline cellulose (E 460), crospovidone, talc (E 553b), povidone K30, anhydrous colloidal silicon dioxide (E551), magnesium stearate (E 470b), triethyl citrate, methacrylic acid/ethyl acrylate copolymer (1:1), hypromellose, titanium dioxide (E 171), triacetin.
Capsule shell: gelatin, titanium dioxide (E171), Brilliant Blue FCF (E133), iron oxide yellow (E172).
Printing ink: shellac, potassium hydroxide, propylene glycol (E1520), iron oxide black (E172), strong ammonia solution.

Description of the appearance of Dimetilfumarato Zentiva Italia and package contents
Dimetilfumarato Zentiva Italia 120 mg gastro-resistant hard capsules (gastro-resistant capsules):
capsules with a green cap and white body, 21.4 mm in size, printed with “DMF 120” in black ink on the body, containing mini-tablets that are white to almost white.
Dimetilfumarato Zentiva Italia 240 mg gastro-resistant hard capsules (gastro-resistant capsules):
capsules with green cap and green body, 23.2 mm in size, printed with “DMF 240” in black ink on the body, containing mini-tablets that are white to almost white.
Blister made of oPA/Al/PVC/Al or unit dose divisible blisters made of oPA/Al/PVC/Al
Dimetilfumarato Zentiva Italia 120 mg gastro-resistant hard capsules
Pack sizes:
14 gastro-resistant capsules (blister)
14 x 1 gastro-resistant capsules (unit dose divisible blister)
Dimetilfumarato Zentiva Italia 240 mg gastro-resistant hard capsules
Pack sizes:
56 gastro-resistant capsules (blister)
56 x 1 gastro-resistant capsules (unit dose divisible blister)
168 gastro-resistant capsules (blister)
168 x 1 gastro-resistant capsules (unit dose divisible blister)
196 gastro-resistant capsules (blister)
196 x 1 gastro-resistant capsules (unit dose divisible blister)
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milano, Italy
Manufacturers
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park,
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 Tzaritza Elenora Str. Office 23
Sofia 1618 Bulgaria
This medicinal product is authorized in the European Economic Area countries under the following names:
Iceland: Dimethyl fumarate Zentiva Group a.s. 120 mg Magasýruþolið hart hylki
Dimethyl fumarate Zentiva Group a.s. 240 mg Magasýruþolið hart hylki
Germany: Dimethylfumarat Zentiva 120 mg magensaftresistente Hartkapseln
Dimethylfumarat Zentiva 240 mg magensaftresistente Hartkapseln
Italy: Dimetilfumarato Zentiva Italia