Dimethyl fumarate Pharmathen

Patient Information Leaflet

Dimethylfumarate Pharmathen 120 mg gastro-resistant hard capsules, 240 mg gastro-resistant hard capsules

dimethylfumarate
Generic medicine
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 their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

What Dimetilfumarato Pharmathen is
Dimetilfumarato Pharmathen is a medicine that contains the active substance dimethyl fumarate.
What Dimetilfumarato Pharmathen is used for
Dimetilfumarato Pharmathen 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), namely the brain and spinal cord. Relapsing-remitting multiple sclerosis is characterised by repeated attacks (relapses) of neurological symptoms. Symptoms vary from patient to patient but generally include walking difficulties, feelings of 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 Pharmathen works
Dimetilfumarato Pharmathen 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 Pharmathen

Do not take Dimetilfumarato Pharmathen

• 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 Pharmathen may affect the number of white blood cells in your blood, your kidneys, and your liver. Before starting Dimetilfumarato Pharmathen, your doctor will perform a blood test to count your white blood cells and check 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 Pharmathen if you have:

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

Treatment with Dimetilfumarato Pharmathen may lead to cases of herpes zoster infection (shingles). In some cases, serious complications have occurred. Inform your doctor immediately if you suspect you have any symptoms of herpes zoster infection.
If you think your 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 increased muscle weakness, or have a fracture or even just pain, contact your doctor as soon as possible so that thorough investigations can be carried out.
Children and adolescents
The warnings and precautions listed above also apply to children. Dimetilfumarato Pharmathen 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 Pharmathen
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 Pharmathen 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 Pharmathen and alcohol
Consumption of alcoholic beverages with high alcohol content (more than 30% alcohol by volume, e.g. spirits) in amounts greater than a small quantity (more than 50 mL) should be avoided within one hour of taking Dimetilfumarato Pharmathen, as alcohol may interact with this medicine. This could cause inflammation of the stomach (gastritis), particularly in people already prone to gastritis.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not use Dimetilfumarato Pharmathen if you are pregnant, unless you have discussed it with your doctor.
Breastfeeding
It is not known whether the active ingredient of Dimetilfumarato Pharmathen passes into breast milk. Dimetilfumarato Pharmathen should not be used during breastfeeding. Your doctor will help you decide whether to discontinue breastfeeding or treatment with Dimetilfumarato Pharmathen. This involves weighing the benefit of breastfeeding for your child against the benefit of therapy for you.
Driving and using machines
The effect of Dimetilfumarato Pharmathen on the ability to drive or use machines is unknown. It is not expected that Dimetilfumarato Pharmathen will affect your ability to drive or use machines.
Dimetilfumarato Pharmathen 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 Pharmathen

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 regular dose.
Regular dose
240 mg twice daily.
Dimetilfumarato Pharmathen 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 Pharmathen with food – this may help reduce some of the more common side effects (listed in section 4).
If you take more Dimetilfumarato Pharmathen 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 Pharmathen
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 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

Dimetilfumarato Pharmathen 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 lead to severe disability or death. PML has occurred after 1–5 years of treatment, so 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 difficulty speaking and communicating 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 Pharmathen, it is very important to contact your doctor as soon as possible. Also inform your partner or caregiver about your treatment, as they may notice symptoms you might not be aware of.

→ 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 (flushing) 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 Pharmathen and call a doctor immediately

Very common:
May affect more than 1 in 10 people:

• flushing 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 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 Dimetilfumarato Pharmathen.

Talk to 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 lining (gastritis)
• gastrointestinal disorder
• burning sensation
• hot flush, sensation of warmth
• itchy skin (pruritus)
• 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 reduction in white blood cell count may indicate that you are 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

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 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, talk to 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 Dimethylfumarate Pharmathen

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 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 Pharmathen contains
The active substance is dimethyl fumarate.
Dimetilfumarato Pharmathen 120 mg: each capsule contains 120 mg of dimethyl fumarate.
Dimetilfumarato Pharmathen 240 mg: each capsule contains 240 mg of dimethyl fumarate.
The other components are: Capsule contents (enteric-coated minitablets):
microcrystalline cellulose, sodium croscarmellose, talc, anhydrous colloidal silica, magnesium stearate,
triethyl citrate, methacrylic acid – methyl methacrylate copolymer (1:1), methacrylic acid – ethyl acrylate
copolymer (1:1) 30% dispersion.
Capsule shell: gelatin, titanium dioxide (E171), Brilliant Blue FCF (E133), yellow iron oxide (E172), black iron oxide (E172).
Capsule printing (black ink): shellac (20% esterified), propylene glycol (E1520) and black iron oxide (E172).

Description of the appearance of Dimetilfumarato Pharmathen and package contents
Dimetilfumarato Pharmathen 120 mg: hard gastro-resistant capsules with an opaque light green cap and an opaque white body, size Length: 21.4±0.4 mm, Width: 7.4±0.4 mm, printed with “120” in black ink on the body, containing minitablets.
Dimetilfumarato Pharmathen 240 mg: hard gastro-resistant capsules with an opaque light green cap and an opaque light green body, size Length: 21.4±0.4 mm, Width: 7.4±0.4 mm, printed with “240” in black ink on the body, containing minitablets.

Pack sizes:
120 mg capsules: 14 capsules
240 mg capsules: 56 or 168 capsules
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder and Manufacturer
Pharmathen S.A.
Dervenakion 6
15351 Pallini, Attiki
Greece

Manufacturer
Pharmathen International S.A.,
Industrial Park Sapes,
Rodopi Prefecture, Block No 5,
69300 Rodopi,
Greece
and/or
Pharmathen S.A.
Dervenakion 6
153 51 Pallini Attiki,
Greece

This medicinal product is authorized in the European Economic Area Member States under the following names: