Mustef: detailed information

Package leaflet: Information for the patient

Mustef 120 mg gastro-resistant hard capsules, 240 mg gastro-resistant hard capsules

Dimethyl fumarate
Equivalent medicine
Please read this leaflet carefully before 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 they have the same symptoms as yours, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Mustef is and what it is used for

What Mustef is
Mustef is a medicine containing the active substance dimethyl fumarate.
What Mustef is used for
Mustef 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, 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 Mustef works
Mustef 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 Mustef

Do not take Mustef

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

Warnings and precautions
Mustef may affect the number of white blood cells in your blood, your kidneys, and your liver. Before starting treatment with Mustef, your doctor will perform a blood test to count your white blood cells and will check that your kidneys and liver are functioning properly. Your doctor will carry out these tests periodically during treatment. If your white blood cell count decreases during treatment, your doctor may consider further testing or discontinuation of therapy.
Talk to your doctor before taking Mustef if you have:

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

Cases of herpes zoster infection (shingles) may occur during treatment with Mustef. 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 getting worse (for example, if you experience weakness or visual disturbances) 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 increased urination, increased thirst and drinking more than usual, muscle weakness, or if you experience a fracture or 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. Mustef can 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 Mustef
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 to treat 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 non-steroidal anti-inflammatory drugs and medicines purchased without a doctor's prescription), and medicines containing lithium
Taking this medicine 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.

Mustef and alcohol
Consumption of alcoholic beverages should be avoided 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 might be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not use Mustef if you are pregnant, unless you have discussed it with your doctor.
Breastfeeding
It is not known whether the active ingredient of Mustef passes into breast milk. Mustef must not be used during breastfeeding. Your doctor will help you decide whether to stop breastfeeding or stop treatment with Mustef. This decision involves weighing the benefit of breastfeeding for your child against the benefit of therapy for you.
Driving and using machines
The effect of this medicine on the ability to drive or use machinery is unknown.
It is not expected that this medicine will affect the ability to drive or use machinery.

3. How to take Mustef

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor.
Initial dose
120 mg twice daily.
Take this initial dose for the first 7 days, then switch to the regular dose.
Regular dose
240 mg twice daily.
Mustef 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 undesirable effects.
Take Mustef with food – this may help reduce some of the more common undesirable effects (listed in section 4).
If you take more Mustef than you should
If you have taken too many capsules, contact your doctor immediately. You may experience undesirable effects similar to those described in section 4 below.
If you forget to take Mustef
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 elapse between doses. Otherwise, wait until your next scheduled dose.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Serious side effects
Mustef 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, 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; or confusion, personality changes, or language and communication difficulties lasting more than a few days.
Therefore, if you feel your MS is worsening or if you notice any new symptoms during treatment with Mustef, it is very important to contact your doctor as soon as possible. Also inform your partner or caregiver about your treatment. Symptoms may arise 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 a 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 Mustef and call a doctor immediately
Very common side effects
These may affect more than 1 in 10 people:

redness of the face or body, feeling 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 dimethyl fumarate treatment. Consult your doctor for information on how to manage these side effects. Your doctor may reduce your dose. Do not reduce the dose unless your doctor tells you to.

Common side effects
These may affect up to 1 in 10 people:

inflammation of the intestinal lining (gastroenteritis)
feeling of discomfort (vomiting)
indigestion (dyspepsia)
inflammation of the stomach (gastritis)
gastrointestinal disorder
burning sensation
hot flush, sensation of heat
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 in the blood may indicate that you are not adequately able to fight infections. If you have 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 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 determined 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 patches 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, speak to your doctor or pharmacist. You may also report side effects directly via 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 Mustef

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister, on the carton, and on the
box after 'EXP.'.
The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Keep the blisters in the original packaging to protect the medicine from light.
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. Contents of the pack and other information

What Mustef contains
The active substance is dimethyl fumarate.
Mustef 120 mg gastro-resistant hard capsules: each capsule contains 120 mg of dimethyl fumarate.
Mustef 240 mg gastro-resistant hard capsules: each capsule contains 240 mg of dimethyl fumarate.
The other components are:

Capsule contents: microcrystalline cellulose, crospovidone type A, talc, povidone K-30, anhydrous colloidal silicon dioxide, magnesium stearate, triethyl citrate, methacrylic acid-ethyl acrylate copolymer (1:1), hypromellose, titanium dioxide (E171), triacetin.
Capsule shell: gelatin, titanium dioxide (E171), Brilliant Blue FCF (E133), yellow iron oxide (E172).
Printing on the capsule (black ink): shellac, potassium hydroxide, propylene glycol (E1520), black iron oxide (E172), concentrated ammonia solution.

Description of the appearance of Mustef and contents of the pack
Mustef 120 mg gastro-resistant hard capsules: 21.4 mm capsules with an opaque green cap and an opaque white body, printed on the body with “DMF 120 mg”, containing white to off-white mini-tablets.
Mustef 240 mg gastro-resistant hard capsules: 21.4 mm capsules with an opaque green cap and an opaque white body, printed on the body with “DMF 240 mg”, containing white to off-white mini-tablets.
Blister packs made of OPA/Alu/PVC//Alu or unit dose blister packs in OPA/Alu/PVC//Alu.
Mustef 120 mg gastro-resistant hard capsules
Pack sizes:
14 capsules (7 capsules x 2 blisters)
14 x 1 capsule (unit dose blister)
Mustef 240 mg gastro-resistant hard capsules
56 capsules (7 capsules x 8 blisters)
56 x 1 capsule (unit dose blister)
168 capsules (7 capsules x 24 blisters)
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Adalvo Limited
Malta Life Science Park,
Building 1, Level 4
Sir Temi Zammit Buildings,
San Gwann, SGN 3000, Malta

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

United Kingdom (Northern Ireland) > with the following names:
Germany Mustef 120 mg, 240 mg magensaftresistente Hartkapseln
Iceland Mustef 120 mg, 240 mg magasýruþolin hörð hylki
Italy Mustef
Spain Mustef 120 mg, 240 mg cápsulas duras gastrorresistentes