Adifemu

Package leaflet: Information for the patient

Adifemu, 120 mg, enteric hard capsules
Adifemu, 240 mg, enteric hard capsules
Dimethyl fumarate
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

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

1. What Adifemu is and what it is used for

What Adifemu is
Adifemu is a medicine that contains dimethyl fumarate as the active substance.

What Adifemu is used for
Adifemu is used to treat relapsing-remitting multiple sclerosis (MS) in patients aged 13 years and older.
Multiple sclerosis is a chronic disease that damages the central nervous system (CNS), including the brain and spinal cord. Relapsing-remitting multiple sclerosis is characterized by recurring, periodic neurological symptom flare-ups (called relapses). Symptoms vary among patients but usually include walking and balance problems and vision impairment (e.g., blurred or double vision). These symptoms may completely resolve after a relapse, although some problems may persist.

How Adifemu works
Adifemu appears to suppress the immune system from causing damage to the brain and spinal cord, which may also help slow the progression of the disease in the future.

2. Important information before using Adifemu

When not to take Adifemu

• if the patient is allergic to dimethyl fumarate or 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 in the patient.

Warnings and precautions

Adifemu may have an adverse effect on white blood cell count, as well as on kidney and liver function. Before starting treatment with Adifemu, the doctor will check the patient's white blood cell count and assess whether the kidneys and liver are functioning properly. These tests will be performed periodically during treatment. If the patient's white blood cell count decreases during treatment, the doctor may consider performing additional tests or discontinuing treatment.

Before starting Adifemu, you should discuss this with your doctor if the patient has:

• severe kidney disease
• severe liver disease
• stomach or intestinal disease
• severe infection (e.g. pneumonia).

Herpes zoster (shingles) may occur during treatment with Adifemu. In some cases, severe complications have occurred. If there is any suspicion of shingles in the patient, the doctor should be informed immediately.

If multiple sclerosis worsens (e.g. the patient experiences weakness or vision disturbances) or if any other new symptoms appear, the patient should contact the doctor immediately, as these may 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.

Rare but serious kidney problems (Fanconi syndrome) have been reported during use of dimethyl fumarate in combination with other fumaric acid esters used to treat psoriasis (a skin disease). If the patient notices increased urination, increased thirst and fluid intake, muscle weakness, bone fractures, or general pain, they should contact their doctor as soon as possible for further evaluation of these symptoms.

Children and adolescents

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

Adifemu with other medicines

Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take, especially:

• medicines containing fumaric acid esters (fumarates) used to treat psoriasis;
• medicines affecting the immune system, including other medicines used to treat multiple sclerosis, such as fingolimod, natalizumab, teriflunomide, alemtuzumab, ocrelizumab, or cladribine, and certain medicines commonly used to treat cancers (rituximab or mitoxantrone);
• medicines affecting the kidneys, including certain antibiotics (used to treat infections), diuretics, certain types of painkillers (such as ibuprofen and other similar anti-inflammatory medicines, including over-the-counter products), and medicines containing lithium.

Administration of certain vaccines (containing live microorganisms) during treatment with Adifemu may lead to infection and should therefore be avoided. Your doctor will advise whether another type of vaccine (containing inactivated microorganisms) should be given instead.

Adifemu and alcohol

Avoid consuming high-strength alcoholic beverages (over 30% alcohol by volume) in amounts exceeding 50 ml within one hour of taking Adifemu, due to the risk of interaction between alcohol and this medicine. This may lead to gastric irritation (inflammation of the stomach lining), especially in individuals predisposed to this condition.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.

Pregnancy

Adifemu should not be taken during pregnancy unless discussed with a doctor.

Breastfeeding

It is not known whether the active ingredient of Adifemu passes into human milk. Adifemu should not be taken during breastfeeding. The doctor will help the patient decide whether to discontinue breastfeeding or Adifemu treatment. The decision will be based on an assessment of the benefit of breastfeeding to the child versus the benefit of treatment to the patient.

Driving and operating machinery

The effect of Adifemu on the ability to drive and operate machinery is unknown. No effect of Adifemu on the ability to drive and operate machinery is expected.

Adifemu contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per capsule; therefore, this medicine is considered "sodium-free".

3. How to take Adifemu

This medicine should always be taken according to the doctor's instructions. If in doubt, consult your
doctor.
Initial dose
120 mg twice daily.
This initial dose should be taken for the first 7 days, after which the usual maintenance dose should be used.
Usual maintenance dose
240 mg twice daily.
Adifemu should be taken orally.
Each capsule must be swallowed whole with water. Capsules must not be divided, crushed,
dissolved, sucked or chewed, as this may increase the occurrence of certain adverse reactions.
Adifemu should be taken with food – this will help reduce the very common adverse reactions
(listed in section 4).
Taking more than the recommended dose of Adifemu
If more capsules than recommended are taken, inform your doctor immediately.
Adverse reactions similar to those described below in section 4 may occur.
Missed dose of Adifemu
Do not take a double dose to make up for a missed dose.
A missed dose may be taken later, provided there is at least a 4-hour interval before the next scheduled dose. Otherwise, take the next dose at the usual time.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Serious adverse reactions
Adifemu may reduce the number of lymphocytes (a type of white blood cells). A low number of white
blood cells may increase the risk of infections, including a rare brain infection called
progressive multifocal leukoencephalopathy (PML). PML can lead to severe disability or death. PML has been observed from 1 year to 5 years after starting treatment; therefore, your doctor should monitor your white blood cell count throughout the entire treatment period, and you should pay attention to the symptoms described below, which may indicate PML. The risk of developing PML may be higher if you have previously taken medicines affecting the immune system.
Symptoms of PML may resemble a relapse of multiple sclerosis. These include new or worsening weakness on one side of the body, disturbances in coordination, vision problems, cognitive or memory problems, confusion (disorientation), or personality changes, speech difficulties and communication problems lasting longer than a few days. For this reason, if you notice worsening symptoms related to multiple sclerosis or any new symptoms while taking Adifemu, you should contact your doctor as soon as possible. You should also talk to your partner or caregivers and inform them about your treatment. Symptoms may occur that you yourself may not be aware of.

• If any of the listed symptoms occur, contact your doctor immediately

Serious allergic reactions
The frequency of serious allergic reactions cannot be determined from available data (unknown).
A very common adverse reaction is sudden (paroxysmal) redness of the face or body. If paroxysmal skin redness is accompanied by a red rash or hives and any of the following symptoms:

• swelling of the face, lips, mouth or tongue ( angioedema );
• wheezing, difficulty breathing or shortness of breath ( dyspnoea, hypoxia );
• dizziness or loss of consciousness ( hypotension ),

this may indicate a serious allergic reaction ( anaphylaxis ).
→ You must stop taking Adifemu and contact your doctor immediately
Very common adverse reactions
These symptoms may occur in more than 1 out of 10 people:

• redness of the face or sensation of increased body temperature, warmth, burning or itching of the skin (paroxysmal skin redness)
• loose stools (diarrhoea)
• nausea (nausea)
• stomach pain or cramps
• Taking the medicine with food may help reduce the adverse reactions listed above. During treatment with Adifemu, ketone bodies (substances normally produced in the body) are very frequently detected in urine tests.

Ask your doctor how to manage these adverse reactions. Your doctor may reduce the dose of the medicine. Do not reduce the dose yourself unless your doctor advises you to do so.
Common adverse reactions
May occur in 1 out of 10 people, but not more frequently:

• inflammation of the intestinal mucosa (gastroenteritis)
• vomiting
• indigestion
• inflammation of the gastric mucosa (gastritis)
• gastrointestinal disorders
• burning of the skin
• hot flushes, feeling of warmth
• itching of the skin (pruritus)
• rash
• pink or red spots on the skin (erythema)
• hair loss (alopecia)

Adverse reactions that may be observed in blood or urine test results

• low number of white blood cells (lymphopenia, leukopenia). A reduced number of white blood cells may mean that the body is less able to fight infections. In case of severe infection (e.g. pneumonia), contact your doctor immediately;
• protein ( albumin ) in urine;
• increased liver enzyme activity (AlAT, AspAT) in blood.

Uncommon adverse reactions
May occur in 1 out of 100 people, but not more frequently:

• allergic reactions ( hypersensitivity )
• decreased number of platelets

Frequency unknown (frequency cannot be determined from available data)

• hepatitis and increased liver enzyme activity ( AlAT or AspAT together with bilirubin)
• shingles, with symptoms such as: skin blisters, burning, itching or pain of the skin, usually on one side of the upper body or face, and other symptoms such as fever and fatigue in the early stages of infection, followed by numbness, itching, red spots and severe pain
• cold ( nasopharyngitis )

Children (aged 13 years and above) and adolescents
The adverse reactions listed above also apply to children and adolescents.
Some adverse reactions have been reported more frequently in children and adolescents than in adults, e.g. headache, abdominal pain or stomach cramps, vomiting, sore throat, cough and painful menstruation.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw,
tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Adifemu

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack and carton after:
"EXP". The expiry date refers to the last day of the stated month.
No special storage conditions apply.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Adifemu contains
The active substance is dimethyl fumarate.
Adifemu 120 mg: each capsule contains 120 mg of dimethyl fumarate.
Adifemu 240 mg: each capsule contains 240 mg of dimethyl fumarate.
Other components are:
Capsule contents (enteric mini-tablets): microcrystalline cellulose, sodium croscarmellose,
talc, colloidal anhydrous silica, magnesium stearate, triethyl citrate, copolymer of methacrylic acid and methyl methacrylate (1:1), copolymer of methacrylic acid and ethyl acrylate (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), black iron oxide (E172).

What Adifemu looks like and contents of the pack
Adifemu 120 mg are hard enteric capsules with an opaque light green cap and an opaque white body, length 21.4 ± 0.4 mm, diameter 7.4 ± 0.4 mm, printed with "120" in black ink on the body, containing mini-tablets.
Adifemu 240 mg are hard enteric capsules with an opaque light green cap and an opaque light green body, length 21.4 ± 0.4 mm, diameter 7.4 ± 0.4 mm, printed with "240" in black ink on the body, containing mini-tablets.

Pack sizes:
Adifemu 120 mg, hard enteric capsules, are available in packs containing 14, 28, 56, 84, or 98 capsules.
Adifemu 240 mg, hard enteric capsules, are available in packs containing 14, 28, 56, 84, 98, or 168 capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Vipharm S.A.
ul. A. i F. Radziwiłłów 9
05-850 Ożarów Mazowiecki
tel.: +48 22 679 51 35
e-mail: [email protected]

Manufacturer
Pharmathen International S.A.
Industrial Park Sapes
Block No 5
69300 Rodopi
Greece
Pharmathen S.A.
Dervenakion 6
15351 Pallini, Attiki
Greece

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Germany Adifemu 120 mg
Adifemu 240 mg
Czech Republic Adifemu
Poland Adifemu
Hungary Adifemu 120 mg gyomornedv-ellenálló kemény kapszula
Adifemu 240 mg gyomornedv-ellenálló kemény kapszula
Slovakia Adifemu 120 mg
Adifemu 240 mg