Dimethyl fumarate frontier

Package leaflet: Information for the patient

Dimethyl Fumarate Frontier, 120 mg, hard enteric capsules
Dimethyl Fumarate Frontier, 240 mg, hard enteric capsules
Dimethylis fumaras
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. The medicine may harm another person, even if their symptoms are similar.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

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

1. What Dimethyl Fumarate Frontier is and what it is used for

What Dimethyl Fumarate Frontier is
Dimethyl Fumarate Frontier is a medicine containing the active substance dimethyl fumarate.
What Dimethyl Fumarate Frontier is used for
Dimethyl Fumarate Frontier 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 episodes of neurological symptoms (called relapses). Symptoms vary between patients but usually include walking and balance difficulties, and vision impairment (e.g. blurred or double vision). These symptoms may completely resolve after a relapse, but some problems may persist.
How Dimethyl Fumarate Frontier works
Dimethyl Fumarate Frontier appears to suppress the immune system from causing damage to the brain and spinal cord. This may also help slow the future progression of multiple sclerosis.

2. Important information before using Dimethyl Fumarate Frontier

When not to use Dimethyl Fumarate Frontier

• if the patient is allergic to dimethyl fumarate or to any of the other ingredients of this medicine (listed in section 6).
• if the patient is suspected of having or has been diagnosed with a rare brain infection called progressive multifocal leukoencephalopathy (PML).

Warnings and precautions
Dimethyl Fumarate Frontier may adversely affect the number of white blood cells and the function of the kidneys and liver. Before starting treatment with Dimethyl Fumarate Frontier, 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 treatment with Dimethyl Fumarate Frontier, the patient should discuss this with their doctor if they have:

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

Herpes zoster (shingles) may occur during treatment with Dimethyl Fumarate Frontier. In some cases, severe complications have occurred. If the patient suspects any symptoms of shingles, they should immediately inform their doctor.
If multiple sclerosis worsens (e.g. the patient experiences weakness or vision disturbances) or new symptoms appear, the patient should contact their doctor immediately, as these may be symptoms of a rare brain infection called progressive multifocal leukoencephalopathy. PML is a serious condition that may lead to severe disability or death.
Rare but serious kidney dysfunction (Fanconi syndrome) has been reported during treatment with dimethyl fumarate in combination with other fumaric acid esters used to treat psoriasis (a skin disease). If the patient notices that they are urinating more than usual, feel increased thirst and drink more than normal, their muscles seem weaker, a bone fracture occurs, or they simply feel pain, they should contact their doctor as soon as possible for further evaluation of these symptoms.

Children and adolescents
This medicine should not be given to children under 10 years of age, as there are no data available for this age group.

Dimethyl Fumarate Frontier and other medicines
The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take, and especially about:

• medicines containing fumaric acid esters (fumarates) used in the treatment of psoriasis;
• medicines affecting the immune system , including chemotherapy drugs , immunosuppressive medicines, or other medicines used in the treatment of multiple sclerosis;
• medicines affecting the kidneys , including certain antibiotics (used to treat infections), diuretics (water pills), certain types of painkillers (such as ibuprofen and similar anti-inflammatory medicines, including over-the-counter products), and medicines containing lithium.
• vaccination with live vaccines (vaccines containing live microorganisms) during treatment with Dimethyl Fumarate Frontier may lead to infection; therefore, such vaccinations should be avoided. The doctor will advise whether other types of vaccines (containing inactivated microorganisms) should be administered.

Dimethyl Fumarate Frontier and alcohol
The patient should avoid consuming high-strength alcoholic drinks (more than 30% alcohol by volume, e.g. spirits) in quantities exceeding 50 mL within one hour of taking Dimethyl Fumarate Frontier, 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 susceptible to this condition.

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, thinks she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
There are limited data on the effects of this medicine on the unborn child when used during pregnancy. Dimethyl Fumarate Frontier should not be used during pregnancy unless the patient has discussed this with her doctor and use of the medicine is considered necessary.

Breastfeeding
It is unknown whether the active substance of this medicine passes into human milk. The doctor will advise the patient whether she should discontinue breastfeeding or discontinue treatment with Dimethyl Fumarate Frontier. The decision will be based on an assessment of the benefits of breastfeeding for the child compared to the benefits of treatment for the patient.

Driving and using machines
No effect of Dimethyl Fumarate Frontier on the ability to drive or operate machinery is expected.

3. How to use Dimethyl Fumarate Frontier

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor.

Starting dose
120 mg twice daily.
This starting dose should be taken for the first 7 days, after which the medicine should be taken at the usual maintenance dose.

Usual maintenance dose
240 mg twice daily.
Dimethyl Fumarate Frontier 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 risk of certain adverse reactions.

Dimethyl Fumarate Frontier should be taken with food – this will help reduce the very common side effects listed in section 4.

Taking more Dimethyl Fumarate Frontier than prescribed
If you take more capsules than recommended, inform your doctor immediately.
Adverse effects similar to those described in section 4 below may occur.

If you miss a dose of Dimethyl Fumarate Frontier
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, wait until the next scheduled dose.

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
Dimethyl Fumarate Frontier may reduce the number of lymphocytes (a type of white blood cells). Low levels of white blood cells may increase the risk of infections, including a rare brain infection called progressive multifocal leukoencephalopathy (PML). PML may lead to severe disability or death. PML has been reported after 1 to 5 years of treatment; therefore, your doctor should monitor your white blood cell count throughout treatment, and you should be alert to the symptoms described below, which may indicate PML. The risk of PML may be higher if you have previously taken medicines that affect the immune system.

Symptoms of PML may resemble a relapse of multiple sclerosis. These include weakness or worsening of weakness on one side of the body, problems with coordination, vision disturbances, changes in thinking or memory, confusion, personality changes, speech problems, and communication difficulties lasting longer than a few days. Therefore, if you notice worsening of symptoms related to multiple sclerosis or any new symptoms while taking Dimethyl Fumarate Frontier, you should contact your doctor immediately. You should also talk to your partner or caregivers and inform them about your treatment, as you may not be aware of some symptoms.

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

Serious allergic reactions
The frequency of serious allergic reactions cannot be determined from available data (frequency unknown).

A very common adverse reaction is sudden (episodic) redness of the face or body. If episodic 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, breathing difficulties or shortness of breath (dyspnea, hypoxia)
• dizziness or loss of consciousness (hypotension)

this may indicate a serious allergic reaction (anaphylaxis). You must stop taking Dimethyl Fumarate Frontier and contact your doctor immediately.

Other adverse reactions

Very common adverse reactions (may occur in more than 1 in 10 people)

• redness of the face or sensation of increased body temperature, hot flushes, burning sensation of the skin or itching (episodic skin flushing)
• loose stools (diarrhea)
• nausea
• stomach pain or cramps

Taking the medicine with food may help reduce the above-mentioned adverse reactions. During treatment with dimethyl fumarate, increased production of ketone bodies (substances normally produced in the body) is very commonly observed in urine tests. You should consult your doctor on how to manage these adverse reactions. Your doctor may reduce the dose of the medicine. Do not reduce the dose yourself unless instructed by your doctor.

Common adverse reactions (may occur in up to 1 in 10 people)

• inflammation of the intestinal mucosa (gastrointestinal irritation)
• vomiting
• indigestion
• inflammation of the stomach lining (gastritis)
• gastrointestinal disorders
• skin burning sensation
• hot flushes, sensation of heat
• skin itching (pruritus)
• rash
• pink or red spots on the skin (flushing)
• hair loss (alopecia)

Adverse reactions that may cause abnormal blood or urine test results:

• low number of white blood cells (lymphopenia, leukopenia). Reduced white blood cell count may mean the body is less able to fight infections. If you develop a severe infection (e.g. pneumonia), contact your doctor immediately.
• protein (albumin) in the urine
• increased liver enzyme activity (AlAT, AspAT) in blood.

Uncommon adverse reactions (may occur in up to 1 in 100 people)

• allergic reactions (hypersensitivity)
• decreased platelet count

Frequency not known (frequency cannot be estimated 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 skin pain, 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, for example: headache, abdominal pain or stomach cramps, vomiting, sore throat, cough, and painful menstruation.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 responsible entity.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Dimethyl Fumarate Frontier

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton after:
Expiry date (EXP). The expiry date refers to the last day of the stated month.
There are no special storage temperature requirements for this medicine.
Store in the original packaging to protect from light.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer in use. This will help protect
the environment.

6. Contents of the pack and other information

What Dimethyl Fumarate Frontier contains
The active substance is dimethyl fumarate.
Dimethyl Fumarate Frontier, 120 mg, hard enteric capsules
Each hard enteric capsule contains 120 mg of dimethyl fumarate.
Dimethyl Fumarate Frontier, 240 mg, hard enteric capsules
Each hard enteric capsule contains 240 mg of dimethyl fumarate.
The other ingredients are:

• Capsule contents: microcrystalline cellulose (E 460), crospovidone (type A), talc (E 553b), povidone K-30 (E 1201), colloidal anhydrous silica (E 551), magnesium stearate (E 470b), triethyl citrate, copolymer of methacrylic acid and ethyl acrylate (1:1), hypromellose, titanium dioxide (E 171), triacetin.
• Capsule shell: gelatin, titanium dioxide (E171), brilliant blue FCF (E 133), yellow iron oxide (E 172).
• Printing ink: shellac, potassium hydroxide, propylene glycol (E 1520), black iron oxide (E 172), concentrated ammonium hydroxide.

What Dimethyl Fumarate Frontier looks like and contents of the pack
Dimethyl Fumarate Frontier, 120 mg, hard enteric capsules: capsule with a green cap and white body, capsule shell 21.4 mm, with black printing "DMF 120" on the body, containing white or almost white minitablets.
Dimethyl Fumarate Frontier, 240 mg, hard enteric capsules: capsule with a green cap and green body, capsule shell 23.2 mm, with black printing "DMF 240" on the body, containing white or almost white minitablets.
Blister made of OPA/Aluminium/PVC//Aluminium or single-dose perforated blister made of OPA/Aluminium/PVC//Aluminium in a cardboard box.
Dimethyl Fumarate Frontier, hard enteric capsules, 120 mg
Pack sizes:
14 hard enteric capsules (blister packs)
14 x 1 hard enteric capsule (single-dose perforated blisters)
Dimethyl Fumarate Frontier, hard enteric capsules, 240 mg
Pack sizes:
56 hard enteric capsules (blister packs)
56 x 1 hard enteric capsule (single-dose perforated blisters)
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Frontier Biopharma Sp. z o.o.
Grzybowska 2/29
00-131 Warsaw
e-mail: [email protected]
Manufacturer/Importer
Pharmadox Healthcare Limited,
Kw20a Kordin Industrial Estate,
PLA 3000 Paola,
Malta
Adalvo Limited,
Malta Life Sciences Park, Building 1, Level 4, Sir Temi Zammit Buildings,
SGN 3000 San Gwan,
Malta
KeVaRo GROUP Ltd,
9 Tzaritza Elenora Str., office 23,
1618 Sofia,
Bulgaria
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Bulgaria: Диметилфумарат Фронтиер 120mg, стомашно-устойчиви твърди капсули
Диметилфумарат Фронтиер 240mg, стомашно-устойчиви твърди капсули
Croatia: Dimetilfumarat Frontier 120 mg tvrde želučanootporne kapsule
Dimetilfumarat Frontier 240 mg tvrde želučanootporne kapsule
Iceland: Dimethyl Fumarate Frontier
Poland: Dimethyl Fumarate Frontier
Romania: Dimethyl Fumarate Frontier 120 mg, capsule gastrorezistente
Dimethyl Fumarate Frontier 240 mg, capsule gastrorezistente
Slovenia: Dimetilfumarat Frontier 120 mg, gastrorezistentne trde kapsule
Dimetilfumarat Frontier 240 mg, gastrorezistentne trde kapsule