Noroplex

Package leaflet: Information for the patient

Noroplex, 120 mg, hard enteric capsules
Noroplex, 240 mg, hard enteric capsules
Dimethyl fumarate
Please read all of 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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Noroplex is and what it is used for

What Noroplex is
Noroplex is a medicine containing the active substance dimethyl fumarate.
What Noroplex is used for
Noroplex 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 episodes of neurological symptoms (called relapses). Symptoms vary between individuals but usually include problems with walking and balance, and vision impairment (e.g. blurred or double vision). These symptoms may completely resolve after a relapse, but some deficits may persist.
How Noroplex works
Noroplex 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 Noroplex

When not to take Noroplex

• if the patient is allergic to dimethyl fumarate or to 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
Noroplex may have an adverse effect on the number of white blood cells and on the function of the kidneys and liver. Before starting treatment with Noroplex, 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 number of white blood cells decreases during treatment, the doctor may consider performing additional tests or discontinuing treatment.

Before starting Noroplex, consult a doctor if the patient has:

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

Shingles (herpes zoster) may occur during treatment with Noroplex. In some cases, serious 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 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 disorders (Fanconi syndrome) have been reported when dimethyl fumarate-containing medicines are used in combination with other fumaric acid esters used in the treatment of psoriasis (a skin disease). If the patient notices that they are passing more urine, feels increased thirst and drinks more than usual, 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
The above warnings and precautions also apply to children. Noroplex may be used in children and adolescents aged 13 years and older. Data in children under 10 years of age are not available.

Noroplex with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines they plan to take, especially:

• medicines containing fumaric acid esters (fumarates) used in the treatment of psoriasis
• medicines affecting the immune system, including other medicines used in the treatment of multiple sclerosis, such as fingolimod, natalizumab, teriflunomid, alemtuzumab, ocrelizumab or cladribine, and certain medicines commonly used in cancer treatment (rituximab or mitoxantrone)
• 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
• administration of certain types of vaccines (live vaccines) during treatment with Noroplex may lead to infection; therefore, they should be avoided. The doctor will advise whether other types of vaccines (inactivated vaccines) can be given.

Use of Noroplex with alcohol
High-strength alcoholic drinks (over 30% alcohol by volume) should be avoided in amounts exceeding 50 ml within one hour of taking Noroplex, due to the risk of interaction between alcohol and this medicine, which 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, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
Noroplex should not be taken during pregnancy unless discussed with the doctor.

Breastfeeding
It is not known whether the active ingredient of Noroplex passes into breast milk. Noroplex should not be taken during breastfeeding. The doctor will help the patient decide whether to discontinue breastfeeding or to stop taking Noroplex. The decision will be based on an assessment of the benefits to the child from breastfeeding compared to the benefits to the patient from treatment.

Driving and operating machinery
The effect of Noroplex on the ability to drive and operate machinery is unknown. It is not expected that this medicine will affect the ability to drive and operate machinery.

3. How to use Noroplex

This medicine should always be taken as directed by your doctor. 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 medicine should be continued at the recommended dose.
Usual dose
240 mg twice daily
Noroplex 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 effects.
Noroplex should be taken with food – this will help reduce the very common adverse effects (listed in section 4).
Taking more Noroplex than recommended
If more capsules than recommended have been taken, inform your doctor immediately. Adverse effects similar to those described below in section 4 may occur.
Missing a dose of Noroplex
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 dose. If it is too late, the missed dose should be skipped and the next dose taken at the usual time.
If you have any further doubts 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
The medicine Noroplex 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 can lead to severe disability or death. PML has been reported after 1 to 5 years of treatment; therefore, the doctor should monitor the patient's white blood cell count throughout the entire duration of treatment, and the patient should be aware of the symptoms described below, which may indicate PML. The risk of developing PML may be higher if the patient has previously taken medicines that impair the immune system.
The symptoms of PML may resemble a relapse of multiple sclerosis. They include: new or worsening weakness on one side of the body, problems with coordination, vision, thinking or memory, confusion (disorientation), personality changes, speech problems and communication difficulties lasting longer than a few days. For this reason, if the patient notices worsening of symptoms related to multiple sclerosis or the occurrence of any new symptoms while taking Noroplex, they should contact their doctor as soon as possible. The patient should also talk to their partner or caregivers and inform them about the treatment. There may be symptoms of which the patient may not be aware.
If any of the symptoms listed above occur, contact a doctor immediately.
Severe allergic reactions
The frequency of severe allergic reactions cannot be determined from the available data (frequency unknown).
A very common adverse reaction is sudden (episodic) redness of the face or body. If the episodic redness of the skin 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 (dyspnea, hypoxia)
• dizziness or loss of consciousness (hypotension)

this may indicate a severe allergic reaction (anaphylaxis). The use of Noroplex must be discontinued and medical advice must be sought immediately.

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

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

Taking the medicine with food may help reduce the adverse reactions listed above.

During treatment with dimethyl fumarate, increased production of ketone bodies (substances normally produced in the body) is very commonly observed in urine tests. The patient should consult their doctor on how to manage adverse reactions. The doctor may reduce the dose of the medicine. The dose should not be reduced by the patient themselves unless advised by the doctor.
Common adverse reactions (may occur in up to 1 in 10 patients)

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

Adverse reactions that may cause abnormal blood or urine test results

• low levels of white blood cells in the blood (lymphopenia, leukopenia). Reduced numbers of white blood cells may mean that the body is less able to fight infections. In case of severe infection (e.g. pneumonia), contact a doctor immediately.
• protein (albumin) in the urine
• increased levels of liver enzymes (ALT, AST) in the blood

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

• allergic reactions (hypersensitivity)
• decreased platelet count

Frequency not known (frequency cannot be determined from the available data)

• hepatitis and increased activity of liver enzymes (ALT or AST 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 or red spots and severe pain
• catarrh (nasal inflammation)

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 adverse symptoms not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +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 authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Noroplex

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister, label,
bottle and carton after "EXP". The expiry date refers to the last day of the specified
month.
This medicine does not require any special storage conditions.
Store in the original packaging to protect from light.
Medicines must not be disposed of via the sewage system or household waste. Ask your
pharmacist how to dispose of medicines no longer required. These measures will help
protect the environment.

6. Contents of the pack and other information

What Noroplex contains

• The active substance is dimethyl fumarate.

Noroplex 120 mg, enteric hard capsules
Each capsule contains 120 mg of dimethyl fumarate.
Noroplex 240 mg, enteric hard capsules
Each capsule contains 240 mg of dimethyl fumarate.

• Other ingredients are: microcrystalline cellulose, crospovidone, talc, povidone, colloidal anhydrous silica, magnesium stearate, triethyl citrate, methacrylic acid and ethyl acrylate copolymer (1:1), hypromellose, titanium dioxide (E 171), triacetin
  Capsule shell: gelatin, titanium dioxide (E 171), brilliant blue FCF (E 133), iron oxide yellow (E 172)
  Ink: shellac, potassium hydroxide, propylene glycol (E 1520), iron oxide black (E 172), concentrated ammonium hydroxide

What Noroplex looks like and contents of the pack
Noroplex 120 mg, enteric hard capsules (enteric capsules)
Hard gelatin capsule, 21.4 mm in size, consisting of a white body with black imprint “DMF 120” and a green cap, containing white to almost white minitablets.
Noroplex is available in blisters made of OPA/Aluminium/PVC/Aluminium or in single-dose blisters OPA/Aluminium/PVC/Aluminium, packed in a cardboard box containing 14 enteric hard capsules.
Noroplex 240 mg, enteric hard capsules (enteric capsules)
Hard gelatin capsule, 23.2 mm in size, consisting of a green body with black imprint “DMF 240” and a green cap, containing white to almost white minitablets.
Noroplex is available in blisters made of OPA/Aluminium/PVC/Aluminium or in single-dose blisters OPA/Aluminium/PVC/Aluminium, packed in a cardboard box containing 56 enteric hard capsules.

Marketing Authorisation Holder
+pharma arzneimittel gmbh
Hafnerstrasse 211
8054 Graz
Austria

Importer
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 authorised in the Member States of the European Economic Area under the following names:
Iceland Noroplex 120 mg magasýruþolin hörð hylki
Noroplex 240 mg magasýruþolin hörð hylki
Poland/Czech Republic Noroplex

For further information about this medicinal product, please contact the representative of the marketing authorisation holder:
+pharma Polska sp. z o.o.
ul. Podgórska 34
31-536 Kraków, Poland
Tel. +48 12 262 32 36