Vumerity

Patient Information Leaflet

Vumerity 231 mg gastro-resistant hard capsules

diroximel fumarate
Please read this leaflet carefully before taking this medicine as 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 pass it on to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Vumerity is and what it is used for

What Vumerity is
Vumerity contains the active substance diroximel fumarate.
What Vumerity is used for
Vumerity is used to treat relapsing-remitting multiple sclerosis (MS) in adult patients.
Multiple sclerosis is a chronic disease in which the immune system (the body's natural defences) does not function properly and attacks parts of the central nervous system (the brain, spinal cord, and optic nerve of the eye), causing inflammation that damages the nerves and the surrounding protective covering. Relapsing-remitting multiple sclerosis is characterised by repeated attacks (relapses) on the nervous system. Symptoms vary from patient to patient, but generally include difficulty walking, a sense 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 Vumerity works
The medicine is thought to work by increasing the activity of a protein called "Nrf2" that regulates certain genes producing "antioxidants", which are involved in cellular defence. This helps control immune system activity and reduce damage to the brain and spinal cord.

2. What you need to know before taking Vumerity

Do not take Vumerity

• if you are allergic to diroximel fumarate, related substances (called fumarates or esters of fumaric acid), 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.

Warnings and precautions
Vumerity may affect your white blood cell count, kidneys, and liver. Before starting Vumerity, your doctor will perform a blood test to check your white blood cell count and assess whether your kidneys and liver are functioning properly. Your doctor will repeat these tests periodically during treatment. If your white blood cell count decreases during treatment, your doctor may consider further testing or discontinuation of therapy.
If you feel that 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 signs of a rare brain infection called progressive multifocal leukoencephalopathy (PML). PML is a serious condition that may lead to severe disability or death. Read the information under “PML and low lymphocyte counts” in section 4 of this leaflet.
Contact your doctor before taking Vumerity if you have:

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

Flushing (redness of the face and body) is a common side effect. Severe flushing together with other symptoms may indicate a serious allergic reaction and has been observed in a small number of patients (see “Serious allergic reactions” in section 4 of this leaflet). If flushing causes you discomfort, contact your doctor, who may provide appropriate treatment.
Vumerity may cause a serious allergic reaction known as hypersensitivity reaction. You should be aware of all important signs and symptoms to monitor while taking Vumerity. Read the information under “Serious allergic reactions” in section 4 of this leaflet.
Cases of herpes zoster infection (shingles) may occur during treatment with Vumerity. In some cases, serious complications have occurred. Contact your doctor immediately if you suspect you have any symptoms of herpes zoster infection listed in section 4 of this leaflet.
With a medicine containing related active substances (dimethyl fumarate in combination with other fumaric acid esters), a rare but serious kidney disorder (Fanconi syndrome) has been observed. If you notice increased urination, increased thirst and fluid intake, or if your muscles become weaker, or in case of fracture or even pain alone, contact your doctor as soon as possible so that appropriate investigations can be initiated.
Children and adolescents
Do not give this medicine to children and adolescents, as there is limited experience regarding the safety and efficacy of Vumerity in this population.
Other medicines and Vumerity
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular:

• medicines containing fumaric acid esters (fumarates)
• medicines that affect the immune system, including chemotherapeutic agents, immunosuppressive therapies, or other medicines used to treat multiple sclerosis
• medicines that affect the kidneys, including certain antibiotics (such as aminoglycosides, used to treat infections), diuretics, some types of analgesics (such as ibuprofen and other similar anti-inflammatory medicines, including over-the-counter products), and medicines containing lithium
• taking Vumerity together with certain types of vaccines ( live vaccines ) could lead to infection and should therefore be avoided. Your doctor will advise you whether other types of vaccines ( non-live vaccines ) should be administered.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not use Vumerity during pregnancy unless you have discussed it with your doctor, as Vumerity may harm the unborn baby. If you are a woman of childbearing age, you must use reliable contraception.
Breastfeeding
It is not known whether diroximel fumarate or its metabolites pass into breast milk. Your doctor will help you decide whether to discontinue breastfeeding or stop treatment with Vumerity, taking into account the benefit of breastfeeding for your child versus the benefit of therapy for you.
Driving and using machines
Vumerity is not expected to affect your ability to drive or use machines.

3. How to take Vumerity

Take this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor.

Starting dose
The recommended starting dose is 231 mg (one capsule) twice daily.
Take this starting dose for the first 7 days, then switch to the maintenance dose.

Maintenance dose
The recommended maintenance dose is 462 mg (two capsules) twice daily.

Vumerity is for oral use.
Swallow each capsule whole with some water. Do not crush, chew, or disperse the capsule contents in food, as this may increase certain side effects.

You may take Vumerity with or without food. If you experience side effects such as flushing or stomach problems, taking it with food may help reduce these symptoms.

If you take more Vumerity than you should
If you have taken too many capsules, contact your doctor immediately. You may experience side effects similar to those described in section 4 below.

If you forget to take Vumerity
Do not take a double dose to make up for a missed dose.
If at least 4 hours remain before your next scheduled dose, you may take the missed dose.
Otherwise, do not take the missed dose and take the next scheduled dose at the usual time.

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 everybody gets them.
Serious side effects
PML and low lymphocyte counts
The frequency of PML cannot be determined from the available data (not known).
Vumerity 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 to 5 years of treatment with the related medicine dimethyl fumarate; therefore, your doctor must continue monitoring your white blood cells 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 suppress 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; poor coordination; changes in vision, thinking, or memory; confusion or personality changes; or difficulty with language and communication lasting longer than a few days.
Therefore, if you feel that your MS is worsening or if you notice any new symptoms during treatment with Vumerity, it is very important to contact your doctor as soon as possible. Also, talk to your partner or caregiver and inform them about the characteristics of the treatment. They may notice symptoms that you do not.
**** 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 is a very common side effect. However, if it 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)

you may be experiencing a severe allergic reaction (anaphylaxis)
**** Stop taking Vumerity and call a doctor immediately
Other side effects
Very common (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

Side effects that may be detected in blood or urine tests

• presence of substances called ketones, which are naturally produced by the body, very commonly detected in urine tests during treatment with Vumerity
• low levels of white blood cells (lymphopenia, leucopenia) in the blood. A reduced number of white blood cells in the blood may indicate that you are not able to fight infections adequately. If you have a serious infection (such as pneumonia), contact your doctor immediately

Contact your doctor to learn how to manage these side effects. Your doctor may reduce the dose of the medicine. Do not reduce the dose unless your doctor tells you to do so.
Common (may affect up to 1 in 10 people)

• inflammation of the intestinal lining (gastroenteritis)
• feeling of illness (vomiting)
• indigestion (dyspepsia)
• inflammation of the stomach (gastritis)
• gastrointestinal disorders (gastrointestinal disease)
• burning sensation
• hot flush, feeling of warmth
• itching
• skin rash
• pink or red spots on the skin (erythema)
• hair loss (alopecia)

Side effects that may be detected in blood or urine tests

• proteins (albumin) in the urine (proteinuria)
• 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

Rare (may affect up to 1 in 1,000 people)

• drug-induced liver damage and increased levels of liver enzymes measured in blood tests (ALT or AST in combination with bilirubin)

Not known (frequency cannot be determined from the available data)

• 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)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Vumerity

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle and carton after "Exp.".
The expiry date refers to the last day of that month.
Store below 25 °C.
Keep in the original bottle to protect the medicine from moisture.
Do not dispose of any medicine 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 Vumerity contains
The active substance is diroximel fumarate.
Each capsule contains 231 mg of diroximel fumarate.
The other components are: capsule contents: methacrylic acid–ethyl methacrylate copolymer (1:1) type A; crospovidone type A; microcrystalline cellulose; anhydrous colloidal silica; triethyl citrate; talc; magnesium stearate; capsule coating: hypromellose; titanium dioxide (E171); potassium chloride; carrageenan; capsule printing ink: iron oxide black (E172), shellac and potassium hydroxide.

Description of the appearance of Vumerity and contents of the pack
Vumerity 231 mg gastro-resistant hard capsules are white and marked with “DRF 231 mg” printed in black ink.
Vumerity is available in packs containing 120 or 360 (3 × 120) capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Biogen Netherlands B.V.
Prins Mauritslaan 13
1171 LP Badhoevedorp
The Netherlands

Manufacturer
Alkermes Pharma Ireland Limited
Connaught House
1 Burlington Road
Dublin 4
Ireland
D04 C5Y6

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Biogen Belgium NV/SA Biogen Lithuania UAB
Tél/Tel: +32 2 2191218 Tel: +370 5 259 6176

България Luxembourg/Luxemburg
ЕВОФАРМА ЕООД Biogen Belgium NV/SA
Teл: +359 2 962 12 00 Tél/Tel: +32 2 2191218

Česká republika Magyarország
Biogen (Czech Republic) s.r.o. Biogen Hungary Kft.
Tel: +420 255 706 200 Tel: +36 1 899 9883

Danmark Malta
Biogen (Denmark) A/S Pharma. MT Ltd.
Tlf.: +45 77 41 57 57 Tel: +356 21337008

Deutschland Nederland
Biogen GmbH Biogen Netherlands B.V.
Tel: +49 (0) 89 99 6170 Tel: +31 20 542 2000

Eesti Norge
Biogen Estonia OÜ Biogen Norway AS
Tel: +372 618 9551 Tlf: +47 23 40 01 00

Ελλάδα Österreich
Genesis Pharma SA Biogen Austria GmbH
Τηλ: +30 210 8771500 Tel: +43 1 484 46 13

España Polska
Biogen Spain, S.L. Biogen Poland Sp. z o.o.
Tel: +34 91 310 7110 Tel: +48 22 351 51 00

France Portugal
Biogen France SAS Biogen Portugal Sociedade Farmacêutica Unipessoal, Lda.
Tél: +33 (0)1 41 37 95 95 Tel: +351 21 318 8450

Hrvatska România
Biogen Pharma d.o.o. Johnson & Johnson Romania S.R.L.
Tel: +385 (0) 1 775 73 22 Tel: +40 21 207 18 00

Ireland Slovenija
Biogen Idec (Ireland) Ltd. Biogen Pharma d.o.o.
Tel: +353 (0)1 463 7799 Tel: +386 1 511 02 90

Ísland Slovenská republika
Icepharma hf Biogen Slovakia s.r.o.
Sími: +354 540 8000 Tel: +421 2 323 340 08

Italia Suomi/Finland
Biogen Italia s.r.l. Biogen Finland Oy
Tel: +39 02 5849901 Puh/Tel: +358 207 401 200

Κύπρος Sverige
Genesis Pharma Cyprus Ltd Biogen Sweden AB
Τηλ: +357 22765715 Tel: +46 8 594 113 60

Latvija
Biogen Latvia SIA
Tel: +371 68 688 158

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu