RIULVY

Patient Information Leaflet

RIULVY 174 mg gastro-resistant hard capsules, 348 mg gastro-resistant hard capsules

tegomil fumarate
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 their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What RIULVY is and what it is used for

What RIULVY is
RIULVY is a medicine that contains the active substance tegomil fumarate.
What RIULVY is used for
RIULVY is used to treat relapsing-remitting multiple sclerosis (RRMS) 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 neurological symptoms. Symptoms vary from patient to patient, but generally include walking difficulties, feelings of imbalance, and vision problems (e.g. blurred or double vision). These symptoms may completely disappear when a relapse resolves, although some residual problems may remain.
How RIULVY works
RIULVY appears to work by preventing the body's immune system from damaging the brain and spinal cord. This may also help delay future disease progression.

2. What you need to know before taking RIULVY

Do not take RIULVY

• if you are allergic to tegomil 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 you are suspected of having a rare brain infection called progressive multifocal leukoencephalopathy (PML) or if a diagnosis of PML has been confirmed.

Warnings and precautions
RIULVY may affect your white blood cell count, kidneys, and liver. Before
starting RIULVY, 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 think 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 PML. PML is a serious condition that may lead to severe disability or death.
Contact your doctor before taking RIULVY if you have:

• a serious kidney disease
• a serious liver disease
• a disease of the stomach or intestines
• a serious infection (such as pneumonia)

Herpes zoster infection (shingles) may occur during treatment with RIULVY.
In some cases, severe complications have occurred. Contact your doctor immediately if you suspect you have any symptoms of herpes zoster infection.
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 called Fanconi syndrome has been observed. If you notice increased urination, increased thirst and fluid intake, muscle weakness, or experience bone fractures or bone pain, contact your doctor as soon as possible so that appropriate investigations can be carried out.
Children and adolescents
Do not give this medicine to children under 13 years of age, as there is no available data in this age group.
Other medicines and RIULVY
Tell 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 chemotherapeutic agents, immunosuppressants, or other medicines used to treat MS;
• medicines that affect the kidneys, including certain antibiotics (used to treat infections), diuretics, some types of painkillers (such as ibuprofen and other anti-inflammatory medicines and similar medicines purchased without a prescription), and medicines containing lithium;
• taking RIULVY 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.

RIULVY and alcohol
Consumption of alcoholic beverages with high alcohol content (more than 30% alcohol by volume, e.g. spirits) exceeding a small amount (more than 50 ml) should be avoided within one hour of taking RIULVY, as alcohol may interact with this medicine. This could cause stomach inflammation ( gastritis ), particularly in individuals already prone to gastritis.
Pregnancy and breastfeeding
Pregnancy
There is limited information on the effects of this medicine on the unborn child when used during pregnancy. Do not use this medicine during pregnancy unless you have discussed it with your doctor and the medicine is clearly necessary for you.
Breastfeeding
It is not known whether the active ingredient of RIULVY passes into breast milk. Your doctor will advise you whether you should stop breastfeeding or stop treatment with RIULVY. This decision will be based on evaluating the benefit of breastfeeding for your child versus the benefit of therapy for you.
Driving and using machines
RIULVY is not expected to affect your ability to drive vehicles or operate machinery.
RIULVY contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. it is essentially "sodium-free".

3. How to take RIULVY

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor.
Initial dose:
The recommended starting dose is 174 mg twice daily.
Take this initial dose for the first 7 days, then proceed to the regular dose.
Regular dose:
The recommended maintenance dose is 348 mg twice daily.
RIULVY 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 side effects.
Take RIULVY with food – this may help reduce some of the more common side effects (listed in section 4).
If you take more RIULVY than you should
If you have taken too many capsules, contact your doctor immediately. You may experience side effects similar to those described below in section 4.
If you forget to take RIULVY
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 doubts about how to use 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

Progressive multifocal leukoencephalopathy (PML) and reduced lymphocyte levels

The frequency of PML cannot be determined from the available data (not known).

RIULVY may reduce levels of lymphocytes (a type of white blood cell). Having 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 cells throughout the duration of treatment. Be vigilant in observing 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 difficulty with language and communication lasting longer than a few days.

Therefore, if you think your MS is worsening or if you notice any new symptoms during treatment, it is very important to contact your doctor as soon as possible. Also, inform your partner or caregiver about your treatment, as symptoms may occur 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).

A very common side effect is redness of the face or body (flushing). However, if flushing is accompanied by a red rash or hives and you experience 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 RIULVY 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

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 treatment with RIULVY.

Contact your doctor for advice on managing these side effects. Your doctor may reduce your dose. Do not reduce the dose unless your doctor tells you to.

Common (may affect up to 1 in 10 people)

• inflammation of the intestinal lining (gastroenteritis)
• feeling of discomfort (vomiting)
• indigestion (dyspepsia)
• inflammation of the stomach lining (gastritis)
• gastrointestinal disorder
• burning sensation
• hot flush, feeling of warmth
• 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, leucopenia) in the blood. A reduced number of white blood cells may indicate that your body is not able to fight infections adequately. 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 (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)

• liver inflammation and increased liver enzyme levels (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 spots 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, feeling of discomfort (vomiting), sore throat, cough, and painful menstruation.

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. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store RIULVY

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the HDPE bottle or blister and on the
carton after "Exp.". The expiry date refers to the last day of that month.
For HDPE bottles: do not ingest the desiccant container(s). The desiccant container(s) must remain
inside the bottle until all capsules have been administered.
For HDPE bottles: this medicine does not require any special storage precautions.
For Alu-Alu blisters: do not store above 30 °C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What RIULVY contains

• The active substance is tegomil fumarate. RIULVY 174 mg: each gastro-resistant hard capsule contains 174.2 mg of tegomil fumarate. RIULVY 348 mg: each gastro-resistant hard capsule contains 348.4 mg of tegomil fumarate.
• The other components are microcrystalline cellulose (E461i), sodium croscarmellose (E466) (essentially “sodium-free”, see section 2), talc, anhydrous colloidal silica, magnesium stearate (E470c), hypromellose (E464), hydroxypropylcellulose (E463), triethyl citrate (E1505), methacrylic acid-ethyl acrylate copolymer (1:1), polyvinyl alcohol (E1203), macrogol, gelatin (E428), titanium dioxide (E171), Brilliant Blue FCF (E133), yellow iron oxide (E172), shellac, potassium hydroxide and propylene glycol (E1520).

Description of the appearance of RIULVY and package contents
HDPE bottles
The gastro-resistant hard capsules of RIULVY 174 mg are opaque white and opaque blue in colour,
printed with "174", and available in packs containing 14 gastro-resistant hard capsules with
one desiccant container per bottle.
The gastro-resistant hard capsules of RIULVY 348 mg are opaque blue in colour, printed with
"348", and available in packs containing 56 or 168 gastro-resistant hard capsules with two
desiccant containers per bottle.
Do not ingest the desiccant container(s).
oPA/aluminium/PVC-aluminium blisters
The gastro-resistant hard capsules of RIULVY 174 mg are opaque white and opaque blue in colour,
printed with "174", and available in packs containing 14 gastro-resistant hard capsules.
The gastro-resistant hard capsules of RIULVY 348 mg are opaque blue in colour, printed with
"348", and available in packs containing 56 gastro-resistant hard capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Neuraxpharm Pharmaceuticals, S.L.
Avda. Barcelona 69
08970 Sant Joan Despí - Barcelona
Spain
Tel.: +34 93 475 96 00
E-mail: [email protected]

Manufacturer
Delorbis Pharmaceuticals LTD
17 Athinon street, Ergates Industrial Area
2643 Ergates Lefkosia
Cyprus
Neuraxpharm Pharmaceuticals, S.L.
Avda. Barcelona 69
08970 Sant Joan Despí - Barcelona
Spain
Tel.: +34 93 475 96 00
E-mail: [email protected]

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

België/Belgique/Belgien Neuraxpharm Lietuva
Belgium Neuraxpharm Pharmaceuticals, S.L.
Tél/Tel: +32 (0)2 732 56 95 Tel: +34 93 475 96 00

България Luxembourg/Luxemburg
Neuraxpharm Pharmaceuticals, S.L. Neuraxpharm France
Teл.: +34 93 475 96 00 Tél/Tel: +32 474 62 24 24

Česká republika Magyarország
Neuraxpharm Bohemia s.r.o. Neuraxpharm Hungary Kft.
Tel: +420 739 232 258 Tel.: +36 (30) 542 2071

Danmark Malta
Neuraxpharm Sweden AB Neuraxpharm Pharmaceuticals, S.L.
Tlf: +46 (0)8 30 91 41 Tel: +34 93 475 96 00
(Sverige)

Deutschland Nederland
neuraxpharm Arzneimittel GmbH Neuraxpharm Netherlands B.V
Tel: +49 2173 1060 0 Tel: +31 70 208 5211

Eesti Norge
Neuraxpharm Pharmaceuticals, S.L. Neuraxpharm Sweden AB
Tel: +34 93 475 96 00 Tlf: +46 (0)8 30 91 41
(Sverige)

Ελλάδα Österreich
Brain Therapeutics ΙΚΕ Neuraxpharm Austria GmbH
Τηλ: +302109931458 Tel.: + 43 (0) 1 208 07 40

España Polska
Neuraxpharm Spain, S.L.U. Neuraxpharm Polska Sp. z.o.o.
Tel.: +34 93 475 96 00 Tel.: +48 783 423 453

France Portugal
Neuraxpharm France Neuraxpharm Portugal, Unipessoal Lda
Tél: +33 1.53.63.42.90 Tel: +351 910 259 536

Hrvatska România
Neuraxpharm Pharmaceuticals, S.L. Neuraxpharm Pharmaceuticals, S.L.
T +34 93 602 24 21 Tel.: +34 93 475 96 00

Ireland Slovenija
Neuraxpharm Ireland Ltd. Neuraxpharm Pharmaceuticals, S.L.
Tel: +353 1 428 7777 T +34 93 475 96 00

Ísland Slovenská republika
Neuraxpharm Sweden AB Neuraxpharm Slovakia a.s.
Sími: +46 (0)8 30 91 41 Tel: +421 255 425 562
(Svíþjóð)

Italia Suomi/Finland
Neuraxpharm Italy S.p.A. Neuraxpharm Sweden AB
Tel: +39 0736 980619 Puh/Tel: +46 (0)8 30 91 41
(Ruotsi/Sverige)

Κύπρος Sverige
Brain Therapeutics ΙΚΕ Neuraxpharm Sweden AB
Τηλ: +302109931458 Tel: +46 (0)8 30 91 41

Latvija
Neuraxpharm Pharmaceuticals, S.L.
Tel.: +34 93 475 96 00

More detailed information on this medicine is available on the European Medicines Agency website:
https://www.ema.europa.eu