Vumerity 231 mg gastro-resistant hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Vumerity 231 mg gastro-resistant hard capsules

diroximel fumarate

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.

• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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 adverse 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 adults. MS is a long-term disease in which the immune system (the body's natural defenses) malfunctions and attacks parts of the central nervous system (the brain, spinal cord, and the eye's optic nerve), causing inflammation that damages nerves and the protective covering surrounding them. Relapsing-remitting MS is characterized by repeated attacks (relapses) of neurological impairment. Symptoms vary from patient to patient but commonly include: difficulty walking, balance problems, and visual disturbances (e.g., blurred or double vision). These symptoms may completely disappear when a relapse ends, although some problems may persist.

How Vumerity works

The medicine is believed to work by enhancing the activity of a protein called "Nrf2," which regulates certain genes that produce "antioxidants" involved in protecting cells from damage. This helps control immune system activity and reduces damage in 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 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 treatment with Vumerity, your doctor will perform a blood test to determine your white blood cell count and to check that your kidneys and liver are functioning properly. Your doctor will carry out periodic blood tests during treatment. If you experience a decrease in white blood cells during treatment, your doctor may consider additional testing or stopping your treatment.

If you feel that your MS is worsening (e.g., weakness or visual changes) or notice any new symptoms, speak to 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 death or severe disability. Please read the information on "PML and low white blood cell count" in section 4 of this leaflet.

Consult your doctor before starting Vumerity if you have:

• a serious infection (e.g., pneumonia)
• severe kidney disease
• severe liver disease
• a stomach or intestinal disorder

Flushing (redness of the face and body) is a common side effect. Severe flushing with additional symptoms may be a sign of a serious allergic reaction and has been observed in a small number of patients; see "Serious allergic reactions" in section 4 of this leaflet. Inform your doctor if flushing is causing you problems, as your doctor may be able to prescribe medication to treat it.

Vumerity may cause a serious allergic reaction known as hypersensitivity reaction.

You should be aware of all important signs and symptoms to watch for while taking Vumerity. Please read the information on "Serious allergic reactions" in section 4 of this leaflet.

Herpes (herpes zoster) may occur during treatment with Vumerity. In some cases, serious complications have occurred. You should inform your doctor immediately if you suspect you have symptoms of herpes zoster. These are listed in section 4 of this leaflet.

A rare but serious kidney disorder (Fanconi syndrome) has been reported with a medicine containing related active substances (dimethyl fumarate in combination with other fumaric acid esters). If you notice that you are urinating more than usual, are more thirsty and drinking more than normal, or if your muscles seem weaker, you break a bone, or simply have aches and pains, inform your doctor as soon as possible so this can be further investigated.

Children and adolescents

Do not give this medicine to children or adolescents, as there is limited experience regarding the safety and efficacy of Vumerity in these populations.

Other medicines and Vumerity

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, especially:

• medicines containing fumaric acid esters (fumarates)
• medicines that affect the body's immune system, including chemotherapeutic agents, immunosuppressants, or other medicines used to treat MS
• medicines that affect the kidneys, including certain antibiotics (such as aminoglycosides used to treat infections), diuretics (tablets that increase urine output), certain types of painkillers (such as ibuprofen or other similar anti-inflammatory medicines, and over-the-counter medicines), and medicines containing lithium
• The use of Vumerity together with certain types of vaccines (attenuated vaccines) could cause you to develop an infection and should therefore be avoided. Your doctor will advise you whether other types of vaccines (inactivated vaccines) should be administered.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

Do not use Vumerity during pregnancy unless you have discussed it with your doctor. This is because Vumerity could harm your unborn baby. If you are able to become pregnant, you should use a reliable method of contraception.

Breastfeeding

It is unknown whether diroximel fumarate or its metabolites are excreted in human milk. Your doctor will help you decide whether to stop breastfeeding or to stop taking Vumerity. This decision involves weighing the benefits of breastfeeding for your child against the benefits of treatment for you.

Driving and using machines

Vumerity is not expected to affect your ability to drive or use machines.

3. How to take Vumerity

Follow exactly your doctor's instructions for taking this medicine. If in doubt, consult your doctor again.

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 taken orally.

The capsules must be swallowed whole with some water. Do not crush, chew, or sprinkle the capsule contents onto food, as this may increase certain adverse effects.

You may take Vumerity with food or on an empty stomach. If you experience adverse effects such as flushing or stomach problems, taking it with food may reduce these symptoms.

If you take more Vumerity than you should

If you have taken too many capsules, inform your doctor immediately. You may experience adverse effects similar to those described in section 4 below.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately, or call the Toxicology Information Service at 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Vumerity

Do not take a double dose to make up for the missed dose.

If there are at least 4 hours remaining before your next scheduled dose, you may take the missed dose. Otherwise, skip the missed dose and take the next dose at the usual time.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everybody will experience them.

Serious adverse effects

PML and low white blood cell count

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

Vumerity may decrease your lymphocyte count (a type of white blood cell in the blood). A low white blood cell count can increase the risk of infection, including a rare brain infection called progressive multifocal leukoencephalopathy (PML). PML can result in death or cause severe disability. PML has occurred after 1 to 5 years of treatment with the related medicine dimethyl fumarate, so your doctor must continue to monitor your white blood cells throughout treatment, and you should remain alert for any possible symptoms of PML, as described below. The risk of PML may be higher if you have previously taken a medicine that suppresses your immune system.

The symptoms of PML may be similar to those of a multiple sclerosis (MS) relapse. Symptoms may include new weakness or worsening of weakness on one side of the body; clumsiness; changes in vision, thinking, or memory; or confusion or personality changes, or difficulty speaking and communicating that may last for several days. Therefore, it is very important that you contact your doctor as soon as possible if you think your MS is worsening or if you notice any new symptoms while being treated with Vumerity. In addition, talk to your partner or caregivers about your treatment. You may develop symptoms that you might not notice yourself.

→ Call your doctor immediately if you experience any of these symptoms

Serious allergic reactions

The frequency of serious allergic reactions cannot be estimated from the available data (frequency not known).

Flushing is a very common adverse effect. However, if the redness 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)
• wheezing, difficulty breathing, or shortness of breath (dyspnea, hypoxia)
• dizziness or loss of consciousness (hypotension)

this could indicate a serious allergic reaction (anaphylaxis).

→ Stop taking Vumerity and call your doctor immediately

Other adverse effects

Very common (may affect more than 1 in 10 people)

• redness of the face or body, feeling of warmth, heat, burning sensation, or itching (flushing)
• soft stools (diarrhea)
• nausea or vomiting
• stomach pain or cramps

Adverse effects that may appear in blood or urine tests

• while being treated with Vumerity, it is very common for urine tests to detect ketones, substances that are naturally produced in the body.
• low levels of white blood cells (lymphopenia, leukopenia) in blood. A decrease in white blood cells may reduce the body's ability to fight infections. If you have a serious infection (such as pneumonia), inform your doctor immediately.

Consult your doctor about how to manage these adverse effects. Your doctor may reduce your dose. Do not reduce the dose yourself unless instructed by your doctor.

Common (may affect up to 1 in 10 people)

• inflammation of the intestinal mucosa (gastroenteritis)
• vomiting
• indigestion (dyspepsia)
• inflammation of the stomach lining (gastritis)
• digestive problems (gastrointestinal disorders)
• burning sensation
• hot flushes, feeling of intense heat
• skin itching (pruritus)
• rash
• itchy, rose-colored or red skin patches (erythema)
• hair loss (alopecia)

Adverse effects that may appear in blood or urine tests

• protein (albumin) in urine (proteinuria)
• increased liver enzymes (ALT, AST) in blood

Uncommon (may affect up to 1 in 100 people)

• allergic reactions (hypersensitivity)
• reduced number of blood platelets

Rare (may affect up to 1 in 1000 people)

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

Frequency not known (cannot be estimated from the available data)

• herpes zoster (shingles) with symptoms such as blisters, burning, itching, or skin pain, usually on one side of the upper body or face, and other symptoms such as fever and weakness in the early stages of infection, followed by numbness, itching, or painful red patches.
• runny nose (rhinorrhea)

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Vumerity

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the bottle and carton after EXP. The expiry date refers to the last day of the month indicated.

Store below 25 °C.

Keep in the original bottle to protect from moisture.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging no longer required. This helps protect the environment.

6. Contents of the pack and other information

Composition of Vumerity

The active substance is diroximel fumarate.

Each capsule contains 231 mg of diroximel fumarate.

The other components are: capsule contents: methacrylic acid and ethyl acrylate copolymer (1:1) type A; crospovidone type A; microcrystalline cellulose; colloidal anhydrous silica; triethyl citrate; talc; magnesium stearate. Capsule coating: hypromellose; titanium dioxide (E171); potassium chloride; carrageenan; capsule printing: black iron oxide (E172), shellac, potassium hydroxide.

Appearance of Vumerity and contents of the pack

Vumerity 231 mg gastro-resistant hard capsules are white and printed with "DRF 231 mg" in black ink.

Vumerity is available in packs containing 120 or 360 capsules (3 x 120).

Only certain pack sizes may be marketed.

Marketing Authorization 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 more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.