Dimethyl fumarate 120 mg gastro-resistant hard capsules

• 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 you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

Dimethyl fumarate 120 mg and 240 mg hard capsules (referred to as dimethyl fumarate throughout this leaflet) is a medicine that contains the active substance dimethyl fumarate.

Dimethyl fumarate is used to treat relapsing-remitting multiple sclerosis (MS) in patients aged 13 years and older.

MS is a long-term condition that affects the central nervous system (CNS), including the brain and the spinal cord. Relapsing-remitting MS is characterised by repeated attacks (relapses) of nervous system symptoms. Symptoms vary from patient to patient, but typically include walking difficulties, feeling off balance and visual difficulties (e.g. blurred or double vision). These symptoms may disappear completely when the relapse is over, but some problems may remain.

Dimethyl fumarate seems to work by stopping the body’s defence system from damaging your brain and spinal cord. This may also help to delay future worsening of your MS.

• if you are allergic to dimethyl fumarate or any of the other ingredients of this medicine (listed in section 6).
• if you are suspected to suffer from a rare brain infection called progressive multifocal leukoencephalopathy (PML) or if PML has been confirmed.

Dimethyl fumarate may affect your white blood cell counts, your kidneys and liver. Before you start dimethyl fumarate, your doctor will do a blood test to count the number of your white blood cells and will check that your kidneys and liver are working properly. Your doctor will test these periodically during treatment. If your number of white blood cells decreases during treatment, your doctor may consider additional tests or discontinue your treatment.

Talk to your doctor before taking dimethyl fumarate if you have:

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

Herpes zoster (shingles) may occur with dimethyl fumarate treatment. In some cases, serious complications have occurred. You should inform your doctor immediately if you suspect you have any symptoms of shingles.

If you believe your MS is getting worse (e.g. weakness or visual changes) or if you notice any new symptoms, talk to your doctor straight away because these may be the symptoms of a rare brain infection called PML. PML is a serious condition that may lead to severe disability or death.

A rare but serious kidney disorder (called Fanconi syndrome) has been reported with a medicine containing dimethyl fumarate, in combination with other fumaric acid esters, used to treat psoriasis (a skin disease). If you notice you are passing more urine, are thirstier and drinking more than normal, your muscles seem weaker, you break a bone, or just have aches and pains, talk to your doctor as soon as possible so that this can be investigated further.

Do not give this medicine to children below 10 years of age because no data are available in this age group.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, in particular:

• medicines that contain fumaric acid esters (fumarates) used to treat psoriasis;
• medicines that affect the body’s immune system including chemotherapy, immunosuppressants, or other medicines used to treat MS;
• medicines that affect the kidneys including some antibiotics (used to treat infections), “water tablets” (diuretics), certain types of painkillers (such as ibuprofen and other similar anti-inflammatories and medicines purchased without a doctor’s prescription) and medicines that contain lithium;
• taking this medicine with certain types of vaccines (live vaccines) may cause you to get an infection and should, therefore, be avoided. Your doctor will advise whether other types of vaccines (non-live vaccines) should be given.

Consumption of more than a small amount (more than 50 ml) of strong alcoholic drinks (more than 30% alcohol by volume, e.g. spirits) should be avoided within an hour of taking dimethyl fumarate, as alcohol can interact with this medicine. This could cause inflammation of the stomach (gastritis), especially in people already prone to gastritis.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

There is limited information about the effects of this medicine on the unborn child if used during pregnancy. Do not use dimethyl fumarate if you are pregnant unless you have discussed this with your doctor and this medicine is clearly necessary for you.

Breast-feeding

It is not known whether the active substance of this medicine passes into breast milk. Your doctor will advise whether you should stop breastfeeding, or stop using dimethyl fumarate. This involves balancing the benefit of breast-feeding for your child, and the benefit of therapy for you.

This medicine is not expected to affect your ability to drive and use machines.

120 mg twice a day.

Take this starting dose for the first 7 days, then take the regular dose.

240 mg twice a day.

Dimethyl fumarate is for oral use.

Swallow each capsule whole, with some water. Do not divide, crush, dissolve, suck or chew the capsule as this may increase some side effects.

Take dimethyl fumarate with food - it may help to reduce some of the very common side effects (listed in section 4).

If you have taken too many capsules, talk to your doctor straight away. You may experience side effects similar to those described below in section 4.

If you forget or miss a dose, do not take a double dose.

You may take the missed dose if you leave at least 4 hours between the doses. Otherwise wait until your next planned dose.

Dimethyl fumarate may lower lymphocyte counts (a type of white blood cell). Having a low white blood cell count can increase your risk of infection, including the risk of a rare brain infection called progressive multifocal leukoencephalopathy (PML). PML may lead to severe disability or death. PML has occurred after 1 to 5 years of treatment and so your physician should continue to monitor your white blood cells throughout your treatment, and you should remain observant of any potential symptoms of PML as described below. The risk of PML may be higher if you have previously taken a medicine impairing the functionality of your body’s immune system.

The symptoms of PML may be similar to an MS relapse. Symptoms may include new or worsening weakness on one side of the body; clumsiness; changes in vision, thinking, or memory; or confusion or personality changes, or speech and communication difficulties lasting for more than several days.

Therefore, if you believe your MS is getting worse or if you notice any new symptoms while you are on dimethyl fumarate treatment, it is very important that you speak to your doctor as soon as possible. Also speak with your partner or caregivers and inform them about your treatment. Symptoms might arise that you might not become aware of by yourself.

Call your doctor straight away if you experience any of these symptoms

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

Reddening of the face or body (flushing) is a very common side effect. However, should flushing be accompanied by a red rash or hives and you get any of these symptoms:

• Swelling of the face, lips, mouth, or tongue (angioedema)
• Wheezing, difficulty breathing or shortness of breath (dyspnoea, hypoxia)
• Dizziness or loss of consciousness (hypotension), then this may represent a severe allergic reaction (anaphylaxis)

Stop taking dimethyl fumarate and call a doctor straight away.

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

• Reddening of the face or body, feeling warm, hot, burning, or itchy (flushing)
• Loose stools (diarrhoea)
• Feeling sick (nausea)
• Stomach pain or stomach cramps

Taking your medicine with food can help to reduce the side effects above.

Substances called ketones, which are naturally produced in the body, very commonly show up in urine tests while taking dimethyl fumarate.

Talk to your doctor about how to manage these side effects. Your doctor may reduce your dose. Do not reduce your dose unless your doctor tells you to.

Common (may affect up to 1 in 10 people)

• Inflammation of the lining of the intestines (gastroenteritis)
• Being sick (vomiting)
• Indigestion (dyspepsia)
• Inflammation of the lining of the stomach (gastritis)
• Gastrointestinal disorder
• Burning sensation
• Hot flush, feeling hot
• Itchy skin (pruritus)
• Rash
• Pink or red blotches on the skin (erythema)
• Hair loss (alopecia)

• Low levels of white blood cells (lymphopenia, leucopenia) in the blood. Reduced white blood cells could mean your body is less able to fight an infection. If you have a serious infection (such as pneumonia), talk to your doctor immediately
• Proteins (albumin) in urine
• Increase in levels of liver enzymes (ALT, AST) in the blood

Uncommon (may affect up to 1 in 100 people)

• Allergic reactions (hypersensitivity)
• Reduction in blood platelets

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

• Liver inflammation and increase in levels of liver enzymes (ALT or AST in combination with bilirubin)
• Herpes zoster (shingles) with symptoms such as blisters, burning, itching or pain of the skin, typically on one side of the upper body or the face, and other symptoms, like fever and weakness in the early stages of infection, followed by numbness, itching or red patches with severe pain
• Runny nose (rhinorrhoea)

The side effects listed above also apply to children and adolescents.

Some side effects were reported more frequently in children and adolescents than in adults, e.g, headache, stomach pain or stomach cramps, being sick (vomiting), throat pain, cough, and painful menstrual periods.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

The active substance is dimethyl fumarate.

Dimethyl fumarate 120 mg: Each capsule contains 120 mg of dimethyl fumarate.

Dimethyl fumarate 240 mg: Each capsule contains 240 mg of dimethyl fumarate.

The other ingredients are:

Capsule content: cellulose, microcrystalline, povidone K30, crospovidone, silica colloidal anhydrous, magnesium stearate, talc, triethyl citrate, methacrylic acid/ethylacrylate copolymer (1:1), hypromellose, titanium dioxide (E171), triacetin.

Capsule shell: gelatin, titanium dioxide (E171), brilliant blue FCF (E133), yellow iron oxide (E172), black ink (shellac, potassium hydroxide, propylene glycol (E1520), black iron oxide (E172), strong ammonia solution).

Dimethyl fumarate 120 mg: Green opaque cap and white opaque body, capsule shell size no. 0, length 21.4 mm, imprinted in black ink with “DMF 120” on the body containing white to off-white minitablets.

Dimethyl fumarate 240 mg: Green opaque cap and body, capsule shell size no. 00, length 23.2 mm, imprinted in black ink with “DMF 240” on the body containing white to off-white minitablets.

Carton containing OPA/Alu/PVC//Alu blisters.

Dimethyl fumarate 120 mg: Packs containing 14 capsules.

Dimethyl fumarate 240 mg: Packs containing 56 or 168 capsules.

Not all pack sizes may be marketed.

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