Tuvigin ® 0,5 mg Capsules

What TUVIGIN is

TUVIGIN contains the active substance fingolimod, which belongs to a group of medicines known as sphingosine-1-phosphate (S1-P) receptor modulators.

What TUVIGIN is used for

TUVIGIN is used in the treatment of relapsing (returning) multiple sclerosis (MS). TUVIGIN does not cure MS, but it helps to reduce the number of relapses (returns) that occur and to slow the build-up of physical problems due to MS (disability progression).

What is multiple sclerosis

Multiple sclerosis (MS) is a long-term condition that affects the central nervous system (CNS), particularly how the brain and spinal cord work. In MS, inflammation destroys the protective sheath (called myelin) around the nerves in the CNS, and stops the nerves from working properly. This process is called demyelination.

The exact cause of MS is unknown. An abnormal response by the body’s immune system is thought to play an important part in the process which damages the CNS. People with MS experience repeated bouts of nervous system symptoms that reflect inflammation within the CNS. These bouts are typically called attacks or relapses. Symptoms vary from patient to patient but typically involve walking difficulties, numbness, vision problems, and problems with balance. The symptoms of a relapse may disappear completely when the relapse is over but some problems may remain. This form of disease is called relapsing MS, or relapsing-remitting MS.

In some cases, people with relapsing MS find that their symptoms gradually increase between relapses, indicating transition to another form of MS (secondary progressive MS).

How TUVIGIN works

TUVIGIN helps to fight against cells that cause inflammation from reaching the brain. This reduces nerve damage caused by MS.

Do not take TUVIGIN

• if you are allergic to fingolimod or any of the other ingredients of TUVIGIN (listed in section 6)
• if you are pregnant or breastfeeding or a woman of childbearing potential not using effective contraception
• if, in the last 6 months, you have had a heart attack, angina, stroke or warning of a stroke or certain types of heart failure
• if you have certain types of irregular or abnormal heartbeat (arrhythmia), or your electrocardiogram (ECG) shows prolonged QT interval before starting TUVIGIN
• if you are taking or have recently taken medicine for irregular heartbeat such as quinidine, procainamide, amiodarone or sotalol.

Warnings and precautions

You will be observed hourly by a health care professional for at least 6 hours after taking the first dose of TUVIGIN so that your heart rate and blood pressure can be checked. You will be required to have an ECG (electrocardiogram) to check the health of your heart before you start TUVIGIN and a second ECG at the end of the 6-hour observation. In case of abnormal ECG recording or slow heart rate at the end of the 6-hour observation period, you may be observed overnight by a health care professional.

The same recommendation may apply if you start treatment after a break in TUVIGIN therapy, depending on how long the break is and how long you have been receiving treatment.

Checking the health of your heart is particularly important if any of the following applies to you. Your doctor may decide not to use TUVIGIN. If your doctor thinks that TUVIGIN is good for you, he/she may refer you first to a cardiologist (doctor specialised in heart disease). You may also be monitored overnight by a health care professional after taking the first dose of TUVIGIN.

Tell your doctor or pharmacist before taking TUVIGIN:

• if you are taking medicines for an irregular heartbeat such as quinidine, procainamide, amiodarone or sotalol (see “Do not take TUVIGIN”)
• if you have uncontrolled high blood pressure, if when you sleep you are severely affected by interruptions of breathing (sleep apnoea that is not treated), Your doctor may decide not to use TUVIGIN if you have or have had one of these conditions.
• if you suffer from a slow heart rate, if at the start of the treatment with TUVIGIN you are taking medicines that slow your heart rate or if you have a history of sudden loss of consciousness (fainting). Your doctor may decide not to use TUVIGIN or may refer you first to a cardiologist to switch you to medicines that do not slow your heart rate or to decide how you should be observed after you take the first dose of TUVIGIN.
• At the beginning of treatment, TUVIGIN can cause the heart rate to slow down. TUVIGIN can also cause an irregular heartbeat, especially after the first dose. Irregular heartbeat usually returns to normal within one day. Slow heart rate usually returns to normal within one month.
• If your heart rate slows down after your first dose, you may feel dizzy or tired, or may become aware of your heartbeat. If your heart rate slows down too much or your blood pressure drops, you may need treatment right away. In this case you will be monitored overnight by a health care professional and the same observation process that took place for your first dose of TUVIGIN will also apply for the second dose of TUVIGIN.
• If you have no history of chickenpox or have not been vaccinated against varicella zoster virus. Your doctor will test your status of the antibody against the virus and may decide to vaccinate you (if you do not have antibodies to this virus). In this case you will start TUVIGIN treatment one month after the full course of the vaccination is completed.
• Your doctor will consider whether you need to have a vaccination against Human Papilloma Virus (HPV) before starting treatment. If you are a female, your doctor will also recommend HPV screening. HPV infection, including papilloma, dysplasia, warts and HPV-related cancer, has been reported in patients treated with TUVIGIN.
• If you have a lowered immune response (due to a disease or medicines that suppress the immune system, see “Other medicines and TUVIGIN”). You may get infections including opportunistic infections more easily or an infection you already have may get worse.
• If you have an infection, tell your doctor before you take TUVIGIN. Any infection that you already have may get worse. Infections could be serious and sometimes life threatening. Before you start taking TUVIGIN, your doctor will confirm whether you have enough white blood cells in your blood.
• If you plan to receive a vaccine. You should not receive certain types of vaccines (called live attenuated vaccines) during and for up to 2 months after treatment with TUVIGIN (see “Other medicines and TUVIGIN”).
• If you have or have had visual disturbances or other signs of swelling in the central vision area at the back of the eye (a condition known as macular oedema), inflammation or infection of the eye (uveitis) or if you have diabetes. Your doctor may want you to undergo an eye examination before you start TUVIGIN and at regular intervals after the start of TUVIGIN treatment.
• If you have liver problems. You will have a blood test to check your liver function and bilirubin (an orange-yellow substance made during the normal breakdown of red blood cells) before you start taking TUVIGIN and until two months after TUVIGIN discontinuation. TUVIGIN may affect your liver function. A few cases of liver failure have been reported. If you notice yellowing of your skin or the whites of your eyes, abnormally dark urine, pain on the right side of your stomach area (abdomen), feeling less hungry than usual or unexplained nausea, vomiting and tiredness during treatment, tell your doctor straight away.
• If you get any of these symptoms or diseases, while you have started TUVIGIN, tell your doctor straight away because it could be serious:
• If you believe your MS is getting worse (e.g. weakness or visual changes) or if you notice any new or unusual symptoms, because these may be the symptoms of a rare brain disorder caused by an infection and called progressive multifocal leukoencephalopathy (PML).
• Some people get an inflammatory reaction as TUVIGIN is removed from the body. This reaction (known as immune reconstitution inflammatory syndrome or IRIS) may lead to your condition getting worse, including worsening of brain function.
• If you think you have an infection, have fever, feel like you have the flu or have a headache accompanied by stiff neck, sensitivity to light, nausea, and/or confusion or seizures (fits) (these may be caused by a fungal or viral (herpes or varicella zoster) infection and be symptoms of cryptococcal meningitis, meningitis and/or encephalitis).
• A condition called posterior reversible encephalopathy syndrome (PRES) has been reported in MS patients treated with TUVIGIN. Symptoms may include sudden onset of severe headache, confusion, seizures and vision changes.
• A condition with unusually large brain lesions associated with MS relapse has been rarely reported in patients treated with TUVIGIN (a condition called tumefactive lesions). In case of severe relapse, your doctor will consider performing an MRI scan to evaluate this condition and will decide whether you need to stop taking TUVIGIN.
• A type of skin cancer called basal cell carcinoma (BCC) and other cutaneous neoplasms such as malignant melanoma, squamous cell carcinoma, Kaposi’s sarcoma and Merkel cell carcinoma have been reported in MS patients treated with TUVIGIN. Your doctor will carry out regular skin examinations during your treatment with TUVIGIN. Symptoms of BCC may include skin nodules (e.g. shiny pearly nodules), patches or open sores that do not heal within weeks. Symptoms of other cutaneous neoplasms may include abnormal growth or changes of skin tissue (e.g. unusual moles) which may present as a change in colour or size over time. Long-term exposure to the sun and a weak immune system can affect the risk of developing Merkel cell carcinoma. You should limit your exposure to the sun and UV rays by wearing appropriate protective clothing and regularly apply sunscreen with a high degree of UV protection.
• A type of cancer of the lymphatic system (lymphoma) has been reported in MS patients treated with TUVIGIN.
• Tell your doctor straight away, if you get any of the following symptoms or diseases after you have stopped your treatment with TUVIGIN because it could be serious:
• If you believe your MS is getting worse (see section 3 “If you stop taking TUVIGIN” and section 4 “Possible side effects”).

Older people (over 65 years old)

Experience with TUVIGIN in older people is limited. Talk to your doctor if you have any concerns.

Children and adolescents (under 18 years old)

TUVIGIN is not intended for use in children and adolescents, as it has not been studied in MS patients aged under 18.

Other medicines and TUVIGIN

Always tell your healthcare provider if you are taking any other medicine. (This includes all complementary or traditional medicines.)

Tell your doctor if you are taking any of the following medicines:

• Medicines for an irregular heartbeat such as, quinidine, procainamide, amiodarone or sotalol. See section 2 “What you need to know before you take TUVIGIN”.
• Medicines that slow down heartbeat such as beta-blockers (such as atenolol), calcium channel blockers (such as verapamil or diltiazem) or ivabradine or digoxin. Your doctor may decide not to use TUVIGIN or may refer you first to a cardiologist to change your medicines due to a possible added effect on slowing down heartbeat on the first days you start TUVIGIN.
• Medicines that suppress or modulate the immune system including other medicines used to treat MS such as beta-interferon, glatiramer acetate, natalizumab, or mitoxantrone, dimethyl fumarate, teriflunomide, alemtuzumab or corticosteroids due to a possible added effect on the immune system.
• Vaccines. If you need to receive a vaccine, seek your doctor’s advice first. During and for up to 2 months after treatment with TUVIGIN, administration of some vaccines containing live virus (live attenuated vaccines) may result in infection that the vaccination should prevent, while others may not work well. Check with your doctor or pharmacist.

Tell your doctor or a pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

TUVIGIN with food and drink

You can take TUVIGIN with or without food.

Pregnancy and breastfeeding

You should avoid becoming pregnant while taking TUVIGIN or in the two months after you stop taking it because of the risks of harm to the baby. Therefore, if you are a female who could become pregnant, before you start treatment with TUVIGIN, your doctor:

• will tell you about the risk to an unborn baby,
• will ask you to do a pregnancy test in order to ensure that you are not pregnant, and

you should use effective contraception while taking TUVIGIN and for two months after you stop taking it.

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, please consult your doctor, pharmacist or other health care provider for advice before taking this medicine. If you do become pregnant while taking TUVIGIN tell your doctor right away. You and your doctor will decide what is best for you and your baby. See also section 3 “If you stop taking TUVIGIN”.

You should not breastfeed your baby while you are taking TUVIGIN. TUVIGIN can pass into breast milk and there is a risk of serious side effects for a breastfed baby. Talk with your doctor before breastfeeding while you take TUVIGIN.

Ask your doctor or pharmacist for advice before taking any medicine, if you are pregnant or breastfeeding.

Driving and using machinery

Your doctor will tell you whether your illness allows you to drive vehicles and use machines safely. TUVIGIN is not expected to affect your ability to drive and use machines.

TUVIGIN contains sugar (mannitol)

Tuvigin contains mannitol which may have an effect on the control of your blood sugar if you have diabetes mellitus. If you have been told that you have an intolerance to some sugars, you should not take TUVIGIN. TUVIGIN contains mannitol and may have a laxative effect.

Do not share medicines prescribed for you with any other person.

Always take TUVIGIN exactly as your doctor or pharmacist has instructed. Check with your doctor or pharmacist if you are not sure.

Do not exceed the recommended dose.

How much TUVIGIN to take

The dose is one capsule per day (0,5 mg of fingolimod).

How and when to take TUVIGIN

Take TUVIGIN once a day, with half a glass of water. TUVIGIN can be taken with or without food. Taking TUVIGIN at the same time each day will help you remember when to take your medicine.

How long to take TUVIGIN

Do not stop taking TUVIGIN or change your dose without talking to your doctor. If you have questions about how long to take TUVIGIN, talk to your doctor or your pharmacist.

If you take more TUVIGIN than you should or if you have taken a first dose of TUVIGIN by mistake

If you take too much TUVIGIN at one time, or if you have taken a first dose of TUVIGIN by mistake, contact your doctor or pharmacist right away. Your doctor may decide to observe you with heart rate and blood pressure measurements every hour, to run ECGs and he may decide to monitor you overnight. If neither is available, contact the nearest hospital or poison control centre.

If you forget to take TUVIGIN

If you forget a dose, take the next dose as planned. Do not take a double dose to make up for a forgotten dose.

If you have been taking TUVIGIN for less than 2 weeks and you forgot to take a dose for one day, contact your doctor right away. Your doctor may decide to observe you at the time you take the next dose.

If you stop taking TUVIGIN

Do not stop taking TUVIGIN or change your dose without talking to your doctor. After TUVIGIN treatment is stopped, symptoms of MS can return and may become worse compared to before or during treatment. Tell your doctor if you have worsening of MS symptoms after stopping TUVIGIN. TUVIGIN will stay in your body for up to 2 months after you stop taking it. Your white blood cell count (lymphocyte count) may also remain low during this time and the side effects described in this leaflet may still occur.

If you are a woman, see “Pregnancy and breast feeding”. If you have stopped TUVIGIN for 1 day or more during the first 2 weeks of TUVIGIN treatment, if you stop for more than 7 days during weeks 3 and 4 of treatment, or if you stop taking TUVIGIN for more than 2 weeks after your first month of TUVIGIN treatment, the initial effect on your heart rate may occur again. When you restart TUVIGIN treatment, your doctor may decide to monitor your heart rate and blood pressure every hour, to run ECG’s or to keep you under monitoring overnight.

TUVIGIN can have side effects. Not all side effects reported for TUVIGIN are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking TUVIGIN, please consult your health care provider for advice.

If any of the following happens, stop taking TUVIGIN and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Swelling of the hands, feet, ankles, face, lips, mouth or throat, which may cause difficulty in swallowing or breathing;
• rash or itching;
• fainting.

These are all very serious side effects. If you have them, you may have had a serious allergic reaction to TUVIGIN. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

Serious side effects include:

Frequent:

• Bronchitis with symptoms such as cough with phlegm, chest pain, fever
• Gastroenteritis with symptoms such as vomiting, nausea, diarrhoea, fever
• Shingles (herpes zoster) with symptoms such as blisters, burning, itching or pain of the skin, typically on the upper body or the face. Other symptoms may be fever and weakness in the early stages of infection, followed by numbness, itching, and red patches, with severe pain
• Slow heartbeat (bradycardia)
• A type of skin cancer called basal cell carcinoma (BCC) which often appears as a pearly nodule, though it can also take other forms.

Less frequent:

• Pneumonia with symptoms such as fever, cough, difficulty breathing
• Macular oedema (swelling in the central vision area of the retina at the back of the eye) with symptoms such as shadows or blind spot in the center of the vision, blurred vision, problems seeing colours or details
• Melanoma, a type of skin cancer usually developing from an unusual mole (nevus). Possible signs of melanoma include moles which may change size, shape, elevation or colour over time, or new moles. The moles may itch, bleed or ulcerate.
• Convulsion, fits
• A condition called posterior reversible encephalopathy syndrome (PRES). Symptoms may include sudden onset of severe headache, confusion, seizures and vision changes.
• Tumour related to infection with human herpes virus 8 (Kaposi’s sarcoma).
• Serious irregularity in heart beat that is temporary and that usually returns to normal during the 6-hour observation period.
• Thrombocytopenia (a condition in which you have a low blood platelet count)

Frequency not known:

• Liver disease with signs such as yellowing of your skin or the whites of your eyes (jaundice), nausea or vomiting, pain on the right side of your stomach area (abdomen), dark urine, feeling less hungry than usual, tiredness and abnormal liver function tests.
• A rare brain disorder caused by infection and called progressive multifocal leukoencephalopathy (PML). The symptoms of PML may be similar to MS (e.g. weakness or visual changes)
• Cryptococcal infections (a type of fungal infection), including cryptococcal meningitis, or meningitis/encephalitis (caused by herpes or varicella zoster virus) with symptoms such as headache accompanied by stiff neck, sensitivity to light, nausea, and/or confusion or seizures (fits).
• After TUVIGIN treatment is stopped, symptoms of MS can return and may become worse compared to before or during treatment.
• Inflammatory disorder after stopping TUVIGIN treatment (known as immune reconstitution inflammatory syndrome or IRIS)
• Autoimmune form of anaemia (decreased amount of red blood cells) where red blood cells are destroyed (autoimmune haemolytic anaemia)

If you experience any of these, tell your doctor straight away. These are all serious side effects. You may need urgent medical attention.

Tell your doctor if you notice any of the following:

Other frequent side effects are:

• Infection from flu virus with symptoms such as tiredness, chills, sore throat, joint or muscles aching, fever
• Headache
• Diarrhoea
• Back pain
• Blood testing showing higher levels of liver enzymes
• Cough
• Feeling of pressure or pain in the cheeks and forehead (sinusitis)
• Ringworm, a fungal infection of the skin (tinea versicolor)
• Nausea
• Dizziness
• Severe headache often accompanied by nausea, vomiting and sensitivity to light (signs of migraine)
• Weakness
• Itchy, red, burning rash (signs of eczema)
• Itchy skin
• Blood fat (triglycerides) level increased
• Breathlessness
• Abnormal lung function test results starting after one month of treatment, remaining stable after that and reversible after treatment discontinuation
• Blurred vision (see also the information on macular oedema above and section 2 “What you need to know before you take TUVIGIN”)
• Hypertension. TUVIGIN may cause a mild increase in blood pressure
• Low level of white blood cells (lymphopenia, leukopenia)
• Muscle pain
• Joint pain
• Weight loss

If any of these affects you severely, tell your doctor. If you notice any other side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor or pharmacist. You can also report side effects to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who- umc.org) found on SAHPRA website. By reporting side effects, you can help provide more information on the safety of TUVIGIN.

• Store at or below 25 °C, protect from moisture.
• TUVIGIN 0,5 mg capsules must always be stored in the blister to protect from moisture and only be removed immediately before use. The blisters should be kept in the carton until required for use.
• Store all medicines out of the reach of children.
• Do not use after the expiry date shown on the box.
• Return all unused medicine to your pharmacist.
• Do not dispose of unused medicine in drains and sewerage systems (e.g. toilets).