Fingolimod Simphar

Leaflet attached to the packaging: information for the user

Fingolimod Symphar, 0.5 mg, hard capsules
Fingolimodum

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• 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 specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Fingolimod Symphar and what is it used for
• 2. Important information before taking Fingolimod Symphar
• 3. How to take Fingolimod Symphar
• 4. Possible side effects
• 5. How to store Fingolimod Symphar
• 6. Contents of the pack and other information

1. What is Fingolimod Symphar and what is it used for

What is Fingolimod Symphar

The active substance contained in Fingolimod Symphar is fingolimod.

What is Fingolimod Symphar used for

Fingolimod Symphar is used in adults and children and adolescents (aged 10 and over) to treat relapsing-remitting multiple sclerosis (MS), particularly in:

• patients who have not responded to MS treatment or
• patients with rapidly evolving severe MS. Fingolimod Symphar does not cure MS, but helps reduce the number of relapses and slows down the progression of disability caused by MS.

What is multiple sclerosis

MS is a chronic disease of the central nervous system (CNS), consisting of the brain and spinal cord. In MS, the inflammatory process destroys the nerve sheath (called myelin) in the CNS, preventing it from functioning properly. This phenomenon is called demyelination. The relapsing-remitting form of MS is characterized by recurring relapses (exacerbations) of neurological symptoms, reflecting the inflammatory process in the CNS. Symptoms vary among patients, but usually include walking difficulties, numbness, vision problems, or balance problems. Relapse symptoms may completely resolve, but some disturbances may persist.

How Fingolimod Symphar works

Fingolimod Symphar helps protect the CNS from immune system attacks, reducing the ability of certain white blood cells (lymphocytes) to move freely in the patient's body and preventing them from entering the brain and spinal cord. In this way, the medicine reduces nerve damage caused by MS. Fingolimod Symphar also weakens some immune responses of the body.

2. Important information before taking Fingolimod Symphar

When not to take Fingolimod Symphar

• if the patient has a reduced immune response (due to immunodeficiency syndrome, disease, or taking immunosuppressive medications);
• if the patient has a severe active infection or chronic active infection, such as hepatitis or tuberculosis;
• if the patient has an active malignant disease;
• if the patient has severe liver disease;
• if the patient has had a heart attack, angina, stroke, or symptoms of stroke in the last 6 months;
• if the patient has a certain type of irregular or abnormal heartbeat (arrhythmia), including patients who have had an electrocardiogram (ECG) showing a prolonged QT interval before starting treatment with Fingolimod Symphar;
• if the patient is currently taking or has recently taken medications for irregular heartbeat, such as quinidine, disopyramide, amiodarone, or sotalol;
• if the patient is pregnant or is of childbearing age and is not using effective contraception;
• if the patient is allergic to fingolimod or any of the other ingredients of this medicine (listed in section 6). If this is the case, tell your doctor and do not take Fingolimod Symphar.

Warnings and precautions

Before starting treatment with Fingolimod Symphar, discuss with your doctor:

• if the patient has severe respiratory problems during sleep (sleep apnea);
• if the patient has been informed that their ECG is abnormal;
• if the patient has symptoms of slow heart rate (e.g., dizziness, nausea, or palpitations);
• if the patient is taking or has recently taken medications that slow heart rate (such as beta blockers, verapamil, diltiazem, or ivabradine, digoxin, cholinesterase inhibitors, or pilocarpine);
• if the patient has had sudden loss of consciousness or fainting in the past;
• if the patient plans to be vaccinated;
• if the patient has never had chickenpox;
• if the patient has vision problems or other symptoms of macular edema (a condition where the macula, the part of the eye responsible for central vision, becomes swollen) with diabetes, which can cause vision problems;
• if the patient has liver disease;
• if the patient has high blood pressure that cannot be controlled with medication;
• if the patient has severe lung disease or a cough typical of smokers. If any of these situations occur, tell your doctor before taking Fingolimod Symphar.

Low heart rate (bradycardia) and irregular heartbeat
At the beginning of treatment or after taking the first dose of 0.5 mg, Fingolimod Symphar slows down the heart rate. As a result, the patient may feel dizzy, tired, have palpitations, or experience low blood pressure. If these symptoms are severe, tell your doctor, as the patient may need immediate treatment. Fingolimod Symphar may also cause irregular heartbeat, especially after taking the first dose. Irregular heartbeat usually returns to normal within less than one day. Low heart rate usually returns to normal within one month.
Your doctor will ask you to stay in the doctor's office or clinic for at least 6 hours after taking the first dose of Fingolimod Symphar or after the first dose of 0.5 mg if you have been taking a daily dose of 0.25 mg, with hourly measurements of heart rate and blood pressure, so that if any adverse reactions occur that can happen at the beginning of treatment, appropriate treatment can be applied. Before the first dose of Fingolimod Symphar and after completing the 6-hour observation, an ECG will be performed on the patient. During this time, the doctor may continuously monitor the patient's heart activity using an electrocardiogram. If after 6 hours of observation, the patient has a very slow or decreasing heart rate or if the ECG shows abnormalities, the patient may require longer monitoring (for at least 2 hours longer or possibly until the next day) until these symptoms resolve. The same procedure may be recommended if the patient resumes treatment with Fingolimod Symphar after a break in treatment, depending on how long the break lasted and how long the patient took Fingolimod Symphar before the break.
If the patient has irregular or abnormal heartbeat, or risk factors for these events, or abnormal ECG or heart disease, or heart failure, Fingolimod Symphar may not be suitable for them.
If the patient has had sudden loss of consciousness or slow heart rate in the past, Fingolimod Symphar may not be suitable for them in these cases. It may be necessary to consult a cardiologist (a heart specialist) who will advise on how to start treatment with Fingolimod Symphar, including how to monitor the patient at night.
If the patient is taking medications that can slow heart rate, Fingolimod Symphar may not be suitable. It may be necessary to consult a cardiologist who will check if the patient can switch to other medications that do not slow heart rate, to allow treatment with Fingolimod Symphar. If such a change in treatment is not possible, the cardiologist will advise the patient on how to start treatment with Fingolimod Symphar, taking into account monitoring until the next day after administration of the first dose of Fingolimod Symphar.
Patients who have never had chickenpox
If the patient has never had chickenpox, the doctor will check the patient's immunity to the varicella-zoster virus. If the patient is not protected against the virus, they may need to be vaccinated before starting treatment with Fingolimod Symphar. If this is the case, the doctor will delay the start of treatment with Fingolimod Symphar for one month after the full vaccination cycle.
Infections
Fingolimod Symphar reduces the number of white blood cells (especially lymphocytes). White blood cells fight infections. While taking Fingolimod Symphar (and for 2 months after stopping treatment), the patient may be more susceptible to infections. Any existing infections may worsen. Infections can be severe and life-threatening. If the patient thinks they have an infection, have a fever, feel flu-like symptoms, have shingles, or have a headache with stiff neck, sensitivity to light, nausea, rash, and/or confusion or seizures (which can be symptoms of meningitis and/or encephalitis caused by fungal or viral infections), they should contact their doctor immediately, as this condition can be severe and life-threatening. If the patient experiences any of the above symptoms after starting treatment with Fingolimod Symphar, they should tell their doctor immediately.
Before, during, and after treatment, the doctor will order blood tests to monitor liver function. If the test results indicate liver function disorders, treatment with Fingolimod Symphar may be discontinued.
High blood pressure
The doctor may regularly check blood pressure, as Fingolimod Symphar can cause a slight increase in blood pressure.
Lung disease
Fingolimod Symphar has a minor effect on lung function. Patients with severe lung disease or a cough typical of smokers are at greater risk of adverse reactions.
Blood cell count
The expected effect of Fingolimod Symphar is a decrease in the number of white blood cells in the blood. Their number usually returns to normal within 2 months after stopping treatment. If blood tests need to be performed, tell your doctor that you are taking Fingolimod Symphar. Otherwise, the doctor may not be able to interpret the results of the blood test, and in the case of certain tests, the doctor may order more blood to be drawn than usual.
Before starting treatment with Fingolimod Symphar, the doctor will check if the patient has a suitable number of white blood cells in the blood to start treatment and may order regular blood tests to be repeated. If there is not enough white blood cells, it may be necessary to discontinue treatment with Fingolimod Symphar.
Reversible posterior encephalopathy syndrome (PRES)
In patients with MS treated with Fingolimod Symphar, there have been rare reports of a condition called reversible posterior encephalopathy syndrome (PRES). Symptoms of this condition may include severe headache, confusion, seizures, and/or vision changes. If any of these symptoms occur during treatment with Fingolimod Symphar, tell your doctor immediately, as this condition can be severe.
Cancer
There have been reports of skin cancers in patients with MS treated with Fingolimod Symphar. If a lump is found on the skin (e.g., a shiny lump with a pearl-like color), a patch, or an open sore that does not heal within a few weeks, tell your doctor immediately. Symptoms of skin cancer may include abnormal growths or changes in skin tissue (e.g., new moles) that change color, shape, or size over time. Before starting treatment with Fingolimod Symphar, it is necessary to examine the skin for any lumps. The treating doctor will also perform regular skin checks during treatment with Fingolimod Symphar. If skin problems occur, the treating doctor may refer the patient to a dermatologist, who may decide on the need for regular visits after consulting with the patient.
Patients with MS treated with Fingolimod Symphar have also reported a type of lymphoma (a type of cancer of the lymphatic system).
Exposure to the sun and protection against sunlight
Fingolimod weakens the immune system. This increases the risk of developing malignant tumors, especially skin cancers. The patient should limit exposure to the sun and UV radiation by:

• wearing protective clothing,
• regularly applying sunscreen with a high level of protection against UV radiation.

Unusual changes in the brain associated with MS relapse
There have been rare reports of unusually large changes in the brain associated with MS relapse in patients treated with Fingolimod Symphar. In the case of a severe MS relapse, the treating doctor will consider performing an MRI to assess this condition and decide on the possible need to discontinue Fingolimod Symphar.

Switching from other medicines to Fingolimod Symphar
The doctor may switch treatment directly from interferon beta, glatiramer acetate, or dimethyl fumarate to Fingolimod Symphar if there are no symptoms of abnormalities caused by previous treatment. The doctor may order a blood test to rule out these abnormalities. After stopping treatment with natalizumab, it may be necessary to wait 2 to 3 months before starting treatment with Fingolimod Symphar. When switching from teriflunomide, the doctor may advise the patient to wait for some time or undergo an accelerated elimination procedure. Patients previously treated with alemtuzumab require careful evaluation and discussion with their doctor before deciding whether Fingolimod Symphar is suitable for them.
Women of childbearing age
If Fingolimod Symphar is used during pregnancy, it may harm the unborn child. Before starting treatment with Fingolimod Symphar, the doctor will explain the risk to the patient and ask them to perform a pregnancy test to rule out pregnancy. The doctor will give the patient a card explaining why they should not become pregnant while taking Fingolimod Symphar. The card also contains information on what to do to avoid becoming pregnant while taking Fingolimod Symphar. Patients must use effective contraception during treatment and for 2 months after stopping treatment (see "Pregnancy and breastfeeding").
If the patient becomes pregnant while taking Fingolimod Symphar, they should tell their doctor immediately. The doctor will decide on discontinuing treatment (see "Discontinuing Fingolimod Symphar" in section 3, and also section 4 "Possible side effects"). The patient will also need to undergo prenatal check-ups.
Breastfeeding
Do not breastfeed while taking Fingolimod Symphar. Fingolimod Symphar may pass into breast milk, posing a risk of severe side effects in the child.

Driving and using machines

The doctor will inform the patient whether their condition allows them to drive vehicles safely, including cycling and operating machinery. It is not expected that Fingolimod Symphar will affect the ability to drive vehicles and operate machinery. However, at the beginning of treatment, the patient must stay in the doctor's office or clinic for 6 hours after taking the first dose of Fingolimod Symphar. During this time and potentially after it, the ability to drive vehicles and operate machinery may be impaired.

3. How to take Fingolimod Symphar

Treatment with Fingolimod Symphar will be supervised by a doctor with experience in treating multiple sclerosis. This medicine should always be taken exactly as prescribed by your doctor. If you are unsure, ask your doctor. The recommended dose is: Adults: The dose is one 0.5 mg capsule per day. Children and adolescents (aged 10 and over): The dose depends on body weight:

• Children and adolescents weighing 40 kg or less: one 0.5 mg capsule per day.
• Children and adolescents weighing more than 40 kg: one 0.5 mg capsule per day.

Fingolimod Symphar is for oral use. Fingolimod Symphar should be taken once a day, with a glass of water. Fingolimod Symphar capsules should always be swallowed whole, without opening. Fingolimod Symphar can be taken with or without food. Taking Fingolimod Symphar at the same time every day will help you remember to take your medicine. If you are unsure about the duration of treatment with Fingolimod Symphar, ask your doctor or pharmacist.

Taking a higher dose of Fingolimod Symphar than recommended

If you have taken more than the recommended dose, contact your doctor immediately.

Missing a dose of Fingolimod Symphar

If you have been taking Fingolimod Symphar for less than 1 month and have missed a dose for the entire day, contact your doctor before taking the next dose. Your doctor may decide to keep you under observation during the next dose. If you have been taking Fingolimod Symphar for at least 1 month and have missed taking the medicine for more than 2 weeks, contact your doctor before taking the next dose. Your doctor may decide to keep you under observation during the next dose. However, if you have missed taking the medicine for up to 2 weeks, you can take the next dose as planned. Do not take a double dose to make up for a missed dose.

Stopping treatment with Fingolimod Symphar

Do not stop taking Fingolimod Symphar or change the dose without consulting your doctor first. Fingolimod Symphar stays in the body for up to 2 months after stopping treatment. During this time, the number of white blood cells (lymphocytes) may also be reduced, and side effects described in this leaflet may still occur. After stopping treatment with Fingolimod Symphar, wait 6-8 weeks before starting new MS treatment. In patients resuming treatment with Fingolimod Symphar after more than 2 weeks off the medicine, the effect on heart rate seen after the first dose may occur again, and monitoring of the patient's condition in the doctor's office or clinic will be necessary due to the resumption of treatment. Do not resume treatment with Fingolimod Symphar after a break of more than 2 weeks without consulting your doctor. The treating doctor will decide whether and how to monitor the patient after stopping treatment with Fingolimod Symphar. If you think your MS is getting worse after stopping treatment with Fingolimod Symphar, tell your doctor immediately. This situation can be serious. If you have any further questions about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Fingolimod Symphar can cause side effects, although not everybody gets them. Some side effects may be serious or become serious
Common(may affect up to 1 in 10 people):

• Cough with expectoration, unspecified unpleasant chest sensation, fever (respiratory symptoms),
• Herpesvirus infections (shingles or herpes) with symptoms such as blisters, burning, itching, or pain of the skin, usually above the upper body or face. Other symptoms may include fever and weakness at the beginning of the infection, followed by numbness, itching, or red spots with severe pain,
• Slow heart rate (bradycardia), irregular heartbeat,
• A type of skin cancer called basal cell carcinoma (BCC), which often appears as a pearl-like lump, although it can have a different appearance,
• Depression and anxiety are known to occur more frequently in the MS population and have also been reported in children and adolescents treated with Fingolimod Symphar.
• Weight loss. Uncommon(may affect up to 1 in 100 people):
• Pneumonia with symptoms such as fever, cough, difficulty breathing,
• Macular edema (swelling in the center of the field of vision in the retina, at the back of the eye) with symptoms such as shadows or blind spots in the center of the field of vision, blurred vision, difficulty seeing colors and details,
• Reduced platelet count, which increases the risk of bleeding or bruising,
• Malignant melanoma (a type of skin cancer that usually develops from an unusual mole). Possible symptoms of melanoma include moles that change in size, shape, or color over time. Moles can be itchy, bleed, or ulcerate.
• Seizures, epileptic seizures (more common in children and adolescents than in adults). Rare(may affect up to 1 in 1,000 people):
• A condition called posterior reversible encephalopathy syndrome (PRES). Symptoms may include severe headache, confusion, seizures, and/or vision changes,
• Lymphoma (a type of cancer affecting the lymphatic system),
• Squamous cell carcinoma: a type of skin cancer that can appear as a hard, red lump, an ulcer covered with a scab, or a fresh ulcer in the place of an existing scar. Very rare(may affect up to 1 in 10,000 people):
• Abnormalities in the ECG recording (T-wave inversion),
• Kaposi's sarcoma (a type of cancer associated with human herpesvirus 8). Frequency not known(frequency cannot be estimated from the available data):
• Allergic reactions, including symptoms such as rash, itching, or hives, swelling of the lips, tongue, or face, which are more likely to occur on the day of starting treatment with Fingolimod Symphar,
• Liver disease symptoms (including liver failure) such as yellowing of the skin or whites of the eyes (jaundice), nausea or vomiting, pain in the right upper abdomen, dark (brown) urine, decreased appetite, fatigue, and abnormal liver function test results. In very rare cases, liver failure can lead to liver transplantation.
• Risk of a rare brain infection called progressive multifocal leukoencephalopathy (PML). Symptoms of PML may be similar to an MS relapse. They may also include symptoms that the patient is not aware of, such as mood or behavior changes, transient memory lapses, difficulty speaking or communicating, which should be evaluated by the doctor to rule out PML. Therefore, if the patient thinks their MS is getting worse or if the patient or their relatives notice any new or unusual symptoms, it is very important to tell their doctor as soon as possible.
• Cryptococcal infections (a type of fungal infection), including cryptococcal meningitis with symptoms such as headache, stiff neck, sensitivity to light, nausea, and/or confusion.
• Merkel cell carcinoma (a type of skin cancer). Possible symptoms of Merkel cell carcinoma include a painless lump with a raw meat or blue-red color, usually located on the face, head, or neck. Merkel cell carcinoma can also appear as a hard, painless lump or mass. Prolonged sun exposure and weakened immune system can affect the risk of Merkel cell carcinoma.
• After stopping treatment with Fingolimod Symphar, MS symptoms may relapse and worsen compared to the period before treatment and during treatment.
• Autoimmune hemolytic anemia (a condition where red blood cells are destroyed). If you experience any of these side effects, tell your doctor immediately.

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

• Influenza infection with symptoms such as fatigue, chills, sore throat, joint or muscle pain, fever,
• Feeling of pressure or pain in the cheeks and forehead (sinusitis),
• Headache,
• Diarrhea,
• Back pain,
• Increased liver enzyme activity in blood tests,
• Cough. Common(may affect up to 1 in 10 people):
• Fungal skin infections (dermatophyte infections) (ringworm),
• Dizziness,
• Severe headache, usually accompanied by nausea, vomiting, and sensitivity to light (migraine symptoms),
• Low white blood cell count (lymphocytes, leukocytes),
• Weakness,
• Itchy, red, burning rash (rash),
• Itching,
• Increased triglyceride levels in the blood,
• Hair loss,
• Shortness of breath,
• Depression,
• Blurred vision (see also the section on macular edema under "Some side effects may be serious or become serious"),
• Hypertension (Fingolimod Symphar may cause a mild increase in blood pressure),
• Muscle pain,
• Joint pain. Uncommon(may affect up to 1 in 100 people):
• Low neutrophil count,
• Depressed mood,
• Nausea. Rare(may affect up to 1 in 1,000 people):
• Lymphoma (a type of cancer affecting the lymphatic system). Frequency not known(frequency cannot be estimated from the available data):
• Peripheral edema. If any of these symptoms occur with significant severity, tell your doctor.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Fingolimod Symphar

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date stated on the carton and blister after EXP. The expiry date refers to the last day of the month stated. Do not store above 30°C. Store in the original package to protect from moisture. Do not use medicines from damaged or opened packages. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What does Fingolimod Symphar contain

• The active substance of the medicinal product is fingolimod. Each capsule contains 0.5 mg of fingolimod (in the form of fingolimod hydrochloride).
• Other ingredients are: Capsule filling: potassium citrate monohydrate, colloidal silica anhydrous, magnesium stearate. Capsule body: gelatin, titanium dioxide (E171). Capsule cap: gelatin, titanium dioxide (E171), iron oxide yellow (E172).

What Fingolimod Symphar looks like and what the pack contains

Fingolimod Symphar 0.5 mg hard capsules (16 mm, size 3) consist of a white, opaque body and a yellow, opaque cap.
Blister:
Fingolimod Symphar 0.5 mg is available in packs containing 7, 28 or 98 hard capsules.
Single-dose blister:
Fingolimod Symphar 0.5 mg is available in packs containing 7, 28, 98 or 100 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder

Symphar Sp. z o. o.
Koszykowa 65 Street
00-667 Warsaw

Manufacturer/Importer

Synthon Hispania S.L.
C/ Castelló 1
Sant Boi De Llobregat
08830 Barcelona
Spain
Synthon BV
Microweg 22
6545 CM Nijmegen
Netherlands

This medicinal product is authorised in the Member States of the European

Economic Area under the following names:

Netherlands
Fingolimod Synthon 0.5 mg, hard capsules
Germany Fingolimod Holsten 0.5 mg hard capsules
Estonia Fingolimod Norameda
Finland
Fingolimod Avansor
France
Fingolimod Synthon 0.5 mg, capsules
Hungary
Fingolimod-Q Pharma 0.5 mg hard capsules
Iceland
Fingolimod WH
Croatia
Fingolimod Alpha-Medical 0.5 mg hard capsules
Latvia
Fingolimod Norameda 0.5 mg hard capsules
Lithuania
Fingolimod Norameda 0.5 mg hard capsules
Poland Fingolimod Symphar
Portugal Fingolimod Reig Jofre
Spain Fingolimod Sala 0.5 mg hard capsules EFG
United Kingdom Fingolimod 0.5 mg, hard capsules
Sweden
Fingolimod Avansor
Date of last revision of the leaflet:January 2022