Fingolimod Zentiva

Package Leaflet: Information for the User

Fingolimod Zentiva, 0.5 mg hard capsules

Fingolimod

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

• Keep this leaflet, as 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the Package Leaflet

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

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

What Fingolimod Zentiva is

Fingolimod Zentiva contains the active substance fingolimod.

What Fingolimod Zentiva is used for

Fingolimod Zentiva is used to treat adults and children and adolescents (aged 10 years and older, weighing over 40 kg) with a relapsing-remitting form of multiple sclerosis (MS), in particular for:

• patients who have not responded to MS treatment, or
• patients with rapidly evolving, severe MS.

Fingolimod Zentiva does not cure MS, but it helps reduce the number of relapses and slows down the progression of disability caused by MS.

What multiple sclerosis is

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 when the relapse is over, but some disturbances may persist.

How Fingolimod Zentiva works

Fingolimod Zentiva helps protect the CNS from immune system attacks by 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 Zentiva also weakens some immune responses of the body.

2. Important information before taking Fingolimod Zentiva

When not to take Fingolimod Zentiva

• if you have a reduced immune response (due to immunodeficiency syndrome, disease, or taking immunosuppressive medicines),
• if your doctor suspects that you have a rare brain infection called progressive multifocal leukoencephalopathy (PML) or if you have been diagnosed with PML,
• if you have a severe active infection or chronic active infection, such as hepatitis or tuberculosis,
• if you have an active malignant disease,
• if you have severe liver disease,
• if you have had a heart attack, angina, stroke, or symptoms of stroke in the last 6 months,
• if you have a certain type of irregular or abnormal heartbeat (arrhythmia), including those with a prolonged QT interval on an electrocardiogram (ECG) before starting treatment with Fingolimod Zentiva,
• if you are currently taking or have recently taken medicines for irregular heartbeat, such as quinidine, disopyramide, amiodarone, or sotalol,
• if you are pregnant or breastfeeding or are of childbearing age and not using effective contraception.
• if you are allergic to fingolimod or any of the other ingredients of this medicine (listed in section 6),

If any of these situations apply to you, or if you are not sure, consult your doctor before taking Fingolimod Zentiva.

Warnings and precautions

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

• if you have severe breathing difficulties during sleep (severe sleep apnea),
• if you have been informed that your ECG is abnormal,
• if you experience symptoms of low heart rate (such as dizziness, nausea, or palpitations),
• if you are taking or have recently taken medicines that slow down your heart rate (such as beta blockers, verapamil, diltiazem, or ivabradine, digoxin, cholinesterase inhibitors, or pilocarpine),
• if you have had a sudden loss of consciousness or fainting in the past,
• if you are planning to be vaccinated,
• if you have never had chickenpox,
• if you have or have had vision problemsor other symptoms of macular edema (a condition where the macula, the part of the eye responsible for central vision, becomes swollen) or uveitis (inflammation of the uvea, the middle layer of the eye) or if you have diabetes(which can cause vision problems),
• if you have liver problems,
• if you have high blood pressure that cannot be controlled with medication,
• if you have severe lung diseaseor a cough typical of smokers. If any of these situations apply to you or if you are not sure, consult your doctor before taking Fingolimod Zentiva.

Low heart rate (bradycardia) and irregular heartbeat At the beginning of treatment or after taking the first dose of 0.5 mg in patients who have previously taken a daily dose of 0.25 mg, Fingolimod Zentiva slows down the heart rate. As a result, the patient may experience dizziness, fatigue, or be aware of their heartbeat or may experience low blood pressure. If these symptoms are severe, you should inform your doctor, as you may need immediate treatment.Fingolimod Zentiva may also cause irregular heartbeat, especially after taking the first dose. Irregular heartbeat usually returns to normal within less than 1 day. Low heart rate usually returns to normal within 1 month. During this period, no clinically significant effect on heart rate is expected. 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 Zentiva or after the first dose of 0.5 mg when changing treatment from a daily dose of 0.25 mg, with hourly measurements of pulse and blood pressure, so that if any adverse reactions occur that happen at the beginning of treatment, appropriate treatment can be applied. Before administering the first dose of Fingolimod Zentiva 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, it may be necessary to extend the monitoring of the patient's condition (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 Zentiva after a break in treatment, depending on how long the break lasted and how long the patient took Fingolimod Zentiva 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 Zentiva may not be suitable for them. If the patient has had a sudden loss of consciousness or slow heart rate in the past, Fingolimod Zentiva may not be suitable for them. It may be necessary to consult a cardiologist (a heart specialist) who will advise on how to start treatment with Fingolimod Zentiva, including how to monitor the patient at night. If the patient is taking medicines that can slow down the heart rate, Fingolimod Zentiva may not be suitable. It may be necessary to consult a cardiologist to check if the patient can switch to other medicines that do not slow down the heart rate to allow treatment with Fingolimod Zentiva. If such a change in treatment is not possible, the cardiologist will advise on how to start treatment with Fingolimod Zentiva, taking into account nighttime monitoring. 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 Zentiva. If this is the case, the doctor will delay the start of treatment with Fingolimod Zentiva by 1 month after completing the full vaccination course. Infections Fingolimod Zentiva reduces the number of white blood cells (especially lymphocytes). White blood cells fight infections. While taking Fingolimod Zentiva (and for up to 2 months after stopping treatment), the patient may be more prone 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 may 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. Cases of human papillomavirus (HPV) infection, including cases of dysplasia, warts, and HPV-related malignancy, have been reported in patients treated with fingolimod. The doctor will consider the need for HPV vaccination before starting treatment. In women, the doctor will also recommend screening for HPV. PML PML is a rare brain disorder caused by infection that can lead to severe disability or death. The treating doctor will order an MRI scan before starting treatment and during treatment to monitor the risk of PML. If the patient thinks their MS is getting worse or if they notice new symptoms, such as mood or behavior changes, new weakness, or vision changes, confusion, memory problems, or speech and communication difficulties, they should talk to their doctor as soon as possible. These may be symptoms of PML. The patient should also talk to their partner or caregivers and inform them about the treatment they are taking. There may be symptoms that the patient is not aware of. If the patient develops PML, the condition can be treated, and Fingolimod Zentiva treatment will be discontinued. In some patients, after Fingolimod Zentiva is removed from the body, an inflammatory reaction (called immune reconstitution inflammatory syndrome, IRIS) may occur, which can worsen the patient's condition, including brain function. Macular edema Before starting treatment with Fingolimod Zentiva, the doctor may refer patients with existing or past vision problems or other symptoms of macular edema (a condition where the macula, the part of the eye responsible for central vision, becomes swollen) or uveitis (inflammation of the uvea, the middle layer of the eye) or diabetes for eye examinations. The doctor may also refer the patient for eye examinations 3 to 4 months after starting treatment with Fingolimod Zentiva. The macula is a small area of the retina that allows for sharp, clear vision of shapes, colors, and other details. Fingolimod Zentiva may cause macular edema, a condition called macular edema. Macular edema usually occurs within the first 4 months of treatment with Fingolimod Zentiva. The risk of macular edema is higher in patients with diabetesor a history of uveitis. In such cases, the doctor will recommend regular eye examinations to detect macular edema. If macular edema occurs, the patient should inform their doctor before resuming treatment with Fingolimod Zentiva. Macular edema may cause vision problems similar to those experienced during an MS relapse (optic neuritis). In the early stages, symptoms may not occur at all. The patient should inform their doctor about any changes in vision. The doctor may refer the patient for eye examinations, especially if:

• The center of the visual field becomes blurry or shaded;
• A defect appears in the center of the visual field;
• There are difficulties with color vision or fine details.

Liver function tests Patients with severe liver disease should not take Fingolimod Zentiva. Fingolimod Zentiva may affect liver function tests. The patient is unlikely to experience any symptoms, but if they notice yellowing of the skin or whites of the eyes, dark (brown) urine, pain in the right upper abdomen, fatigue, decreased appetite, or unexplained nausea and vomiting, they should tell their doctor immediately. If any of these symptoms occur after starting treatment with Fingolimod Zentiva, the patient 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 Zentiva may be discontinued. High blood pressure The doctor may regularly check the patient's blood pressure, as Fingolimod Zentiva can cause a slight increase in blood pressure. Lung problems Fingolimod Zentiva has a minor effect on lung function. Patients with severe lung disease or a cough typical of smokers are at higher risk of adverse reactions. Blood cell count The expected effect of Fingolimod Zentiva is a reduction 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 are needed, the patient should inform their doctor that they are taking Fingolimod Zentiva. Otherwise, the doctor may not be able to interpret the blood test results, and in the case of certain tests, the doctor may order more blood to be drawn than usual. Before starting treatment with Fingolimod Zentiva, 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. If there are not enough white blood cells, it may be necessary to discontinue treatment with Fingolimod Zentiva. Posterior reversible encephalopathy syndrome (PRES) In patients with MS treated with fingolimod, rare cases of a condition called posterior reversible encephalopathy syndrome (PRES) have been reported. Symptoms of this condition may include severe headache, confusion, seizures, and vision changes. If any of these symptoms occur during treatment with Fingolimod Zentiva, the patient should tell their doctor immediately, as this condition can be severe. Cancer In patients with MS treated with fingolimod, cases of skin cancer have been reported. If the patient notices any lumps on the skin (such as shiny lumps with a pearl-like color), spots, or open sores that do not heal within a few weeks, they should tell their doctor immediately. Symptoms of skin cancer may include abnormal growths or changes in skin tissue (such as new moles) that change color, shape, or size over time. Before starting treatment with Fingolimod Zentiva, it is necessary to examine the skin for any lumps. The treating doctor will also perform regular skin checks during treatment with Fingolimod Zentiva. If skin problems occur, the doctor may refer the patient to a dermatologist, who may decide on the need for regular visits after consulting with the patient. In patients with MS treated with fingolimod, cases of a type of cancer of the lymphatic system (lymphoma) have been reported. Exposure to sunlight and protection from ultraviolet radiation Fingolimod weakens the immune system. This increases the risk of developing malignant tumors, especially skin cancer. The patient should limit exposure to sunlight and ultraviolet radiation by:

• wearing protective clothing.
• applying sunscreen with a high sun protection factor regularly.

Unusual changes in the brain associated with MS relapse In patients treated with fingolimod, rare cases of unusually large brain lesions associated with MS relapse have been reported. In the event of a severe MS relapse, the treating doctor will consider performing an MRI scan to assess this condition and decide whether to discontinue Fingolimod Zentiva. Changing treatment from other medicines to Fingolimod Zentiva The doctor may switch treatment directly from interferon beta, glatiramer acetate, or dimethyl fumarate to Fingolimod Zentiva if there are no symptoms of abnormality 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 Zentiva. When changing treatment from teriflunomide, the doctor may advise the patient to wait for a certain period or undergo an accelerated elimination procedure. Patients previously treated with alemtuzumab require careful evaluation and discussion with their doctor before deciding whether Fingolimod Zentiva is suitable for them. Women of childbearing age If fingolimod is used during pregnancy, it may harm the unborn baby. Before starting treatment with Fingolimod Zentiva, the doctor will explain the risk to the patient and ask them to have 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 Zentiva. The card also contains information on what to do to avoid becoming pregnant while taking Fingolimod Zentiva. Female patients must use effective contraception during treatment and for 2 months after stopping treatment (see "Pregnancy and breastfeeding").

The doctor will give the patient a card explaining why they should not become pregnant while taking Fingolimod Zentiva.

If the patient becomes pregnant while taking Fingolimod Zentiva, they should tell their doctor immediately.

The doctor will decide whether to discontinue treatment (see "Stopping Fingolimod Zentiva" in section 3, and also section 4 "Possible side effects"). The patient will also need to attend prenatal check-ups. Breastfeeding Do not breastfeed while taking Fingolimod Zentiva. Fingolimod may pass into breast milk, posing a risk of severe side effects to the baby.

Driving and using machines

The doctor will inform the patient whether their condition allows them to drive vehicles, including bicycles, and operate machinery. It is not expected that Fingolimod Zentiva 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 at least 6 hours after taking the first dose of Fingolimod Zentiva. During this time and potentially after it, the ability to drive vehicles and operate machinery may be impaired.

3. How to take Fingolimod Zentiva

Treatment with Fingolimod Zentiva will be supervised by a doctor with experience in treating multiple sclerosis.

This medicine should always be taken exactly as prescribed by the doctor. If the patient is unsure, they should ask their doctor.

The recommended dose is:

Adults

The dose is one 0.5 mg capsule per day.

Children and adolescents (aged 10 years and older): The dose depends on body weight:

• Children and adolescents weighing over 40 kgshould take one 0.5 mg capsule per day.
• Children and adolescents weighing 40 kg or lessshould take other suitable doses. Children and adolescents starting treatment with a 0.25 mg capsule per day and later achieving a stable weight over 40 kg will be advised by their doctor to switch to a 0.5 mg capsule per day. In this case, it is recommended to repeat the observation period as after the first dose of Fingolimod Zentiva.

Do not exceed the recommended dose of Fingolimod Zentiva. Fingolimod Zentiva is for oral use. Fingolimod Zentiva should be taken once a day, with a glass of water. The capsules of Fingolimod Zentiva should always be swallowed whole, without opening. Fingolimod Zentiva can be taken with or without food. Taking Fingolimod Zentiva at the same time every day will help the patient remember to take their medicine. If the patient has any questions about the duration of treatment with Fingolimod Zentiva, they should ask their doctor or pharmacist.

Taking a higher dose of Fingolimod Zentiva than recommended

If the patient has taken more Fingolimod Zentiva than they should, they should contact their doctor immediately.

Missing a dose of Fingolimod Zentiva

If the patient has been taking Fingolimod Zentiva for less than 1 month and has missed a dose for a whole day, they should contact their doctor before taking the next dose. The doctor may decide to monitor the patient during the next dose. If the patient has been taking Fingolimod Zentiva for at least 1 month and has missed taking the medicine for more than 2 weeks, they should contact their doctor before taking the next dose. The doctor may decide to monitor the patient during the next dose. However, if the patient has missed taking the medicine for up to 2 weeks, they can take the next dose as planned. Do not take a double dose to make up for a missed dose.

Stopping treatment with Fingolimod Zentiva

Do not stop taking Fingolimod Zentiva or change the dose without consulting your doctor first. Fingolimod Zentiva 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 Zentiva, it may be necessary to wait 6-8 weeks before starting new MS treatment. In patients resuming treatment with Fingolimod Zentiva after more than 2 weeks off the medicine, the effect on heart rate observed after the first dose may recur, 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 Zentiva after a break of more than 2 weeks without consulting the treating doctor. The treating doctor will decide whether and how to monitor the patient after stopping treatment with Fingolimod Zentiva. If the patient thinks their MS is getting worse after stopping treatment with Fingolimod Zentiva, they should tell their doctor immediately. This situation may be serious. If the patient has any further questions about the use of this medicine, they should ask their doctor or pharmacist.

4. Possible side effects

Like all medicines, Fingolimod Zentiva can cause side effects, although not everybody gets them.

Some side effects may be serious or life-threatening

Common (may affect up to 1 in 10 people):

• Cough with expectoration, feeling of discomfort in the chest, fever (symptoms of respiratory disorders).
• Herpesvirus infections (shingles or herpes) with symptoms such as blisters, burning, itching, or pain on the skin, usually on the upper body or face. Other symptoms may include fever and weakness at the beginning of the infection, followed by numbness, itching, or severe pain.
• Slow heartbeat (bradycardia), irregular heartbeat.
• A type of skin cancer called basal cell carcinoma (BCC), which often appears as a pearl-like nodule, although it can have other forms.
• Depression and anxiety, which are more common in the MS population and have also been reported in children and adolescents treated with fingolimod.
• 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 visual field in the retina, at the back of the eye) with symptoms such as shadows or defects in the center of the visual field, blurred vision, difficulties with color vision and fine details.
• Reduced platelet count, which increases the risk of bleeding or bruising.
• Malignant melanoma (a type of skin cancer that usually develops from an abnormal mole). Possible symptoms of melanoma include moles that change in size, shape, or color over time or new moles. Moles can be itchy, bleed, or ulcerate.
• Seizures, convulsions (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 sudden, 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 nodule, an ulcer covered with a scab, or a fresh ulcer in the area of an existing scar.

Very rare (may affect up to 1 in 10,000 people):

• Abnormalities in the ECG recording (T-wave inversion).
• A tumor associated with human herpesvirus 8 infection (Kaposi's sarcoma).

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

• Allergic reactions, including symptoms such as rash or itchy hives, swelling of the lips, tongue, or face, which are more likely to occur on the day of starting treatment with Fingolimod Zentiva.
• Symptoms of liver disease (including liver failure) such as yellowing of the skin or whites of the eyes (jaundice), nausea or vomiting, pain in the right upper abdomen, fatigue, decreased appetite, or unexplained nausea and vomiting. 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 those of an MS relapse. There may also be symptoms that the patient is not aware of, such as mood or behavior changes, transient memory problems, or speech and communication difficulties, which the doctor should evaluate to rule out PML. Therefore, if the patient thinks their MS is getting worse or if they or their relatives notice any new or unusual symptoms, it is very important to tell their doctor as soon as possible.
• Inflammatory reactions after stopping treatment with Fingolimod Zentiva (known as immune reconstitution inflammatory syndrome or IRIS)
• 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 nodule with a fleshy color, usually located on the face, head, or neck. Merkel cell carcinoma can also appear as a hard, painless nodule or mass. Prolonged sun exposure and weakened immune system may affect the risk of developing Merkel cell carcinoma.
• After stopping treatment with Fingolimod Zentiva, MS symptoms may recur and worsen compared to the period before treatment and during treatment.
• Autoimmune hemolytic anemia (a condition where red blood cells are destroyed). If the patient experiences any of these side effects, they should tell their doctor immediately.

5. How to Store Fingolimod Zentiva

The medicinal product should be stored out of sight and reach of children.
Do not use this medicinal product after the expiry date stated on the carton and blister pack after
“EXP”. The expiry date refers to the last day of the month stated.
Store in a temperature below 25°C. Store in the original package to protect from moisture.
Do not use medicinal products from damaged or opened packages.
Medicinal products should not be disposed of via wastewater or household waste containers. You should ask
your pharmacist how to dispose of medicinal products that are no longer needed. This will help protect
the environment.

6. Package Contents and Other Information

What Fingolimod Zentiva Contains

• The active substance is fingolimod. Each capsule contains 0.5 mg of fingolimod

(in the form of hydrochloride).

• Other ingredients are: Capsule filling: microcrystalline cellulose 101 and 102, calcium hydrogen phosphate, magnesium stearate. Capsule shell: gelatin, titanium dioxide (E171), iron oxide, yellow (E172) (capsule cap).

What Fingolimod Zentiva Looks Like and Package Contents

Fingolimod Zentiva, hard capsules, with a light yellow, opaque cap and a white opaque body, size 3 (15.8±0.4 mm), filled with a white to off-white, granular powder.
Fingolimod Zentiva is available in packs of 7, 28, 30, 56, 90, or 98 capsules.
Not all pack sizes may be marketed.

Marketing Authorization Holder

Zentiva, k.s.,
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer/Importer

S.C. Zentiva S.A.
B-dul Theodor Pallady nr. 50,
sector 3,
03226 Bucharest
Romania
LABORMED-PHARMA S.A.
Bd.Theodor Pallady nr. 44B,
sector 3,
032266 Bucharest
Romania

To Obtain More Detailed Information About the Medicinal Product, Please Contact the Representative of the Marketing Authorization Holder in Poland:

Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00
This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Fingolimod Zentiva: Austria, Bulgaria, Czech Republic, Denmark, Estonia, Finland, France, Germany, Iceland,
Italy, Latvia, Lithuania, Norway, Poland, Portugal, Romania, Slovakia, Spain, Sweden,
United Kingdom (Northern Ireland).
Date of Last Update of the Leaflet:July 2025