Fingolimod zentiva: detailed information

Package leaflet: Information for the user

Fingolimod Zentiva, 0.5 mg hard capsules
fingolimodum
Please read all of this leaflet carefully before 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 further questions, ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

What Fingolimod Zentiva is and what it is used for
What you need to know before taking Fingolimod Zentiva
How to take Fingolimod Zentiva
Possible side effects
How to store Fingolimod Zentiva
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 in adults, and in children and adolescents (aged 10 years and older with body weight > 40 kg) for the treatment of relapsing-remitting multiple sclerosis (MS, Latin: Sclerosis multiplex), particularly in:

patients who have not responded to previous MS treatments, or
patients with rapidly evolving, severe form of MS.

Fingolimod Zentiva 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), which consists of the brain and spinal cord. In MS, the inflammatory process damages the protective covering of nerves (called myelin) in the CNS, impairing their proper function. This phenomenon is known as demyelination.
Relapsing-remitting MS is characterized by recurrent episodes (relapses) of neurological symptoms reflecting inflammatory activity within the CNS. Symptoms vary among patients but usually include walking difficulties, numbness, vision or balance disturbances. Symptoms of relapses may completely resolve when the relapse ends, although some deficits may persist.
How Fingolimod Zentiva works
Fingolimod Zentiva helps protect the CNS from attack by the immune system by reducing the ability of certain white blood cells (lymphocytes) to circulate freely throughout the body and by preventing them from entering the brain and spinal cord. In this way, the medicine reduces nerve damage causing MS. Fingolimod Zentiva also weakens certain immune responses of the body.

2. Important information before taking Fingolimod Zentiva

When not to take Fingolimod Zentiva

if the patient has reduced immune response (due to immunodeficiency syndrome, disease, or taking immunosuppressive medicines),
if the doctor suspects that the patient has a rare brain infection called progressive multifocal leukoencephalopathy (PML) or if PML has been confirmed in the patient,
if the patient has severe active infection or chronic active infection, such as hepatitis or tuberculosis,
if the patient has active cancer,
if the patient has severe liver disease,
if the patient has had a heart attack, angina pectoris, stroke, or warning signs of stroke, or certain types of heart failure within the last 6 months,
if the patient has a certain type of irregular or abnormal heartbeat (arrhythmia), including patients in whom an electrocardiogram (ECG) has shown QT interval prolongation before starting treatment with Fingolimod Zentiva,
if the patient is currently taking or has recently taken medicines for irregular heartbeat, such as quinidine, disopyramide, amiodarone or sotalol,
if the patient is pregnant or is of childbearing potential 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 any of these situations apply to the patient or the patient is unsure, the patient should consult a doctor before taking Fingolimod Zentiva.

Warnings and precautions

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

if the patient has severe breathing problems during sleep (severe sleep apnoea),
if the patient has been informed that their ECG recording is abnormal,
if the patient experiences symptoms of slow heart rate (e.g. dizziness, nausea or palpitations),
if the patient is taking or has recently taken medicines that slow heart rate (such as beta-blockers, verapamil, diltiazem or ivabradine, digoxin, cholinesterase inhibitors or pilocarpine),
if the patient has previously experienced sudden loss of consciousness or fainting episodes,
if the patient plans to be vaccinated,
if the patient has never had chickenpox,
if the patient has or has had vision problems or other symptoms of swelling in the centre of the visual field (macula) at the back of the eye (a condition called macular oedema, see below), inflammation or infection of the eye (uveitis), or if the patient has diabetes (which may cause vision problems),
if the patient has liver problems,
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 apply to the patient or the patient is unsure, the patient should consult a doctor before taking Fingolimod Zentiva.

Slow heart rate (bradycardia) and irregular heartbeat
At the beginning of treatment or after taking the first 0.5 mg dose in patients previously taking a 0.25 mg daily dose, Fingolimod Zentiva slows the heart rate.
As a result, the patient may feel dizzy, tired, or aware of their heartbeat, or may experience low blood pressure. If these symptoms are severe, the patient should inform the doctor immediately, as immediate treatment may be necessary.
Fingolimod Zentiva may also cause irregular heartbeat, especially after the first dose. Irregular heartbeat usually returns to normal within less than 1 day. Slow heart rate usually returns to normal within 1 month. During this period, no clinically significant effect on heart rate is expected.
The doctor will ask the patient to remain in the doctor's office or clinic for at least 6 hours after taking the first dose of Fingolimod Zentiva or after the first 0.5 mg dose when switching from a 0.25 mg daily dose, with hourly monitoring of pulse and blood pressure, so that appropriate treatment can be administered if adverse effects occur at the beginning of treatment. An ECG will be performed before the first dose of Fingolimod Zentiva and again after the 6-hour observation period. During this time, the doctor may continuously monitor the patient's heart function using electrocardiography. If, after 6 hours of observation, the patient has a very slow or decreasing heart rate, or if the ECG shows abnormalities, longer monitoring of the patient may be required (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 treatment interruption, depending on the duration of the interruption and how long the patient had been taking Fingolimod Zentiva before the interruption.

If the patient has irregular or abnormal heartbeat or risk factors for such events, abnormal ECG findings, heart disease, or heart failure, Fingolimod Zentiva may not be suitable.

If the patient has previously experienced sudden loss of consciousness or slowed heart function, Fingolimod Zentiva may not be appropriate. A consultation with a cardiologist (a heart specialist) may be needed to advise on how to start treatment with Fingolimod Zentiva, including how to monitor the patient overnight.

If the patient is taking medicines that may reduce heart rate, Fingolimod Zentiva may not be suitable. A consultation with a cardiologist may be necessary to determine whether the patient can switch to other medicines that do not reduce 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, including overnight 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, vaccination may be required 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 completion of the full vaccination course.

Infections
Fingolimod Zentiva reduces the number of white blood cells (particularly lymphocytes). White blood cells fight infections. While taking Fingolimod Zentiva (and for up to 2 months after stopping treatment), the patient may be more susceptible to infections. Existing infections may worsen. Infections may be severe and life-threatening. If the patient suspects they have an infection, has a fever, flu-like symptoms, shingles, or a headache accompanied by neck stiffness, light sensitivity, nausea, rash and/or confusion or seizures (which may be symptoms of meningitis and/or encephalitis caused by fungal or herpes virus infection), they should contact the doctor immediately, as this condition may be serious and life-threatening.

In patients treated with fingolimod, human papillomavirus (HPV) infection has been reported, including cases of warts, dysplasia, and HPV-related malignant tumours. The doctor will consider the need for HPV vaccination before starting treatment. In women, the doctor will also recommend screening tests for HPV.

PML
PML is a rare brain disorder caused by infection that may lead to severe disability or death. The treating doctor will order magnetic resonance imaging (MRI) scans before starting and during treatment to monitor the risk of PML.

If the patient feels their multiple sclerosis is worsening or notices new symptoms, such as changes in mood or behaviour, new weakness or worsening of existing weakness on one side of the body, changes in vision, confusion, temporary memory lapses, or difficulties with speech and communication, they should speak to the 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. Symptoms may occur that the patient is not aware of.

If PML occurs, treatment may be required and treatment with Gilenya will be stopped. In some patients, an inflammatory reaction may occur after Gilenya is cleared from the body. This reaction (called immune reconstitution inflammatory syndrome, IRIS) may lead to worsening of the patient's condition, including worsening brain function.

Macular oedema
Before starting treatment with Fingolimod Zentiva, the doctor may refer patients with current or previous vision problems or other symptoms of swelling in the centre of the visual field (macula) at the back of the eye, eye inflammation or infection (uveitis), or diabetes for ophthalmological examination.

The doctor may refer the patient for ophthalmological examination 3 to 4 months after starting treatment with Fingolimod Zentiva.

The macula is a small area of the retina at the back of the eye that enables clear, sharp vision of shapes, colours and other details. Fingolimod Zentiva may cause swelling of the macula, a condition called macular oedema. This swelling usually occurs within the first 4 months of treatment with Fingolimod Zentiva.

The risk of macular oedema is higher in patients with diabetes or a history of uveitis. In such cases, the doctor will order regular ophthalmological examinations to detect macular oedema.

If the patient develops macular oedema, they should inform the doctor before resuming treatment with Fingolimod Zentiva. Macular oedema may cause vision disturbances similar to those in an MS attack (optic neuritis). In the early stages, symptoms may be absent. The patient should inform the doctor of any changes in vision.

The doctor may refer the patient for ophthalmological examination, especially if:

the centre of the visual field becomes blurred or shadowed;
a gap appears in the centre of the visual field;
there are difficulties with colour vision or seeing fine details.

Liver function tests
Patients with severe liver disease should not take Fingolimod Zentiva. Fingolimod Zentiva may affect liver function test results. The patient may not experience any symptoms, but if yellowing of the skin or whites of the eyes, abnormally dark (brown) urine, pain in the right side of the abdomen, fatigue, reduced appetite, or unexplained nausea and vomiting occur, the patient should inform the doctor immediately.

If any of these symptoms occur after starting treatment with Fingolimod Zentiva, the patient should inform the doctor immediately.

Before, during and after treatment, the doctor will order blood tests to monitor liver function. If test results indicate liver dysfunction, treatment with Fingolimod Zentiva may be discontinued.

High blood pressure
The doctor may regularly check blood pressure, as Fingolimod Zentiva causes 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 greater risk of adverse effects.

Blood cell count
A known effect of Fingolimod Zentiva is a reduction in the number of white blood cells in the blood. The number usually returns to normal within 2 months after stopping treatment.

If blood tests are needed, the patient should inform the doctor that they are taking Fingolimod Zentiva. Otherwise, the doctor may not be able to interpret the blood test results correctly, and for certain tests, the doctor may order a larger blood sample than usual.

Before starting treatment with Fingolimod Zentiva, the doctor will confirm that the number of white blood cells in the blood is adequate to start treatment and may order regular repeat tests. If there are not enough white blood cells, treatment with Fingolimod Zentiva may need to be discontinued.

Posterior reversible encephalopathy syndrome (PRES)
Rare cases of a condition called posterior reversible encephalopathy syndrome (PRES) have been reported in patients with MS treated with fingolimod. Symptoms may include sudden severe headache, confusion, seizures and vision changes. If the patient experiences any of these symptoms while taking Fingolimod Zentiva, they should inform the doctor immediately, as this condition may be serious.

Cancer
Skin cancers have been reported in patients with MS treated with fingolimod. If any lumps (e.g. shiny, pearly lumps), spots or open sores that do not heal within a few weeks are noticed on the skin, the patient should inform the doctor immediately. Symptoms of skin cancer may include abnormal growths or changes in skin tissue (e.g. new moles) that change in colour, shape or size over time. Before starting treatment with Fingolimod Zentiva, a skin examination should be performed to check for any skin lumps. The treating doctor will also perform regular skin checks during treatment with Fingolimod Zentiva. If skin problems occur, the treating doctor may refer the patient to a dermatologist, who may decide after consultation that regular visits are necessary.

Lymphoma, a type of lymphatic system cancer, has been reported in patients with MS treated with fingolimod.

Sun exposure and sun protection
Fingolimod weakens the immune system. This condition increases the risk of malignant tumours, especially skin cancers. The patient should limit exposure to sunlight and UV radiation by:

wearing protective clothing,
regularly applying sunscreen with a high UV protection factor.

Unusual brain changes associated with MS relapse
Rare cases of unusually large brain lesions associated with MS relapse have been reported in patients treated with fingolimod. In the case of a severe MS relapse, the treating doctor may consider performing an MRI scan to assess this condition and decide whether to discontinue Fingolimod Zentiva.

Switching 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 abnormalities caused by previous treatment. The doctor may order blood tests to rule out such abnormalities. After stopping natalizumab treatment, it may be necessary to wait 2 to 3 months before starting Fingolimod Zentiva. When switching from teriflunomide, the doctor may advise waiting a certain time or undergoing an accelerated elimination procedure. Patients previously treated with alemtuzumab require careful evaluation and discussion of their situation with the doctor before deciding whether Fingolimod Zentiva is suitable.

Women of childbearing potential
If fingolimod is used during pregnancy, it may have harmful effects on the unborn child. Before starting treatment with Fingolimod Zentiva, the doctor will explain the risks to the patient and request a pregnancy test to rule out pregnancy. The doctor will provide the patient with an information card explaining why pregnancy should be avoided while taking Fingolimod Zentiva. The card also contains information on how to avoid pregnancy while taking Fingolimod Zentiva. Patients must use an effective method of contraception during treatment and for 2 months after stopping treatment (see section "Pregnancy and breastfeeding").

Worsening of MS after stopping treatment with Fingolimod Zentiva
Do not stop taking Fingolimod Zentiva or change the dose without first consulting the doctor.
The patient should inform the doctor immediately if they feel their MS is worsening after stopping treatment with Fingolimod Zentiva. This situation may be serious (see "Stopping treatment with Fingolimod Zentiva" in section 3 and section 4 "Possible side effects").

Elderly patients
Experience with Fingolimod Zentiva in elderly patients (over 65 years) is limited. If in doubt, consult a doctor.

Children and adolescents
Fingolimod Zentiva is not intended for use in children under 10 years of age, as it has not been studied in patients with MS in this age group.
The medicine is intended for use in children with a body weight > 40 kg. Alternative formulations should be used in children with a body weight ≤ 40 kg.
The warnings and precautions listed above also apply to children and adolescents.
The following information is particularly important for children, adolescents and their caregivers:

Before starting treatment with Fingolimod Zentiva, the doctor will check the patient's vaccination status. If the patient has not received certain vaccinations, vaccination may be necessary before starting treatment with Fingolimod Zentiva.
During the first dose of Fingolimod Zentiva or when changing the daily dose from 0.25 mg to 0.5 mg, the doctor will monitor heart rate and pulse (see "Slow heart rate (bradycardia) and irregular heartbeat" above).
If the patient experiences seizures or epileptic fits before or during treatment with Fingolimod Zentiva, they should inform the doctor.
If the patient develops depression or anxiety or feels low mood or anxiety while taking Fingolimod Zentiva, they should inform the doctor. The patient may require closer monitoring.

Fingolimod Zentiva and other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. Inform the doctor if the patient is taking any of the following medicines:

Medicines that suppress or modulate the immune system, including other medicines used to treat MS, such as interferon beta, glatiramer acetate, natalizumab, mitoxantrone, teriflunomide, dimethyl fumarate or alemtuzumab. Fingolimod Zentiva must not be used together with these medicines, as this could intensify the effect on the immune system (see also "When not to take Fingolimod Zentiva").
Corticosteroids, due to the potential for additive effects on the immune system.
Vaccines. If the patient requires vaccination, they should first consult the doctor. During and for 2 months after treatment with Fingolimod Zentiva, patients should not receive certain types of vaccines (live attenuated vaccines), as they could cause the infection they are intended to prevent. Other vaccines may also be ineffective if administered during this period.
Medicines that slow heart rate (e.g. beta-blockers such as atenolol). Using Fingolimod Zentiva together with these medicines could intensify the effect on heart function in the first days of treatment with Fingolimod Zentiva.
Medicines for irregular heartbeat, such as quinidine, disopyramide, amiodarone or sotalol. Fingolimod Zentiva must not be used in patients taking these medicines, as it could intensify the effect on irregular heartbeat (see also "When not to take Fingolimod Zentiva").
Other medicines:
- protease inhibitors, antiviral medicines such as ketoconazole, azole antifungals, clarithromycin or telithromycin.
- carbamazepine, rifampicin, phenobarbital, phenytoin, efavirenz or St John's wort (possible risk of reduced effectiveness of Fingolimod Zentiva).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult the doctor before using this medicine.

Pregnancy
Fingolimod Zentiva should not be used during pregnancy, if the patient is trying to become pregnant, or if the patient may become pregnant and is not using effective contraception. If fingolimod is used during pregnancy, there is a risk of harmful effects on the unborn child. The rate of congenital malformations observed in children exposed to fingolimod during pregnancy is about twice that observed in the general population (where the rate of congenital malformations is about 2-3%). The most commonly reported congenital malformations include heart, kidney and musculoskeletal system developmental defects.

Therefore, if the patient is of childbearing age:

before starting treatment with Fingolimod Zentiva, the doctor will inform the patient of the risk to the unborn child and request a pregnancy test to confirm that the patient is not pregnant,

and

effective contraception must be used during treatment with Fingolimod Zentiva and for 2 months after stopping treatment to avoid pregnancy. The patient should discuss effective contraceptive methods with the doctor.

The doctor will provide the patient with an information card explaining why pregnancy should be avoided while taking Fingolimod Zentiva.
If the patient becomes pregnant while taking Fingolimod Zentiva, she should inform the doctor immediately. The doctor will decide whether to discontinue treatment (see "Stopping treatment with Fingolimod Zentiva" in section 3 and section 4 "Possible side effects"). The patient will also need to attend follow-up prenatal examinations.

Breastfeeding
Breastfeeding is not recommended while taking Fingolimod Zentiva. Fingolimod may pass into breast milk, posing a risk of serious adverse effects in the infant.

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

3. How to take Fingolimod Zentiva

Treatment with Fingolimod Zentiva will be supervised by a doctor experienced in the treatment of multiple sclerosis.
This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor.
Recommended dose:
Adults
The recommended dose is one 0.5 mg capsule once daily.
Children and adolescents (aged 10 years and above): The dose depends on body weight:

Children and adolescents with body weight above 40 kg should take one 0.5 mg capsule once daily.
Children and adolescents with body weight equal to or less than 40 kg should receive other appropriate doses. Children and adolescents starting treatment with one 0.25 mg capsule once daily who later achieve a stable body weight above 40 kg will be advised by the doctor to switch to one 0.5 mg capsule once daily. In this case, repeat observation period as after the first dose is recommended.

Do not exceed the recommended dose of Fingolimod Zentiva.
Fingolimod Zentiva is intended for oral use.
Fingolimod Zentiva should be taken once daily, with a glass of water. Fingolimod Zentiva capsules should always be swallowed whole, without opening. Fingolimod Zentiva may be taken with or without food.
Taking Fingolimod Zentiva at the same time each day will help you remember to take your dose.
If you have any questions about how long treatment with Fingolimod Zentiva should last, consult your doctor or pharmacist.
Taking more Fingolimod Zentiva than recommended
If you have taken too much Fingolimod Zentiva, contact your doctor immediately.
Missing a dose of Fingolimod Zentiva
If you have been taking Fingolimod Zentiva for less than 1 month and have missed one dose for a full day, contact your doctor before taking the next dose. Your doctor may decide to keep you under observation when you take the next dose.
If you have been taking Fingolimod Zentiva for at least 1 month and have missed doses for more than 2 weeks, contact your doctor before taking the next dose. Your doctor may decide to keep you under observation when you take the next dose. However, if you have missed doses for up to 2 weeks, you may take the next dose as scheduled.
Do not take a double dose to make up for a missed dose.
Stopping Fingolimod Zentiva
Do not stop taking Fingolimod Zentiva or change the dose without first discussing it with your doctor.
Fingolimod Zentiva remains in the body for up to 2 months after stopping treatment. During this time, white blood cell count (lymphocyte count) may still be reduced and side effects described in this leaflet may continue to occur. After stopping Fingolimod Zentiva, you may need to wait 6–8 weeks before starting a new multiple sclerosis treatment.
In patients restarting Fingolimod Zentiva after a break of more than 2 weeks, the effect on heart rate observed usually after starting treatment for the first time may reoccur, and monitoring in a doctor's office or clinic will be necessary when restarting treatment.
Do not restart Fingolimod Zentiva after a break of more than 2 weeks without consulting your treating doctor.
Your treating doctor will decide whether and how you should be monitored after stopping Fingolimod Zentiva. Inform your doctor immediately if you feel your multiple sclerosis is worsening after stopping Fingolimod Zentiva. This situation may be serious.
If you have any further questions about using this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Some adverse reactions may be or may become serious
Common (may affect less than 1 in 10 people):

Cough with sputum, feeling of discomfort in the chest, fever (symptoms of lung function disorders).
Herpesvirus infection (shingles or herpes simplex) with symptoms such as blisters, burning sensation, itching or pain in the skin, usually on the upper part of the body or face. Other symptoms may include fever and weakness in the early stage of infection, followed by numbness, itching or very painful red patches.
Slow heartbeat (bradycardia), irregular heartbeat.
A type of skin cancer called basal cell carcinoma (BCC), which often appears as a pearly lump, although it may also have a different appearance.
Depression and anxiety are known to occur more frequently in patients with MS and have also been reported in children and adolescents treated with fingolimod.
Decrease in body weight.

Uncommon (may affect less than 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 blind spots in the center of vision, blurred vision, difficulty perceiving colors and details.
Decreased number of platelets, which increases the risk of bleeding or bruising.
Malignant melanoma (a type of skin cancer that usually develops from an atypical mole). Possible symptoms of melanoma include moles that change in size, shape, elevation or color over time, or new moles appearing. Moles may itch, bleed or ulcerate.
Seizures, epileptic seizures (more common in children and adolescents than in adults).

Rare (may affect less than 1 in 1,000 people):

A condition called posterior reversible encephalopathy syndrome (PRES). Symptoms may include sudden, severe headache, confusion, seizures and (or) visual disturbances.
Lymphoma (a type of cancer affecting the lymphatic system).
Squamous cell carcinoma: a type of skin cancer that may appear as a hard, red lump, an ulcer covered with a scab or a new ulcer developing at the site of an existing scar.

Very rare (may affect less than 1 in 10,000 people):

Abnormalities in the ECG test (T-wave inversion).
Tumor associated with human herpesvirus type 8 infection (Kaposi’s sarcoma).

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

Allergic reactions, including symptoms such as rash or itchy hives, swelling of lips, tongue or face, which are more likely to occur on the day treatment with Fingolimod Zentiva is started.
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 side of the abdomen, dark (brown) urine, reduced appetite, fatigue and abnormal liver function tests. In very rare cases, liver failure may lead to liver transplantation.
Risk of a rare brain infection called progressive multifocal leukoencephalopathy (PML). Symptoms of PML may resemble a relapse of MS. There may also be symptoms the patient is not aware of, such as changes in mood or behavior, temporary memory lapses, difficulty speaking and communicating, which should be evaluated by a doctor to rule out PML. Therefore, if the patient feels that their MS is worsening, or if the patient or their family notice any new or unusual symptoms, it is very important to inform the treating doctor as soon as possible.
Inflammatory disorders after stopping treatment with Gilenya (known as immune reconstitution inflammatory syndrome or IRIS).
Cryptococcal infections (a type of fungal infection), including cryptococcal meningitis with symptoms such as headache accompanied by neck stiffness, light sensitivity, nausea and (or) confusion.
Merkel cell carcinoma (a type of skin cancer). Possible symptoms of Merkel cell carcinoma include the presence of a painless, flesh-colored or bluish-red nodule, often located on the face, head or neck. Merkel cell carcinoma may also appear as a firm, painless lump or mass. Long-term sun exposure and weakened immune system may influence the risk of Merkel cell carcinoma.
After discontinuation of Fingolimod Zentiva treatment, MS symptoms may return and worsen compared to the period before and during treatment.
Autoimmune form of anemia (reduced number of red blood cells), in which red blood cells are destroyed (autoimmune hemolytic anemia). If the patient experiences any of these reactions, they should immediately inform their doctor.

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

Influenza virus infection with symptoms such as fatigue, chills, sore throat, joint or muscle pain, fever.
Feeling of pressure or pain in cheeks and forehead (sinusitis).
Headache.
Diarrhea.
Back pain.
Increased liver enzyme activity in blood tests.
Cough.

Common (may affect less than 1 in 10 people):

Ringworm, fungal skin infection (tinea versicolor).
Dizziness.
Severe headache, often accompanied by nausea, vomiting and sensitivity to light (migraine symptoms).
Low number of white blood cells (lymphocytes, leukocytes).
Weakness.
Itchy, red, burning rash (rash).
Itching.
Increased levels of fats (triglycerides) in the blood.
Hair loss.
Shortness of breath.
Depression.
Blurred vision (see also the section on macular edema under the heading “Some adverse reactions may be or may become serious”).
Hypertension (fingolimod may cause a mild increase in blood pressure).
Muscle pain.
Joint pain.

Uncommon (may affect less than 1 in 100 people):

Low number of white blood cells (neutrophils).
Depressed mood.
Nausea.

Rare (may affect less than 1 in 1,000 people):

Cancer of the lymphatic system (lymphoma).

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

Peripheral edema.

If any of these symptoms occur severely, the patient should inform
their doctor.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed
in this leaflet, the patient should inform their doctor or pharmacist. Adverse reactions can be reported
directly to the Department of Monitoring Adverse Drug Reactions of the 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
Adverse reactions can also be reported to the marketing authorization holder or its representative
in Poland.
By reporting adverse reactions, more information on the safety of this medicine can be collected.

5. How to store Fingolimod Zentiva

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and blister pack after "EXP". The expiry date refers to the last day of the specified month.
Store below 25°C. Keep in the original packaging to protect from moisture.
Do not use medicines from packaging that is damaged or shows signs of tampering.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the pack and other information

What Fingolimod Zentiva contains

The active substance is fingolimod. Each capsule contains 0.5 mg of fingolimod
(as hydrochloride).
The other ingredients are:
Capsule fill: 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 contents of the pack
Fingolimod Zentiva, hard capsules, with a light yellow, opaque cap and a white, opaque body, size No. 3 (15.8±0.4 mm), filled with white to off-white, powdery, 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 Authorisation 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 No. 50,
sector 3,
03226 Bucharest
Romania
LABORMED-PHARMA S.A.
Bd. Theodor Pallady No. 44B,
sector 3,
032266 Bucharest
Romania

For further information about this medicinal product, contact the local representative of the Marketing Authorisation 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 authorised for marketing 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).