Fingolimod alvogen

Package leaflet: Information for the patient

Fingolimod Alvogen, 0.5 mg
hard capsules
Fingolimodum
Please read the entire leaflet carefully before taking this 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, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

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

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

What Fingolimod Alvogen is
Fingolimod Alvogen contains the active substance fingolimod.
What Fingolimod Alvogen is used for
Fingolimod Alvogen is used in adults, as well as in children and adolescents (aged 10 years and older) for the treatment of relapsing-remitting multiple sclerosis (MS, Latin: Sclerosis multiplex), particularly in:

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

Fingolimod Alvogen 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.

The relapsing-remitting form of MS is characterized by recurrent episodes (relapses) of neurological symptoms reflecting inflammatory activity within the CNS. Symptoms vary among patients but typically include difficulty walking, numbness, vision disturbances, or problems with balance. Symptoms of relapses may resolve completely, although some deficits may persist.

How Fingolimod Alvogen works
Fingolimod Alvogen helps protect the CNS from attack by the immune system by reducing the ability of certain white blood cells (lymphocytes) to move freely throughout the patient's body, and by preventing them from entering the brain and spinal cord. In this way, the medicine limits nerve damage caused by MS. Fingolimod Alvogen also suppresses certain immune responses in the body.

2. Important information before taking Fingolimod Alvogen

When not to take Fingolimod Alvogen

• if the patient is allergic to fingolimod or any of the other ingredients of this medicine (listed in section 6);
• if the patient has a weakened immune response (due to immunodeficiency syndrome, disease, or taking medicines that suppress the immune system);
• 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 within the last 6 months the patient has had a heart attack, angina, stroke, or warning signs of stroke, or certain types of heart failure;
• 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 Alvogen;
• 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 of childbearing potential and not using effective contraception. If this is the case or the patient has any doubts, the patient should inform the doctor before taking Fingolimod Alvogen.

Warnings and precautions
Before starting Fingolimod Alvogen, discuss with the doctor:

• if the patient has severe breathing problems during sleep (sleep apnoea);
• if the patient has been told that their ECG tracing is abnormal;
• if the patient experiences symptoms of a slow heart rate (e.g. dizziness, nausea, or palpitations);
• if the patient is taking or has recently taken medicines that slow the 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;
• 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 center 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 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 apply or the patient has any doubts, the patient should inform the doctor before taking Fingolimod Alvogen.

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 daily dose of 0.25 mg, Fingolimod Alvogen slows the heart rate. As a result, the patient may experience dizziness, fatigue, strong heartbeats, or a drop in blood pressure. If these symptoms are severe, the patient should inform the doctor, as immediate treatment may be required. Fingolimod Alvogen may also cause an irregular heartbeat, especially after the first dose. Irregular heartbeat usually returns to normal within less than one day. Slow heart rate usually returns to normal within one month. During this period, no clinically significant effect on heart rate is generally 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 Alvogen 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 given if adverse effects occur at the beginning of treatment. An ECG will be performed before the first dose of Fingolimod Alvogen and again at the end of the 6-hour observation period. During this time, the doctor may continuously monitor the patient's heart function using electrocardiographic monitoring. 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's condition may be required (for at least 2 additional hours or possibly until the next day) until these symptoms resolve. The same procedure may be recommended if the patient resumes treatment with Fingolimod Alvogen after a treatment interruption, depending on how long the interruption lasted and how long the patient had been taking Fingolimod Alvogen before the interruption.
If the patient has an irregular or abnormal heartbeat, risk factors for such events, an abnormal ECG, heart disease, or heart failure, Fingolimod Alvogen may not be suitable.
If the patient has a history of sudden loss of consciousness or slowed heart function, Fingolimod Alvogen may not be suitable. A consultation with a cardiologist (a heart specialist) may be needed, who will advise on how to start treatment with Fingolimod Alvogen, including how to monitor the patient overnight.
If the patient is taking medicines that may reduce heart rate, Fingolimod Alvogen may not be appropriate. 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 Alvogen. If such a change in treatment is not possible, the cardiologist will advise the patient on how to start treatment with Fingolimod Alvogen, including monitoring until the day after the first dose of Fingolimod Alvogen.

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 Alvogen. If this is the case, the doctor will delay the start of treatment with Fingolimod Alvogen by one month after completing the full vaccination course.

Infections
Fingolimod Alvogen reduces the number of white blood cells (particularly lymphocytes). White blood cells fight infections. While taking Fingolimod Alvogen (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, have 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 infection or herpes virus infection), they should contact their doctor immediately, as this condition may be serious and life-threatening. If the patient feels their condition is worsening (e.g. weakness or vision problems) or if they notice any new symptoms, they should speak to their doctor immediately, as these may be symptoms of a rare brain disease caused by infection called progressive multifocal leukoencephalopathy (PML). PML is a serious condition that may lead to severe disability or death. The doctor will consider performing a magnetic resonance imaging (MRI) scan to assess the patient's condition and decide whether it is necessary to discontinue treatment with Fingolimod Alvogen.
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.

Macular oedema
Before starting treatment with Fingolimod Alvogen, the doctor may refer patients with current or past vision problems or other symptoms of swelling in the center of the visual field (macula) at the back of the eye, inflammation or infection of the eye (uveitis), or diabetes for ophthalmological examination.
The doctor may refer the patient for ophthalmological examination 3 to 4 months after starting treatment with Fingolimod Alvogen.
The macula is a small area of the retina at the back of the eye that enables clear and sharp vision of shapes, colours, and other details. Fingolimod Alvogen may cause swelling of the macula, a condition called macular oedema. This swelling usually occurs within the first 4 months of treatment with Fingolimod Alvogen.
The risk of macular oedema is higher in patients with diabetes or a history of uveitis. In such cases, the doctor will arrange regular ophthalmological examinations to detect macular oedema.
If the patient develops macular oedema, they should inform the doctor before resuming treatment with Fingolimod Alvogen.
Macular oedema may cause certain vision problems, similar to those during 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 center of the visual field becomes blurry or shadowed;
• a blind spot appears in the center of the visual field;
• difficulty seeing colours or fine details occurs

Liver function tests
Patients with severe liver disease should not take Fingolimod Alvogen. Fingolimod Alvogen 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 the above symptoms occur after starting treatment with Fingolimod Alvogen, 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 Alvogen may be discontinued.

High blood pressure
The doctor may regularly check blood pressure, as Fingolimod Alvogen causes a slight increase in blood pressure.

Lung diseases
Fingolimod Alvogen has a minor effect on lung function. Patients with severe lung disease or a smoker's cough are at higher risk of adverse effects.

Blood cell count
A known effect of Fingolimod Alvogen 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 the doctor about taking Fingolimod Alvogen. Otherwise, the doctor may not be able to interpret the blood test results correctly, and for certain tests, the doctor may require a larger blood sample than usual.
Before starting Fingolimod Alvogen, the doctor will confirm that the white blood cell count is adequate to begin treatment and may recommend regular repeat testing. If there are insufficient white blood cells, treatment with Fingolimod Alvogen may need to be discontinued.

Posterior reversible encephalopathy syndrome (PRES)
In patients with MS treated with fingolimod, a rare condition called posterior reversible encephalopathy syndrome (PRES) has been reported. Symptoms of this condition may include sudden severe headache, confusion, seizures, and vision changes. If any of these symptoms occur during treatment with Fingolimod Alvogen, the patient should inform the doctor immediately, as this condition may be serious.

Cancer
In patients with MS treated with fingolimod, skin cancers have been reported. If any lumps (e.g. shiny, pearly lumps), spots, or open sores that do not heal within several weeks are noticed on the skin, the patient should inform their doctor immediately. Symptoms of skin cancer may include abnormal growths or changes in the skin tissue (e.g. new moles) that change in colour, shape, or size over time. Before starting treatment with Fingolimod Alvogen, a skin examination is necessary to detect any skin lumps. The treating doctor will also perform regular skin checks during treatment with Fingolimod Alvogen. If skin problems occur, the treating doctor may refer the patient to a dermatologist, who may, after consultation, recommend regular visits.
In patients with MS treated with fingolimod, a certain type of lymphatic system cancer (lymphoma) has been reported.

Changing treatment from other medicines to Fingolimod Alvogen
Your doctor may switch your treatment directly from interferon beta, glatiramer acetate or dimethyl fumarate to Fingolimod Alvogen, if there are no signs of abnormalities caused by previous treatment. Your doctor may order a blood test to rule out such abnormalities. After stopping natalizumab treatment, it may be necessary to wait 2 to 3 months before starting treatment with Fingolimod Alvogen. When switching from teriflunomide, your doctor may advise waiting a certain period or undergoing an accelerated drug elimination procedure. Patients previously treated with alemtuzumab require careful evaluation and discussion with their doctor before deciding whether Fingolimod Alvogen is suitable for them.

Women of childbearing potential
If fingolimod is used during pregnancy, it may have harmful effects on the unborn child. Before starting treatment with Fingolimod Alvogen, your doctor will explain the risks to you and request a pregnancy test to exclude pregnancy. Your doctor will give you a patient alert card explaining why you should not become pregnant while taking Fingolimod Alvogen. The card also contains information on how to avoid pregnancy while taking Fingolimod Alvogen. Women must use effective contraception during treatment and for 2 months after stopping treatment (see section "Pregnancy and breastfeeding").

Worsening of MS after stopping treatment with Fingolimod Alvogen
Do not stop taking Fingolimod Alvogen or change the dose without first consulting your doctor.
Inform your doctor immediately if you feel your MS is worsening after stopping treatment with Fingolimod Alvogen. This situation may be serious (see "Stopping treatment with Fingolimod Alvogen" in section 3, and section 4 "Possible side effects").

Elderly patients
Experience with the use of Fingolimod Alvogen in elderly patients (over 65 years of age) is limited. In case of doubt, consult your doctor.

Children and adolescents
Fingolimod Alvogen 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 warnings and precautions listed above also apply to children and adolescents. The following information is particularly important for children and adolescents and their caregivers:

• Before starting treatment with Fingolimod Alvogen, your doctor will check your vaccination status. If you have not received certain vaccinations, it may be necessary to get vaccinated before starting treatment with Fingolimod Alvogen.
• When taking Fingolimod Alvogen for the first time or when changing the daily dose from 0.25 mg to 0.5 mg, your doctor will monitor your heart rate and pulse (see "Slow heart rate (bradycardia) and irregular heartbeat" above).
• If you experience seizures or epileptic fits before or during treatment with Fingolimod Alvogen, inform your doctor.
• If you develop depression or anxiety, or if you feel low mood or anxiety while taking Fingolimod Alvogen, inform your doctor. You may require closer monitoring.

Fingolimod Alvogen and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. Inform your doctor if you are taking 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 Alvogen 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 Alvogen").

• Corticosteroids, due to the possibility of additive effects on the immune system.

• Vaccines. If you need a vaccine, you should first consult your doctor. During treatment and for 2 months after stopping treatment with Fingolimod Alvogen, 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 down heart function (e.g. beta-blockers such as atenolol). Taking Fingolimod Alvogen together with these medicines could intensify the effect on heart function in the first days of treatment with Fingolimod Alvogen.

• Medicines for irregular heartbeat, such as quinidine, disopyramide, amiodarone or sotalol. Fingolimod Alvogen 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 Alvogen").

• Other medicines:

• protease inhibitors, medicines used in infections, such as ketoconazole, azole antifungals, clarithromycin or telithromycin.

• carbamazepine, rifampicin, phenobarbital, phenytoin, efavirenz or St John's wort preparations (possible risk of reduced efficacy of Fingolimod Alvogen).

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, consult your doctor before using this medicine.

Pregnancy
Fingolimod Alvogen should not be used during pregnancy, if you are trying to become pregnant, or if you could become pregnant and are 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 (in which the rate of congenital malformations is about 2-3%). The most commonly reported congenital malformations include heart, kidney and musculoskeletal developmental defects.
For this reason, if you are of childbearing potential:

• before starting treatment with Fingolimod Alvogen, your doctor will inform you about the risk to the unborn child and request a pregnancy test to confirm that you are not pregnant, and
• you must use effective contraception while taking Fingolimod Alvogen and for two months after stopping treatment to avoid becoming pregnant. Discuss effective contraceptive methods with your doctor. Your doctor will give you a patient alert card explaining why you should not become pregnant while taking Fingolimod Alvogen.

If you become pregnant while taking Fingolimod Alvogen, inform your doctor immediately. Your doctor will decide whether to stop treatment (see "Stopping treatment with Fingolimod Alvogen" in section 3, and section 4 "Possible side effects"). You will also need to attend regular prenatal check-ups.

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

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

3. How to take Fingolimod Alvogen

Treatment with Fingolimod Alvogen 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
Dosage is one 0.5 mg capsule per day.
Children and adolescents (aged 10 years and older):
Dose depends on body weight :

• Children and adolescents with body weight of 40 kg or less: one 0.25 mg capsule per day.
• Children and adolescents with body weight above 40 kg: one 0.5 mg capsule per day.

Fingolimod Alvogen is not available in a 0.25 mg dosage strength. If such a dose is required, another medicinal product with this strength available on the market should be used. Ask your doctor or pharmacist for advice.
Children and adolescents who start treatment with one 0.25 mg capsule per day and later achieve a stable body weight above 40 kg will be advised by their doctor to change the dose to one 0.5 mg capsule once daily. In this case, a repeat observation period, similar to that after the first dose, is recommended.
Do not exceed the prescribed dose.
Fingolimod Alvogen is intended for oral use.
Fingolimod Alvogen should be taken once daily, with a glass of water. Fingolimod Alvogen capsules must always be swallowed whole, without opening. Fingolimod Alvogen may be taken with or without food.
Taking Fingolimod Alvogen at the same time each day will help you remember to take your dose.
If you have any questions about the duration of treatment with Fingolimod Alvogen, consult your doctor or pharmacist.
Taking more Fingolimod Alvogen than prescribed
If you have taken too much medicine, contact your doctor immediately.
Missing a dose of Fingolimod Alvogen
If you have been taking Fingolimod Alvogen for less than 1 month and miss 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 Alvogen 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 treatment with Fingolimod Alvogen
Do not stop treatment with Fingolimod Alvogen or change your dose without first consulting your doctor.
Fingolimod Alvogen may remain 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 adverse effects described in this leaflet may continue to occur. After stopping treatment with Fingolimod Alvogen, wait 6–8 weeks before starting a new type of MS treatment.
In patients restarting Fingolimod Alvogen 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 of the patient in a doctor's office or clinic will be necessary when restarting treatment. Do not restart treatment with Fingolimod Alvogen after a break of more than two weeks without consulting your treating doctor.
Your treating doctor will decide whether and how you should be monitored after stopping treatment with Fingolimod Alvogen. Inform your doctor immediately if you feel that your MS is worsening after stopping Fingolimod Alvogen. 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 they do not occur in everyone.
Some adverse reactions may be or may become serious.

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

• Cough with sputum, unspecified discomfort in the chest, fever (symptoms of lung disorders)
• Herpesvirus infection (shingles or herpes simplex) with symptoms such as blisters, burning sensation, itching or pain of the skin, usually above 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 red patches with severe pain.
• Slow heart rate (bradycardia), irregular heartbeat
• A type of skin cancer called basal cell carcinoma (BCC), which often appears as a pearly nodule, although it may also have a different appearance
• Depression and anxiety are known to occur more frequently in the population of patients with MS and have also been reported in children and adolescents treated with fingolimod.
• Weight loss.

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 the visual field, 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 which usually develops from an atypical mole). Possible symptoms of melanoma include moles whose size, shape, elevation or color may change 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 tumor involving the lymphatic system)
• Squamous cell carcinoma: a type of skin cancer which may appear as a hard, red nodule, 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 the lips, tongue or face, which are more likely to occur on the day treatment with Fingolimod Alvogen 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 test results. 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 may not be aware of, such as changes in mood or behavior, temporary memory lapses, difficulty speaking and communicating, which should be evaluated by a physician to rule out PML. Therefore, if the patient feels that their MS is worsening, or if the patient or their family members notice any new or unusual symptoms, it is very important to inform the treating physician as soon as possible.
• 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 hard, painless nodule or mass. Long-term exposure to sunlight and a weakened immune system may influence the risk of developing Merkel cell carcinoma.
• After discontinuation of treatment with Fingolimod Alvogen, MS symptoms may return and worsen compared to the period before treatment and during treatment.
• Autoimmune form of anemia (reduced number of red blood cells), in which red blood cells are destroyed (autoimmune hemolytic anemia).

If any of these adverse reactions occur in the patient, you should immediately inform the
physician.

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 the 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):

• Fungal skin infections (dermatophytosis) (pityriasis versicolor)
• Dizziness
• Severe headache, often accompanied by nausea, vomiting and light sensitivity (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 "Some adverse reactions may be or may become serious")
• Hypertension (Fingolimod Alvogen 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):

• Lymphatic system tumor (lymphoma)

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

• Peripheral edema

If any of these symptoms occur severely, you should inform the physician.

Reporting of adverse reactions

If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, you should inform your physician, pharmacist or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at 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.
Reporting of adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Fingolimod Alvogen

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 after "Expiry date (EXP)". The expiry date refers to the last day of the stated month.
Do not store above 25°C.
Keep in the original packaging to protect from moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Fingolimod Alvogen contains

• The active substance is fingolimod. Each capsule contains 0.5 mg of fingolimod (in the form of fingolimod hydrochloride).
• Other ingredients are:
  Capsule fill: microcrystalline cellulose, talc.
  Capsule cap: iron oxide, yellow (E 172), titanium dioxide (E 171), gelatin.
  Capsule body: titanium dioxide (E 171), gelatin.
  Printing ink: shellac, propylene glycol, ammonia, black iron oxide (E 172), potassium hydroxide.

What Fingolimod Alvogen looks like and contents of the pack
Hard, self-closing Coni-Snap type capsules, size 3, with a yellow cap and a white body. The cap is printed in black ink with "FGM 0.5 mg". The capsule contains a white powder.
Blisters made of OPA/Aluminium/PVC/Aluminium or OPA/Aluminium/PE/Aluminium with a desiccant, containing 7, 28 or 98 capsules in a cardboard carton.
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
Bluepharma - Indústria Farmacêutica, S.A.
S. Martinho do Bispo
3045-016 Coimbra, Portugal

This medicinal product is authorised in the European Economic Area under the following names:
Iceland, Bulgaria, Croatia, Hungary, Poland: Fingolimod Alvogen

For further information about this medicinal product, please contact the representative of the Marketing Authorisation Holder:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00