Fingolimod Alvogen

Leaflet accompanying the packaging: patient information

Fingolimod Alvogen, 0.5 mg

Hard capsules
Fingolimodum

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

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any side effects, including any possible side effects not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is Fingolimod Alvogen and what is it 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. Package contents and other information

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

What is Fingolimod Alvogen

Fingolimod Alvogen contains the active substance fingolimod.

What is Fingolimod Alvogen used for

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

• patients who have not responded to MS treatment or
• patients who have rapidly evolving, severe 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 destroys the nerve sheath (called myelin) in the CNS, making it difficult for them to function 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 difficulty walking, numbness, vision disturbances, or balance problems. Relapse symptoms may completely resolve, but some disturbances may persist.

How Fingolimod Alvogen works

Fingolimod Alvogen 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.
This way, the medicine reduces nerve damage caused by MS. Fingolimod Alvogen also weakens some immune responses of the body.

2. Important information before taking Fingolimod Alvogen

When not to take Fingolimod Alvogen

• If the patient is allergic to fingolimodor any of the other ingredients of this medicine (listed in section 6).
• If the patient has reduced 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 malignant disease;
• If the patient has severe liver disease;
• If the patient has had a heart attack, angina pectoris, stroke, or symptoms of stroke in the last 6 months;
• If the patient has a certain type of irregular or abnormal heartbeat(arrhythmia), which includes patients who have had an electrocardiogram (ECG) showing a prolonged QT interval 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 breastfeeding or is of childbearing age and not using effective contraception.If such a situation occurs or the patient has doubts, they should tell their doctor before taking Fingolimod Alvogen.

Warnings and precautions

Before starting treatment with Fingolimod Alvogen, the patient should discuss the following with their doctor:

• If the patient has severe respiratory disorders during sleep (sleep apnea);
• If the patient has been informed that their ECG is abnormal;
• If the patient has symptoms of slow heart rate (e.g., dizziness, nausea, or palpitations);
• If the patient is taking or has recently taken medicines that slow down the heart rate(such as beta blockers, verapamil, diltiazem, or ivabradine, digoxin, cholinesterase inhibitors, or pilocarpine);
• If the patient has a history of 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 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 the patient has diabetes, which can cause vision problems;
• If the patient has liver disease;
• If the patient has high blood pressure that cannot be controlled with medication;
• If the patient has severe lung disease or a cough typical of smokers.If any of these situations occur or the patient has doubts, they should tell their doctor before taking Fingolimod Alvogen.

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 previously took a daily dose of 0.25 mg, Fingolimod Alvogen slows down the heart rate. As a result, the patient may experience dizziness, fatigue, palpitations, or a decrease in blood pressure. If these symptoms are severe, the patient should inform their doctor immediately, as they may require immediate treatment.
Fingolimod Alvogen may also cause irregular heartbeat, especially after taking the first dose. Irregular heartbeat usually returns to normal within less than one day. Low heart rate usually returns to normal within one month. During this period, no clinically significant effect on heart rate is expected.
The doctor will ask the patient to stay in the doctor's office or clinic for at least 6 hours after taking the first dose of Fingolimod Alvogen or after the first dose of 0.5 mg in case of a change in 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 the first dose of Fingolimod Alvogen and after the 6-hour observation period, the patient will undergo an ECG.
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 Alvogen after a break in treatment, depending on how long the break lasted and how long the patient took Fingolimod Alvogen 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 Alvogen may not be suitable for them.
If the patient has a history of sudden loss of consciousness or slow heart rate, Fingolimod Alvogen may not be suitable for them. It may be necessary to consult a cardiologist (a specialist in heart diseases) who will advise on how to start treatment with Fingolimod Alvogen, including how to monitor the patient at night.
If the patient is taking medicines that can slow down the heart rate, Fingolimod Alvogen may not be suitable. It may be necessary to consult a cardiologist who will check if the patient can switch to other medicines that do not slow down the 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, taking into account monitoring until the next day after administration of 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, they may need to be vaccinated 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 the full vaccination cycle.
Infections
Fingolimod Alvogen reduces the number of white blood cells (especially lymphocytes). White blood cells fight infections. While taking Fingolimod Alvogen (and 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, flu-like symptoms, 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.
If the patient experiences any of the above symptoms after starting treatment with Fingolimod Alvogen, they should tell their doctor immediately.
Before, during, and after treatment, the doctor will order blood tests to monitor liver function. If the test results indicate liver function disorders, treatment with Fingolimod Alvogen may be discontinued.
High blood pressure
The doctor may regularly check the patient's blood pressure, as Fingolimod Alvogen can cause a slight increase in blood pressure.
Lung diseases
Fingolimod Alvogen has a minor effect on lung function. Patients with severe lung disease or a cough typical of smokers are at greater risk of adverse reactions.
White blood cell count
The expected effect of Fingolimod Alvogen is a decrease in the number of white blood cells in the blood. Their number usually returns to normal within 2 months after stopping treatment. If blood tests need to be performed, the patient should inform their doctor that they are taking Fingolimod Alvogen. 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 Alvogen, the doctor will check if the patient has a sufficient number of white blood cells to start treatment and may order regular repeat tests. If there are not enough white blood cells, it may be necessary to discontinue treatment with Fingolimod Alvogen.
Posterior reversible encephalopathy syndrome (PRES)
In patients with MS treated with fingolimod, there have been rare reports of a condition called posterior reversible encephalopathy syndrome (PRES). Symptoms of this condition may include severe headache, confusion, seizures, and/or vision changes. If any of these symptoms occur during treatment with Fingolimod Alvogen, the patient should tell their doctor immediately, as this condition can be severe.
Cancer
In patients with MS treated with fingolimod, there have been reports of skin cancer. If the patient notices any lumps on their skin (e.g., 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 (e.g., new moles) that change color, shape, or size over time. Before starting treatment with Fingolimod Alvogen, it is necessary to examine the skin to detect any lumps. The doctor will also perform regular skin checks during treatment with Fingolimod Alvogen. If skin problems occur, the doctor may refer the patient to a dermatologist who, after consultation, may decide on the need for regular visits.

Changing treatment from other medicines to Fingolimod Alvogen
The doctor may change the treatment directly from interferon beta, glatiramer acetate, or dimethyl fumarate to Fingolimod Alvogen if there are no symptoms of abnormalities caused by previous treatment. The doctor may order a blood test to rule out these abnormalities. After stopping treatment with natalizumab, it may be necessary to wait 2 to 3 months before starting treatment with Fingolimod Alvogen. In the case of a change in treatment from teriflunomide, the doctor may advise the patient to wait for some time or undergo an accelerated elimination procedure. Patients previously treated with alemtuzumab require careful evaluation and discussion with their doctor before deciding whether Fingolimod Alvogen is suitable for them.
Women of childbearing age
If fingolimod is used during pregnancy, it may have a harmful effect on the unborn child. Before starting treatment with Fingolimod Alvogen, the doctor will explain the risk to the patient and ask them to perform a pregnancy test to rule out pregnancy. The doctor will provide the patient with a card explaining why they should not become pregnant while taking Fingolimod Alvogen. The card also contains information on what to do to avoid becoming pregnant while taking Fingolimod Alvogen. Female patients must use effective contraception during treatment and for 2 months after stopping treatment (see "Pregnancy and breastfeeding").
Pregnancy
Fingolimod Alvogen 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 incidence of birth defects observed in children exposed to fingolimod during pregnancy is about twice as high as that observed in the general population (in which the incidence of birth defects is about 2-3%). The most commonly reported birth defects include developmental heart defects, kidney defects, and musculoskeletal defects.
Therefore, if the patient is of childbearing age:

• before starting treatment with Fingolimod Alvogen, the doctor will inform the patient about the risk to the unborn child and ask them to perform a pregnancy test to ensure that the patient is not pregnant, and
• the patient must use effective contraception during treatment with Fingolimod Alvogen and for 2 months after stopping treatment to avoid becoming pregnant. The patient should discuss effective contraception methods with their doctor.

The doctor will provide the patient with a card explaining why they should not become pregnant while taking Fingolimod Alvogen.

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

The doctor will decide on discontinuing treatment (see "Discontinuing Fingolimod Alvogen" in section 3, as well as section 4 "Possible side effects").The patient will also need to undergo prenatal check-ups.
Breastfeeding
Do not breastfeed while taking Fingolimod Alvogen.Fingolimod may pass into breast milk, posing a risk of severe side effects in the child.

Driving and operating machinery

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

3. How to take Fingolimod Alvogen

Treatment with Fingolimod Alvogen 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 has any doubts, they should consult 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 with a body weight of 40 kg or less:one 0.25 mg capsule per day.
• Children and adolescents with a body weight over 40 kg:one 0.5 mg capsule per day.

Fingolimod Alvogen is not available in a 0.25 mg strength. If such dosing is necessary, other fingolimod products available on the market should be used. The patient should ask their doctor or pharmacist about this.
Children and adolescents starting treatment with one 0.25 mg capsule per day and later reaching a stable body weight over 40 kg will be advised by their doctor to change the dose to one 0.5 mg capsule per day. In this case, it is recommended to repeat the observation period as after the first dose.
Do not exceed the recommended dose.
Fingolimod Alvogen is for oral use.
Fingolimod Alvogen should be taken once a day, with a glass of water. Fingolimod Alvogen capsules should always be swallowed whole, without opening. Fingolimod Alvogen can be taken with or without food.
Taking Fingolimod Alvogen 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 Alvogen, they should consult their doctor or pharmacist.

Taking a higher dose of Fingolimod Alvogen than recommended

If the patient takes too much of the medicine, they should contact their doctor immediately.

Missing a dose of Fingolimod Alvogen

If the patient takes Fingolimod Alvogen for less than 1 month and forgets to take 1 dose for the whole day, they should contact their doctor before taking the next dose. The doctor may decide to keep the patient under observation during the administration of the next dose.
If the patient takes Fingolimod Alvogen for at least 1 month and forgets to take the medicine for more than 2 weeks, they should contact their doctor before taking the next dose. The doctor may decide to keep the patient under observation during the administration of the next dose. However, if the patient forgets to take 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 the missed dose.

Discontinuing Fingolimod Alvogen

Do not stop taking Fingolimod Alvogen or change the dose without consulting your doctor first.
Fingolimod Alvogen 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 Alvogen, the patient should wait 6-8 weeks before starting a new type of MS treatment.
In patients resuming treatment with Fingolimod Alvogen after more than 2 weeks of stopping the medicine, the effect on heart rate observed after starting treatment for the first time may occur again, and monitoring of the patient's condition in the doctor's office or clinic will be necessary due to the resumption of treatment. Do not resume treatment with Fingolimod Alvogen after a break of more than 2 weeks without consulting the doctor.
The doctor will decide how to monitor the patient after stopping treatment with Fingolimod Alvogen. If the patient thinks that their MS is getting worse after stopping treatment with Fingolimod Alvogen, they should tell their doctor immediately.This situation may be serious.
If the patient has any further doubts about using this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

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

• Cough with expectoration, unspecified unpleasant feeling in the chest, fever (respiratory disorders)
• Herpesvirus infections (shingles or herpes) with symptoms such as blisters, burning, itching, or pain on the skin, usually above the upper body or face. Other symptoms may include fever and weakness at the beginning of the infection, followed by numbness, itching, or red spots with severe pain.
• Slow heart rate (bradycardia), irregular heartbeat
• A type of skin cancer called basal cell carcinoma (BCC), which often appears as a pearl-like nodule, although it can have other forms
• It is known that depression and anxiety 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 up to 1 in 100 people):

• Pneumonia with symptoms such as fever, cough, difficulty breathing
• Macular edema (swelling in the center of the field of vision in the retina, at the back of the eye) with symptoms such as shadows or gaps in the center of the field of vision, blurred vision, difficulty perceiving colors and details
• Reduced platelet count, which increases the risk of bleeding or bruising
• Malignant melanoma (a type of skin cancer that usually develops from an abnormal mole). Possible symptoms of melanoma include moles whose size, shape, elevation, or color changes over time or new moles that appear. Moles can be itchy, bleeding, or ulcerated

Rare(may affect up to 1 in 1,000 people):

• Seizures, epileptic seizures (more common in children and adolescents than in adults)
• 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 place 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(frequency 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 Alvogen.
• 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, dark (brown) urine, decreased appetite, fatigue, and abnormal liver function test results. In very rare cases, liver failure can lead to liver transplantation.
• Risk of a rare brain infection called progressive multifocal leukoencephalopathy (PML). Symptoms of PML may be similar to those of an MS relapse. They may also include symptoms that the patient is not aware of, such as changes in mood or behavior, transient memory lapses, difficulty speaking or communicating, which the doctor should assess to rule out PML. PML is a serious disease that can lead to severe disability or death. The doctor will consider performing an MRI scan to assess the patient's condition and decide whether to discontinue Fingolimod Alvogen.
• 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 raw meat color, often 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 increase the risk of Merkel cell carcinoma
• After stopping treatment with Fingolimod Alvogen, MS symptoms may relapse and worsen compared to the period before treatment and during treatment.
• Autoimmune hemolytic anemia (a condition in which red blood cells are destroyed).

If the patient experiences any of these side effects, they should tell their doctor immediately.
Other side effects
Very common(may affect more than 1 in 10 people):

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

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

• Fungal skin infections (dermatophytosis) (ringworm)
• Dizziness
• Severe headache, often accompanied by nausea, vomiting, and sensitivity to light (migraine symptoms)
• Low white blood cell count (lymphocytes, leukocytes)
• Weakness
• Itchy, red, burning rash (rash)
• Itching
• Increased triglyceride levels in the blood
• Hair loss
• Shortness of breath
• Depression
• Blurred vision (see also the section on macular edema under "Some side effects may be or may become serious")
• Hypertension (Fingolimod Alvogen may cause a mild increase in blood pressure)
• Muscle pain
• Joint pain

Uncommon(may affect up to 1 in 100 people):

• Low neutrophil count
• Depressed mood
• Nausea

Rare(may affect up to 1 in 1,000 people):

• Lymphoma (a type of cancer affecting the lymphatic system)

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

• Peripheral edema

If any of these symptoms occur with significant severity, the patient should tell their doctor.

5. How to store Fingolimod Alvogen

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

6. Package contents and other information

What Fingolimod Alvogen contains

• The active substance is fingolimod. Each capsule contains 0.5 mg of fingolimod (as fingolimod hydrochloride).
• The other ingredients are: Capsule filling: microcrystalline cellulose, talc. Capsule cap:iron oxide yellow (E 172), titanium dioxide (E 171), gelatin Capsule body: titanium dioxide (E 171), gelatin Ink:shellac, propylene glycol, ammonia, iron oxide black (E 172), potassium hydroxide

What Fingolimod Alvogen looks like and package contents

Self-locking hard capsules, size 3, with a yellow cap and a white body. The cap is printed with black ink "FGM 0.5 mg". The capsule contains a white powder.
OPA/Aluminium/PVC/Aluminium or OPA/Aluminium/PE/Aluminium blisters with a desiccant, containing 7, 28 or 98 capsules in a cardboard box.
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

Bluepharma - Indústria Farmacêutica, S.A.

• S. Martinho do Bispo 3045-016 Coimbra, Portugal

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Iceland, Bulgaria, Croatia, Hungary, Poland: Fingolimod Alvogen

To obtain further information on this medicinal product, please contact the representative of the marketing authorization holder:

Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00
Date of last revision of the leaflet:March 2022