Fingolimod Tarbis 0.25 mg hard capsules EFG: detailed information

Patient Information Leaflet

Introduction

Patient Information Leaflet

Fingolimod Tarbis 0.25 mg hard capsules EFG

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

Keep this leaflet as you may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it may harm them.
If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Leaflet Contents

What Fingolimod Tarbis is and what it is used for
What you need to know before taking Fingolimod Tarbis
How to take Fingolimod Tarbis
Possible side effects
How to store Fingolimod Tarbis
Contents of the pack and other information

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

What Fingolimod Tarbis is

The active substance in this medicine is fingolimod.

What Fingolimod Tarbis is used for

This medicine is used in adults, and in children and adolescents (from 10 years of age onwards), to treat relapsing-remitting multiple sclerosis (MS) (characterized by relapses), particularly in:

Patients who do not respond to treatment despite receiving therapy for MS.

Patients who rapidly develop severe MS.

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

What is multiple sclerosis

MS is a chronic disease that affects the central nervous system (CNS), which consists of the brain and spinal cord. In MS, inflammation destroys the protective sheath (called myelin) that surrounds the nerves in the CNS, preventing nerves from functioning properly. This process is known as demyelination.

Relapsing-remitting MS is characterized by repeated attacks (relapses) of neurological symptoms reflecting inflammation occurring in the CNS. Symptoms vary from patient to patient but typically include difficulty walking, loss of sensation in parts of the body (numbness), vision problems, or balance disorders. Symptoms of a relapse may completely disappear when the relapse ends, although some problems may persist.

How Fingolimod works

Fingolimod helps combat immune system attacks on the CNS by reducing the ability of certain white blood cells (lymphocytes) to move freely throughout the body and by preventing them from entering the brain and spinal cord. This limits nerve damage caused by multiple sclerosis. Fingolimod also reduces some of the immune responses in your body.

2. What you need to know before starting Fingolimod Tarbis

Do not take fingolimod

if you have a reduced immune response (due to an immunodeficiency syndrome, an illness, or medications that suppress the immune system).
if you have an active serious infection or an active chronic infection such as hepatitis or tuberculosis.
if you have active cancer.
if you have severe liver problems.
if you have had a heart attack, angina, stroke, transient ischemic attack (TIA), or any type of heart failure within the last 6 months.
if you have any type of irregular or abnormal heartbeat (arrhythmia), including patients in whom the electrocardiogram (ECG) shows QT interval prolongation before starting treatment with Fingolimod.
if you are taking or have recently taken medications for irregular heartbeat such as quinidine, disopyramide, amiodarone, or sotalol.
if you are pregnant or if you are a woman of childbearing potential and are not using an effective contraceptive method.
if you are allergic to fingolimod or any of the other components of this medicine (listed in section 6).

If any of the above apply to you or you are unsure, inform your doctor before taking fingolimod.

Warnings and precautions

Talk to your doctor before starting this medicine:

if you have severe breathing problems while sleeping (severe sleep apnea).
if you have been told you have an abnormal electrocardiogram (ECG).
if you have symptoms of a slow heartbeat (e.g., dizziness, nausea, or palpitations).
if you are taking or have recently taken medications that slow your heart rate (such as beta-blockers, verapamil, diltiazem, ivabradine, digoxin, anticholinesterase agents, or pilocarpine).
if you have a history of sudden loss of consciousness or fainting (syncope).
if you are planning to get vaccinated.
if you have never had chickenpox.
if you have or have had disorders or other signs of inflammation in the central area of vision (the macula) at the back of the eye (a condition known as macular edema, see below), eye inflammation or infection (uveitis), or if you have diabetes (which can cause eye problems).
if you have liver problems.
if you have uncontrolled high blood pressure despite medication.
if you have severe lung problems or "smoker's cough".

If any of the above apply to you or you are unsure, inform your doctor before taking fingolimod.

Slow heart rate (bradycardia) and irregular heartbeats

At the start of treatment or after taking the first 0.5 mg dose when switching from a daily dose of 0.25 mg, fingolimod causes a reduction in heart rate. As a result, you may feel dizzy or fatigued, become aware of your heartbeat, or your blood pressure may drop. If these effects are severe, inform your doctor immediately, as you may need immediate treatment. Fingolimod may also cause irregular heartbeats, especially after the first dose. Irregular heartbeats usually return to normal within less than a day. The slow heart rate typically returns to normal within one month. During this period, clinically significant effects on heart rate are generally not expected.

Your doctor will ask you to remain at the clinic or hospital for at least 6 hours, with hourly monitoring of pulse and blood pressure, after taking the first dose of this medicine or after taking the first 0.5 mg dose when switching from a daily dose of 0.25 mg, so that appropriate measures can be taken if adverse effects occur at the beginning of treatment. You will have an electrocardiogram (ECG) before the first dose and again after the 6-hour monitoring period. Your doctor may perform continuous ECG monitoring during this time. If, after the 6-hour period, you have a very slow or decreasing heart rate or your ECG shows abnormalities, you will need to be monitored for a longer period (at least 2 additional hours, possibly overnight, until the issue resolves). The same may apply if you are restarting this medicine after a treatment interruption, depending on the duration of the interruption and how long you had previously taken the medicine.

If you have or are at risk of having irregular or abnormal heartbeats, if your ECG is abnormal, or if you have heart disease or heart failure, this medicine may not be suitable for you.

If you have previously experienced sudden fainting or a slow heart rate, fingolimod may not be appropriate for you. You will be evaluated by a cardiologist (heart specialist) who will advise on how to start treatment with fingolimod, including overnight monitoring.

If you are taking other medicines that may slow your heart rate, this medicine may not be suitable for you. A cardiologist must evaluate you and determine whether you can switch to alternative medicines that do not reduce heart rate to allow treatment with this medicine. If such a switch is not possible, the cardiologist will advise on how to start treatment with this medicine, including overnight monitoring.

If you have never had chickenpox

If you have never had chickenpox, your doctor will check your immunity to the virus that causes it (varicella-zoster virus). If you are not protected against the virus, you will likely need to be vaccinated before starting treatment with this medicine. If so, your doctor will delay the start of treatment with this medicine by one month after completing the vaccination series.

Infections

Fingolimod reduces the number of white blood cells in the blood (especially lymphocytes). White blood cells fight infections. During treatment with this medicine (and up to two months after stopping treatment), you may be more susceptible to infections. An existing infection may also worsen. Infections can be serious and potentially fatal. If you think you have an infection, have a fever, flu-like symptoms, herpes (shingles), or a headache accompanied by neck stiffness, light sensitivity, nausea, rash, and/or confusion or seizures (fits) (which may be symptoms of meningitis and/or encephalitis caused by fungal or herpes virus infection), contact your doctor immediately, as this could be serious and life-threatening.

If you think your MS is worsening (e.g., weakness or visual changes) or notice any new symptoms, inform your doctor immediately, as they could be symptoms of a rare brain disorder caused by infection called progressive multifocal leukoencephalopathy (PML). PML is a serious condition that can lead to severe disability or death. Your doctor will assess whether a magnetic resonance imaging (MRI) scan is needed to evaluate your condition and decide whether you need to stop taking this medicine.

Human papillomavirus (HPV) infection, including papilloma, dysplasia, warts, and HPV-related cancer, has been reported in patients treated with fingolimod. Your doctor will assess whether you need HPV vaccination before starting treatment. If you are a woman, your doctor will also recommend regular HPV screening.

Macular edema

Before starting fingolimod treatment, if you have or have had visual disorders or other signs of inflammation in the central area of vision (the macula) at the back of the eye, eye inflammation or infection (uveitis), or diabetes, your doctor may request an eye examination.

After starting fingolimod treatment, your doctor may request an eye examination 3 to 4 months after starting treatment.

The macula is a small area of the retina located at the back of the eye that allows you to see shapes, colors, and fine details clearly and sharply. Fingolimod can cause inflammation of the macula, a condition known as macular edema. This inflammation usually occurs within the first four months of treatment with fingolimod.

If you have diabetes or have previously had eye inflammation known as uveitis, you are more likely to develop macular edema. In these cases, your doctor may want you to have regular eye check-ups to detect macular edema.

If you have previously had macular edema, discuss this with your doctor before continuing fingolimod treatment.

Macular edema can cause visual symptoms similar to those of an MS attack (optic neuritis). You may not have symptoms at first. You must inform your doctor of any changes in your vision. Your doctor may want to perform an eye examination, especially if:

The center of your visual field becomes blurry or contains shadows;
A blind spot appears in the center of your visual field;
You have difficulty seeing colors or small details.

Liver function tests

If you have severe liver problems, you must not take fingolimod. Fingolimod can affect liver function. You may not experience any symptoms, but if you notice yellowing of the skin or whites of the eyes, abnormally dark (brown-colored) urine, pain in the right side of your abdomen, fatigue, loss of appetite, or nausea and vomiting without apparent cause, inform your doctor immediately.

If you experience any of these symptoms after starting fingolimod treatment, inform your doctor immediately.

Before, during, and after treatment, your doctor will order blood tests to monitor your liver function. You may need to stop fingolimod treatment if test results indicate a liver problem.

High blood pressure

Since fingolimod causes a slight increase in blood pressure, your doctor will want you to have your blood pressure monitored regularly.

Lung problems

Fingolimod has a mild effect on lung function. Patients with severe lung problems or "smoker's cough" are more likely to develop adverse effects.

Blood count

The expected effect of fingolimod treatment is to reduce the number of white blood cells in your blood. This effect usually returns to normal within 2 months after stopping treatment. If you have blood tests, inform your doctor that you are taking fingolimod, as otherwise your doctor may not understand the test results. For certain blood tests, your doctor may require more blood than usual.

Before starting fingolimod treatment, your doctor will confirm that you have sufficient white blood cells in your blood and may want to repeat monitoring regularly. If you do not have enough white blood cells, you may need to stop treatment with this medicine.

Reversible posterior encephalopathy syndrome (RPES)

Rarely, a condition called reversible posterior encephalopathy syndrome (RPES) has been reported in multiple sclerosis patients treated with fingolimod. Symptoms may include sudden and severe headache, confusion, seizures, and vision changes. Inform your doctor immediately if you experience any of these symptoms during fingolimod treatment, as it could be serious.

Cancer

Cases of skin cancer have been reported in MS patients treated with fingolimod. Inform your doctor immediately if you notice any skin nodules (e.g., shiny, pearl-like nodules), spots, or open sores that do not heal for weeks. Symptoms of skin cancer may include abnormal growth or changes in skin tissue (e.g., unusual moles) that change in color, shape, or size over time. Before starting fingolimod treatment, a skin examination is required to check for skin nodules. Your doctor will also perform periodic skin checks during treatment. If any skin problems arise, your doctor may refer you to a dermatologist, who may decide whether regular visits are necessary.

A type of cancer of the lymphatic system (lymphoma) has been reported in MS patients treated with fingolimod.

Sun exposure and sun protection

Fingolimod weakens your immune system, increasing the risk of developing cancer, especially skin cancer. You should limit your exposure to sunlight and UV rays by:

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

Unusual brain lesions associated with MS relapses

Rare cases of large, unusual brain lesions associated with MS relapses have been reported in patients treated with fingolimod. In the case of severe relapses, your doctor will assess whether an MRI scan is needed to evaluate your condition and decide whether you need to stop taking fingolimod.

Switching from other treatments to fingolimod

Your doctor may switch you directly from interferon beta, glatiramer acetate, or dimethyl fumarate to fingolimod if there are no signs of abnormalities caused by the previous treatment. Your doctor may need to perform a blood test to rule out such abnormalities. After stopping natalizumab, you may need to wait 2–3 months before starting fingolimod. When switching from teriflunomide, your doctor may advise waiting a period or undergoing an accelerated elimination procedure. If you have been treated with alemtuzumab, a thorough evaluation is required, and you should discuss with your doctor whether fingolimod is suitable for you.

Women of childbearing potential

Fingolimod may be harmful to the fetus if used during pregnancy. Before starting fingolimod treatment, your doctor will explain the risks and ask you to take a pregnancy test to confirm you are not pregnant. Your doctor will give you a card explaining why you must not become pregnant while taking fingolimod and what you should do to avoid pregnancy. During treatment and for 2 months after stopping treatment, you must use an effective contraceptive method (see section “Pregnancy and breastfeeding”).

If you become pregnant while taking fingolimod, inform your doctor immediately. Your doctor will decide to stop treatment (see section 3 “If you stop taking fingolimod” and section 4 “Possible side effects”). You will receive specific prenatal follow-up.

Breastfeeding

You must not breastfeed during treatment with fingolimod. Fingolimod passes into breast milk and there is a risk that the baby may experience serious adverse effects.

Driving and using machines

Your doctor will advise you whether your condition allows you to drive vehicles, including bicycles, and safely operate machinery. This medicine is not expected to affect your ability to drive or use machines.

However, at the start of treatment, you will need to remain at the medical clinic or hospital for 6 hours after taking the first dose of fingolimod. During this time and possibly afterward, your ability to drive and use machines may be impaired.

Fingolimod Tarbis contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per capsule; therefore, it is essentially "sodium-free."

3. How to take Fingolimod Tarbis

Treatment with fingolimod will be supervised by a physician experienced in the treatment of multiple sclerosis.

Follow exactly the dosing instructions for this medicine as provided by your doctor. If in doubt, consult your doctor again.

The recommended dose is:

Adults:

The dose is 0.5 mg of fingolimod per day.

Children and adolescents (aged 10 years and older):

The dose depends on body weight:

Children and adolescents weighing 40 kg or less: one 0.25 mg capsule per day.
Children and adolescents weighing more than 40 kg: one 0.5 mg capsule per day. For children and adolescents who started with one 0.25 mg capsule per day and later reach a stable weight above 40 kg, the doctor will instruct them to switch to one 0.5 mg capsule per day. In this case, it is recommended to repeat the first-dose observation period.

Do not exceed the recommended dose.

This medicine is for oral use.

Take this medicine once daily with a glass of water. The capsules must always be swallowed whole and must not be opened. You may take fingolimod with or without food. Taking fingolimod at the same time each day will help you remember when to take the medicine.

If you have any doubts about how long to continue treatment with this medicine, consult your doctor or pharmacist.

If you take more fingolimod than you should

If you have taken more fingolimod than you should, inform your doctor immediately.

In case of overdose or accidental ingestion, contact your doctor or pharmacist, or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take fingolimod

If you have been taking fingolimod for less than 1 month and forget to take a dose for a full day, speak with 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 for at least 1 month and have missed taking your treatment for more than 2 weeks, speak with 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 taking your treatment for up to 2 weeks, you may take the next dose as originally scheduled.

Do not take a double dose to make up for missed doses.

If you stop taking fingolimod

Do not stop taking fingolimod or change your dose without first discussing it with your doctor.

Fingolimod will remain in your body for up to two months after stopping treatment. The number of white blood cells (lymphocyte count) may remain low during this period, and adverse effects described in this leaflet may still occur. After stopping treatment with fingolimod, you may need to wait 6–8 weeks before starting a new treatment for MS.

If you need to restart treatment with fingolimod after a break of more than two weeks, the effect on heart rhythm that may occur at the beginning of treatment could reappear, and it will be necessary for you to be monitored by your doctor when restarting treatment. Do not restart treatment with fingolimod after having stopped for more than two weeks without first consulting your doctor.

Your doctor will decide whether follow-up is needed after stopping treatment with fingolimod and how this should be managed. Inform your doctor immediately if you think your MS is worsening after stopping treatment with fingolimod, as this could be serious.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Some adverse effects may be serious or potentially serious

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

Cough with phlegm (sputum), chest discomfort, fever (signs of pulmonary disorders).
Herpes virus infection (shingles or herpes zoster) with symptoms such as blisters, stinging, itching, or skin pain, especially on the upper body or face. Other symptoms may include fever and weakness in the early phase of infection, followed by numbness, itching, or red patches with severe pain.
Slow heartbeat (bradycardia), irregular heart rhythm.
A type of skin cancer known as basal cell carcinoma (BCC), which often appears as a pearly nodule, although it may also have other forms.
Depression and anxiety are known to occur more frequently in patients with multiple sclerosis, and have also been reported in pediatric patients treated with fingolimod.
Weight loss.

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

Pneumonia, with symptoms such as fever, cough, and difficulty breathing.
Macular edema (swelling in the central vision area of the retina at the back of the eye), with symptoms such as shadows or a blind spot or loss of vision in the center of the visual field, blurred vision, problems seeing colors or details.
Decrease in the number of blood platelets, increasing the risk of bleeding or bruising.
Malignant melanoma (a type of skin cancer that usually develops from an unusual mole). Possible signs of melanoma include moles that may change over time in size, shape, thickness, or color, or the formation of new moles. Moles may become itchy, bleed, or ulcerate.
Seizures, fits (more frequent in children and adolescents than in adults).

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

A condition called reversible posterior encephalopathy syndrome (PRES). Symptoms may include sudden and 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 firm red nodule, a crusted sore, or a new sore developing on an existing scar.

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

Abnormality in the electrocardiogram (ECG) (T-wave inversion).
Tumor associated with human herpesvirus 8 infection (Kaposi's sarcoma).

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

Allergic reactions, including rash or hives with itching, swelling of lips, tongue, or face, which are more likely to occur on the day treatment with fingolimod is started.
Signs of liver disease (including liver failure), such as yellowing of the skin or whites of the eyes (jaundice), nausea or vomiting, pain on the right side of the stomach area (abdomen), dark (brown-colored) urine, reduced appetite, fatigue, and abnormal liver function tests. In a small number of cases, liver failure could require a liver transplant.
Risk of a rare brain infection called progressive multifocal leukoencephalopathy (PML). Symptoms of PML may be similar to those of an MS relapse. Other symptoms may not be noticeable by the patient, such as changes in mood or behavior, memory loss, or speech and communication difficulties, which your doctor may need to investigate further to rule out PML. Therefore, if you think your MS is worsening or if you or people close to you notice any new or unusual symptoms, it is very important to inform your doctor 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 signs include the formation of a painless flesh-colored or bluish-red nodule, usually on the face, head, or neck. Merkel cell carcinoma may also appear as a firm, painless nodule or mass. Long-term sun exposure and a weakened immune system may influence the risk of developing Merkel cell carcinoma.
After stopping treatment with fingolimod, MS symptoms may reappear and may be worse than before or during treatment.
Autoimmune form of anemia (decrease in red blood cells) in which red blood cells are destroyed (autoimmune hemolytic anemia).

If you experience any of these symptoms, contact your doctor immediately.

Other adverse effects

Very frequent (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.
Blood tests showing abnormal liver enzyme levels.
Cough.

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

Tinea, a fungal infection of the skin (pityriasis versicolor).
Dizziness.
Severe headache, usually accompanied by nausea, vomiting, and light sensitivity (migraine).
Low levels of white blood cells (lymphocytes, leukocytes).
Weakness.
Itchy rash, skin redness, and burning (eczema).
Itching.
Increased blood levels of certain lipids (triglycerides).
Hair loss.
Difficulty breathing.
Depression.
Blurred vision (see also the section on macular edema under the heading "Some adverse effects may be serious or potentially serious").
Hypertension (fingolimod may cause a slight increase in blood pressure).
Muscle pain.
Joint pain.

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

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

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

Cancer of the lymphatic system (lymphoma).

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

Peripheral inflammation.

If you consider any of the adverse effects you experience to be severe, inform your doctor.

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Fingolimod Tarbis Storage

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the packaging and on the aluminium blister after EXP. The expiry date refers to the last day of the month indicated.

Store below 30°C.

Do not use any pack that is damaged or shows signs of tampering.

Medicines must not be disposed of via wastewater drains or household waste. Return unused packs and medicines to the SIGRE collection point at your pharmacy. If you have any doubts, ask your pharmacist how to dispose of packs and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Fingolimod Tarbis

The active substance is fingolimod.
Each hard capsule contains 0.25 mg of fingolimod (as hydrochloride).
The other components are:

Capsule contents: powdered cellulose (E460), titanium dioxide (E171), magnesium stearate.

Capsule shell: gelatin, yellow iron oxide (E172), titanium dioxide (E171), sodium lauryl sulfate.

Black printing ink: shellac, propylene glycol (E1520), black iron oxide (E172), strong ammonia solution, potassium hydroxide.

Blue printing ink: shellac, propylene glycol (E1520), strong ammonia solution, indigo carmine (E132).

Appearance of the product and contents of the pack

Fingolimod Tarbis 0.25 mg hard capsules are supplied as size '4' hard gelatin capsules, ivory-colored, with opaque cap and body, printed with 'H' in black ink on the cap and 'F10' in blue ink on the body.

Fingolimod Tarbis is available in blister packs and peelable blisters.

Pack sizes containing 28 capsules and unit-dose perforated blisters containing 28 x 1 capsule.

Marketing Authorization Holder

Tarbis Farma, S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Manufacturer

Amarox Pharma B.V.

Rouboslaan 32

Voorschoten, 2252TR

The Netherlands

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

Germany: Fingolimod Amarox 0.25 mg Hard Capsules

Spain: Fingolimod Tarbis 0.25 mg hard capsules EFG

Date of the most recent review of this leaflet: July 2022

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/