Fingolimod Bluefish

Leaflet accompanying the packaging: patient information

Fingolimod Bluefish, 0.5 mg, hard capsules
Fingolimod

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, pharmacist, or nurse.
• 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 not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Fingolimod Bluefish and what is it used for
• 2. Important information before taking Fingolimod Bluefish
• 3. How to take Fingolimod Bluefish
• 4. Possible side effects
• 5. How to store Fingolimod Bluefish
• 6. Package contents and other information

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

Fingolimod Bluefish contains the active substance fingolimod.
Fingolimod Bluefish is used in adults and children and adolescents (aged 10 years and older)
to treat relapsing-remitting multiple sclerosis (MS),
especially in:

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

Fingolimod Bluefish does not cure MS, but it 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), consisting of the brain
and spinal cord. In MS, the inflammatory process destroys the nerve sheath (called myelin) in the CNS,
preventing it from functioning properly. This phenomenon is called demyelination.
The relapsing-remitting form of MS is characterized by recurring relapses (exacerbations) of neurological symptoms
reflecting the inflammatory process in the CNS. Symptoms vary among patients but usually include walking difficulties, numbness, vision disturbances, or balance problems. Relapse symptoms may completely resolve, but some disturbances may persist.

How Fingolimod Bluefish works

Fingolimod Bluefish helps protect the CNS from immune system attacks by reducing
the ability of certain white blood cells (lymphocytes) to move freely in the patient's body
and preventing them from entering the brain and spinal cord. In this way, the medicine reduces nerve damage caused by MS. Fingolimod Bluefish also weakens some immune system reactions.

2. Important information before taking Fingolimod Bluefish

When not to take Fingolimod Bluefish

• if the patient has reduced immune response(due to immunodeficiency syndrome, disease, or taking immunosuppressive medications);
• 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, stroke, or symptoms of stroke within 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 Bluefish;
• if the patient is currently taking or has recently taken medications for irregular heartbeat, such as quinidine, disopyramide, amiodarone, or sotalol;
• if the patient is pregnantor is of childbearing age and not using effective contraception;
• if the patient is allergicto fingolimod or any of the other ingredients of this medicine (listed in section 6). If this is the case or the patient has doubts, consult a doctor before taking Fingolimod Bluefish.

Warnings and precautions

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

• if the patient has severe respiratory problems during sleep (sleep apnea);
• if the patient has been informed that their ECG 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 medications that slow 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 affecting the retina) or uveitis (inflammation or infection of the eye), or if the patient has diabetes(which can 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 diseaseor a cough typical of smokers. If any of these situations occur or the patient has doubts, consult a doctor before taking Fingolimod Bluefish.

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 Bluefish slows down the heart rate.
As a result, the patient may experience dizziness, fatigue, strong heartbeat, or low blood pressure. If these symptoms are severe, inform your doctor immediately,
as immediate treatment may be necessary.Fingolimod Bluefish 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 Bluefish 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 measurement of pulse and blood pressure, so that if any adverse reactions occur at the beginning of treatment, appropriate treatment can be applied. Before the first dose of Fingolimod Bluefish and after completing the 6-hour observation, the patient will undergo an ECG examination.
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 overnight), until these symptoms resolve. The same procedure may be recommended if the patient resumes treatment with Fingolimod Bluefish after a break in treatment, depending on how long the break lasted and how long the patient took Fingolimod Bluefish 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 Bluefish may not be suitable for them.
If the patient has a history of sudden loss of consciousness or slow heart rate, Fingolimod Bluefish may not be suitable for them. It may be necessary to consult a cardiologist who will advise on how to start treatment with Fingolimod Bluefish, including how to monitor the patient at night.
If the patient is taking medications that can slow down the heart rate, Fingolimod Bluefish may not be suitable. It may be necessary to consult a cardiologist who will check if the patient can switch to other medications that do not slow down the heart rate, to allow treatment with Fingolimod Bluefish. If such a change in treatment is not possible, the cardiologist will advise the patient on how to start treatment with Fingolimod Bluefish, taking into account monitoring until the next day after administration of the first dose of the medicine.
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 Bluefish. If this is the case, the doctor will delay the start of treatment with Fingolimod Bluefish by one month after the full vaccination course.
Infections
Fingolimod Bluefish reduces the number of white blood cells (especially lymphocytes). White blood cells fight infections. During treatment with Fingolimod Bluefish (and up to 2 months after stopping treatment), the patient may be more susceptible to infections. 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, headache with stiff neck, sensitivity to light, nausea, rash, and/or confusion or seizures (which may be symptoms of meningitis and/or brain infection caused by fungal or viral infection), they should contact their doctor immediately, as this condition can be severe and life-threatening.
If the patient thinks their disease is worsening (e.g., weakness or vision disturbances) or if the patient notices any new symptoms, they should contact 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 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 stop taking Fingolimod Bluefish.
Patients treated with Fingolimod Bluefish have reported infections with the human papillomavirus (HPV), including cases of warts, dysplasia, and HPV-related cancer. The doctor will consider vaccinating the patient against HPV before starting treatment with Fingolimod Bluefish. In women, the doctor will also recommend screening for HPV.
Macular edema
Before starting treatment with Fingolimod Bluefish, the doctor may refer patients with existing or past vision problems or other symptoms of macular edema (a condition affecting the retina) or uveitis (inflammation or infection of the eye) or diabetes for ophthalmological examinations.
The doctor may refer the patient for ophthalmological examinations after 3 to 4 months of starting treatment with Fingolimod Bluefish.
The macula is a small area of the retina at the back of the eye that allows for sharp and detailed vision. Fingolimod Bluefish may cause macular edema, a condition called macular edema. Macular edema usually occurs within the first 4 months of treatment with Fingolimod Bluefish.
The risk of macular edema is higher in patients with diabetesor with a history of uveitis. In such cases, the doctor will prescribe regular ophthalmological examinations to detect macular edema.
If the patient experiences macular edema, they should inform their doctor before resuming treatment with Fingolimod Bluefish.
Macular edema may cause vision disturbances similar to those experienced during an MS relapse (optic neuritis). In the early stages, symptoms may not occur at all.
The patient should inform their doctor about any changes in vision. The doctor may refer the patient for ophthalmological examinations, especially if:

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

Liver function tests
Patients with severe liver disease should not take Fingolimod Bluefish. Fingolimod Bluefish may affect liver function. The patient is unlikely to experience any symptoms, but if they notice yellowing of the skin or eyes, dark (brown) urine, pain in the right side of the abdomen, fatigue, decreased appetite, or unexplained nausea and vomiting, they should inform their doctor immediately.
If any of the above symptoms occur after starting treatment with Fingolimod Bluefish, the patient should inform their doctor immediately.
Before, during, and after treatment, the doctor will prescribe blood tests to monitor liver function.
If the test results indicate liver function disorders, treatment with Fingolimod Bluefish may be stopped.
High blood pressure
The doctor may regularly check blood pressure, as Fingolimod Bluefish can cause a slight increase in blood pressure.
Lung problems
Fingolimod Bluefish has a minor effect on lung function. Patients with severe lung disease or a cough typical of smokers are at higher risk of adverse reactions.
Blood cell count
An expected effect of Fingolimod Bluefish 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 necessary, the patient should inform their doctor that they are taking Fingolimod Bluefish. Otherwise, the doctor may not be able to interpret the test results, and in the case of certain tests, the doctor may order a larger blood sample than usual.
Before starting treatment with Fingolimod Bluefish, the doctor will check if the patient has a sufficient number of white blood cells to start treatment and may prescribe regular blood tests.
In case of insufficient white blood cell count, it may be necessary to stop treatment with Fingolimod Bluefish.
Posterior reversible encephalopathy syndrome (PRES)
Rarely, patients with MS treated with Fingolimod Bluefish have reported a condition called posterior reversible encephalopathy syndrome (PRES). Symptoms of this condition may include severe headache with sudden onset, disorientation, seizures, and/or vision changes. If any of these symptoms occur during treatment with Fingolimod Bluefish, the patient should inform their doctor immediately, as this condition can be severe.
Cancer
Patients with MS treated with Fingolimod Bluefish have reported skin cancers.
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 inform 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 Bluefish, it is necessary to examine the skin for any lumps. The doctor will also perform regular skin checks during treatment with Fingolimod Bluefish. If skin problems occur, the doctor may refer the patient to a dermatologist, who may decide on the need for regular visits after consulting with the patient.
Patients with MS treated with Fingolimod Bluefish have also reported a type of lymphoma (a cancer of the lymphatic system).

Exposure to sunlight and protection from ultraviolet radiation

Fingolimod weakens the immune system. This increases the risk of developing cancers, especially skin cancers. The patient should limit exposure to sunlight and UV radiation by:

• wearing protective clothing;
• regularly applying sunscreen with a high level of UV protection.

Unusual changes in the brain related to MS relapse
Patients treated with Fingolimod Bluefish have rarely reported unusually large changes in the brain related to MS relapse. In case of a severe MS relapse, the doctor may consider performing an MRI scan to assess the patient's condition and decide whether to stop taking Fingolimod Bluefish.
Switching from other medicines to Fingolimod Bluefish
The doctor may switch treatment directly from interferon beta, glatiramer acetate, or dimethyl fumarate to Fingolimod Bluefish if there are no symptoms of adverse reactions caused by previous treatment. The doctor may prescribe a blood test to rule out these adverse reactions. After stopping treatment with natalizumab, it may be necessary to wait 2 to 3 months before starting treatment with Fingolimod Bluefish. When switching 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 Bluefish is suitable for them.
Women of childbearing age
If Fingolimod Bluefish is used during pregnancy, it may harm the unborn child. Before starting treatment with Fingolimod Bluefish, 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 Bluefish. The card also contains information on what to do to avoid becoming pregnant while taking Fingolimod Bluefish. Female patients must use effective contraception during treatment and for 2 months after stopping treatment (see "Pregnancy and breastfeeding").
If the patient becomes pregnant while taking Fingolimod Bluefish, they should inform their doctor immediately.
The doctor will decide whether to stop treatment (see "Stopping Fingolimod Bluefish" in section 3 and section 4 "Possible side effects"). The patient will also need to undergo prenatal check-ups.
Breastfeeding
Do not breastfeed while taking Fingolimod Bluefish. Fingolimod Bluefish may pass into breast milk, posing a risk of severe side effects in the baby.

Driving and using machines

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

Fingolimod Bluefish contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per hard capsule, which means it is considered "sodium-free".

3. How to take Fingolimod Bluefish

Treatment with Fingolimod Bluefish will be supervised by a doctor experienced in treating multiple sclerosis.
This medicine should always be taken as directed by the doctor. If in doubt, consult the doctor.
The recommended dose is:

Adults:

The dose is one 0.5 mg capsule per day.

Use in 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. 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 switch to one 0.5 mg capsule per day. In this case, it is recommended to repeat the observation period as after the first dose of the medicine.

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

Taking a higher dose of Fingolimod Bluefish than recommended

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

Missing a dose of Fingolimod Bluefish

If the patient has been taking Fingolimod Bluefish 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 when taking the next dose.
If the patient has been taking Fingolimod Bluefish 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 when taking 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 a missed dose.

Stopping Fingolimod Bluefish

Do not stop taking Fingolimod Bluefish or change the dose without consulting your doctor first.
Fingolimod Bluefish stays in the body for up to 2 months after stopping treatment. During this time, the number of white blood cells (lymphocytes) may also remain low, and side effects described in this leaflet may still occur. After stopping treatment with Fingolimod Bluefish, wait 6-8 weeks before starting new MS treatment.
In patients resuming treatment with Fingolimod Bluefish after more than 2 weeks of stopping the medicine, the effect on heart rate observed after the first dose may recur, and monitoring of the patient's condition in the doctor's office or clinic will be necessary due to the resumption of treatment. Do not resume treatment with Fingolimod Bluefish 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 Bluefish. If the patient thinks their MS is worsening after stopping treatment with Fingolimod Bluefish, they should inform 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 Bluefish 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, unpleasant feeling in the chest, fever (respiratory symptoms)
• Herpesvirus infections (shingles or herpes) with symptoms such as blisters, burning, itching, or pain on the skin, usually on the upper body or face. Other symptoms may include fever and weakness at the beginning of the infection, followed by numbness, itching, or 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 appearances.
• Depression and anxiety, which 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 Bluefish.
• 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 retina) with symptoms such as shadows or defects in the center of the visual field, blurred vision, difficulties with color vision and fine details
• Reduced platelet count, which increases the risk of bleeding or bruising
• Malignant melanoma (a type of skin cancer that usually develops from an abnormal mole). Possible symptoms of melanoma include moles that change in size, shape, or color over time or new moles that appear. Moles can be itchy, bleed, or ulcerate.
• Seizures, convulsions (more common in children and adolescents than in adults)

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

• A condition called posterior reversible encephalopathy syndrome (PRES). Symptoms may include severe headache with sudden onset, disorientation, 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 with a scab, or a new sore in the area of an existing scar.

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

• Abnormalities in the ECG recording (T-wave inversion)
• Tumor associated with human herpesvirus 8 (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 Bluefish.
• Liver disease symptoms (including liver failure) such as yellowing of the skin or eyes, nausea or vomiting, dark (brown) urine, pain in the right side of the abdomen, fatigue, decreased appetite, 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). PML symptoms may be similar to those of an MS relapse. The patient or their relatives may also notice changes in mood or behavior, transient memory loss, difficulties with speech and communication, which the doctor should evaluate to rule out PML. Therefore, if the patient thinks their MS is worsening or if the patient or their relatives notice any new or unusual symptoms, it is very important to inform the doctor immediately.
• Infections with Cryptococcus (a type of fungal infection), including symptoms such as headache with stiff neck, sensitivity to light, nausea, and/or disorientation.
• Merkel cell carcinoma (a type of skin cancer). Possible symptoms of Merkel cell carcinoma include a painless nodule with a raw meat color, usually located on the face, head, or neck, although it can also appear as a hard, painless nodule or mass. Long-term sun exposure and weakened immune system can increase the risk of Merkel cell carcinoma.
• After stopping treatment with Fingolimod Bluefish, MS symptoms may recur 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 inform 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 (e.g., 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 Bluefish 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 estimated from the available data):

• Peripheral edema

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

5. How to store Fingolimod Bluefish

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.
PVC/PVDC/Aluminium blisters: Store in a temperature below 30°C.
PVC/PE/PVDC/Aluminium blisters: No special storage precautions are required for the medicinal product.
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 Bluefish contains

• The active substance is fingolimod. Each hard capsule contains fingolimod hydrochloride equivalent to 0.5 mg of fingolimod.
• The other ingredients are: calcium hydrogen phosphate dihydrate (E 341), sodium croscarmellose (E 468), hydroxypropylcellulose (E 463), and magnesium stearate. Cap shell: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172). Ink: shellac, propylene glycol (E 1520), concentrated ammonia solution, black iron oxide (E 172), potassium hydroxide.

What Fingolimod Bluefish looks like and package contents

Fingolimod Bluefish is a hard capsule with a yellow cap and a white, opaque body, with a black ink print “FD 0.5 mg” on the cap.
Fingolimod Bluefish is available in blisters of 28 or 98 hard capsules.
The blisters are packaged in cardboard boxes.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Bluefish Pharmaceuticals AB
P.O. Box 49013
100 28 Stockholm
Sweden

Manufacturer

Genepharm S.A.
18 km Marathonos Avenue
153 51 Pallini Attiki
Greece

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

Date of last update of the leaflet: