Golpimec

Leaflet accompanying the packaging: information for the user

Golpimec, 0.5 mg, hard capsules

Fingolimod

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet so that you can read it again if you need to.
• If you have any doubts, you should consult a 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 as yours.
• If the patient experiences any side effects, including any possible side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

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

1. What is Golpimec and what is it used for

What is Golpimec

Golpimec contains the active substance fingolimod.

What is Golpimec used for

Golpimec 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 a rapidly evolving, severe form of MS.

Golpimec 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.

How Golpimec works

Golpimec 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. Golpimec also weakens some immune responses of the body.

• 2. Important information before taking Golpimec

When not to take Golpimec

• If the patient has a reduced immune response(due to immunodeficiency syndrome, disease, or taking immunosuppressive drugs);
• if the patient has a severe active infection or chronic active infection, such as hepatitis or tuberculosis;
• if the patient has an 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 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 Golpimec;
• if the patient is currently taking or has recently taken drugs for irregular heartbeat, such as quinidine, disopyramide, amiodarone, or sotalol;
• if the patient is pregnantor is of childbearing age and does not use effective contraception.
• if the patient is allergicto fingolimod or any of the other ingredients of this medicine (listed in section 6). If such a situation occurs or the patient has doubts, they should consult a doctor before taking Golpimec.

Warnings and precautions

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

• -if the patient has severe breathing difficulties 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 drugs that slow down the heart rate(such as beta blockers, verapamil, diltiazem, or ivabradine, digoxin, cholinesterase inhibitors, or pilocarpine);
• if the patient has had sudden loss of consciousness or slow heart rate in the past;
• 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 (macular edema) in the back of the eye, inflammation, or infection of the eye (uveitis), or if the patient has diabetes, which may cause vision problems;
• if the patient has liver problems;
• if the patient has high blood pressure that cannot be lowered 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 consult a doctor before taking Golpimec.

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 have previously taken a daily dose of 0.25 mg, Golpimec slows down the heart rate. As a result, the patient may feel dizzy, tired, 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.Golpimec 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 Golpimec 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 occur at the beginning of treatment, appropriate treatment can be applied. Before the first dose of Golpimec and after the 6-hour observation period, an ECG will be performed on the patient. 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, there may be a need for longer monitoring of the patient's condition (for at least 2 hours longer or possibly until the next day), until these symptoms subside. The same procedure may be recommended if the patient resumes treatment with Golpimec after a break in treatment, depending on how long the break lasted and how long the patient took Golpimec before the break.

If the patient has irregular or abnormal heartbeat, or risk factors for these events, if there is an abnormal ECG or heart disease, or heart failure, Golpimec may not be suitable for them.

If the patient has a history of sudden loss of consciousness or slow heart rate, Golpimec may not be suitable for them. There may be a need for consultation with a cardiologist (a specialist in heart diseases), who will advise how to start treatment with Golpimec, including how to monitor the patient at night.

If the patient is taking drugs that can slow down the heart rate, Golpimec may not be suitable. There may be a need for consultation with a cardiologist, who will check if the patient can switch to other drugs that do not slow down the heart rate, to allow treatment with Golpimec. If such a change in treatment is not possible, the cardiologist will advise the patient on how to start treatment with Golpimec, taking into account monitoring until the next day after administration of the first dose of Golpimec.

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

Infections

Golpimec reduces the number of white blood cells (especially lymphocytes). White blood cells fight infections. During treatment with Golpimec (and up to 2 months after stopping treatment), the patient may be more susceptible 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, feel flu-like symptoms, have shingles, or a headache with stiff neck, sensitivity to light, nausea, and (or) 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 may be severe.

If the patient thinks their disease is getting worse (e.g., weakness or vision problems) or if the patient notices any new symptoms, they should talk 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 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 Golpimec.

Macular edema

Before starting treatment with Golpimec, the doctor may refer patients with existing or past vision problems or other symptoms of macular edema (macular edema) in the back of the eye, inflammation, or infection of the eye (uveitis), or with diabetes, for ophthalmological examinations.

The doctor may also refer the patient for ophthalmological examinations after 3 to 4 months of starting treatment with Golpimec.

Macula is a small area of the retina, located at the back of the eye, which enables sharp and clear vision of shapes, colors, and other details. Golpimec may cause macular edema, a condition called macular edema. Macular edema usually occurs within the first 4 months of treatment with Golpimec.

The risk of macular edema is higher in patients with diabetesor with a history of uveitis. In such cases, the doctor will instruct the patient to undergo regular ophthalmological examinations to detect macular edema.

If the patient develops macular edema, they should inform their doctor before resuming treatment with Golpimec.

Macular edema may cause certain vision problems, such as those that occur 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 blurred or shaded;
• A defect appears in the center of the visual field;
• There are difficulties in seeing colors or fine details.

Liver function tests

Patients with severe liver disease should not take Golpimec. Golpimec may affect liver function tests. The patient is unlikely to experience any symptoms, but if they notice yellowing of the skin or whites of the eyes (jaundice), abnormal dark (brown) urine, pain in the right upper abdomen, fatigue, decreased appetite, or unexplained nausea and vomiting, they should tell their doctor immediately.

If any of these symptoms occur after starting treatment with Golpimec, the patient 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 Golpimec may be discontinued.

High blood pressure

The doctor may regularly check the patient's blood pressure, as Golpimec can cause a slight increase in blood pressure.

Lung problems

Golpimec 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.

Blood cell count

A expected effect of Golpimec 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 Golpimec. Otherwise, the doctor may not be able to interpret the test results, and in the case of certain tests, the doctor may order more blood to be drawn than usual.

Before starting treatment with Golpimec, the doctor will confirm that the patient has a sufficient number of white blood cells in the blood to start treatment and may order regular repetition of tests. If there are not enough white blood cells, it may be necessary to discontinue treatment with Golpimec.

Reversible posterior encephalopathy syndrome (PRES)

In patients with MS treated with Golpimec, there have been rare reports of a disease called reversible posterior encephalopathy syndrome (PRES). The symptoms of this disease may include severe headache, confusion, seizures, and (or) vision changes. If any of these symptoms occur during treatment with Golpimec, the patient should tell their doctor immediately, as this condition may be severe.

Cancer

In patients with MS treated with Golpimec, there have been reports of 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 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 Golpimec, it is necessary to examine the skin for any lumps. The treating doctor will also perform regular skin checks during treatment with Golpimec. If skin problems occur, the treating doctor may refer the patient to a dermatologist, who may decide on the need for regular visits after consulting with them.

In patients with MS treated with Golpimec, there have been reports of a type of cancer of the lymphatic system (lymphoma).

Exposure to the sun and protection against sunlight

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

• wearing protective clothing.
• regularly applying sunscreen with a high degree of protection against UV radiation.

Unusual changes in the brain associated with MS relapse

In patients treated with Golpimec, there have been rare reports of unusually large changes in the brain associated with MS relapse. In the case of a severe MS relapse, the treating doctor will consider performing an MRI scan to assess this condition and decide on the possible need to stop taking Golpimec.

Changing treatment from other drugs to Golpimec

The doctor may change treatment directly from interferon beta, glatiramer acetate, or dimethyl fumarate to Golpimec 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 Golpimec. 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 for the drug. Patients previously treated with alemtuzumab require careful evaluation and discussion with their doctor before deciding whether Golpimec is suitable for them.

Women of childbearing age

If Golpimec is used during pregnancy, it may harm the unborn child. Before starting treatment with Golpimec, the doctor will explain the risk to the patient and ask them to perform a pregnancy test to ensure that they are not pregnant, and will provide the patient with a card explaining why they should not become pregnant while taking Golpimec.

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 Golpimec, they should tell their doctor immediately. The doctor will decide on the discontinuation of treatment (see "Discontinuing Golpimec" in section 3, and also section 4 "Possible side effects"). The patient will also need to undergo prenatal check-ups.

Breastfeeding

Golpimec should not be taken while breastfeeding. Golpimec may pass into breast milk, posing a risk of severe side effects in the child.

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 Golpimec 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 Golpimec. During this time and potentially after it, the ability to drive vehicles and operate machinery may be impaired.

• 3. How to take Golpimec

Treatment with Golpimec 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 hard capsule of 0.5 mg 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 capsule of 0.25 mg per day. Golpimec 0.5 mg capsules are not suitable for children with a body weight of 40 kg or less. Other medicinal products containing fingolimod are available in lower strengths (0.25 mg hard capsules).
• Children and adolescents with a body weight over 40 kg: one hard capsule of 0.5 mg per day. Children and adolescents starting treatment with one 0.25 mg capsule per day and later achieving a stable body weight over 40 kg will be advised by their doctor to switch to one 0.5 mg hard capsule per day. In this case, it is recommended to repeat the observation period as after the first dose of Golpimec.

The patient should not exceed the recommended dose.

Golpimec is intended for oral use.

Golpimec should be taken once a day, with a glass of water. The hard capsules of Golpimec should always be swallowed whole, without opening. Golpimec can be taken with or without food.

Taking Golpimec 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 Golpimec, they should consult their doctor or pharmacist.

Taking a higher dose of Golpimec than recommended

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

Missing a dose of Golpimec

If the patient has been taking Golpimec for less than 1 month and has missed 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 has been taking Golpimec for at least 1 month and has missed taking 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 has missed taking the medicine for up to 2 weeks, they can take the next dose as planned.

The patient should not take a double dose to make up for a missed dose.

Discontinuing Golpimec

The patient should not stop taking Golpimec or change the dose without first consulting their doctor.

Golpimec 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 Golpimec, the patient should wait 6-8 weeks before starting new MS treatment.

In patients resuming treatment with Golpimec after more than 2 weeks of stopping the medicine, the effect on heart rate observed usually 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. The patient should not resume treatment with Golpimec after a break of more than 2 weeks without consulting their doctor.

The treating doctor will decide how to monitor the patient after stopping treatment with Golpimec. The patient should tell their doctor immediately if they think their MS is getting worse after stopping treatment with Golpimec. This situation may be serious.

If the patient has any further doubts about the use of this medicine, they should consult their doctor or pharmacist.

• 4. Possible side effects

Like all medicines, Golpimec 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 (symptoms of respiratory disorders)
• Herpesvirus infections (shingles or herpes) with symptoms such as blisters, burning sensation, itching, or skin pain, 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 very painful red spots.
• Slow heartbeat (bradycardia), irregular heartbeat
• A type of skin cancer called basal cell carcinoma (BCC), which often occurs as a pearl-like nodule, although it may have a different appearance
• 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 visual field in the retina, at the back of the eye) with symptoms such as shadows or defects in the center of the visual field, blurred vision, difficulty seeing colors and details
• Decreased 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 ulcerating
• Seizures, epileptic seizures (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, confusion, seizures, and (or) vision changes
• Lymphoma (a type of cancer affecting the lymphatic system)
• Squamous cell carcinoma: a type of skin cancer that may 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, whose occurrence is more likely on the day of starting treatment with Golpimec
• 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 may 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, difficulties with speech and communication, which the doctor should assess to rule out PML. Therefore, if the patient thinks their MS is getting worse or if the patient or their relatives notice any new or unusual symptoms, it is very important to tell their doctor as soon as possible
• Cryptococcal infections (a type of fungal infection), including cryptococcal meningitis with symptoms such as headache, stiff neck, sensitivity to light, nausea, and (or) confusion or seizures
• Merkel cell carcinoma (a type of skin cancer). Possible symptoms of Merkel cell carcinoma include the presence of a painless nodule with a raw meat color or bluish-red, usually located on the face, head, or neck. Merkel cell carcinoma can also appear as a hard, painless nodule or mass. Long-term sun exposure and weakened immune system may affect the risk of Merkel cell carcinoma
• After stopping treatment with fingolimod, 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 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, usually 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 may cause a mild increase in blood pressure)
• Muscle pain
• Joint pain

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

• Low white blood cell count (neutrophils)
• 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 a high intensity, the patient should tell their doctor.

Reporting side effects

If side effects occur, including any side effects not listed in the leaflet, the patient should tell their doctor or pharmacist.

Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl

Side effects can also be reported to the marketing authorization holder.

By reporting side effects, more information can be collected on the safety of the medicine.

• 5. How to store Golpimec

The medicine should be stored out of sight and reach of children.

Do not use this medicine 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 light and moisture.

Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

• 6.

Contents of the pack and other information

What the medicine Golpimec contains

• The active substance of the medicine is fingolimod.
• Each hard capsule contains fingolimod hydrochloride in an amount equivalent to 0.5 mg of fingolimod. The other ingredients are: Hard capsule filling: microcrystalline cellulose (E 460), low-substituted hydroxypropyl cellulose (E 463), magnesium stearate (E 470b). Hard capsule shell: gelatin, titanium dioxide (E 171). Ink: shellac (E 904), propylene glycol (E 1520), potassium hydroxide, iron oxide, black (E 172).

What Golpimec looks like and what the pack contains

Golpimec 0.5 mg hard capsules have a white opaque body and a white opaque cap with black printing "FIN0.5".
Golpimec, 0.5 mg, hard capsules are available in packs of 28 hard capsules.

Responsible entity

neuraxpharm Arzneimittel GmbH
Elisabeth-Selbert Strasse 23
40764 Langenfeld
Germany

Manufacturer

PRASFARMA, S.L.
Cr. Sant Joan, 11-15
08560 Manlleu (Barcelona)
Spain
neuraxpharm Arzneimittel GmbH
Elisabeth-Selbert Strasse 23,
40764 Langenfeld
Germany
To obtain more detailed information, please contact the representative of the responsible entity
in Poland:
Neuraxpharm Polska sp. z o.o.
ul. Poleczki 35
02-822 Warsaw
info-poland@neuraxpharm.com

Date of last update of the leaflet: 06/2022