Package leaflet: Information for the user

Golpimec, 0.5 mg, hard capsules
fingolimod
Please read this entire leaflet carefully before taking this medicine, because it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please ask your doctor or pharmacist.
This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of the leaflet:

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

1. What Golpimec is and what it is used for

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

patients who have not responded to MS treatment, or
patients who have rapidly evolving, severe relapsing-remitting MS.

Golpimec does not cure MS, but helps reduce the number of relapses and slows 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, an inflammatory process damages the protective covering of nerves (called myelin) in the CNS, impairing their proper function. This phenomenon is known as demyelination.
Relapsing-remitting MS is characterized by recurrent episodes (relapses) of neurological symptoms reflecting inflammatory activity within the CNS. Symptoms vary between patients but usually include walking difficulties, numbness, vision or balance problems. Symptoms of relapses may completely resolve, although some deficits may persist.
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 throughout the body and by preventing them from entering the brain and spinal cord. In this way, Golpimec reduces nerve damage caused by MS. Golpimec also dampens certain immune responses in the body.

2. What you need to know before taking Golpimec

Do not take Golpimec if:

you have a reduced immune response (due to immunodeficiency syndrome, disease, or taking immunosuppressive medicines);
you have a severe active infection or chronic active infection, such as hepatitis or tuberculosis;
you have active cancer;
you have severe liver disease;
you have had a heart attack, angina pectoris, stroke, or warning signs of stroke, or certain types of heart failure within the last 6 months;
you have a certain type of irregular or abnormal heartbeat (arrhythmia), including patients whose electrocardiogram (ECG) showed QT interval prolongation before starting treatment with Golpimec;
you are currently taking or have recently taken medicines for irregular heartbeat, such as quinidine, disopyramide, amiodarone, or sotalol;
you are pregnant or are of childbearing potential and are not using effective contraception;
you are allergic to fingolimod or any of the other ingredients of this medicine (listed in section 6). If any of these situations apply or you have any doubts, please consult your doctor before taking Golpimec.

Warnings and precautions
Before starting Golpimec, discuss the following with your doctor:

if you have severe breathing problems during sleep (sleep apnoea);
if you have been told that your ECG tracing is abnormal;
if you have symptoms of a slow heart rate (e.g. dizziness, nausea, or palpitations);
if you are taking or have recently taken medicines that slow heart rate (such as beta-blockers, verapamil, diltiazem, ivabradine, digoxin, cholinesterase inhibitors, or pilocarpine);
if you have previously experienced sudden loss of consciousness or fainting;
if you are planning to be vaccinated;
if you have never had chickenpox;
if you have or have had vision problems or other symptoms of swelling in the center of the visual field (macula) at the back of the eye (a condition called macular oedema, see below), inflammation or infection of the eye (uveitis), or if you have diabetes, which may cause vision problems;
if you have liver problems;
if you have high blood pressure that cannot be controlled with medication;
if you have severe lung disease or a smoker's cough. If any of these situations apply or you have any doubts, please consult your doctor before taking Golpimec.

Slow heart rate (bradycardia) and irregular heartbeat
At the start of treatment or after the first dose of 0.5 mg in patients previously taking a 0.25 mg daily dose, Golpimec slows the heart rate. As a result, you may experience dizziness, fatigue, strong heartbeat, or low blood pressure. If these symptoms are severe, inform your doctor immediately, as immediate treatment may be required. Golpimec may also cause irregular heartbeat, especially after the first dose. Irregular heartbeat usually returns to normal within less than one day. Slow heart rate usually returns to normal within one month. During this period, no clinically significant effect on heart rate is expected.
Your doctor will ask you to remain in the doctor's office or clinic for at least 6 hours after taking the first dose of Golpimec or the first 0.5 mg dose when switching from a 0.25 mg daily dose, with hourly monitoring of pulse and blood pressure, so that appropriate treatment can be administered if any adverse effects occur at the beginning of treatment. An ECG will be performed before the first dose and after the 6-hour observation period. During this time, your doctor may continuously monitor your heart function using electrocardiography. If, after 6 hours of observation, you have a very slow or decreasing heart rate or if the ECG shows abnormalities, longer monitoring (for at least 2 additional hours or possibly until the next day) may be required until these symptoms resolve. The same procedure may be recommended if you restart Golpimec after a treatment interruption, depending on the duration of the break and how long you had previously taken Golpimec.
If you have irregular or abnormal heartbeat, risk factors for such events, an abnormal ECG, heart disease, or heart failure, Golpimec may not be suitable for you.
If you have a history of sudden loss of consciousness or slowed heart function, Golpimec may not be suitable. You may need to consult a cardiologist (a heart specialist) who will advise on how to start treatment with Golpimec, including overnight monitoring.
If you are taking medicines that may slow heart rate, Golpimec may not be suitable. You may need to consult a cardiologist to determine whether you can switch to other medicines that do not slow heart rate, to allow treatment with Golpimec. If such a change is not possible, the cardiologist will advise on how to start treatment with Golpimec, including monitoring until the day after the first dose.

Patients who have never had chickenpox
If you have never had chickenpox, your doctor will check your immunity to the varicella zoster virus. If you are not protected against the virus, you may need to be vaccinated before starting Golpimec. In such cases, your doctor will delay starting Golpimec by one month after completing the full vaccination course.

Infections
Golpimec reduces the number of white blood cells (particularly lymphocytes). White blood cells fight infections. While taking Golpimec (and for up to 2 months after stopping treatment), you may be more susceptible to infections. Existing infections may worsen. Infections may be severe and life-threatening. If you suspect you have an infection, have a fever, flu-like symptoms, shingles, or a headache accompanied by neck stiffness, light sensitivity, nausea, rash, and/or confusion or seizures (which may be symptoms of meningitis and/or encephalitis caused by fungal or herpes virus infection), contact your doctor immediately, as this condition may be serious and life-threatening. If you feel your condition is worsening (e.g. weakness or vision problems) or notice any new symptoms, contact your doctor immediately, as these may be symptoms of a rare brain disease called progressive multifocal leukoencephalopathy (PML). PML is a serious condition that may lead to severe disability or death. Your doctor may consider performing a magnetic resonance imaging (MRI) scan to assess your condition and decide whether to discontinue Golpimec.
Infections with human papillomavirus (HPV) have been reported in patients treated with fingolimod, including cases of warts, dysplasia, and HPV-related cancers. Your doctor may consider HPV vaccination before starting treatment. In women, your doctor may also recommend routine HPV screening.

Macular oedema
Before starting Golpimec, your doctor may refer you for ophthalmological examination if you currently have or have had vision problems, other symptoms of swelling in the center of the visual field (macula) at the back of the eye, eye inflammation or infection (uveitis), or diabetes.
Your doctor may also refer you for ophthalmological examination 3 to 4 months after starting Golpimec.
The macula is a small area of the retina at the back of the eye that enables clear, sharp vision of shapes, colors, and details. Golpimec may cause swelling of the macula, a condition called macular oedema. This usually occurs within the first 4 months of treatment with Golpimec.
The risk of macular oedema is higher in patients with diabetes or a history of uveitis. In such cases, your doctor will recommend regular ophthalmological examinations to detect macular oedema.
If you develop macular oedema, inform your doctor before restarting Golpimec.
Macular oedema may cause vision disturbances similar to those in an MS attack (optic neuritis). In early stages, symptoms may be absent. Inform your doctor of any changes in vision. Your doctor may refer you for ophthalmological examination, especially if:

the center of your visual field becomes blurred or shadowed;
a blind spot appears in the center of your visual field;
you have difficulty seeing colors or fine details.

Liver function tests
Patients with severe liver disease should not take Golpimec. Golpimec may affect liver function test results. You may not experience any symptoms, but if you develop yellowing of the skin or whites of the eyes, abnormally dark (brown) urine, pain in the right side of the abdomen, fatigue, reduced appetite, or unexplained nausea and vomiting, inform your doctor immediately. If any of these symptoms occur after starting Golpimec, inform your doctor immediately.
Before, during, and after treatment, your doctor will order blood tests to monitor liver function. If test results indicate liver dysfunction, treatment with Golpimec may be discontinued.

High blood pressure
Your doctor may regularly check your blood pressure, as Golpimec causes a slight increase in blood pressure.

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

Blood cell count
A known effect of Golpimec is a reduction in white blood cells. Their number usually returns to normal within 2 months after stopping treatment. If blood tests are needed, inform your doctor that you are taking Golpimec. Otherwise, your doctor may misinterpret test results, and for certain tests, a larger blood sample may be required.
Before starting Golpimec, your doctor will confirm that your white blood cell count is adequate and may recommend regular monitoring. If white blood cell count is insufficient, treatment with Golpimec may need to be discontinued.

Posterior reversible encephalopathy syndrome (PRES)
Rarely, patients with MS treated with Golpimec have reported a condition called posterior reversible encephalopathy syndrome (PRES). Symptoms may include sudden, severe headache, confusion, seizures, and/or vision changes. If any of these symptoms occur during treatment with Golpimec, inform your doctor immediately, as this condition may be serious.

Cancer
Skin cancers have been reported in patients with MS treated with Golpimec. If you notice any lumps (e.g. shiny, pearly lumps), spots, or non-healing skin ulcers lasting several weeks, inform your doctor immediately. Skin cancer symptoms may include abnormal skin growths or changes (e.g. new moles) that change in color, shape, or size over time. Before starting Golpimec, a skin examination should be performed to check for skin lumps. Your doctor will also perform regular skin checks during treatment. If skin problems occur, your doctor may refer you to a dermatologist, who may recommend regular visits.
A type of lymphatic system cancer (lymphoma) has been reported in patients with MS treated with Golpimec.

Sun exposure and sun protection
Fingolimod suppresses the immune system. This increases the risk of malignancies, especially skin cancers. You should minimize sun and UV radiation exposure by:

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

Unusual brain lesions associated with MS relapse
Rare cases of unusually large brain lesions associated with MS relapse have been reported in patients treated with Golpimec. In case of a severe MS relapse, your doctor may consider performing an MRI scan to assess this condition and decide whether to discontinue Golpimec.

Switching from other treatments to Golpimec
Your doctor may switch treatment directly from interferon-beta, glatiramer acetate, or dimethyl fumarate to Golpimec if there are no signs of abnormalities from previous treatment. Your doctor may order blood tests to rule out such abnormalities. After stopping natalizumab, a 2- to 3-month waiting period may be required before starting Golpimec. When switching from teriflunomide, your doctor may advise waiting a certain time or undergoing an accelerated elimination procedure. Patients previously treated with alemtuzumab require careful evaluation and discussion with their doctor to determine if Golpimec is suitable.

Women of childbearing potential
If Golpimec is used during pregnancy, it may harm the unborn child. Before starting Golpimec, your doctor will explain the risks and request a pregnancy test to exclude pregnancy. Your doctor will provide you with an information card explaining why you should not become pregnant while taking Golpimec, including advice on how to avoid pregnancy.
You must use effective contraception during treatment and for 2 months after stopping treatment (see section "Pregnancy and breastfeeding").
If you become pregnant while taking Golpimec, inform your doctor immediately. Your doctor will decide whether to discontinue treatment (see "Stopping Golpimec" in section 3 and section 4 "Possible side effects"). You will also need to attend prenatal check-ups.
Breastfeeding
Do not breastfeed while taking Golpimec. Golpimec may pass into breast milk, posing a risk of serious adverse effects in the infant.

Driving and using machines
Your doctor will advise whether your condition allows safe driving, including cycling, and operating machinery. Golpimec is not expected to affect your ability to drive or operate machinery.
However, you must remain in the doctor's office or clinic for 6 hours after taking the first dose of Golpimec. During this time and potentially afterwards, your ability to drive and operate machinery may be impaired.

3. How to take Golpimec

Treatment with Golpimec will be supervised by a doctor experienced in treating multiple sclerosis.
Always take this medicine exactly as prescribed by your doctor. If in doubt, consult your doctor.
Recommended dosage:
Adults:
One 0.5 mg hard capsule once daily.
Children and adolescents (aged 10 years and older):
Dosage depends on body weight:

Children and adolescents with body weight ≤ 40 kg: one 0.25 mg capsule once daily. Golpimec 0.5 mg hard capsules are not suitable for children with body weight ≤ 40 kg. Other medicinal products containing fingolimod are available in lower strengths (0.25 mg hard capsules).
Children and adolescents with body weight > 40 kg: one 0.5 mg hard capsule once daily. Children and adolescents starting with one 0.25 mg capsule daily who later achieve a stable body weight above 40 kg will receive instructions from their doctor to switch to one 0.5 mg hard capsule once daily. In this case, repeat observation period as after the first dose is recommended.

Do not exceed the recommended dose.
Golpimec is for oral use.
Take Golpimec once daily with a glass of water. Golpimec hard capsules must always be swallowed whole, without opening. Golpimec may be taken with or without food.
Taking Golpimec at the same time each day will help you remember to take it.
For questions about the duration of treatment with Golpimec, consult your doctor or pharmacist.
Taking more Golpimec than prescribed
If you take too much Golpimec, contact your doctor immediately.
Missing a dose of Golpimec
If you have taken Golpimec for less than 1 month and miss one dose for a full day, contact your doctor before taking the next dose. Your doctor may decide to observe you when taking the next dose.
If you have taken Golpimec for at least 1 month and have missed doses for more than 2 weeks, contact your doctor before taking the next dose. Your doctor may decide to observe you when taking the next dose. However, if you missed doses for up to 2 weeks, you may take the next dose as scheduled.
Do not take a double dose to make up for a missed dose.
Stopping Golpimec
Do not stop taking Golpimec or change the dose without first consulting your doctor.
Golpimec remains in the body for up to 2 months after stopping treatment. During this time, white blood cell count (lymphocyte count) may remain reduced, and side effects described in this leaflet may persist. After stopping Golpimec, wait 6–8 weeks before starting a new MS treatment.
In patients restarting Golpimec after more than 2 weeks without treatment, effects on heart rate may reoccur, as seen at the start of treatment, and monitoring in the doctor's office or clinic may be required due to treatment resumption. Do not restart Golpimec after a break longer than two weeks without consulting your doctor.
Your doctor will decide whether and how to monitor you after stopping Golpimec. Inform your doctor immediately if you feel your MS is worsening after stopping Golpimec. This may be serious.
For any further questions about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Some side effects may be or become severe.
Common (may affect less than 1 in 10 people):

Cough with sputum, unspecified chest discomfort, fever (lung-related symptoms)
Herpesvirus infections (shingles or cold sores) with symptoms such as blisters, burning, itching, or skin pain, usually above the upper body or face. Other symptoms may include fever and fatigue early in the infection, followed by numbness, itching, or very painful red patches.
Slow heartbeat (bradycardia), irregular heartbeat
A type of skin cancer called basal cell carcinoma (BCC), which often appears as a pearly lump, although it may look different
Depression and anxiety are known to occur more frequently in the MS patient population and have also been reported in children and adolescents treated with fingolimod.
Weight loss

Uncommon (may affect less than 1 in 100 people):

Pneumonia with symptoms such as fever, cough, difficulty breathing
Macular oedema (swelling in the center of the retina at the back of the eye) with symptoms such as shadows or blind spots in the center of the visual field, blurred vision, difficulty seeing colors and details
Reduced platelet count, increasing the risk of bleeding or bruising
Malignant melanoma (a type of skin cancer that usually develops from an atypical mole). Possible symptoms include moles that change in size, shape, elevation, or color over time or new moles. Moles may itch, bleed, or ulcerate
Seizures, epileptic fits (more common in children and adolescents than in adults)

Rare (may affect less than 1 in 1,000 people):

A condition called posterior reversible encephalopathy syndrome (PRES). Symptoms may include sudden, severe headache, confusion, seizures, and/or vision disturbances
Lymphoma (a type of cancer involving the lymphatic system)
Squamous cell carcinoma: a type of skin cancer that may appear as a hard, red lump, an ulcer covered with a scab, or a fresh ulcer in the site of an existing scar

Very rare (may affect less than 1 in 10,000 people):

Abnormalities in ECG findings (T-wave inversion)
Tumour associated with human herpesvirus type 8 infection (Kaposi's sarcoma)

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

Allergic reactions, including rash or itchy hives, swelling of lips, tongue, or face, more likely to occur on the day treatment with Golpimec is started
Liver disease symptoms (including liver failure), such as yellowing of the skin or whites of the eyes (jaundice), nausea or vomiting, pain in the right side of the abdomen, dark (brown) urine, reduced appetite, fatigue, and abnormal liver function tests. In very rare cases, liver failure may require liver transplantation.
Risk of a rare brain infection called progressive multifocal leukoencephalopathy (PML). PML symptoms may resemble an MS relapse. Symptoms not noticed by the patient may include mood or behavior changes, temporary memory lapses, or speech and communication difficulties, which should be evaluated by a doctor to rule out PML. Therefore, if you feel your MS is worsening or if you or your family notice any new or unusual symptoms, it is very important to inform your doctor immediately.
Cryptococcal infections (a type of fungal infection), including cryptococcal meningitis with symptoms such as headache accompanied by neck stiffness, light sensitivity, nausea, and/or confusion
Merkel cell carcinoma (a type of skin cancer). Possible symptoms include a painless, flesh-colored or bluish-red nodule, often on the face, head, or neck. Merkel cell carcinoma may also appear as a hard, painless nodule or mass. Prolonged sun exposure and immune suppression may increase the risk of Merkel cell carcinoma
After stopping fingolimod treatment, MS symptoms may recur and worsen compared to the period before and during treatment.
Autoimmune form of anemia (reduced red blood cells), in which red blood cells are destroyed (autoimmune hemolytic anemia).

If you experience any of these effects, inform your doctor immediately.
Other side effects
Very common (may affect more than 1 in 10 people):

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

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

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

Uncommon (may affect less than 1 in 100 people):

Low white blood cell count (neutrophils)
Depressive mood
Nausea

Rare (may affect less than 1 in 1,000 people):

Lymphatic system cancer (lymphoma)

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

Peripheral oedema

If any of these symptoms are severe, inform your doctor.
Reporting side effects
If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist.
Side effects can be reported directly to the Department for Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 4921301, fax: +48 22 4921309, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Golpimec

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack after “Expiry date (EXP)” / “EXP”. The expiry date refers to the last day of the stated month.
Do not store above 25°C.
Keep in the original packaging to protect from light and moisture.
Do not dispose of medicines via the wastewater system or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This helps protect the environment.

6. Contents of the pack and other information

What Golpimec contains

The active substance is fingolimod.
Each hard capsule contains fingolimod hydrochloride equivalent to 0.5 mg of fingolimod. Other ingredients: Capsule core: microcrystalline cellulose (E 460), low-substituted hydroxypropylcellulose (E 463), magnesium stearate (E 470b). 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 contents of the pack
Golpimec 0.5 mg hard capsules have a white opaque body and white opaque cap with black print “FIN0.5”.
Golpimec 0.5 mg hard capsules are available in packs of 28 hard capsules.
Marketing authorization holder
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
For more detailed information, please contact the representative of the marketing authorization holder in Poland:
Neuraxpharm Polska sp. z o.o.
ul. Poleczki 35
02-822 Warsaw
[email protected]