Bonaxon

Leaflet accompanying the packaging: information for the user

Bonaxon, 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, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific person. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• -If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

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

1. What is Bonaxon and what is it used for

What is Bonaxon

Bonaxon contains the active substance fingolimod.

What is Bonaxon used for

Bonaxon is used in adults to treat the relapsing-remitting form of multiple sclerosis (MS), particularly in:

• patients who have not responded to MS treatment or
• patients with rapidly evolving, severe MS.

Bonaxon 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 problems, or balance problems. Relapse symptoms may completely resolve, but some disturbances may persist.

How does Bonaxon work

Bonaxon 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 limits nerve damage caused by MS. Bonaxon also weakens some immune system reactions.

2. Important information before taking Bonaxon

When not to take Bonaxon

• if the patient has a 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 pectoris, stroke, or symptoms of stroke within the last 6 months;
• if the patient has a certain type of irregular or abnormal heart rhythm(arrhythmia), including patients who have had an electrocardiogram (ECG) showing a prolonged QT interval before starting Bonaxon treatment;
• if the patient is currently taking or has recently taken medications for irregular heart rhythm, 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 any of these situations apply, or if the patient is unsure, they should tell their doctorand not take Bonaxon.

Warnings and precautions

Before starting Bonaxon treatment, the patient should discuss the following with their 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 medications that slow 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 fainting in the past;
• if the patient plans to get vaccinated;
• if the patient has never had chickenpox;
• if the patient has or has had vision problemsor other symptoms of macular edema (a condition where the macula, the part of the eye responsible for central vision, becomes swollen) or uveitis (inflammation of the uvea, the middle layer of the eye), or if the patient has diabetes, which can cause vision problems;
• if the patient has liver disease;
• if the patient has high blood pressure that cannot be controlled with medication;
• if the patient has severe lung diseaseor a cough typical of smokers.

If any of these situations apply, or if the patient is unsure, they should tell their doctor before taking Bonaxon. The patient may need to be monitored more closely while taking Bonaxon.

Low heart rate (bradycardia) and irregular heart rhythm

At the beginning of Bonaxon treatment, the patient's heart rate may slow down. As a result, the patient may feel dizzy, tired, have palpitations, or experience low blood pressure.

If these symptoms are severe, the patient should tell their doctor immediately, as they may need urgent treatment.

Bonaxon may also cause irregular heart rhythms, especially after taking the first dose. Irregular heart rhythms usually return to normal within a day. Low heart rate usually returns to normal within a 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 Bonaxon, with hourly measurements of pulse and blood pressure, so that if any side effects occur at the beginning of treatment, appropriate treatment can be given. Before the first dose of Bonaxon and after the 6-hour observation period, the patient will have an ECG. During this time, the doctor may also 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, the patient may need longer monitoring (for at least 2 hours longer or possibly until the next day) until these symptoms resolve. The same procedure may be recommended if the patient restarts Bonaxon treatment after a break in treatment, depending on how long the break was and how long the patient was taking Bonaxon before the break.

Patients who have never had chickenpox

If the patient has never had chickenpox, the doctor will check if the patient is immune to the varicella-zoster virus. If the patient is not protected against the virus, they may need to be vaccinated before starting Bonaxon treatment. If this is the case, the doctor will delay starting Bonaxon treatment for 1 month after the full vaccination cycle.

Infections

Bonaxon reduces the number of white blood cells (especially lymphocytes). White blood cells fight infections. While taking Bonaxon (and for 2 months after stopping treatment), the patient may be more prone to infections. Any existing infections may worsen. Infections can be severe and life-threatening. If the patient thinks they have an infection, have a fever, flu-like symptoms, shingles, or a headache with stiff neck, sensitivity to light, nausea, and (or) confusion or seizures (which can be symptoms of meningitis and/or encephalitis caused by fungal or viral infections), they should contact their doctor immediately, as this can be a serious condition.

Macular edema

Before starting Bonaxon treatment, the doctor may refer patients with existing or past vision problems or other symptoms of macular edema or uveitis for eye examinations. The doctor may also refer the patient for eye examinations 3 to 4 months after starting Bonaxon treatment. The macula is a small area of the retina that allows for sharp, clear vision of shapes, colors, and other details. Bonaxon may cause macular edema, a condition where the macula becomes swollen. Macular edema usually occurs within the first 4 months of Bonaxon treatment. The risk of macular edema is higher in patients with diabetesor a history of uveitis. In such cases, the doctor will prescribe regular eye examinations to detect macular edema. If the patient develops macular edema, they should tell their doctor before restarting Bonaxon treatment. Macular edema may cause vision problems similar to those experienced during an MS relapse (optic neuritis). In the early stages, symptoms may not be noticeable. The patient should tell their doctor about any changes in vision. The doctor may refer the patient for eye examinations, especially if:

• the center of the visual field becomes blurry or shaded;
• a defect appears in the center of the visual field;
• the patient experiences difficulty seeing colors or fine details.

Liver function tests
Patient with severe liver disease should not take Bonaxon. Bonaxon may affect liver function tests. The patient is unlikely to experience any symptoms, but if they notice yellowing of the skin or eyes, dark urine (brown in color), pain in the right upper abdomen, fatigue, loss of appetite, or unexplained nausea and vomiting, they should tell their doctor immediately.
If any of these symptoms occur after starting Bonaxon treatment, 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, Bonaxon treatment may be discontinued.
High blood pressure
The doctor may regularly check the patient's blood pressure, as Bonaxon may cause a slight increase in blood pressure.
Lung disease
Bonaxon has a minor effect on lung function. Patients with severe lung disease or a cough typical of smokers are at higher risk of side effects.
Blood cell count
A expected effect of Bonaxon 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 are necessary, the patient should tell their doctor that they are taking Bonaxon. Otherwise, the doctor may not be able to interpret the blood test results, and in the case of certain tests, the doctor may order more blood to be drawn than usual.
Before starting Bonaxon treatment, the doctor will check if the patient has a sufficient number of white blood cells in the blood to start treatment and may order regular blood tests. If there are not enough white blood cells, it may be necessary to discontinue Bonaxon treatment.
Reversible posterior encephalopathy syndrome (PRES)
In patients with MS treated with fingolimod, there have been rare reports of a condition called reversible posterior encephalopathy syndrome (PRES). Symptoms of this condition may include sudden, severe headache, confusion, seizures, and (or) vision changes. If the patient experiences any of these symptoms while taking Bonaxon, they should tell their doctor immediately, as this can be a serious condition.
Cancer
In patients with MS treated with fingolimod, 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., unusual moles) that change color, shape, or size over time. Before starting fingolimod treatment, it is necessary to examine the skin for any lumps. The doctor will also perform regular skin checks during fingolimod treatment. 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 doctor.
In patients with MS treated with fingolimod, there have been reports of a type of lymphoma (a cancer of the lymphatic system).
Exposure to the sun and protection against UV radiation
Fingolimod weakens the immune system. This 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 sun protection factor.

Unusual changes in the brain associated with MS relapse
In patients treated with Bonaxon, 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 doctor may consider performing an MRI to assess this condition and decide whether to discontinue Bonaxon treatment.
Switching from other medicines to Bonaxon
The doctor may switch treatment directly from interferon beta, glatiramer acetate, or dimethyl fumarate to Bonaxon, if there are no symptoms of abnormality caused by previous treatment. The doctor may order a blood test to rule out these abnormalities. After stopping natalizumab treatment, it may be necessary to wait 2 to 3 months before starting Bonaxon treatment. When switching from teriflunomide treatment, the doctor may advise the patient to wait for a certain period or undergo an accelerated elimination procedure. Patients previously treated with alemtuzumab require careful evaluation and discussion with their doctor before deciding whether Bonaxon is suitable for them.
Women of childbearing age
If Bonaxon is used during pregnancy, it may harm the unborn child. Before starting Bonaxon treatment, the doctor will explain the risks to the patient and ask them to have a pregnancy test to rule out pregnancy. The doctor will give the patient a card explaining why they should not become pregnant while taking Bonaxon. The card also contains information on what to do to avoid becoming pregnant while taking Bonaxon. Female patients must use effective contraception during treatment and for 2 months after stopping treatment (see "Pregnancy and breastfeeding" below).
If the patient becomes pregnant while taking Bonaxon, they should tell their doctor immediately. The doctor will decide whether to discontinue treatment (see "Stopping Bonaxon treatment" in section 3 and "Possible side effects" in section 4). The patient will also need to have regular prenatal check-ups.
Breastfeeding
Do not breastfeed while taking Bonaxon. Bonaxon may pass into breast milk, posing a risk of serious side effects to the baby.

Driving and using machines

The doctor will inform the patient whether their condition allows them to drive vehicles, including bicycles, and operate machinery safely. It is not expected that Bonaxon 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 Bonaxon. During this time and potentially after it, the patient's ability to drive vehicles and operate machinery may be impaired.

3. How to take Bonaxon

Bonaxon treatment 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 is unsure, they should ask their doctor.
The recommended dose is:

Adults:

The dose is one hard capsule of 0.5 mg once a day.

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

Taking a higher dose of Bonaxon than recommended

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

Missing a dose of Bonaxon

If the patient has been taking Bonaxon for less than 1 month and misses a dose for a whole day, they should contact their doctor before taking the next dose. The doctor may decide to monitor the patient during the next dose. If the patient has been taking Bonaxon for at least 1 month and misses a dose for more than 2 weeks, they should contact their doctor before taking the next dose. The doctor may decide to monitor the patient during the next dose. However, if the patient misses a dose 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 Bonaxon treatment

Do not stop taking Bonaxon or change the dose without consulting the doctor first.
Bonaxon 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 Bonaxon treatment, the patient should wait 6-8 weeks before starting new MS treatment. In patients who restart Bonaxon treatment after more than 2 weeks off the medicine, the effect on heart rate observed after the first dose may occur again, and monitoring of the patient's condition in the doctor's office or clinic will be necessary due to the restart of treatment. Do not restart Bonaxon treatment after a break of more than 2 weeks without consulting the doctor. The doctor will decide how to monitor the patient after stopping Bonaxon treatment. If the patient thinks their MS is getting worse after stopping Bonaxon treatment, they should tell their doctor immediately, as this can be a serious condition. If the patient has any further questions about taking Bonaxon, they should ask their doctor or pharmacist.

4. Possible side effects

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

• Cough with expectoration, feeling of discomfort in the chest, fever (symptoms of respiratory problems).
• 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 patches with severe pain.
• Slow heart rate (bradycardia), irregular heart rhythm.
• A type of skin cancer called basal cell carcinoma (BCC), which often appears as a pearl-like nodule, although it can have other forms.
• It is known that depression and anxiety occur more frequently in the MS population.
• 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.
• Low platelet count, which increases the risk of bleeding or bruising.
• Malignant melanoma (a type of skin cancer that usually develops from an unusual mole). Possible symptoms of melanoma include moles that change color, shape, or size over time. Before starting fingolimod treatment, it is necessary to examine the skin for any moles. The doctor will also perform regular skin checks during fingolimod treatment. 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 doctor.
• Seizures, epileptic fits.

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

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

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

• Abnormalities in the ECG (inversion of the T wave).
• A 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 itching hives, swelling of the lips, tongue, or face, which are more likely to occur on the day of starting Bonaxon treatment.
• Liver disease symptoms (including liver failure), such as yellowing of the skin or eyes, nausea or vomiting, pain in the right upper abdomen, dark urine (brown in color), loss of appetite, or unexplained nausea and vomiting. 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 lapses, difficulty speaking or communicating, 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 the doctor immediately.
• Cryptococcal infections (a type of fungal infection), including cryptococcal meningitis, with symptoms such as headache, stiff neck, sensitivity to light, nausea, and (or) confusion.
• Merkel cell carcinoma (a type of skin cancer). Possible symptoms of Merkel cell carcinoma include a painless nodule with a raw meat color, often located on the face, head, or neck. Merkel cell carcinoma can also appear as a hard, painless nodule or mass. Long-term sun exposure and weakened immune system can increase the risk of Merkel cell carcinoma.
• After stopping Bonaxon treatment, MS symptoms may return and worsen compared to the period before treatment and during treatment.
• Autoimmune hemolytic anemia (a condition where 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):

• Flu-like 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.
• Itching, red, burning rash (rash).
• Itching.
• Increased triglyceride levels in the blood.
• Hair loss.
• Shortness of breath.
• Depression.
• Blurred vision (see also "Macular edema" in the section on serious side effects).
• High blood pressure (Bonaxon 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 severe intensity, the patient should tell their doctor.

Reporting side effects

If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. 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, Tel.: +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 gathered on the safety of the medicine.

5. How to store Bonaxon

Keep the medicine out of the 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.
There are no special storage instructions for this medicine.
Do not use medicines from damaged or opened packages.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer need. This will help protect the environment.

6. Contents of the pack and other information

What Bonaxon contains

• The active substance of Bonaxon is fingolimod. Each hard capsule contains 0.5 mg of fingolimod (as fingolimod hydrochloride).
• The other ingredients are: calcium phosphate, stearic acid. Capsule shell:gelatin, titanium dioxide (E 171), yellow iron oxide (E 172). Printing ink:shellac, black iron oxide (E 172).

What Bonaxon looks like and contents of the pack

Bonaxon, 0.5 mg, hard capsules are a white or almost white powder in a size 3 hard gelatin capsule, 15.9 mm ± 0.3 mm in length, consisting of a yellow, opaque cap and a white, opaque body, with "0.5 mg" printed in black ink on the cap.
Bonaxon, 0.5 mg, hard capsules are packaged in a carton containing the appropriate number of blisters made of PVC/PE/PVDC/Aluminum with the corresponding number of capsules and a patient information leaflet.
Package sizes:
A carton containing 28 hard capsules.

Marketing authorization holder and manufacturer

Marketing authorization holder

Egis Pharmaceuticals PLC
Keresztúri út 30-38
1106 Budapest
Hungary

Manufacturer

Pharmathen International S.A
Industrial Park Sapes
Rodopi Prefecture
Block No 5
69300 Rodopi
Greece
PHARMATHEN S.A.
Dervenakion 6
15351 Pallini
Attiki
Greece

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

Denmark, Bulgaria, Czech Republic, Hungary, Poland, Slovakia:
Bonaxon
Date of last revision of the leaflet:24.02.2022