Fenoxa

Package Leaflet: Information for the Patient

Fenoxa, 0.5 mg, hard capsules
Fingolimod

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• In case of any doubts, 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.
• If the patient experiences any side effects, including any possible side effects not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

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

1. What is Fenoxa and what is it used for

What is Fenoxa

The active substance in Fenoxa is fingolimod.

What is Fenoxa used for

Fenoxa 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 with rapidly evolving, severe MS.

Fenoxa 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 disturbances, numbness, vision problems, or balance problems. Relapse symptoms may completely resolve, but some disturbances may persist.

How Fenoxa works

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

2. Important information before taking Fenoxa

When not to take Fenoxa

• 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 in 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 Fenoxa;
• 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 pregnant or is of childbearing age and not using effective contraception;
• if the patient is allergic to 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 Fenoxa.

Warnings and precautions

Before starting treatment with Fenoxa, 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 experiences symptoms of slow heart rate (e.g., dizziness, nausea, or palpitations);
• if the patient is taking or has recently taken 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 losses of consciousness or fainting 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 problems or other symptoms of macular edema (a condition where the macula, the part of the eye responsible for central vision, becomes swollen) or 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 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 Fenoxa.

Low heart rate (bradycardia) and irregular heartbeat
At the beginning of treatment or after taking the first dose of 0.5 mg, patients who have previously taken a daily dose of 0.25 mg of fingolimod may experience a slowing of the heart rate. As a result, the patient may feel dizzy, tired, have palpitations, or experience a drop in blood pressure. If these symptoms are severe, the patient should inform their doctor immediately, as they may require immediate treatment. Fenoxa 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 Fenoxa or after the first dose of 0.5 mg when changing treatment from a daily dose of 0.25 mg of fingolimod, with hourly measurements of pulse and blood pressure, so that if any adverse reactions occur that happen at the beginning of treatment, appropriate treatment can be applied. Before the first dose of Fenoxa and after completing the 6-hour observation, the patient will undergo an ECG. During this time, the doctor may continuously monitor the patient's heart activity using an electrocardiogram. If after 6 hours of observation, the patient is found to have a very slow or decreasing heart rate or if the ECG shows abnormalities, the patient may require 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 resumes treatment with Fenoxa after a break in treatment, depending on how long the break lasted and how long the patient took Fenoxa 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, Fenoxa may not be suitable for them.
If the patient has had sudden losses of consciousness or slow heart rate in the past, Fenoxa may not be suitable for them. It may be necessary to consult a cardiologist (a heart specialist) who will advise on how to start treatment with Fenoxa, including how to monitor the patient at night.
If the patient is taking medications that can slow the heart rate, Fenoxa 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 the heart rate, to allow treatment with Fenoxa. If such a change in treatment is not possible, the cardiologist will advise the patient on how to start treatment with Fenoxa, taking into account monitoring until the next day after administering the first dose of Fenoxa.
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 Fenoxa. If this is the case, the doctor will delay the start of treatment with Fenoxa by one month after completing the full vaccination cycle.
Infections
Fenoxa reduces the number of white blood cells (especially lymphocytes). White blood cells fight infections. While taking Fenoxa (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, flu-like symptoms, shingles, or a headache with stiff neck, sensitivity to light, nausea, and/or vomiting, they should contact their doctor immediately, as this condition can be severe.
Patients taking Fenoxa have reported infections with the human papillomavirus (HPV), including cases of warts, dysplasia, warts, and HPV-related cancer.
The doctor will consider the need for HPV vaccination in the patient. In women, the doctor will also recommend screening for HPV.
Macular edema
Before starting treatment with Fenoxa, the doctor may refer patients with existing or past vision problems or other symptoms of macular edema, uveitis, or diabetes to an ophthalmologist.
The doctor may refer the patient to an ophthalmologist 3 to 4 months after starting treatment with Fenoxa.
The macula is a small area of the retina, located at the back of the eye, that enables sharp, clear vision of shapes, colors, and other details. Fenoxa may cause macular edema, a condition where the macula becomes swollen. Macular edema usually occurs within the first 4 months of treatment with Fenoxa.
The risk of macular edema is higher in patients with diabetes or 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 Fenoxa.
Macular edema may cause vision problems 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 to an ophthalmologist, especially if:

• the center of the visual field becomes blurred or shaded;
• a defect appears in the center of the visual field;
• the patient experiences difficulties with color vision or fine details.

Liver function tests
Patients with severe liver disease should not take Fenoxa. Fenoxa 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, abnormal dark (brown) urine color, pain in the right upper abdomen, fatigue, decreased appetite, or unexplained nausea and vomiting, they should inform their doctor immediately. If any of these symptoms occur after starting treatment with Fenoxa, the patient should inform 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 Fenoxa may be discontinued.
High blood pressure
The doctor may regularly check the patient's blood pressure, as Fenoxa can cause a slight increase in blood pressure.
Lung disease
Fenoxa 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
A expected effect of Fenoxa 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 need to be performed, the patient should inform their doctor that they are taking Fenoxa. Otherwise, the doctor may not be able to interpret the blood test results, and in the case of certain tests, the doctor may order a larger amount of blood to be drawn than usual.
Before starting treatment with Fenoxa, 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 blood tests. If there are not enough white blood cells, it may be necessary to discontinue treatment with Fenoxa.
Reversible posterior encephalopathy syndrome (PRES)
In patients with MS treated with Fenoxa, there have been rare reports of a condition called reversible posterior encephalopathy syndrome (PRES). Symptoms of this condition may include severe headache, confusion, seizures, and/or vision changes. If any of these symptoms occur during treatment with Fenoxa, the patient should inform their doctor immediately, as this condition can be severe.
Cancer
In patients with MS treated with Fenoxa, there have been reports of skin cancers. If the patient notices any lumps (e.g., shiny lumps with a pearly 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., unusual moles) that change color, shape, or size over time.
Before starting treatment with Fenoxa, it is necessary to perform a skin examination to detect any lumps on the skin. The treating doctor will also perform regular skin checks during treatment with Fenoxa. 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 the patient.
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 from sunlight
Fingolimod weakens the immune system. This increases the risk of developing cancers, especially skin cancers. The patient should limit exposure to the sun and UV radiation by:

• wearing protective clothing.
• applying sunscreen with a high sun protection factor regularly.

Unusual changes in the brain related to MS relapse
In patients treated with Fenoxa, there have been rare reports of unusually large changes in the brain related to MS relapse. In the case of a severe MS relapse, the treating doctor will consider performing an MRI to assess this condition and decide on the possible need to discontinue Fenoxa.
Switching from other medicines to Fenoxa
The doctor may switch treatment directly from interferon-beta, glatiramer acetate, or dimethyl fumarate to Fenoxa 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, it may be necessary to wait 2 to 3 months before starting treatment with Fenoxa. When switching from teriflunomide, 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 Fenoxa is suitable for them.
Women of childbearing age
If Fenoxa is used during pregnancy, it may harm the unborn child. Before starting treatment with Fenoxa, the doctor will explain the risk to the patient and ask them to perform a pregnancy test to ensure they are not pregnant. The doctor will give the patient a card explaining why they should not become pregnant while taking Fenoxa.
The patient must use effective contraception during treatment and for 2 months after stopping treatment (see "Pregnancy and breastfeeding").
If the patient becomes pregnant while taking Fenoxa, they should inform their doctor immediately.
The doctor will decide whether to discontinue treatment (see "Discontinuing Fenoxa" in section 3 and section 4 "Possible side effects"). The patient will also need to undergo prenatal check-ups.
Breastfeeding
Fenoxa should not be used during breastfeeding. Fenoxa may pass into breast milk, posing a risk of severe side effects to the baby.

Driving and using machines

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

3. How to take Fenoxa

Treatment with Fenoxa will be supervised by a doctor experienced in treating multiple sclerosis.
This medicine should always be taken exactly as prescribed by the doctor. In case of doubt, the patient should consult their doctor.
The recommended dose is:

• One 0.5 mg capsule per day for adults.
• For children and adolescents (aged 10 and older), the dose depends on body weight:
• Children and adolescents weighing 40 kg or less: one 0.25 mg fingolimod capsule per day. Other medicines containing fingolimod are available in a lower dose (0.25 mg capsules) marketed by other pharmaceutical companies.
• Children and adolescents weighing more than 40 kg: one 0.5 mg capsule per day.

Children and adolescents starting treatment with one 0.25 mg fingolimod capsule per day and later reaching a stable weight above 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 Fenoxa.
The patient should not exceed the recommended dose.
Fenoxa is intended for oral use.
Fenoxa should be taken once a day, with a glass of water. Fenoxa capsules should always be swallowed whole, without opening. Fenoxa can be taken with or without food.
Taking Fenoxa at the same time every day will help the patient remember to take their medicine.
In case of doubts about the duration of treatment with Fenoxa, the patient should consult their doctor or pharmacist.

Taking a higher dose of Fenoxa than recommended

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

Missing a dose of Fenoxa

If the patient has been taking Fenoxa for less than 1 month and has missed a dose for the entire day, they should contact their doctor before taking the next dose. The doctor may decide to keep the patient under observation during the next dose.
If the patient has been taking Fenoxa 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 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 Fenoxa

The patient should not stop taking Fenoxa or change the dose without consulting their doctor first.
Fenoxa remains 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 Fenoxa, the patient should wait 6-8 weeks before starting new MS treatment.
In patients resuming treatment with Fenoxa after more than 2 weeks of stopping the medicine, the heart rate effect 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. The patient should not resume treatment with Fenoxa after a break of more than 2 weeks without consulting their doctor.
The treating doctor will decide whether and how to monitor the patient after stopping Fenoxa. The patient should inform their doctor immediately if they think their MS has worsened after stopping Fenoxa. This situation can be serious.
In case of any further doubts about using this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Fenoxa can cause side effects, although not everybody gets them.
Some side effects may be serious or become serious
Common(occurring in up to 1 in 10 patients):

• Cough with expectoration, unspecified unpleasant chest sensation, fever (symptoms of respiratory disorders)
• Herpes virus infections (shingles or herpes simplex) 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 onset of 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 pearly nodule, although it can have other appearances
• Depression and anxiety are known to occur more frequently in the MS population and have also been reported in children and adolescents treated with Fenoxa.
• Weight loss.

Uncommon(occurring in up to 1 in 100 patients):

• 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 perceiving colors and details
• Reduced 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 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(occurring in up to 1 in 1,000 patients):

• 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 ulcerated nodule, or a fresh ulcer in the site of an existing scar.

Very rare(occurring in up to 1 in 10,000 patients):

• Abnormalities in the ECG recording (T-wave inversion)
• Kaposi's sarcoma (a type of cancer associated with human herpesvirus 8)

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 Fenoxa
• 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 upper abdomen, dark (brown) urine color, decreased appetite, fatigue, 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 an MS relapse. They may also include symptoms that the patient is not aware of, such as mood or behavior changes, transient memory lapses, speech or communication difficulties, 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 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
• Merkel cell carcinoma (a type of skin cancer). Possible symptoms of Merkel cell carcinoma include a painless nodule with a fleshy or bluish-red 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 Fenoxa, MS symptoms may recur 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 inform their doctor immediately.
Other side effects
Very common(occurring in more than 1 in 10 patients):

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

Common(occurring in up to 1 in 10 patients):

• Fungal skin infections (dermatophytosis) (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 (erythema)
• 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 serious or become serious")
• Hypertension (Fenoxa may cause a mild increase in blood pressure)
• Muscle pain
• Joint pain

Uncommon(occurring in up to 1 in 100 patients):

• Low neutrophil count
• Depressed mood
• Nausea

Rare(occurring in up to 1 in 1,000 patients):

• 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.

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych (Department of Drug Safety, 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.
Reporting side effects will help gather more information on the safety of this medicine.

5. How to store Fenoxa

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 EXP.
The expiry date refers to the last day of the month.
The entry on the packaging after the abbreviation EXP indicates the expiry date, and after the abbreviation LOT, it indicates the batch number.
Do not store above 30°C.
Store in the original packaging to protect from moisture. Do not use medicines from damaged or opened packaging.
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. Package contents and other information

What Fenoxa contains

• The active substance is fingolimod.
• Other ingredients are:
• Filler:potassium citrate monohydrate, colloidal silicon dioxide, anhydrous, magnesium stearate. Body:gelatin, titanium dioxide (E171). Capsule:gelatin, titanium dioxide (E171), yellow iron oxide (E172).

What Fenoxa looks like and package contents

Fenoxa is a hard gelatin capsule, size 3, with a white opaque body and a yellow opaque cap.
Fenoxa is available in packs of 7, 28, and 98 capsules.
Not all pack sizes may be marketed.

Marketing authorization holder

Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
phone: +48 22 364 61 01

Manufacturer

Synthon Hispania S.L.
C/ Astelló 1
Sant Boi De Llobregat
08830 Barcelona
Spain
Synthon BV
Microweg 22
6545 CM Nijmegen
Netherlands
Date of last revision of the leaflet:September 2021