Inzolfi

Leaflet accompanying the packaging: patient information

INZOLFI, 0.25 mg, hard capsules
Fingolimod

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

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

1. What is Inzolfi and what is it used for

What is Inzolfi

Inzolfi contains the active substance fingolimod.

What is Inzolfi used for

Inzolfi 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.

Inzolfi 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 Inzolfi works

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

2. Important information before taking Inzolfi

When not to take Inzolfi

• if the patient has reduced immune response(due to immunodeficiency syndrome, disease, or taking immunosuppressive drugs);
• 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 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 Inzolfi;
• 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 is not using effective contraception.
• if the patient is allergicto fingolimod or any of the other ingredients of this medicine (listed in section 6). If this is the case or the patient has doubts, they should consult their doctor before taking Inzolfi.

Warnings and precautions

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

• if the patient has severe respiratory disorders during sleep (sleep apnea);
• if the patient has been informed that their ECG is abnormal;
• if the patient experiences symptoms of slow heart rate (such as dizziness,
• nausea or palpitations);
• if the patient is taking or has recently taken medications that slow heart rate(such as beta blockers, verapamil, diltiazem, or ivabradine, digoxin, cholinesterase inhibitors, or pilocarpine);
• if the patient has had sudden loss 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 vision problemsor other symptoms of macular edema (such as blurred vision or blind spots) or has diabetes, which can cause vision problems;
• if the patient has liver disease;
• if the patient has uncontrolled high blood pressure;
• if the patient has severe lung diseaseor a cough typical of smokers. If any of these situations occur or the patient has doubts, they should consult their doctor before taking Inzolfi.

Low heart rate (bradycardia) and irregular heartbeat
At the beginning of treatment or after taking the first dose of 0.5 mg in patients who previously took a daily dose of 0.25 mg, Inzolfi slows down the heart rate. As a result, the patient may experience dizziness, fatigue, 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.Inzolfi 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 Inzolfi 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 side effects occur at the beginning of treatment, appropriate treatment can be applied. Before the first dose of Inzolfi and after the 6-hour observation period, 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 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 Inzolfi after a break in treatment, depending on how long the break lasted and how long the patient took Inzolfi 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, Inzolfi may not be suitable for them.
If the patient has a history of sudden loss of consciousness or slow heart rate, Inzolfi may not be suitable for them. There may be a need for consultation with a cardiologist (a heart specialist) who will advise on how to start treatment with Inzolfi, including how to monitor the patient at night.
If the patient is taking medications that can slow down the heart rate, Inzolfi may not be suitable. There may be a need for consultation with a cardiologist who will check if the patient can switch to other medications that do not slow down the heart rate, to enable treatment with Inzolfi. If such a change in treatment is not possible, the cardiologist will advise the patient on how to start treatment with Inzolfi, taking into account monitoring until the next day after administering the first dose of Inzolfi.
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 Inzolfi. If this is the case, the doctor will delay the start of treatment with Inzolfi for one month after the full vaccination course.
Infections
Inzolfi reduces the number of white blood cells (especially lymphocytes). White blood cells fight infections. While taking Inzolfi (and for 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) 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 can be serious.
If the patient experiences any of the above symptoms after starting treatment with Inzolfi, they 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 Inzolfi may be discontinued.
High blood pressure
The doctor may regularly check the patient's blood pressure, as Inzolfi can cause a slight increase in blood pressure.
Lung diseases
Inzolfi 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 Inzolfi 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 Inzolfi.
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 treatment with Inzolfi, the doctor will confirm that the patient has a suitable number of white blood cells in the blood to start treatment and may order regular blood tests. If there is an insufficient number of white blood cells, it may be necessary to discontinue treatment with Inzolfi.
Posterior reversible encephalopathy syndrome (PRES)
Rarely, patients with MS treated with Inzolfi have reported a condition called posterior reversible 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 Inzolfi, the patient should inform their doctor immediately, as this can be serious.
Cancer
Patients with MS treated with Inzolfi have reported skin cancers. If the patient notices any lumps on their skin (e.g., shiny lumps with a pearl-like color), spots, or open sores that do not heal within a few weeks, they should inform their doctor. 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 Inzolfi, it is necessary to examine the skin for any lumps. The treating doctor will also perform regular skin checks during treatment with Inzolfi. 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.
Patients with MS treated with fingolimod have reported a type of lymphoma (a type of 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 their exposure to the sun and UV radiation by:

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

Unusual changes in the brain related to MS relapse
Patients treated with Inzolfi have rarely reported rare cases 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 Inzolfi.
Switching from other medicines to Inzolfi
The doctor may switch treatment directly from interferon beta, glatiramer acetate, or dimethyl fumarate to Inzolfi, 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 Inzolfi. In the case of 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 Inzolfi is suitable for them.
Women of childbearing age
If Inzolfi is used during pregnancy, it may harm the unborn child.
Before starting treatment with Inzolfi, the doctor will explain the risk to the patient and ask them to perform a pregnancy test to rule out pregnancy. The doctor will provide the patient with a card explaining why they should not become pregnant while taking Inzolfi. The card also contains information on what to do to avoid becoming pregnant while taking Inzolfi. 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 Inzolfi, they should inform their doctor immediately. The doctor will decide on discontinuing treatment (see "Discontinuing Inzolfi" in section 3, and also section 4 "Possible side effects"). The patient will also need to undergo prenatal check-ups.
Breastfeeding
Do not breastfeed while taking Inzolfi.Inzolfi may pass into breast milk, posing a risk of serious side effects to the child.

Driving and using machines

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

3. How to take Inzolfi

Treatment with Inzolfi will be supervised by a doctor with experience in treating multiple sclerosis.
This medicine should always be taken as directed by the doctor. If the patient has any doubts, they should consult their doctor.
The recommended dose is:

Adults:

The dose is two 0.25 mg capsules 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 0.25 mg capsule per day.
• Children and adolescents with a body weight over 40 kg: two 0.25 mg capsules per day. Children and adolescents starting treatment with one 0.25 mg capsule per day and later reaching a stable body weight over 40 kg will be advised by their doctor to change the dose to two 0.25 mg capsules per day. In this case, it is recommended to repeat the observation period as after the first dose of Inzolfi.

Do not exceed the recommended dose.
Inzolfi is intended for oral use.
Inzolfi should be taken once a day, with a glass of water. Inzolfi capsules should always be swallowed whole, without opening. Inzolfi can be taken with or without food.
Taking Inzolfi 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 Inzolfi, they should consult their doctor or pharmacist.

Taking a higher dose of Inzolfi than recommended

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

Missing a dose of Inzolfi

If the patient has been taking Inzolfi for less than 1 month and has forgotten to take 1 dose for the whole day, they should contact their doctor before taking the next dose. The doctor may decide to keep the patient under observation during the next dose.
If the patient has been taking Inzolfi for at least 1 month and has forgotten to take the medicine for more than 2 weeks, they should contact their doctor before taking the next dose. The doctor may decide to keep the patient under observation during the next dose. However, if the patient has forgotten to take the medicine for up to 2 weeks, they can take the next dose as planned.
Do not take a double dose to make up for a missed dose.

Discontinuing Inzolfi

Do not stop taking Inzolfi or change the dose without consulting the doctor first. Inzolfi 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 Inzolfi, the patient should wait 6-8 weeks before starting new MS treatment.
For patients resuming treatment with Inzolfi 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. Do not resume treatment with Inzolfi after a break of more than 2 weeks without consulting the treating doctor. The treating doctor will decide whether and how to monitor the patient after stopping treatment with Inzolfi. If the patient thinks that their MS has worsened after stopping treatment with Inzolfi, they should inform their doctor immediately. This situation may be serious.
If the patient has any further doubts about using this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

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

• Cough with expectoration, unspecified unpleasant feeling in the chest, fever (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 early stage 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 pearl-like nodule, although it may have a different appearance
• Depression and anxiety are known to occur more frequently in the MS population and have also been reported in children and adolescents treated with Inzolfi.
• 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 field of vision in the retina, at the back of the eye) with symptoms such as shadows or blind spots in the center of the field of vision, blurred vision, difficulty perceiving 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. Moles may 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):

• 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 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 (inversion of the T wave)
• Tumor associated with human herpesvirus 8 (Kaposi's sarcoma)

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

• Allergic reactions, including symptoms such as rash or itchy hives, swelling of the lips, tongue, or face, which are more likely to occur on the day of starting treatment with Inzolfi
• 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, decreased appetite, fatigue, and abnormal liver function test results. In very rare cases, liver failure may require a liver transplant
• Risk of a rare brain infection called progressive multifocal leukoencephalopathy (PML). PML symptoms may be similar to an MS relapse. There may also be symptoms that the patient is not aware of, such as mood or behavior changes, temporary memory lapses, difficulty speaking or communicating, which the doctor should evaluate to rule out PML. Therefore, if the patient thinks that 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 raw meat color or blue-red, usually located on the face, head, or neck. Merkel cell carcinoma may also appear as a hard, painless nodule or mass. Prolonged sun exposure and weakened immune system may affect the risk of Merkel cell carcinoma
• After stopping treatment with Inzolfi, MS symptoms may relapse and worsen compared to the period before treatment and during treatment.
• Autoimmune hemolytic anemia (a condition in which red blood cells are destroyed).

If the patient experiences any of these side effects, they should inform their doctor immediately.
Other possible 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 (Inzolfi may cause a mild increase in blood pressure)
• Muscle pain
• Joint pain

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

• Low neutrophil count
• Depressed mood
• Nausea

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

• Lymphoma (a type of cancer affecting the lymphatic system)

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

• Peripheral edema

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

If side effects occur, including any side effects not listed in the leaflet, the patient should inform 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:
Jerozolimskie Avenue 181C, 02-222 Warsaw
phone: 22 49 21 301, fax: 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 the medicine.

5. How to store Inzolfi

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.
Do not store above 25°C.
Store in the original package to protect from moisture.
Do not use this medicine if the packaging is damaged or shows signs of opening.
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 Inzolfi contains

• The active substance of the medicine is fingolimod.
• Each hard capsule contains 0.25 mg of fingolimod in the form of fingolimod hydrochloride.
• Other ingredients are: capsule contents: mannitol, hydroxypropyl cellulose (E 463), hydroxypropyl betadex, magnesium stearate (E 470b). capsule shell: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172). printing ink: shellac (E 904), black iron oxide (E 172), propylene glycol (E 1520).

What Inzolfi looks like and what the pack contains

A 16 mm sized capsule with an opaque cap and body in ivory color,
with a radially arranged black print “FTY 0.25 mg” on the cap and a black printed ring
on the body.
Inzolfi capsules are available in:

• transparent blisters of PVC/PVDC/Aluminium foil containing 28 capsules, in a cardboard box.

Marketing Authorisation Holder

Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria

Manufacturer/Importer

Novartis Pharma GmbH
Roonstrasse 25
90429 Nuremberg, Bavaria
Germany

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

Economic Area under the following names:

Netherlands
Inzolfi 0.25 mg, hard capsules
Denmark
Inzolfi
Finland
Inzolfi 0.25 mg, hard capsules
Iceland
Inzolfi 0.25 mg hard shell
Norway
Inzolfi
Poland
INZOLFI
Sweden
Inzolfi 0.25 mg hard capsules

For further information about this medicinal product, contact the local representative of the Marketing Authorisation Holder:

Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
tel. 22 209 70 00

Date of last revision of the leaflet: