Patient Information Leaflet

Inrebic100mg Hard Capsules

fedratinib

This medicine is subject to additional monitoring, which will speed up the detection of any new safety information. You can contribute by reporting any side effects you experience. The final part of section4includes information on how to report these side effects.

Read this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you are unsure, consult your doctor or pharmacist.

‑This medicine has been prescribed for you only, and you should not give it to others even if they have the same symptoms as you, as it may harm them.

• If you experience side effects, consult your doctor or pharmacist,even if they are not listed in this leaflet. See section4.

1.What Inrebic is and what it is used for

2.What you need to know before you start taking Inrebic

3.How to take Inrebic

4.Possible side effects

5.Storage of Inrebic

6.Contents of the pack and additional information

What is Inrebic

Inrebic contains the active ingredient fedratinib. It is a type of medication known as “protein kinase inhibitors.”

What is Inrebic used for

Inrebic is used to treat adult patients with splenomegaly or symptoms related to myelofibrosis, a rare form of blood cancer.

How Inrebic works

A significantly enlarged spleen is one of the characteristics of myelofibrosis. Myelofibrosis is a bone marrow disorder in which the marrow is replaced by scar tissue. The abnormal marrow fails to produce a sufficient number of normal blood cells, and as a result, the spleen becomes much larger. By blocking the action of certain enzymes (called Janus-associated kinases), Inrebic can reduce the size of the spleen in patients with myelofibrosis and alleviate symptoms such as fever, nocturnal sweats, bone pain, and weight loss in patients with myelofibrosis.

Do not take Inrebic

‑if you are allergic to fedratinib or any of the other ingredients in this medication (listed in section6).

‑if you are pregnant or think you may be pregnant.

Warnings and precautions

Consult your doctor or pharmacist before starting to take these capsules and during treatment if you have any of the following signs or symptoms:

BRAIN DISEASE CALLED ENCEPHALOPATHY, INCLUDING WERNICKE ENCEPHALOPATHY

• Confusion, memory loss, or difficulty thinking; loss of balance or difficulty walking.
• Eye problems such as random eye movement, double vision, blurred vision, and loss of vision.

These may be signs of a brain disease called encephalopathy, including Wernicke encephalopathy, which can cause death.

Immediately contact your doctor if you experience any of these signs or symptoms.

Consult your doctor or pharmacist during treatment

• if you have excessive fatigue, shortness of breath, pale skin, or rapid heartbeat: these may be signs of low red blood cell count.
• if you have unusual bleeding or bruising on the skin, more than usual after blood is drawn, or bleeding gums: these may be signs of low platelet count.
• if you have frequent infections or recurring infections, which may be a sign of low white blood cell count.
• if you have nausea, vomiting, or diarrhea.
• if you have or have had any kidney problems.
• if you have or have had any liver problems.
• if you have or have had any pancreas problems.

It has been observed that the following has occurred with another type of medication similar to Inrebic used to treat rheumatoid arthritis: heart problems, blood clots, and cancer. Consult your doctor or pharmacist before or during treatment if:

• you are over 65 years old. Patients 65 years old or older may have a higher risk of developing heart problems, including heart attack, and some types of cancer.
• you have or have had heart problems.
• you have or have had cancer.
• you are a smoker or have smoked in the past.
• you have had previous blood clots in the veins of the legs (deep vein thrombosis) or lungs (pulmonary embolism).
• if you suddenly feel short of breath or have difficulty breathing, chest pain or pain in the upper back, swelling of the legs or arms, pain or tenderness in the legs, redness or change in color in the legs or arms, as these may be signs of blood clots in the veins.
• if you notice new growths on the skin or changes in existing ones. Your doctor may recommend that you undergo regular skin checks while taking Inrebic.

Your doctor will indicate if Inrebic is suitable for you.

Blood tests

Before and during treatment, blood tests will be performed to check the levels of blood cells (red blood cells, white blood cells, and platelets), vitamin B1 levels, and liver and pancreas function. Based on the results of the blood tests, your doctor may adjust the dose or discontinue treatment.

Children and adolescents

Inrebic should not be used in children or young people under18years because this medication has not been studied in this age group.

Other medications and Inrebic

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, as Inrebic may affect the functioning of some medications. Additionally, some medications may affect the functioning of Inrebic.

The following medications may increase the risk of adverse effects with Inrebic:

• Ketoconazole, fluconazole (used to treat fungal infections);
• Fluvoxamine (used to treat depression);
• Ritonavir (used to treat HIV/AIDS).

The following medications may reduce the effectiveness of Inrebic:

• Rifampicin (used to treat tuberculosis (TB) and other infections);
• Phenytoin (used to treat epilepsy and control seizures or convulsions);
• Efavirenz (used to treat HIV/AIDS).

Inrebic may affect other medications:

• Midazolam (used to help you sleep or alleviate anxiety);
• Omeprazole (used to treat stomach problems);
• Metoprolol (used to treat angina or high blood pressure);
• Metformin (used to reduce blood sugar levels);
• Also simvastatin, S-mephenytoin, and dextromethorphan.

Your doctor will decide if a dose adjustment is necessary.

Additionally, inform your doctor if you have recently undergone surgery or are about to undergo a procedure or procedure, as Inrebic may interact with some sedatives.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Do not take Inrebic during pregnancy. If you can become pregnant, use effective contraception while taking these capsules and avoid pregnancy for at least one month after the last dose.

Do not breastfeed while taking Inrebic and for at least one month after the last dose, as it is unknown if this medication passes into breast milk.

Driving and operating machinery

If you feel dizzy, do not drive or operate machinery until these side effects have disappeared.

Inrebic contains sodium

This medication contains less than23mg of sodium (1mmol) per dose; this is essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The recommended dose is400mg (fourcapsules of100mg) taken orally once a day.

You will have blood tests before and while taking this medication to monitor your progress.

If you experience certain side effects while taking Inrebic (see section4), your doctor may reduce the dose or pause or discontinue treatment.

How to Take These Capsules

• Swallow the capsules whole, preferably with water.
• Do not break, open, or chew the capsules.
• The capsules can be taken with or without food, but it is recommended to take them with food to prevent nausea (vomiting).

You must continue taking Inrebic for the time period indicated by your doctor. This is a long-term treatment.

If You Take More Inrebic Than You Should

If you accidentally take too many Inrebic capsules or a higher dose than you should, contact your doctor or pharmacist immediately.

If You Forget to Take Inrebic

If you forget a dose or vomit after taking a capsule, skip the missed dose and take the next scheduled dose at the usual time the following day. Do not take a double dose to make up for the missed or vomited capsules.

If You Discontinue Treatment with Inrebic

Do not stop taking Inrebic unless your doctor tells you to.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Inform your doctor immediately if you notice any of the following symptoms, which could be a sign of a serious brain disease called encephalopathy (including Wernicke's encephalopathy):

Consult your doctor if you experience any other side effect. These may include:

Very common side effects(may affect more than1person in every10)

• Low red blood cell counts, which can cause fatigue, shortness of breath, pale skin, or rapid heartbeats(anemia).
• Reduced platelet counts in the blood, which can cause bleeding or easy bruising(thrombocytopenia).
• Reduced white blood cell counts(neutropenia), sometimes with fever. Low white blood cell counts can reduce the ability to fight infections.
• Nausea and vomiting.
• Diarrhea.
• Constipation.
• Bleeding.
• Urinary tract infection.
• Headache.
• Muscle spasms.
• Fatigue or weakness(asthenia).
• Abnormal results in blood tests (increased alanine aminotransferase,increased aspartate aminotransferase,increased creatinine in blood,increased levels ofamylase,andlipase). These may be signs of liver, kidney, or pancreas problems.

Common side effects(may affect up to1person in every10people)

• Dizziness.
• Increased blood pressure(hypertension).
• Indigestion(dyspepsia).
• Bone pain.
• Pain in the limbs, hands, or feet (limb pain).
• Weight gain.
• Painful urination.

Reporting side effects

If you experience side effects, consult your doctor or pharmacist, even if they are possible side effects not listed in this leaflet.You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box and the bottle after “CAD”. The expiration date is the last day of the month indicated.

Keep the bottle perfectly closed to protect it from moisture.

This medication does not require any special storage temperature.

Medicines should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Content of Inrebic

• The active ingredient is fedratinib. Each hard capsule contains fedratinib dihydrochloride monohydrate equivalent to 100 mg of fedratinib.
• The other components are:

• The capsule content contains microcrystalline cellulose silicified (contains microcrystalline cellulose (E460) and anhydrous colloidal silica (E551)) and sodium stearate fumarate (see section 2, “Inrebic contains sodium”).
• The capsule coating contains gelatin (E441), titanium dioxide (E171), and iron oxide red (E172).
• The white printing ink is composed of shellac (E904), titanium dioxide (E171), and propylene glycol (E1520).

Appearance of Inrebic and contents of the package

• Inrebic are brownish-red capsules of 21.4-22.0 mm, with “FEDR” printed on the coating and “100 mg” on the body in white ink.
• The capsules are packaged in a high-density polyethylene (HDPE) bottle with a child-resistant safety cap and a polypropylene stopper. Each bottle contains 120 capsules and is packaged in a cardboard box.

Marketing Authorization Holder

Bristol-Myers Squibb Pharma EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Responsible for manufacturing

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BD Utrecht

Netherlands

Last review date of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website:http://www.ema.europa.eu.There are also links to other websites on rare diseases and orphan medicines.

You can access detailed information on this medicine by scanning the QR code included in the outer packaging with your smartphone. You can also access this information at the following internet address:http://www.inrebic-eu-pil.com.