Inrebic 100 mg hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Inrebic 100 mg hard capsules

fedratinib

Read the entire 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 have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Inrebic is and what it is used for

What Inrebic is

Inrebic contains the active substance fedratinib. It is a type of medicine known as "protein kinase inhibitors".

What Inrebic is 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

An 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 spleen size in patients with myelofibrosis and relieve symptoms such as fever, night sweats, bone pain, and weight loss in patients with myelofibrosis.

2. What you need to know before taking Inrebic

Do not take Inrebic

• if you are allergic to fedratinib or to any of the other ingredients of this medicine (listed in section 6).

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

Warnings and precautions

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

Brain disorder called encephalopathy, including Wernicke's encephalopathy

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

These may be signs of a brain condition called encephalopathy, including Wernicke's encephalopathy, which can lead to death.

Contact your doctor immediately if you experience any of these signs or symptoms.

Consult your doctor or pharmacist during your treatment

• if you feel very tired, have shortness of breath, pale skin, or a fast 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 draws, or bleeding gums: these may be signs of low platelet count.
• if you have frequent infections or recurring infections, which may indicate low white blood cell count.
• if you have nausea, vomiting, or diarrhea.
• if you have or have ever had kidney problems.
• if you have or have ever had liver problems.
• if you have or have ever had pancreas problems.
• if you have eye problems, especially an eye inflammation called uveitis.

The following have been observed with another similar type of medicine used to treat rheumatoid arthritis: heart problems, blood clots, and cancer. Talk to your doctor or pharmacist before or during treatment if:

• you are over 65 years of age. Patients aged 65 years or older may have a higher risk of heart problems, including heart attack, and certain 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 previously had blood clots in the veins of your legs (deep vein thrombosis) or lungs (pulmonary embolism).
• you suddenly become short of breath or have difficulty breathing, chest pain or upper back pain, swelling of arms or legs, pain or tenderness in arms or legs, redness or discoloration in arms or legs, as these may be signs of blood clots in the veins.
• you notice new skin growths or changes in existing ones. Your doctor may recommend regular skin examinations while you are taking Inrebic.

Your doctor will determine whether Inrebic is suitable for you.

Blood tests

Before and during treatment, you will have blood tests to check your blood cell levels (red blood cells, white blood cells, and platelets) and the function of your liver and pancreas.

Before treatment begins, you will have a blood test to check your vitamin B1 levels. Your doctor will also instruct you to take a daily 100 mg vitamin B1 supplement during treatment. Your doctor may also request additional blood tests to monitor your vitamin B1 levels during treatment.

Depending on the results of your blood tests, your doctor may adjust your dose or interrupt treatment.

Children and adolescents

Inrebic must not be used in children or young people under 18 years of age, as this medicine has not been studied in this age group.

Other medicines and Inrebic

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, because Inrebic may affect how some medicines work. Also, some medicines may affect how Inrebic works.

The following medicines may increase the risk of side effects with Inrebic:

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

The following medicines 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 infections).

Inrebic may affect other medicines:

• Midazolam (used to help you sleep or relieve 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 whether a dose adjustment is needed.

Also, inform your doctor if you have recently had surgery or are scheduled for a surgical procedure, as Inrebic may interact with certain sedatives.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Do not take Inrebic during pregnancy. If you can become pregnant, you must use an effective method of 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 whether this medicine passes into breast milk.

Driving and using machines

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

Inrebic contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per dose; this is essentially “sodium-free”.

3. How to take Inrebic

Follow exactly the instructions for taking this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The recommended dose is 400 mg (four 100 mg capsules) taken orally once daily.

You will have blood tests before and while taking this medicine to monitor your progress. Your doctor will also instruct you to take a daily 100 mg vitamin B1 supplement during treatment (see section 2, “Blood tests”).

If you experience certain side effects while taking Inrebic (see section 4), your doctor may reduce your dose or pause or stop treatment.

How to take these capsules

• swallow the capsules whole, preferably with water.
• do not break, open, or chew the capsules.
• the capsules may be taken with or without food, but it is preferable to take them with food to help prevent nausea and vomiting.

You should continue taking Inrebic for as long as your doctor tells you. 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 miss 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 forgotten or vomited capsules.

If you stop taking Inrebic

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

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

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

Consult your doctor if you experience any other adverse effects. These may include:

Very common adverse effects (may affect more than 1 in 10 people)

• Low red blood cell levels, which may cause tiredness, shortness of breath, pale skin, or rapid heartbeat (anaemia).
• Reduced blood platelets, which may cause you to bleed or bruise easily (thrombocytopenia).
• Reduction in white blood cells (neutropenia), sometimes with fever. Low white blood cell levels may reduce the ability to fight infections.
• Feeling sick (nausea) and vomiting (vomiting).
• Diarrhoea.
• Constipation.
• Bleeding.
• Urinary tract infection.
• Headache.
• Muscle spasms.
• Tiredness (fatigue) or weakness (asthenia).
• Changes in blood test results (increased alanine aminotransferase, increased aspartate aminotransferase, increased blood creatinine, increased levels of amylase and lipase). These may be signs of liver, kidney, or pancreas problems.

Common adverse effects (may affect up to 1 in 10 people)

• Dizziness.
• Increased blood pressure (hypertension).
• Indigestion (dyspepsia).
• Bone pain.
• Pain in the limbs, hands, or feet (limb pain).
• Weight gain.
• Pain when urinating.
• Eye inflammation (causing pain and redness, vision problems, or blurred vision).

Reporting of adverse effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Inrebic

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

Do not use this medicine after the expiry date stated on the carton and bottle after "EXP". The expiry date refers to the last day of the month indicated.

Keep the bottle tightly closed to protect it from moisture.

This medicine does not require any special storage temperature.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Contents of Inrebic

• The active substance is fedratinib. Each hard capsule contains fedratinib dihydrochloride monohydrate equivalent to 100 mg of fedratinib.

• The other components are:

• The capsule contents contain silicified microcrystalline cellulose (containing microcrystalline cellulose (E460) and colloidal anhydrous silica (E551)) and sodium stearoyl fumarate (see section 2, “Inrebic contains sodium”).

• The capsule shell contains gelatin (E441), titanium dioxide (E171), and red iron oxide (E172).

• The white printing ink consists of shellac (E904), titanium dioxide (E171), and propylene glycol (E1520).

Appearance of Inrebic and contents of the pack

• Inrebic is a reddish-brown hard capsule measuring 21.4–22.0 mm, printed with “FEDR” on the cap and “100 mg” on the body in white ink.

• The capsules are packed in a high-density polyethylene (HDPE) bottle with an induction seal and child-resistant polypropylene cap. Each bottle contains 120 capsules and is presented in a cardboard carton.

Marketing Authorization Holder

Bristol-Myers Squibb Pharma EEIG
Plaza 254
Blanchardstown Corporate Park 2
Dublin 15, D15 T867
Ireland

Manufacturer

Celgene Distribution B.V.
Orteliuslaan 1000
3528 BD Utrecht
The Netherlands

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

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.euopa.eu. Links to other websites on rare diseases and orphan medicinal products are also available.

You can access detailed information on this medicinal product by scanning with your mobile phone (smartphone) the QR code included on the outer packaging. You can also access this information at the following internet address: www.inrebic-eu-pil.com.