Inrebic

Patient Information Leaflet

Inrebic 100 mg hard capsules

fedratinib
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this 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 a "protein kinase inhibitor".
What Inrebic is used for
Inrebic is used to treat adult patients with an enlarged spleen 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 disorder of the bone marrow in which the bone marrow is replaced by scar tissue. The abnormal bone marrow can no longer produce enough normal blood cells, and as a result, the spleen becomes significantly enlarged. 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 should 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 suspect you may be pregnant.

Warnings and precautions
Contact your doctor or pharmacist before and during treatment if you experience any of the following signs or symptoms:
Condition affecting the brain 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 could 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.

During treatment, contact your doctor or pharmacist:

• If you feel extreme tiredness, shortness of breath, paleness of the skin, or rapid heartbeat: these may be signs of low red blood cell count.
• If you have unusual bleeding or bruising, longer-than-usual bleeding after a blood draw, or bleeding gums: these may be signs of low platelet count in the blood.
• If you have frequent 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 kidney problems.
• If you have or have had liver problems.
• If you have or have had pancreas problems.
• If you have eye problems, particularly an eye inflammation called uveitis.

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

• you are over 65 years of age. Patients aged 65 years and older may have an increased risk of heart problems, including heart attack and certain types of tumors.
• you have or have had heart problems.
• you have or have had a tumor.
• you are a smoker or have previously smoked.
• you have previously had blood clots in the veins of your legs (deep vein thrombosis) or lungs (pulmonary embolism).
• you suddenly develop shortness of breath or difficulty breathing, chest pain, back pain, swelling of an arm or leg, leg pain or tenderness, or redness or discoloration in an arm or leg, as these may be signs of blood clots in the veins.
• you notice new skin growths or changes in existing skin growths. Your doctor may recommend regular skin examinations during treatment with Inrebic.

Your doctor will discuss whether Inrebic is appropriate for you.
Blood tests
Before and during treatment, you will need to have blood tests to monitor levels of blood cells (red blood cells, white blood cells, and platelets) and to check liver and pancreas function.
Before starting treatment, you will need a blood test to check your vitamin B1 (thiamine) levels.
Your doctor will also instruct you to take a daily 100 mg thiamine supplement during treatment. Your doctor may also require additional blood tests to monitor your thiamine levels during treatment.
Your doctor may adjust your dose or stop treatment based on the results of blood tests.
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
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Inrebic may affect how some other medicines work. Also, some other 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 certain other infections);
• phenytoin (used to treat epilepsy and control epileptic seizures or convulsions);
• efavirenz (used to treat HIV/AIDS infections).

Inrebic may affect other medicines:

• midazolam (used to promote sleep or relieve anxiety);
• omeprazole (used to treat stomach problems);
• metoprolol (used to treat angina or high blood pressure);
• metformin (used to lower blood sugar levels);
• also simvastatin, S-mephenytoin, and dextromethorphan.

Your doctor will determine whether any dose adjustments are needed.
Additionally, inform your doctor if you have recently undergone or are scheduled for surgery or a medical procedure, as Inrebic may interact with certain sedatives.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not take Inrebic during pregnancy. If you are of childbearing potential, you must use an effective method of contraception while taking the capsules and avoid pregnancy for at least one month after the last dose.
Avoid breastfeeding 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 experience dizziness, avoid driving or operating machinery until these side effects have resolved.
Inrebic contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially "sodium-free".

3. How to take Inrebic

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is 400 mg (four 100 mg capsules) taken orally once daily.
You will have blood tests before and during treatment with 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 the dose or temporarily or permanently stop treatment.

How to take the capsules

• Swallow the capsules whole, preferably with a glass of 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 avoid nausea or vomiting.

You must continue taking Inrebic for the entire duration prescribed 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 prescribed, 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 a missed or vomited capsule.

If you stop taking Inrebic
Do not stop treatment with Inrebic unless instructed by your doctor.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Immediately tell your doctor if you notice any of the following symptoms, which could be signs of a
serious brain condition called encephalopathy (including Wernicke's encephalopathy):

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

If you experience any other side effect, talk to your doctor. These may include:
Very common side effects (may affect more than 1 in 10 people)

• Low levels of red blood cells, which may cause tiredness, shortness of breath, pale skin, or a fast heartbeat ( anaemia ).
• Reduction in blood platelets, which may cause a tendency to bleed or bruise easily ( thrombocytopenia ).
• Reduction in white blood cells ( neutropenia ), sometimes accompanied by fever. Low levels of white blood cells may reduce the ability to fight infections.
• Feeling sick ( nausea ) or being sick ( 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 could be signs of problems affecting the liver, kidneys, or pancreas.

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

• Dizziness.
• High blood pressure ( hypertension ).
• Indigestion ( dyspepsia ).
• Bone pain.
• Pain in arms, legs, hands, or feet ( pain in extremities ).
• Weight gain.
• Pain during urination.
• Inflammation of the eye (causing pain, redness, vision problems, or blurred vision).

Reporting of side effects
If you get any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store 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 on the vial after
Exp. The expiry date refers to the last day of that month.
Keep the vial tightly closed to protect the medicine from moisture.
This medicine requires no special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Inrebic contains

• The active substance is fedratinib. Each hard capsule contains fedratinib dihydrochloride monohydrate, equivalent to 100 mg of fedratinib.
• The other components are:
  o The capsule core contains silicified microcrystalline cellulose (contains microcrystalline cellulose [E460] and anhydrous colloidal silica [E551]) and sodium stearyl fumarate (see section 2, “Inrebic contains sodium”).
  o The capsule coating contains gelatin (E441), titanium dioxide (E171), and red iron oxide (E172).
  o The white printing ink consists of shellac (E904), titanium dioxide (E171), and propylene glycol (E1520).

Description of the appearance of Inrebic and contents of the pack

• Inrebic capsules are reddish-brown in colour, 21.4–22.0 mm in size, printed in white ink with “FEDR” on the cap and “100 mg” on the body.
• The capsules are packed in a high-density polyethylene (HDPE) bottle with a seal and a child-resistant polypropylene cap. Each bottle contains 120 capsules and is supplied in a cardboard carton.

Marketing Authorisation 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 on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Belgique/België/Belgien Lietuva
N.V. Bristol-Myers Squibb Belgium S.A. Swixx Biopharma UAB
Tél/Tel: + 32 2 352 76 11 Tel: + 370 52 369140
[email protected] [email protected]

България Luxembourg/Luxemburg
Swixx Biopharma EOOD N.V. Bristol-Myers Squibb Belgium S.A.
Teл.: + 359 2 4942 480 Tél/Tel: + 32 2 352 76 11
[email protected] [email protected]

Česká republika Magyarország
Bristol-Myers Squibb spol. s r.o. Bristol-Myers Squibb Kft.
Tel: + 420 221 016 111 Tel.: + 36 1 301 9797
[email protected] [email protected]

Danmark Malta
Bristol-Myers Squibb Denmark A.M. Mangion Ltd
Tlf: + 45 45 93 05 06 Tel: + 356 23976333
[email protected] [email protected]

Deutschland Nederland
Bristol-Myers Squibb GmbH & Co. KGaA Bristol-Myers Squibb B.V.
Tel: 0800 0752002 (+ 49 89 121 42 350) Tel: + 31 (0)30 300 2222
[email protected] [email protected]

Eesti Norge
Swixx Biopharma OÜ Bristol-Myers Squibb Norway AS
Tel: + 372 640 1030 Tlf: + 47 67 55 53 50
[email protected] [email protected]

Ελλάδα Österreich
Bristol-Myers Squibb A.E. Bristol-Myers Squibb GesmbH
Τηλ: + 30 210 6074300 Tel: + 43 1 60 14 30
[email protected] [email protected]

España Polska
Bristol-Myers Squibb, S.A. Bristol-Myers Squibb Polska Sp. z o.o.
Tel: + 34 91 456 53 00 Tel.: + 48 22 2606400
[email protected] [email protected]

France Portugal
Bristol-Myers Squibb SAS Bristol-Myers Squibb Farmacêutica Portuguesa, S.A.
Tél: + 33 (0)1 58 83 84 96 Tel: + 351 21 440 70 00
[email protected] [email protected]

Hrvatska România
Swixx Biopharma d.o.o. Bristol-Myers Squibb Marketing Services S.R.L.
Tel: + 385 1 2078 500 Tel: + 40 (0)21 272 16 19
[email protected] [email protected]

Ireland Slovenija
Bristol-Myers Squibb Pharmaceuticals uc Swixx Biopharma d.o.o.
Tel: 1 800 749 749 (+ 353 (0)1 483 3625) Tel: + 386 1 2355 100
[email protected] [email protected]

Ísland Slovenská republika
Vistor ehf. Swixx Biopharma s.r.o.
Sími: + 354 535 7000 Tel: + 421 2 20833 600
[email protected] [email protected]

Italia Suomi/Finland
Bristol-Myers Squibb S.r.l. Oy Bristol-Myers Squibb (Finland) Ab
Tel: + 39 06 50 39 61 Puh/Tel: + 358 9 251 21 230
[email protected] [email protected]

Κύπρος Sverige
Bristol-Myers Squibb A.E. Bristol-Myers Squibb Aktiebolag
Τηλ: 800 92666 (+ 30 210 6074300) Tel: + 46 8 704 71 00
[email protected] [email protected]

Latvija
Swixx Biopharma SIA
Tel: + 371 66164750
[email protected]

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/. Links to other websites on rare diseases and related treatments are also provided.
For detailed information on this medicinal product, you can also scan the QR code on the outer packaging using a smartphone. The same information is available at the following address: www.inrebic-eu-pil.com.