Inrebic - Fedratinib uses, dose and side effects

An enlarged spleen is one of the hallmarks of myelofibrosis. Myelofibrosis is a disorder of the bone marrow, which means that the marrow is replaced by scar tissue. The abnormal bone marrow can no longer produce enough normal blood cells, which results in the spleen is significantly enlarged. By blocking the function of certain enzymes (so-called Janus-associated kinases ), Inrebic can reduce the size of the spleen and relieve symptoms such as fever, night sweats, skeletal 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 any of the other ingredients of this medicine (listed in section 6).
if you are pregnant or think you may be pregnant.

Warnings and cautions

If you have any of these signs or symptoms, talk to your doctor or pharmacist before taking these capsules and during treatment:

Conditions that affect the brain, so-called encephalopathy, including Wernicke’s encephalopathy

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

These can be signs of a condition affecting the brain, called encephalopathy, including Wernicke’s encephalopathy, which can lead to death.

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

Talk to your doctor or pharmacist during your treatment

if you feel very tired, short of breath, have pale skin or rapid heartbeat – this may be a sign of a low red blood cell count .
if you have unusual bleeding or bruising under the skin, longer bleeding than usual after a blood sample has been taken, or bleeding from the gums – these may be signs of a low platelet count.
if you have frequent or recurrent infections , which may be a sign of a low white blood cell count .
if you are nauseous, have 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 problems with your pancreas .

Blood tests

Before and during treatment, blood samples will be taken from you to check your blood cell levels ( red blood cells, white blood cells, and platelets ), your vitamin B1 levels in your body, and the function of your liver and pancreas. Your doctor may need to adjust the dose or discontinue treatment depending on the results of the blood tests.

Children and young people

Inrebic should not be used in children or adolescents 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 take any other medicines. This is because Inrebic may affect the way some other medicines work. In addition, some other medicines may affect the way Inrebic works.

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

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

The following may reduce the effect of Inrebic:

Rifampicin (used to treat tuberculosis (TBC) and certain other infections )
Phenytoin (used to treat epilepsy and control epileptic seizures)
Efavirenz (used to treat HIV / AIDS).

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 lower blood sugar levels)
Also simvastatin , S-mefenytoin and dextromethorphan.

Your doctor will decide if it is necessary to change the dosage.

Also tell your doctor if you have recently had an operation or if you are going to have an operation or a procedure, as Inrebic may affect or be affected by certain sedatives.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Do not take Inrebic during pregnancy. If you can get pregnant, you must use effective contraception while taking these capsules and avoid getting pregnant 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 because it is unknown whether the medicine is excreted in human milk.

Driving and using machines

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

Inrebic contains sodium

This medicine contains less than 1 mmol (23 mg) sodium per dose, ie essentially ‘sodium-free.

3. How to take Inrebic

Always take this medicine exactly as described in this leaflet or as your doctor or pharmacist has told you. Ask your doctor or pharmacist if you are unsure.

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

Blood samples will be taken before and while you are taking this medicine, to monitor your progress.

If you get any side effects while taking Inrebic (see section 4), your doctor may lower your dose or pause or stop treatment temporarily or permanently.

Take these capsules

by swallowing the capsules whole, preferably with water.
Do not open, break or chew on the capsules.
The capsules can be taken with or without food, but it is recommended to take them with a meal to avoid nausea (vomiting).

You should continue to take Inrebic for as long as your doctor tells you to. 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 recommended, 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 your usual time the next day. Do not take a double dose to make up for a forgotten capsule or capsule that you vomited.

If you stop taking Inrebic

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately if you notice any of the following symptoms, which may be a sign of a serious condition affecting the brain, called encephalopathy (including Wernicke’s encephalopathy ):

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

Talk to your doctor if you get any other side effects. These may include:

Very common side effects are (may affect more than 1 in 10 people):

Low levels of red blood cells , which can cause fatigue, shortness of breath, pale skin or rapid heartbeat ( anemia ).
Decrease in the number of platelets in the blood, which may increase the risk of bleeding or bruising ( thrombocytopenia ).
Decreased white blood cell count ( neutropenia ), sometimes with fever. Low white blood cell counts can lead to higher risk of infection.
Nausea or vomiting.
Diarrhea.
Constipation.
Bleeding.
Urinary tract infection.
Headache.
Muscle spasms.
Fatigue (fatigue) or weakness ( asthenia ).
Changes in blood test results ( increase in alanine aminotransferase , increase in aspartate aminotransferase , increase in blood creatinine , increase in amylase and lipase levels). These may be signs of problems with the liver, kidneys or pancreas.

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

Dizziness.
High blood pressure ( hypertension ).
Indigestion ( dyspepsia ).
Skeletal pain.
Pain in arms and legs, hands or feet ( pain in extremity ).
Weight gain.
Painful urination.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This also applies to any side effects not mentioned in this information. You can also report side effects directly to the Medical Products Agency. By reporting side effects, you can help increase drug safety information.

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 which is stated on the carton and can after EXP. The expiration date is the last day of the specified month.

Close the jar tightly. Moisture sensitive.

No special temperature instructions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Contents of the packaging and other information

Content declaration

The active substance is fedratinib. Each hard capsule contains 100 mg of fedratinib dihydrochloride monohydrate equivalent to 100 mg of fedratinib.
Other ingredients are:
- The capsule contents contain silicified microcrystalline cellulose (contains microcrystalline cellulose (E460) and anhydrous colloidal silica (E551)) and sodium stearyl fumarate (see section 2, “Inrebic contains sodium”).
- The capsule shell contains gelatin (E441), titanium dioxide (E171) and red iron oxide (E172).
- The white ink consists of shellac (E904), titanium dioxide (E171) and propylene glycol (E1520).
What the medicine looks like and contents of the pack
- Inrebic is 21.4–22.0 mm, reddish-brown capsules, embossed in white ink with “FEDR” on the top and “100 mg” on the bottom.
- The capsules are packaged in a high density polyethylene (HDPE) jar, with a childproof polypropylene lid and heat seal. Each jar contains 120 capsules and is packed in a carton.

Marketing Authorization Holder and Manufacturer

Marketing Authorisation Holder

Celgene Europe BV

Winthontlaan 6 N

3526 KV Utrecht

Netherlands

Manufacturer

Celgene Distribution BV