Fedratinib

Pronunciation: fed-RA-ti-nib
Generic name: fedratinib
Brand name: Inrebic
Dosage form: oral capsule (100 mg)
Drug class: Multikinase inhibitors

Medically reviewed by Carmen Pope, BPharm. Last updated on Dec 3, 2024.

What is fedratinib?

Fedratinib (brand name Inrebic) is used to reduce symptoms of myelofibrosis (MF) in adults, such as night sweats, itching, pain, and feeling full when eating, and it also helps reduce spleen volume. Myelofibrosis is a rare type of bone marrow disorder.

Fedratinib's mechanism of action involves blocking certain types of enzymes called kinases that are overactive in myelofibrosis, such as Janus-associated kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). These enzymes are involved in signaling pathways that contribute to excessive inflammation in bone marrow, an enlarged spleen, and symptoms of myelofibrosis. Fedratinib belongs to the drug class called kinase inhibitors.

Fedratinib gained FDA approval on August 16, 2019, under the brand name Inrebic. There is no fedratinib generic.

Fedratinib uses

Fedratinib is used to treat intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis in adults.

Fedratinib side effects

The most common side effects of fedratinib are:

• diarrhea
• nausea
• low red blood cell count (anemia)
• vomiting.

Serious side effects and warnings

Fedratinib carries a Boxed Warning for encephalopathy, including Wernicke's encephalopathy.

Encephalopathy (including Wernicke's encephalopathy). A serious and sometimes fatal neurological problem called encephalopathy (including Wernicke's encephalopathy) has happened in some people who take fedratinib. Wernicke’s encephalopathy is a neurologic emergency that can happen if you do not have enough Vitamin B1 (thiamine) in your body. Your healthcare provider will do a blood test to check your Vitamin B1 level and treat you with Vitamin B1 if your level is too low before starting treatment with fedratinib. Your healthcare provider may also check your Vitamin B1 level during treatment and you should take a Vitamin B1 supplement (100 mg of thiamine) throughout treatment with fedratinib. Get emergency medical help right away if you develop the following:

• confusion, memory problems, or drowsiness
• problems with balance and movement, such as difficulty walking
• eye problems, such as double or blurred vision or abnormal eye movements.

Call your healthcare provider right away if you experience diarrhea, nausea, vomiting, and weight loss that does not get better with treatment.

Low blood cell counts. Fedratinib may cause new or worsening low red blood cell counts (anemia) and low platelet counts (thrombocytopenia) in some people. You may need a blood transfusion if your blood counts drop too low. Your healthcare provider will do blood tests to check your blood counts before you start and during treatment with fedratinib. Tell your healthcare provider if you develop any bleeding or bruising during treatment with fedratinib.

Diarrhea, nausea, and vomiting. Your healthcare provider may give you certain medicines to help treat diarrhea, nausea, and vomiting caused by fedratinib. Call your healthcare provider or get emergency medical help right away if you have diarrhea, nausea, or vomiting that does not get better with treatment.

Liver problems. Fedratinib may cause increased liver enzymes. Your healthcare provider will do blood tests to check your liver function before starting and during treatment with fedratinib.

Amylase and lipase increases. You may have increases in your blood amylase or lipase levels that may indicate a problem with your pancreas. Your healthcare provider will do blood tests to check your amylase or lipase levels before starting and during treatment with fedratinib.

Major cardiac events such as heart attack, stroke, or death. An increased risk of major cardiac events has happened in people, especially those who have cardiovascular risk factors and who are current or past smokers, while taking another Janus Kinase (JAK)-inhibitor to treat rheumatoid arthritis. Get emergency help right away if you have any symptoms of a heart attack or stroke while taking fedratinib, including:

• discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back
• severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
• pain or discomfort in your arms, back, neck, jaw, or stomach
• shortness of breath with or without chest discomfort
• breaking out in a cold sweat
• nausea or vomiting
• feeling lightheaded
• weakness in one part or on one side of your body
• slurred speech.

Blood clots. Increased risk of blood clots in the veins of the legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) have happened in people taking another JAK inhibitor for rheumatoid arthritis and may be life-threatening. Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with fedratinib, including:

• swelling, pain, or tenderness in one or both legs
• sudden unexplained chest or upper back pain
• shortness of breath, or difficulty breathing.

New (secondary) cancers. People who take another JAK inhibitor for rheumatoid arthritis have an increased risk of new (secondary) cancers, including lymphoma and other cancers, except nonmelanoma skin cancer. People who smoke or who smoked in the past have an increased risk of new cancers.

Fedratinib may cause an allergic reaction. Get emergency medical help if you have signs of an allergic reaction to fedratinib: hives, difficulty breathing, swelling of your face, lips, tongue, or throat.

Driving and using machines: While using this medicine, you may feel weak, tired, dizzy, or confused. You may have blurred vision. Before driving a vehicle or using machinery, wait to see how you feel after taking fedratinib.

Call your doctor at once if you have:

• severe or ongoing nausea, vomiting, or diarrhea (even while you are taking medication to prevent these effects);
• easy bruising, unusual bleeding, purple or red spots under your skin;
• low red blood cells (anemia) - pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet; or
• low white blood cell counts - fever, mouth sores, skin sores, sore throat, cough, trouble breathing.

You may need a blood transfusion if your blood counts get too low.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Before taking this medicine

To make sure fedratinib is safe for you, tell your doctor if you:

• have low vitamin B1 (thiamine) levels
• have low red blood cell or platelet counts
• have or have had liver problems
• have or have had kidney problems
• are a current or past smoker
• have had a blood clot, heart attack, other heart problems, or stroke
• have or have had any other cancer
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Fedratinib is not for use in patients under the age of 18 years.

Pregnancy

It is not known if fedratinib may harm your unborn baby.

Breastfeeding

It is not known if fedratinib passes into your breast milk. You should not breastfeed during treatment with fedratinib and for at least 1 month after your last dose. Talk to your healthcare provider about the best way to feed your baby during treatment.

How should I take fedratinib?

Take fedratinib exactly as prescribed by your doctor. Follow all directions on your Inrebic (fedratinib) Package Insert and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

• Fedratinib is taken 1 time a day.
• You may take fedratinib capsules with or without food. Taking fedratinib with a high-fat meal may help to reduce nausea and vomiting symptoms.
• Take Vitamin B1 (thiamine 100 mg) by mouth daily to prevent low Vitamin B1 levels during treatment with fedratinib.

You may be given other medications to help prevent nausea, vomiting, and diarrhea. Keep using these medicines for as long as your doctor has prescribed.

Call your doctor if you are sick with vomiting or diarrhea even while taking medications to prevent these side effects. You can easily become malnourished from vomiting and diarrhea. This can lead to low vitamin B1 levels.

Fedratinib can lower your blood cell counts and affect liver function. Your blood will need to be tested often. Your treatments may be delayed based on the results.

Do not change your dose or stop taking fedratinib without your doctor's advice.

Fedratinib dosing

Usual Adult Dose of Fedratinib for Myelofibrosis: Fedratinib 400 mg orally once a day for patients with a baseline platelet count of 50 x 10⁹/L or greater

Management of thiamine levels and Wernicke's encephalopathy (WE):

• Assess thiamine levels and nutritional status before starting therapy, periodically during therapy, and as indicated.
• Do not initiate this drug in patients with thiamine deficiency; replete thiamine before therapy initiation and ensure thiamine is taken during treatment. 
• If Wernicke's encephalopathy is suspected, immediately discontinue therapy and initiate parenteral thiamine treatment.
• Monitor until symptoms resolve or improve and thiamine levels normalize.

Related/similar drugs

Jakafi, ruxolitinib, momelotinib, Ojjaara, Vonjo, pacritinib

What happens if I miss a dose?

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What to avoid

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Fedratinib may make you feel drowsy or dizzy and make it difficult for you to operate machinery or to drive. Do not drive or operate machinery or perform other hazardous tasks if fedratinib affects you in this way.

What other drugs will affect fedratinib?

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective. 

Other drugs may interact with fedratinib, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using. Especially tell your doctor if you are taking any of the following medicines:

• macrolide antibiotics (clarithromycin, erythromycin)
• antifungal medicines (itraconazole, ketoconazole, posaconazole, voriconazole)
• HIV medicines that contain atazanavir, darunavir, efavirenz, etravirine, indinavir, nelfinavir, nevirapine, ritonavir, saquinavir, or cobicistat
• heart or blood pressure medicines (quinidine, amiodarone, diltiazem, verapamil)
• cimetidine
• mifepristone
• nefazodone
• cannabidiol
• cyclosporine
• phenytoin
• rifampin
• St. John's wort;
• ondansetron
• apalutamide, enzalutamide, mitotane
• sumatriptan
• methadone;
• carbamazepine, oxcarbazepine, phenytoin, primidone
• dexamethasone, prednisone.

Not all possible interactions are listed here. Know the medicines you take. Keep a list of the medicines you take to show your healthcare provider and pharmacist when you get a new medicine.

Fedratinib Package Insert

Review the Inrebic (fedratinib) Package Insert for more detailed information about this medicine. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

Storage

Store fedratinib capsules at room temperature, away from moisture and heat.

Fedratinib ingredients

Fedratinib is only available as the brand name Inrebic.

Active Ingredient: fedratinib.

Inactive ingredients: silicified microcrystalline cellulose and sodium stearyl fumarate. The capsule shell contains gelatin, red iron oxide, titanium dioxide, and white ink.

Who makes fedratinib?

Bristol-Myers Squibb Company makes fedratinib under the brand name Inrebic.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer