Fedratinib

Fedratinib is a prescription medicine used for the treatment of intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis in adults.

• Fedratinib is available under the following different brand names: Inrebic

Common side effects of Fedratinib include:

• nausea
• vomiting
• diarrhea
• anemia
• fatigue
• weakness
• muscle spasms
• pain in extremities
• headache
• weight gain
• dizziness
• bone pain
• urinary tract infections
• painful urination

Serious side effects of Fedratinib include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• drowsiness
• confusion
• memory problems
• vision problems
• unusual eye movements
• problems with coordination and muscle movement
• severe or ongoing nausea
• vomiting
• diarrhea (even when you are taking medication to prevent these effects)
• easy bruising
• unusual bleeding
• purple or red spots under the skin
• pale skin
• unusual tiredness
• light-headedness
• shortness of breath
• cold hands and feet
• fever
• mouth sores
• skin sores
• cough

Rare side effects of Fedratinib include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Capsule

• 100 mg

Myelofibrosis

Adult dosage

• Baseline platelets count more than 50 × 109/L: 400 mg orally once a day.

Dosage Considerations – Should be Given as Follows:

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Fedratinib has severe interactions with the following drugs:
  • lonafarnib
  • mavacamten
• Fedratinib has serious interactions with at least 115 other drugs.
• Fedratinib has moderate interactions with at least 356 other drugs.
• Fedratinib has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Fedratinib?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Fedratinib?"

Cautions

• Serious cases of encephalopathy, including Wernicke encephalopathy, were reported in clinical trials
• May cause anemia and thrombocytopenia; manage by dose reduction, interruption, or transfusion
• Elevations of ALT and AST during the randomized treatment period occurred; monitor hepatic function at baseline and periodically during treatment; dose reduction may be needed for hepatoxicity of grade 3 or more
• Grade 3 or more of amylase and/or lipase elevations developed; one patient developed pancreatitis in the clinical development program, which resolved once treatment was discontinued
• Gastrointestinal toxicities
  • Gastrointestinal toxicities are the most frequent adverse reactions reported
  • Manage by dose reduction or interruption if the patient develops severe diarrhea, nausea, or vomiting
  • Consider prophylaxis with antiemetics and treatment with antidiarrheals
• Major adverse cardiac events (MACE)
  • Another JAK-inhibitor has increased the risk for MACE, including cardiovascular death, myocardial infarction, and stroke (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which this drug is not indicated
  • Consider the benefits and risks for individual patients before initiating or continuing therapy, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors
  • Patients should be informed about symptoms of serious cardiovascular events and steps to take if they occur
• Thrombosis
  • Another JAK inhibitor has an increased risk for thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which this drug is not indicated; in patients with MF treated with this drug in clinical trials, the rates of thromboembolic events were similar in drug-treated and placebo-treated patients
  • Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately
• Secondary malignancies
  • Another JAK inhibitor has an increased risk for lymphoma and other malignancies excluding non-melanoma skin cancer (NMSC) (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which this drug is not indicated; patients who are current or past smokers are at additional increased risk
  • Consider benefits and risks for the individual patient before initiating or continuing therapy, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers
• Drug interaction overview
  • Fedratinib is a CYP3A4 and CYP2C19 substrate; a moderate CYP3A4, CYP2C19, or CYP2D6 inhibitor
  • In vitro studies showed that Fedratinib is a P-gp substrate; it also inhibits P-gp, BCRP, OATP1B1, OATP1B3, organic cation transporter (OCT)2, multidrug and toxin extrusion (MATE) protein 1, and MATE-2K
• Strong CYP3A4 inhibitors
  • Coadministration with a strong CYP3A4 inhibitor increases Fedratinib exposure; increased exposure may increase the risk for adverse reactions
  • Consider other therapies that do not strongly inhibit CYP3A4
  • If unable to avoid coadministration, reduce the Fedratinib dose
• Strong and moderate CYP3A4 inducers
  • Avoid coadministration
  • The effect of concomitant use with a strong or moderate CYP3A4 inducer has not been studied
• Dual CYP3A4 and CYP2C19 inhibitors
  • Avoid coadministration
  • Coadministration with a dual CYP3A4 and CYP2C19 inhibitor increases exposure to this drug; increased exposure may increase the risk for adverse reactions
  • Patients taking concomitant dual CYP3A4 and CYP2C19 inhibitors require more intensive safety monitoring and, if necessary, dose modifications based on adverse reactions
• CYP3A4, CYP2C19, or CYP2D6 substrates
  • Coadministration with CYP3A4, CYP2C19, or CYP2D6 substrates increases the concentrations of these drugs, which may increase the risk for adverse reactions to these drugs
  • Monitor for adverse reactions and modify the dose of these drugs as necessary

Pregnancy and Lactation

• No data are available on use in pregnant women to evaluate for a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Lactation
  • There are no data on the presence of Fedratinib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production
  • Owing to the potential for serious adverse reactions in a breastfed child, advise patients not to breastfeed during treatment and for at least 1 month after the last dose