Fedratinib Dosage

Medically reviewed by Drugs.com. Last updated on Oct 2, 2023.

Usual Adult Dose for Myelofibrosis

For patients with a baseline platelet count of 50 x 10(9)/L or greater:
400 mg orally once a day

Comments:

• Patients who are taking ruxolitinib: Patients should taper off and discontinue ruxolitinib prior to starting this drug.
• Assess thiamine (vitamin B1) levels and nutritional status prior to starting therapy, periodically during therapy, and as indicated.
• Administration with a high fat meal may reduce the incidence of nausea and vomiting.
• Subsequent doses of this drug are subject to dose adjustments based on the concomitant use of CYP450 3A4 inhibitors, renal function, prior adverse reactions, and/or thiamine levels.

Use: For the treatment of patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF)

Renal Dose Adjustments

Mild to moderate renal dysfunction (CrCl 30 to 89 mL/min): No adjustment recommended.
Severe renal dysfunction (CrCl 15 to 29 mL/min): Reduce the dose to 200 mg/day.

Liver Dose Adjustments

Mild to moderate liver dysfunction: No adjustment recommended.
Severe liver dysfunction (total bilirubin greater than 3 times the upper limit of normal [3 x ULN] and any AST): Not recommended.

Baseline liver function test levels should be obtained before starting treatment; levels should be obtained periodically and when clinically indicated throughout treatment.

Dose Adjustments

DISCONTINUATION OF TREATMENT:

• Treatment should be discontinued in patients unable to tolerate 200 mg/day.

DOSE MODIFICATIONS WITH CONCOMITANT USE OF STRONG CYP450 3A4 INHIBITORS:

• Reduce the dose of this drug when administering with strong CYP450 3A4 inhibitors to 200 mg orally once a day.
• If the strong CYP450 3A4 inhibitor is discontinued, increase the dose of this drug to 300 mg orally once d day during the first 2 weeks after discontinuation of the CYP450 3A4 inhibitor, and then to 400 mg orally once a day thereafter as tolerated.

DOSE MODIFICATIONS FOR HEMATOLOGIC ADVERSE REACTIONS:

• Consider dose reductions in patients who become transfusion-dependent during therapy with this drug.
• Grade 4 Thrombocytopenia or Grade 3 Thrombocytopenia with Active Bleeding: Withhold therapy until resolved to Grade 2 or less or baseline; restart at 100 mg/day below the last given dose.
• Grade 4 Neutropenia: Withhold therapy until resolved to Grade 2 or less or baseline, restart dose at 100 mg/day below the last given dose.

DOSE MODIFICATIONS FOR NONHEMATOLOGIC ADVERSE REACTIONS:

• Grade 3 or Higher Nausea, Vomiting, or Diarrhea Not Responding to Supportive Measures Within 48 Hours: Withhold therapy until resolved to Grade 1 or less or baseline; restart dose at 100 mg/day below the last given dose.
• Grade 3 or Higher ALT, AST, or Bilirubin: Withhold therapy until resolved to Grade 1 or less or baseline; restart dose at 100 mg/day below the last given dose; monitor ALT, AST, and bilirubin (total and direct) more frequently following the dose reduction.
• Discontinue therapy if a Grade 3 or higher elevation recurs
• Grade 3 or Higher Other Nonhematologic Toxicities: Withhold therapy until resolved to Grade 1 or less or baseline; restart dose at 100 mg/day below the last given dose.

MANAGEMENT OF THIAMINE LEVELS AND WERNICKE'S ENCEPHALOPATHY (WE):

• Assess thiamine (vitamin B1) levels and nutritional status prior to starting therapy, periodically during therapy, and as indicated.
• Do not initiate this drug in patients with thiamine deficiency; replete thiamine prior to therapy initiation and during therapy if thiamine levels are low.
• If WE is suspected, immediately discontinue therapy and initiate parenteral thiamine treatment.
• Monitor until symptoms resolve or improve and thiamine levels normalize.

Precautions

US BOXED WARNINGS:
ENCEPHALOPATHY INCLUDING WERNICKE'S:

• Serious and fatal encephalopathy, including Wernicke's, occurred in patients treated with this drug.
• Wernicke's encephalopathy is a neurologic emergency.

Recommendations:

• Thiamine levels should be assessed in all patients prior to starting treatment, and then should be assessed periodically during treatment, as clinically indicated.
• This drug should not be started in patients with thiamine deficiency; thiamine should be repleted prior to initiating treatment.
• Treatment should be immediately discontinued and parenteral thiamine initiated if encephalopathy is suspected.
• Patients should be monitored until symptoms resolve and/or thiamine levels resolve.

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug may be taken with or without food.
• If a dose is missed, the next scheduled dose should be taken the following day.
• Patients taking ruxolitinib before initiation of this drug should taper and discontinue according to the ruxolitinib prescribing information.

Storage requirements:

• Store below 86F (30C).

Monitoring:
Levels of the following should be obtained prior to initiation, periodically during therapy, and as indicated:

• GASTROINTESTINAL: Amylase and lipase levels
• GENITOURINARY: Creatinine
• HEMATOLOGIC: Complete blood count with platelets
• HEPATIC: Liver function tests
• METABOLIC: Thiamine (Vitamin B1) levels
• RENAL: BUN

Patient advice:

• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.

Further information

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

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