fedratinib (Rx)

Brand and Other Names:Inrebic

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 100mg

Myelofibrosis

Indicated for adults with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF)

Baseline platelet count ≥50 x 109/L: 400 mg PO qDay

Dosage Modifications

Discontinue treatment if unable to tolerate 200 mg qDay

Coadministration of strong CYP3A4 inhibitors

  • Reduce fedratinib dose to 200 mg qDay
  • If strong CYP3A4 inhibitor is discontinued, increase fedratinib dose to 300 mg qDay during the first 2 weeks after discontinuing the CYP3A4 inhibitor, and then to 400 mg qDay thereafter as tolerated

Dual CYP3A4 and CYP2C19 inhibitors

  • Requires more intensive safety monitoring and, if necessary, dose modifications based on adverse reactions

Hematologic adverse reactions

  • Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding, or Grade 4 neutropenia
    • Interrupt dose until resolved to Grade ≤2 or baseline
    • Restart at 100 mg qDay below the last given dose
    • Consider dose reduction in patients who become transfusion-dependent during treatment

Nausea, vomiting, diarrhea

  • Grade ≥3 nausea, vomiting, diarrhea nonresponsive to supportive measure after 48 hr: Interrupt dose until resolved to Grade ≤1 or baseline
  • Restart at 100 mg qDay below the last given dose

Hepatoxicity

  • Grade ≥3 ALT, AST, bilirubin: Interrupt dose until resolved to Grade ≤1 or baseline
  • Restart at 100 mg qDay below the last given dose
  • Closely monitor ALT, AST, and bilirubin after dose reduction
  • If Grade ≥3 recurs, discontinue treatment

Other nonhematologic toxicities

  • Grade ≥3: Interrupt dose until resolved to Grade ≤2 or baseline
  • Restart at 100 mg qDay below the last given dose

Renal impairment

  • Mild-to-moderate (CrCl 30 to <90 mL/min): No dosage adjustment necessary; patients with preexisting moderate renal impairment require close monitoring and dosage modifications based on adverse reactions if necessary
  • Severe (CrCl 15 to <30 mL/min): Reduce to 200 mg qDay

Hepatic impairment

  • Mild-to-moderate (total bilirubin ≤3x ULN and any AST): No dosage adjustment necessary
  • Severe (total bilirubin >3x ULN and any AST): Avoid use; pharmacokinetics not evaluated

Dosing Considerations

Patients treated with ruxolitinib before initiating fedratinib must taper and discontinue according to the ruxolitinib prescribing information

Monitor parameters

  • Monitor the following before starting treatment, periodically during treatment, and as clinically indicated
    • Thiamine (vitamin B-1) level
    • Complete blood cell count
    • Creatinine and BUN
    • Hepatic panel
    • Amylase and lipase

Management of thiamine levels and Wernicke encephalopathy

  • Assess thiamine levels and nutritional status before starting treatment, periodically during treatment, and as clinically indicated
  • Do not start in patients with thiamine deficiency; replete thiamine before initiating and during treatment if thiamine levels are low
  • If Wernicke encephalopathy is suspected, immediately discontinue treatment and initiate parenteral thiamine treatment
  • Monitor until symptoms resolve or improve and thiamine levels normalize

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and fedratinib

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            Contraindicated (2)

            • lonafarnib

              fedratinib will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

            • mavacamten

              fedratinib will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            Serious - Use Alternative (117)

            • amiodarone

              amiodarone will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • amobarbital

              amobarbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • apalutamide

              apalutamide will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • apomorphine

              apomorphine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • aprepitant

              aprepitant will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • armodafinil

              armodafinil will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a moderate CYP3A4 inducer with fedratinib has not been studied.

            • atazanavir

              atazanavir will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • avapritinib

              fedratinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

            • azelastine

              azelastine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • bexarotene

              bexarotene will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a moderate CYP3A4 inducer with fedratinib has not been studied.

            • bortezomib

              bortezomib will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • bosentan

              bosentan will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • brigatinib

              brigatinib will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a moderate CYP3A4 inducer with fedratinib has not been studied.

            • butabarbital

              butabarbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • butalbital

              butalbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • carbamazepine

              carbamazepine will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • ceritinib

              ceritinib will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • chloramphenicol

              chloramphenicol will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

              chloramphenicol will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • cimetidine

              cimetidine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • clarithromycin

              clarithromycin will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • clobazam

              clobazam will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a moderate CYP3A4 inducer with fedratinib has not been studied.

            • clozapine

              clozapine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • cobicistat

              cobicistat will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • conivaptan

              conivaptan will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • dabrafenib

              dabrafenib will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • darunavir

              darunavir will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • dexlansoprazole

              dexlansoprazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • diazepam

              diazepam will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • drospirenone

              drospirenone will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • efavirenz

              efavirenz will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • elacestrant

              fedratinib will increase the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • encorafenib

              encorafenib will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a moderate CYP3A4 inducer with fedratinib has not been studied.

            • enzalutamide

              enzalutamide will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a moderate CYP3A4 inducer with fedratinib has not been studied.

            • ethinylestradiol

              ethinylestradiol will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • etrasimod

              etrasimod, fedratinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod.

            • etravirine

              etravirine will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • felodipine

              felodipine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • fexinidazole

              fexinidazole will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fluconazole

              fluconazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • fluoxetine

              fluoxetine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • fluvoxamine

              fluvoxamine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadminitration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib not studied

            • fosaprepitant

              fosaprepitant will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • grapefruit

              grapefruit will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • idelalisib

              idelalisib will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • imatinib

              imatinib will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • indinavir

              indinavir will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

              indinavir will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • infigratinib

              fedratinib will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • isoniazid

              isoniazid will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

              isoniazid will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • itraconazole

              itraconazole will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • ivosidenib

              ivosidenib will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • ketoconazole

              ketoconazole will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

              ketoconazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • lansoprazole

              lansoprazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • larotrectinib

              larotrectinib will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • lemborexant

              fedratinib will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

            • lenvatinib

              lenvatinib will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • levoketoconazole

              levoketoconazole will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

              levoketoconazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • lopinavir

              lopinavir will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • lorlatinib

              lorlatinib will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • losartan

              losartan will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • lurbinectedin

              fedratinib will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • mestranol

              mestranol will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • methimazole

              methimazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • methoxsalen

              methoxsalen will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • mifepristone

              mifepristone will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • mitotane

              mitotane will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • mobocertinib

              fedratinib will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.

            • modafinil

              modafinil will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • nafcillin

              nafcillin will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • nefazodone

              nefazodone will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • nelfinavir

              nelfinavir will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

              nelfinavir will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • nicardipine

              nicardipine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • nirogacestat

              fedratinib will increase the level or effect of nirogacestat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • olanzapine

              olanzapine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • omaveloxolone

              fedratinib will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 100 mg/day. Closely monitor for adverse effects. If adverse effects emerge, further reduce to 50 mg/day.

            • omeprazole

              omeprazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • orphenadrine

              orphenadrine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • pacritinib

              fedratinib will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • paroxetine

              paroxetine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • pemigatinib

              fedratinib will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

            • pentamidine

              pentamidine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • pentobarbital

              pentobarbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • pexidartinib

              fedratinib will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

            • phenobarbital

              phenobarbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • phenytoin

              phenytoin will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • pimozide

              pimozide will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • posaconazole

              posaconazole will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • primidone

              primidone will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • progesterone intravaginal gel

              progesterone intravaginal gel will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • progesterone micronized

              progesterone micronized will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • progesterone, natural

              progesterone, natural will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • propofol

              propofol will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • rabeprazole

              rabeprazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • repotrectinib

              fedratinib will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.

            • rifabutin

              rifabutin will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • rifampin

              rifampin will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • rifapentine

              rifapentine will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • ritonavir

              ritonavir will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

              ritonavir will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • saquinavir

              saquinavir will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

              saquinavir will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • secobarbital

              secobarbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • selegiline

              selegiline will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • selegiline transdermal

              selegiline transdermal will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • selumetinib

              fedratinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

            • sertraline

              sertraline will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • St John's Wort

              St John's Wort will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

            • stiripentol

              stiripentol will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • tazemetostat

              fedratinib will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce tazemetostat current dose (see drug monograph Dosage Modifications).

            • telotristat ethyl

              telotristat ethyl will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a moderate CYP3A4 inducer with fedratinib has not been studied.

            • tipranavir

              tipranavir will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

            • tranylcypromine

              tranylcypromine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • tucatinib

              tucatinib will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • valproic acid

              valproic acid will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • voriconazole

              voriconazole will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

              voriconazole will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • voxelotor

              voxelotor will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            • zafirlukast

              zafirlukast will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            Monitor Closely (359)

            • abemaciclib

              fedratinib will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • acalabrutinib

              fedratinib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ado-trastuzumab emtansine

              fedratinib will increase the level or effect of ado-trastuzumab emtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • alfentanil

              fedratinib will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • alfuzosin

              fedratinib will increase the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • alpelisib

              fedratinib will increase the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • alprazolam

              fedratinib will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ambrisentan

              fedratinib will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • amiodarone

              fedratinib will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of amiodarone by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • amitriptyline

              fedratinib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • amlodipine

              fedratinib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • amoxapine

              fedratinib will increase the level or effect of amoxapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • apalutamide

              fedratinib will increase the level or effect of apalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • apixaban

              fedratinib will increase the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • apremilast

              fedratinib will increase the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • aprepitant

              fedratinib will increase the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • aripiprazole

              fedratinib will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • armodafinil

              fedratinib will increase the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • atazanavir

              fedratinib will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • atogepant

              fedratinib will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atomoxetine

              fedratinib will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • atorvastatin

              fedratinib will increase the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • avanafil

              fedratinib will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • axitinib

              fedratinib will increase the level or effect of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • bedaquiline

              fedratinib will increase the level or effect of bedaquiline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • belzutifan

              belzutifan will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • benzhydrocodone/acetaminophen

              fedratinib will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • benzphetamine

              fedratinib will increase the level or effect of benzphetamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • bortezomib

              fedratinib will increase the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of bortezomib by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • bosentan

              fedratinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • bosutinib

              fedratinib will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • brentuximab vedotin

              fedratinib will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • brexpiprazole

              fedratinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • brigatinib

              fedratinib will increase the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • bromocriptine

              fedratinib will increase the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • budesonide

              fedratinib will increase the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • buprenorphine

              fedratinib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • buprenorphine subdermal implant

              fedratinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • buprenorphine transdermal

              fedratinib will increase the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • buspirone

              fedratinib will increase the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • busulfan

              fedratinib will increase the level or effect of busulfan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • cabozantinib

              fedratinib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • calcifediol

              fedratinib will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • calcitriol

              fedratinib will increase the level or effect of calcitriol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • capivasertib

              fedratinib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.

            • captopril

              fedratinib will increase the level or effect of captopril by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • carbamazepine

              fedratinib will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • cariprazine

              fedratinib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • carisoprodol

              fedratinib will increase the level or effect of carisoprodol by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • carvedilol

              fedratinib will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • cenobamate

              cenobamate will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • ceritinib

              fedratinib will increase the level or effect of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • chlordiazepoxide

              fedratinib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • chloroquine

              fedratinib will increase the level or effect of chloroquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of chloroquine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • chlorpheniramine

              fedratinib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • chlorpromazine

              fedratinib will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • ciclesonide inhaled

              fedratinib will increase the level or effect of ciclesonide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ciclesonide intranasal

              fedratinib will increase the level or effect of ciclesonide intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • cilostazol

              fedratinib will increase the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • cinacalcet

              fedratinib will increase the level or effect of cinacalcet by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • citalopram

              fedratinib will increase the level or effect of citalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

              fedratinib will increase the level or effect of citalopram by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • clarithromycin

              fedratinib will increase the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • clobazam

              fedratinib will increase the level or effect of clobazam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • clomipramine

              fedratinib will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

              fedratinib will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • clorazepate

              fedratinib will increase the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • cobicistat

              fedratinib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • cobimetinib

              fedratinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • cocaine topical

              fedratinib will increase the level or effect of cocaine topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • codeine

              fedratinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • colchicine

              fedratinib will increase the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • conivaptan

              fedratinib will increase the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • conjugated estrogens

              fedratinib will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • copanlisib

              fedratinib will increase the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • crizotinib

              fedratinib will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • cyclophosphamide

              fedratinib will increase the level or effect of cyclophosphamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • cyclosporine

              fedratinib will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • dabrafenib

              fedratinib will increase the level or effect of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • dantrolene

              fedratinib will increase the level or effect of dantrolene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • dapsone

              fedratinib will increase the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • daridorexant

              fedratinib will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.

            • darifenacin

              fedratinib will increase the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • darolutamide

              fedratinib will increase the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • darunavir

              fedratinib will increase the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • dasatinib

              fedratinib will increase the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • deflazacort

              fedratinib will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • desipramine

              fedratinib will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • deutetrabenazine

              fedratinib will increase the level or effect of deutetrabenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • dexamethasone

              fedratinib will increase the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • dexlansoprazole

              fedratinib will increase the level or effect of dexlansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of dexlansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • diazepam

              fedratinib will increase the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • diazepam intranasal

              fedratinib will increase the level or effect of diazepam intranasal by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Strong or moderate CYP2C19 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

              fedratinib will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • dihydroergotamine

              fedratinib will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • dihydroergotamine inhaled

              fedratinib will increase the level or effect of dihydroergotamine inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • diltiazem

              fedratinib will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • disopyramide

              fedratinib will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • docetaxel

              fedratinib will increase the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • doravirine

              fedratinib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • doxepin

              fedratinib will increase the level or effect of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • doxepin cream

              fedratinib will increase the level or effect of doxepin cream by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • doxorubicin

              fedratinib will increase the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of doxorubicin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • doxorubicin liposomal

              fedratinib will increase the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of doxorubicin liposomal by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • dronabinol

              fedratinib will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • dronedarone

              fedratinib will increase the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • duloxetine

              fedratinib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • duvelisib

              fedratinib will increase the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • efavirenz

              fedratinib will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • elagolix

              fedratinib will increase the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              elagolix decreases levels of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • elbasvir/grazoprevir

              fedratinib will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • eletriptan

              fedratinib will increase the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • eliglustat

              fedratinib will increase the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • encorafenib

              fedratinib will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • entrectinib

              fedratinib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • enzalutamide

              fedratinib will increase the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • eplerenone

              fedratinib will increase the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ergoloid mesylates

              fedratinib will increase the level or effect of ergoloid mesylates by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ergotamine

              fedratinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • erlotinib

              fedratinib will increase the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • erythromycin base

              fedratinib will increase the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • erythromycin ethylsuccinate

              fedratinib will increase the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • erythromycin lactobionate

              fedratinib will increase the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • erythromycin stearate

              fedratinib will increase the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • escitalopram

              fedratinib will increase the level or effect of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • esomeprazole

              fedratinib will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • estradiol

              fedratinib will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • estrogens conjugated synthetic

              fedratinib will increase the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • estrogens esterified

              fedratinib will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • estropipate

              fedratinib will increase the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • eszopiclone

              fedratinib will increase the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ethinylestradiol

              fedratinib will increase the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • etoposide

              fedratinib will increase the level or effect of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • etravirine

              fedratinib will increase the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • everolimus

              fedratinib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • exemestane

              fedratinib will increase the level or effect of exemestane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • felbamate

              fedratinib will increase the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenofibrate

              fedratinib will increase the level or effect of fenofibrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenofibrate micronized

              fedratinib will increase the level or effect of fenofibrate micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenofibric acid

              fedratinib will increase the level or effect of fenofibric acid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fentanyl

              fedratinib will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fentanyl intranasal

              fedratinib will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fentanyl transdermal

              fedratinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fentanyl transmucosal

              fedratinib will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • finerenone

              fedratinib will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • flecainide

              fedratinib will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • flibanserin

              fedratinib will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of flibanserin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • flunisolide intranasal

              fedratinib will increase the level or effect of flunisolide intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fluoxetine

              fedratinib will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • fluphenazine

              fedratinib will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • flurazepam

              fedratinib will increase the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • flutamide

              fedratinib will increase the level or effect of flutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fluticasone furoate

              fedratinib will increase the level or effect of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fluticasone inhaled

              fedratinib will increase the level or effect of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fluticasone intranasal

              fedratinib will increase the level or effect of fluticasone intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fluvoxamine

              fedratinib will increase the level or effect of fluvoxamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of CYP2D6 substrates as necessary

            • fosamprenavir

              fedratinib will increase the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fosaprepitant

              fedratinib will increase the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fosphenytoin

              fedratinib will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • fostamatinib

              fedratinib will increase the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • gefitinib

              fedratinib will increase the level or effect of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • gepirone

              fedratinib will increase the level or effect of gepirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce gepirone dose by 50% when used concomitantly with a moderate CYP3A4 inhibitor.

            • glasdegib

              fedratinib will increase the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • glecaprevir/pibrentasvir

              fedratinib will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • guanfacine

              fedratinib will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • haloperidol

              fedratinib will increase the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • hydrocodone

              fedratinib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • hydroxyprogesterone caproate (DSC)

              fedratinib will increase the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ibrutinib

              fedratinib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • idelalisib

              fedratinib will increase the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ifosfamide

              fedratinib will increase the level or effect of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of ifosfamide by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • iloperidone

              fedratinib will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • imatinib

              fedratinib will increase the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • imipramine

              fedratinib will increase the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

              fedratinib will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • indinavir

              fedratinib will increase the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • irinotecan

              fedratinib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • irinotecan liposomal

              fedratinib will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • isavuconazonium sulfate

              fedratinib will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isosorbide dinitrate

              fedratinib will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • isosorbide mononitrate

              fedratinib will increase the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • isradipine

              fedratinib will increase the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • istradefylline

              istradefylline will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

              fedratinib will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ivacaftor

              fedratinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • ivosidenib

              fedratinib will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ixabepilone

              fedratinib will increase the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ixazomib

              fedratinib will increase the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ketamine

              fedratinib will increase the level or effect of ketamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • lacosamide

              fedratinib will increase the level or effect of lacosamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • lansoprazole

              fedratinib will increase the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • lapatinib

              fedratinib will increase the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • larotrectinib

              fedratinib will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • lefamulin

              fedratinib will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.

            • lenacapavir

              lenacapavir will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • levamlodipine

              fedratinib will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

            • levomilnacipran

              fedratinib will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • levonorgestrel oral

              fedratinib will increase the level or effect of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • linagliptin

              fedratinib will increase the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • lomitapide

              fedratinib will increase the level or effect of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • lumateperone

              fedratinib will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.

            • lurasidone

              fedratinib will increase the level or effect of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • macimorelin

              fedratinib will increase the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • macitentan

              fedratinib will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • maprotiline

              fedratinib will increase the level or effect of maprotiline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • maraviroc

              fedratinib will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • marijuana

              fedratinib will increase the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • mavacamten

              fedratinib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • medroxyprogesterone

              fedratinib will increase the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • mefloquine

              fedratinib will increase the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • mestranol

              fedratinib will increase the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • metaxalone

              fedratinib will increase the level or effect of metaxalone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • methadone

              fedratinib will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • methamphetamine

              fedratinib will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • methsuximide

              fedratinib will increase the level or effect of methsuximide by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • methylergonovine

              fedratinib will increase the level or effect of methylergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • methylprednisolone

              fedratinib will increase the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • metoprolol

              fedratinib will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • midazolam

              fedratinib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • midostaurin

              fedratinib will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • mifepristone

              fedratinib will increase the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • mirtazapine

              fedratinib will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of mirtazapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • modafinil

              fedratinib will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of modafinil by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • montelukast

              fedratinib will increase the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • naldemedine

              fedratinib will increase the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • naloxegol

              fedratinib will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • nebivolol

              fedratinib will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • nefazodone

              fedratinib will increase the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • nelfinavir

              fedratinib will increase the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of nelfinavir by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • netupitant/palonosetron

              fedratinib will increase the level or effect of netupitant/palonosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • nevirapine

              fedratinib will increase the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • nicardipine

              fedratinib will increase the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • nifedipine

              fedratinib will increase the level or effect of nifedipine by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • nilotinib

              fedratinib will increase the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • nimodipine

              fedratinib will increase the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • norethindrone

              fedratinib will increase the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • norethindrone acetate

              fedratinib will increase the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • nortriptyline

              fedratinib will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • olaparib

              fedratinib will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • oliceridine

              fedratinib will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

              fedratinib will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              fedratinib will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • omeprazole

              fedratinib will increase the level or effect of omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ondansetron

              fedratinib will increase the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • osimertinib

              fedratinib will increase the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ospemifene

              fedratinib will increase the level or effect of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • oxycodone

              fedratinib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • paclitaxel

              fedratinib will increase the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • paclitaxel protein bound

              fedratinib will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • palbociclib

              fedratinib will increase the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • palovarotene

              fedratinib will increase the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of palovarotene, a CYP3A substrate, with moderate CYP3A inhibitors. If unavoidable, reduce palovarotene dose by 50%.

            • panobinostat

              fedratinib will increase the level or effect of panobinostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • paricalcitol

              fedratinib will increase the level or effect of paricalcitol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • paroxetine

              fedratinib will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • pazopanib

              fedratinib will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • pentamidine

              fedratinib will increase the level or effect of pentamidine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • perampanel

              fedratinib will increase the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • perphenazine

              fedratinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • phenobarbital

              fedratinib will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • pimavanserin

              fedratinib will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • pimozide

              fedratinib will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of pimozide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • pitolisant

              fedratinib will increase the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of pitolisant by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • polatuzumab vedotin

              fedratinib will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • pomalidomide

              fedratinib will increase the level or effect of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • praziquantel

              fedratinib will increase the level or effect of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • progesterone intravaginal gel

              fedratinib will increase the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of progesterone intravaginal gel by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • progesterone micronized

              fedratinib will increase the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • progesterone, natural

              fedratinib will increase the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of progesterone, natural by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • promethazine

              fedratinib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • propafenone

              fedratinib will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • propranolol

              fedratinib will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • protriptyline

              fedratinib will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • quazepam

              fedratinib will increase the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • quetiapine

              fedratinib will increase the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • quinidine

              fedratinib will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • quinine

              fedratinib will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • rabeprazole

              fedratinib will increase the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • ranolazine

              fedratinib will increase the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • regorafenib

              fedratinib will increase the level or effect of regorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • repaglinide

              fedratinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ribociclib

              fedratinib will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              ribociclib will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              fedratinib will increase the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • rimegepant

              fedratinib will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid repeating rimegepant dose within 48 hr if coadministered with a moderate CYP3A4 inhibitor.

            • riociguat

              fedratinib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • risperidone

              fedratinib will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • ritonavir

              fedratinib will increase the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of ritonavir by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • rivaroxaban

              fedratinib will increase the level or effect of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • roflumilast

              fedratinib will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • rolapitant

              fedratinib will increase the level or effect of rolapitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • romidepsin

              fedratinib will increase the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ropivacaine

              fedratinib will increase the level or effect of ropivacaine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • rucaparib

              rucaparib will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • ruxolitinib

              fedratinib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ruxolitinib topical

              fedratinib will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • salmeterol

              fedratinib will increase the level or effect of salmeterol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • saquinavir

              fedratinib will increase the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • saxagliptin

              fedratinib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • sertraline

              fedratinib will increase the level or effect of sertraline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

              fedratinib will increase the level or effect of sertraline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • sildenafil

              fedratinib will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • simvastatin

              fedratinib will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • siponimod

              siponimod and fedratinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              fedratinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • sirolimus

              fedratinib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • solifenacin

              fedratinib will increase the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • sonidegib

              fedratinib will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • sorafenib

              fedratinib will increase the level or effect of sorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • sparsentan

              fedratinib will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors.

            • stiripentol

              fedratinib will increase the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of stiripentol by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • sufentanil

              fedratinib will increase the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • sufentanil SL

              fedratinib increases and sufentanil SL decreases affecting hepatic/intestinal enzyme CYP3A4 metabolism. Effect of interaction is not clear, use caution. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary..

            • sunitinib

              fedratinib will increase the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • suvorexant

              fedratinib will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • tacrolimus

              fedratinib will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • tadalafil

              fedratinib will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • tamoxifen

              fedratinib will increase the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of tamoxifen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • tamsulosin

              fedratinib will increase the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • tasimelteon

              fedratinib will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • tazemetostat

              tazemetostat will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • temsirolimus

              fedratinib will increase the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • teniposide

              fedratinib will increase the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • tetracycline

              fedratinib will increase the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • tezacaftor

              fedratinib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • theophylline

              fedratinib will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • thioridazine

              fedratinib will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • tiagabine

              fedratinib will increase the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ticagrelor

              fedratinib will increase the level or effect of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • ticlopidine

              fedratinib will increase the level or effect of ticlopidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • timolol

              fedratinib will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • timolol ophthalmic

              fedratinib will increase the level or effect of timolol ophthalmic by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • tinidazole

              fedratinib will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • tipranavir

              fedratinib will increase the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • tofacitinib

              fedratinib will increase the level or effect of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of tofacitinib by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • tolterodine

              fedratinib will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • toremifene

              fedratinib will increase the level or effect of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • trabectedin

              fedratinib will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • tramadol

              fedratinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • trazodone

              fedratinib will increase the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • triazolam

              fedratinib will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • trimethoprim

              fedratinib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • trimipramine

              fedratinib will increase the level or effect of trimipramine by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of trimipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

              fedratinib will increase the level or effect of trimipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • ublituximab

              ublituximab and fedratinib both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministered

            • ulipristal

              fedratinib will increase the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • umeclidinium bromide/vilanterol inhaled

              fedratinib will increase the level or effect of umeclidinium bromide/vilanterol inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • valbenazine

              fedratinib will increase the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of valbenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • vandetanib

              fedratinib will increase the level or effect of vandetanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • vardenafil

              fedratinib will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Vardenafil dose may need to be reduced if coadministered with moderate or strong CYP3A4 inhibitors

            • velpatasvir

              fedratinib will increase the level or effect of velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • vemurafenib

              fedratinib will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • venetoclax

              fedratinib will increase the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • venlafaxine

              fedratinib will increase the level or effect of venlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of venlafaxine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • verapamil

              fedratinib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • vilanterol/fluticasone furoate inhaled

              fedratinib will increase the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • vilazodone

              fedratinib will increase the level or effect of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • vinblastine

              fedratinib will increase the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • vincristine

              fedratinib will increase the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • vincristine liposomal

              fedratinib will increase the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • vinorelbine

              fedratinib will increase the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • voclosporin

              fedratinib will increase the level or effect of voclosporin by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Reduce voclosporin daily dosage to 15.8 mg PO in AM and 7.9 mg PO in PM.

            • vorapaxar

              fedratinib will increase the level or effect of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • voriconazole

              fedratinib will increase the level or effect of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • vortioxetine

              fedratinib will increase the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of vortioxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • voxilaprevir

              fedratinib will increase the level or effect of voxilaprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • zanubrutinib

              fedratinib will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID to when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.

            • zolpidem

              fedratinib will increase the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • zonisamide

              fedratinib will increase the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            Minor (3)

            • acetazolamide

              acetazolamide will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • anastrozole

              anastrozole will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cyclophosphamide

              cyclophosphamide will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            All grades

            • Diarrhea (66%)
            • Nausea (62%)
            • Anemia (40-74%)
            • Blood creatinine increased (10-59%)
            • Thrombocytopenia (47%)
            • ALT increased (9-43%)
            • AST increased (5-40%)
            • Vomiting (39%)
            • Lipase increased (35%)
            • Hyponatremia (26%)
            • Amylase increased (24%)
            • Neutropenia (23%)
            • Fatigue or asthenia (19%)
            • Muscle spasms (12%)

            Grade 3 or 4

            • Anemia (30-34%)
            • Thrombocytopenia (12%)

            1-10%

            All grades

            • Pain in extremity (10%)
            • Headache (9%)
            • Weight increased (9%)
            • Dizziness (8%)
            • Bone pain (8%)
            • Urinary tract infection (6%)
            • Dysuria (6%)
            • Hypertension (5%)

            Grade 3 or 4

            • Lipase increased (10%)
            • Diarrhea (5%)
            • Fatigue or asthenia (5%)
            • Neutropenia (5%)
            • Hyponatremia (5%)
            • Vomiting (3.1%)
            • Blood creatinine increased (1-3.1%)
            • Hypertension (3%)
            • Amylase increased (2.1%)
            • ALT increased (1%)
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            Warnings

            Encephalopathy

            Serious and fatal encephalopathy, including Wernicke, has occurred

            Wernicke encephalopathy is a neurologic emergency

            Assess thiamine levels in all patients before starting treatment, periodically during treatment, and as clinically indicated

            Do not start in patients with thiamine deficiency; replete thiamine before starting treatment

            If encephalopathy suspected, immediately discontinue treatment and initiate parenteral thiamine

            Monitor until symptoms resolve or improve and thiamine levels normalize

            Contraindications

            None

            Cautions

            Serious cases of encephalopathy, including Wernicke encephalopathy, 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 Grade ≥3

            Grade ≥3 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 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 of 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 prior to 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 increased risk of 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 increased risk of 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 prior to 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 risk of adverse reactions
              • Consider other therapies that do not strongly inhibit CYP3A4
              • If unable to avoid coadministration, reduce fedratinib dose
            • Strong and moderate CYP3A4 inducers
              • Avoid coadministration
              • 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 risk of 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 of adverse reactions of these drugs
              • Monitor for adverse reactions and modify dose of these drugs as necessary
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            Pregnancy & Lactation

            Pregnancy

            No data available on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

            Animal data

            • In animal reproduction studies, oral administration of fedratinib to pregnant rats during organogenesis at doses of 400 mg/day resulted in adverse developmental outcomes
            • Consider the benefits and risks for the mother and possible risks to the fetus when prescribing to a pregnant woman

            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.

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Kinase inhibitor; inhibits Janus-associated kinase-2 (JAK2), which mediates signaling of cytokines and growth factors that are important for hematopoiesis and immune function

            JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation, and subsequent localization of STATs to the nucleus, leading to modulation of gene expression

            Myelofibrosis is a myeloproliferative neoplasm known to be associated with dysregulated JAK signaling

            Absorption

            Peak plasma time: ~3 hr (steady-state)

            Peak plasma concentration: 1,804 ng/mL

            AUC: 26,870 ng⋅hr/mL

            Steady-state reached within 15 days

            Effect of food

            • A low-fat, low-calorie or a high-fat, high-calorie meal increased AUC up to 24% and peak plasma concentration up to 14% of a single 500-mg dose

            Distribution

            Vd (steady-state): 1,770 L

            Protein bound:≥92%

            Metabolism

            Primarily metabolized by CYP3A4, CYP2C19, and flavin-containing monooxygenase 3 (FMO3)

            Fedratinib accounts for ~80% of total circulating drug in plasma after oral administration

            Elimination

            Half-life: ~ 114 hr

            Clearance: 13 L/hr

            Excretion: Feces (77% [23% unchanged]); urine (5% [3% unchanged])

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            Administration

            Oral Administration

            Take orally with or without food

            Administration with a high-fat meal may reduce incidence of nausea and vomiting

            Missed dose

            • Take the next scheduled dose the following day

            Storage

            Store <30ºC (86ºF)

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            • View the formulary and any restrictions for each plan.
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            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.