- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of fedratinib hydrochloride.
Treatment of disease-related splenomegaly in myelofibrosis
Treatment of disease-related splenomegaly or symptoms in adults with primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis who are Janus Associated Kinase (JAK) inhibitor naive or have been treated with ruxolitinib.
400mg once daily.
Patients with Renal Impairment
Severe renal impairment (Creatinine clearance 15ml/minute to 29ml/minute)
Reduce dose to 200mg once daily.
Additional Dosage Information
Grade 3 thrombocytopenia with active bleeding (platelet count less than 50 x 10 to the power 9/L) or Grade 4 thrombocytopenia (platelet count less than 25 x 10 to the power 9/L): Interrupt treatment until resolved to less than or equal to Grade 2 (platelet count less than 75 x 10 to the power 9/L) or baseline. Upon resolution, restart dose at 100mg below the last dose.
Grade 4 neutropenia (absolute neutrophil count less than 0.5 x 10 to the power 9/L: Interrupt treatment until resolved to less than or equal to Grade 2 (absolute neutrophil count less than 1.5 x 10 to the power 9/L) or baseline. Upon resolution, restart dose at 100mg below the last dose. Use of granulocyte growth factor may be considered.
Grade 3 and higher anaemia, transfusion indicated (haemoglobin level less than 8g/dL): Interrupt treatment until resolved to less than or equal to Grade 2 (haemoglobin level less than 10g/dL) or baseline. Upon resolution, restart dose at 100mg below the last dose.
Recurrence of Grade 4 haematological toxicity: Consider discontinuing treatment.
Grade 3 or greater nausea, vomiting or diarrhoea not responding to supportive measures within 48 hours: Interrupt treatment until resolved to less than or equal to Grade 1 or baseline. Upon resolution, restart dose at 100mg below the last dose.
Grade 3 or greater AST/ALT (greater than 5 times ULN to 20 times the upper limit of normal (ULN)) or bilirubin (greater than 3 times ULN to 10 times ULN): Interrupt treatment until resolved to less than or equal to Grade 1 (AST/ALT greater than ULN to 3 times ULN) or bilirubin (greater than ULN to 1.5 times ULN) or baseline. Upon resolution, restart dose at 100mg below the last dose. Monitor ALT/AST and bilirubin every 2 weeks and for at least 3 months following the dose reduction. If re-occurrence of a Grade 3 or higher elevation, discontinue treatment.
Grade 3 or greater amylase/lipase (greater than 2 times ULN to 5 times ULN): Interrupt treatment until resolved to Grade 1 (greater than ULN to 1.5 times ULN) or baseline. Upon resolution, restart dose at 100mg below the last dose.
Grade 3 or greater other non-haematological toxicities: Interrupt treatment until resolved to less than or equal to Grade 1 or baseline. Upon resolution, restart dose at 100mg below the last dose.
Management of thiamine levels and Wernicke's encephalopathy (WE)
Thiamine levels less than normal range (74nanomole/L to 222nanomole/L) but greater than or equal to 30nmol/L without signs and symptoms of WE: Interrupt treatment. Treat with 100mg oral thiamine until thiamine levels are resolved to normal range. Upon resolution, consider re-starting fedratinib treatment.
Thiamine levels less than 30nanomole/L without signs and symptoms of WE: Interrupt treatment. Treat with parenteral thiamine until thiamine levels are resolved to normal range. Upon resolution, consider re-starting fedratinib treatment.
For signs and symptoms of WE regardless of thiamine levels: Discontinue treatment. Immediately administer parenteral thiamine.
Concomitant administration of fedratinib with strong CYP3A4 inhibitors increases fedratinib exposure. If concomitant use of fedratinib and strong CYP3A4 cannot be avoid, the dose of fedratinib should be reduced to 200mg.
Other dose modifications
Treatment should be discontinued in patients who are unable to tolerate a dose of 200mg daily.
If the adverse reaction due to fedratinib that resulted in dose reduction is controlled and toxicity is resolved for at least 28 days, then the dose may be re-escalated to one dose level higher per month back up to the original dose level.
Dose re-escalation should not be performed if the dose reduction was due to a Grade 4 non-haematological toxicity, greater than or equal to Grade 3 ALT, AST or total bilirubin elevation, or reoccurence of a Grade 4 haematologic toxicity.
Children under 18 years
Neutrophil count below 1.0 x 10 to the power of 9 / L
Platelet count below 50 x 10 to the power of 9 / L
Severe hepatic impairment
Precautions and Warnings
Haemoglobin concentration below 10g/dL
Patients over 75 years
Platelet count below 100 x 10 to the power of 9 / L at baseline
Renal impairment - creatinine clearance 15-29ml/minute
Monitor patients at risk of thiamine deficiency for signs of encephalopathy
Reduce dose in patients with severe renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Take with food - particularly high fat food
Correct anaemia with transfusions before and during treatment
Monitor haemoglobin prior to initiating therapy and periodically thereafter
Monitor hepatic function before, monthly for 3 months, then periodically
Monitor platelets before starting and during treatment
Monitor serum amylase and lipase before and regularly during treatment
Monitor serum creatinine prior to and during treatment
Monitor thiamine levels prior to initiating treatment and during treatment
Monitor AST, ALT and total bilirubin every 2 weeks for first 3 months
Monitor blood urea nitrogen (BUN)
Monitor full blood count regularly
Advise patient to report headaches, seizures, confusion, visual disturbance
Consider discontinuation if encephalopathy is suspected
Discontinue treatment and initiate thiamine if encephalopathy is suspected
Prophylactic antiemetic recommended before each dose
Suspend/reduce dose if grade 3 diarrhoea despite anti-diahorreal treatment
Suspend/reduce dose if grade 3 nausea despite anti-emetic treatment
Consider dose reduction if grade 3 or greater elevations of amylase/lipase
Discontinue if AST or ALT level exceeds 5x ULN and persists
Discontinue if grade 3 or greater elevation in lipase or amylase occurs
Discontinue if grade 4 haematological toxicity recurs
Interrupt if haemoglobin falls below 8 g/dL
Interrupt if thiamine levels < 74 nanomole/L without signs of WE
Interrupt therapy if elevations in bilirubin of > 3 x ULN occur
Interrupt therapy if severe non-haematological reaction occurs
Interrupt treatment if ALT or AST > 5 x ULN
Suspend if grade 3/ intolerable gastrointestinal toxicity despite treatment
Suspend treatment and reduce dose if grade 4 neutropenia occurs
Suspend treatment and/or reduce dose if grade 4 thrombocytopenia
Suspend treatment if grade 3 or greater elevations in lipase or amylase
Suspend treatment if grade 3 vomiting unresponsive to antiemetic occurs
Suspend treatment/reduce dose for grade 3 thrombocytopenia with bleeding
Advise patient to avoid grapefruit products
Female: Contraception required during and for 1 month after treatment
Breastfeeding: Do not breastfeed during & for 1 month after treatment
Advise patient of risk of bleeding
Encephalopathy including Wernicke's encephalopathy
Encephalopathy including Wernicke's encephalopathy has been reported in some patients treated with this agent. If patients present with symptoms indicating WE such as ataxia, altered mental state, ophthalmoplegia, confusion and memory impairment, a full evaluation including neurological exam, assessment of thiamine levels and an MRI should be performed. If encephalopathy is suspected, treatment should be discontinued immediately and parenteral thiamine should be initiated.
If a dose is missed the next scheduled dose should be taken the following day.
Pregnancy and Lactation
Fedratinib is contraindicated during pregnancy.
The manufacturer recommends that fedratinib is contraindicated during pregnancy. There is no data in the use in pregnant women, however animal studies have shown reproductive toxicity. Based on its mechanism of action, fedratinib may cause foetal harm.
Fedratinib is contraindicated during breastfeeding.
The manufacturer recommends that women should not breastfeed during treatment with fedratinib and for at least 1 month after the last dose. It is unknown whether fedratinib or its metabolites are excreted in human milk and therefore a risk to the infant cannot be excluded.
Alanine aminotransferase increased
Aspartate aminotransferase increased
Elevated amylase levels
Elevated serum lipase
Serum creatinine increased
Urinary tract infections
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: October 2021
Summary of Product Characteristics: Inrebic 100 mg hard capsules. Celgene Ltd. Revised September 2021.
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.