Oral formulations of glasdegib.
Treatment of adults with newly diagnosed de novo or secondary acute myeloid leukaemia (AML) who are not candidates for standard induction chemotherapy, in combination with low-dose cytarabine.
100mg once daily.
Additional Dosage Information
If a dose reduction is necessary based on individual safety and tolerability, then the dose should be reduced to 50mg once daily.
Dose adjustments due to adverse reactions
QT interval 480msec to 500msec: Review and adjust concomitant medicinal products with known QT prolonging effects.
QT interval greater than 500msec: Review and adjust concomitant medicinal products with known QT prolonging effects. Interrupt glasdegib treatment. Resume glasdegib at a reduced dose of 50mg once daily once the QT interval returns to within 30msec of baseline or less than or equal to 480msec. Consider re-escalating the dose of glasdegib to 100mg once daily if an alternative aetiology for the QT prolongation can be identified.
Corrected QT interval prolongation and life-threatening arrhythmia: Discontinue permanently.
Serum creatine kinase (CK) elevation
Grade 1 CK elevation (serum CK ULN to 2.5 x ULN): Continue at same dose and monitor CK levels until resolution to baseline and then monthly. Monitor muscle symptoms for changes until resolution to baseline. Check serum creatinine regularly and ensure patient is adequately hydrated.
Grade 2 CK elevation without renal impairment (serum creatinine less than or equal to ULN and CK between 2.5 to 5 x ULN): Interrupt glasdegib and monitor CK levels weekly until resolution to baseline. Monitor muscle symptoms for changes until resolution to baseline. Upon resolution, continue at same dose and monitor CK levels monthly. Check serum creatinine regularly and ensure patient is adequately hydrated. If symptoms re-occur, interrupt treatment until resolution to baseline. Resume treatment at 50mg daily, if symptoms persist, consider discontinuing treatment.
Grade 3 or 4 CK elevation without renal impairment (serum creatinine less than or equal to ULN and CK greater than 5 x ULN): Interrupt glasdegib and monitor CK levels weekly until resolution to baseline. Monitor muscle symptoms for changes until resolution to baseline. Check serum creatinine regularly and ensure patient is adequately hydrated. Upon resolution of CK to baseline, consider resuming glasdegib at 50mg daily. Monitor CK levels weekly for 2 months after re-administration of glasdegib and monthly thereafter.
Grade 2, 3 or 4 CK elevation with renal impairment (serum creatinine greater than ULN): Interrupt glasdegib and ensure patient is adequately hydrated. Evaluate other secondary causes of renal impairment. Monitor CK and serum creatinine levels weekly until resolution to baseline. Monitor muscle symptoms for changes until resolution to baseline. If CK and serum creatinine levels return to baseline consider resuming glasdegib at 50mg daily and measure CK levels weekly for 2 months and monthly thereafter, otherwise discontinue treatment permanently.
Platelets less than 10 x 10 to the power 9/L for more than 42 days in the absence of disease: Discontinue glasdegib and low-dose cytarabine permanently.
Neutrophil count less than 0.5 x 10 to the power 9/L for more than 42 days in the absence of disease: Discontinue glasdegib and low-dose cytarabine permanently.
Grade 3 non-haematological toxicity: Interrupt glasdegib and/or low-dose cytarabine until symptoms improve to grade 1 or lower, or return to baseline. Resume glasdegib at the same dose level, or at a reduced dose of 50mg. Resume low-dose cyatarabine at the same dose level, or at a reduced dose of 15mg or 10mg. If toxicity recurs, discontinue glasdegib and/or low-dose cytarabine.
Grade 4 non-haematological toxicity: Withhold glasdegib until symptoms improve to grade 1 or lower, or return to baseline. Resume glasdegib at a dose of 50mg or discontinue treatment at the discretion of the prescriber.
Dose modification for concomitant use with moderate CYP3A4 inducers
Concomitant use of glasdegib with moderate CYP3A4 inducers should be avoided. If the concomitant use of glasdegib and CYP3A4 cannot be avoided, then the dose of glasdegib should be increased as below.
Current dose 100mg once daily: Adjusted dose 200mg once daily
Current dose 50mg once daily: Adjusted 100mg once daily
After the moderate CYP3A4 inducer has been discontinued for 7 days, the glasdegib dose taken before initiating the moderate CYP3A4 inducer should be resumed.
If a dose is missed by more than 10 hours, then the missed dose should not be taken and the next dose should be taken at the next scheduled time.
Pregnancy and Lactation
Glasdegib is contraindicated during pregnancy.
The manufacturer recommends that glasdegib should not be used during pregnancy and in women of childbearing potential not using contraception. Based on animal embryo-foetal developmental toxicity studies and the mechanism of action of glasdegib, glasdegib can cause embryo-foetal death or severe birth defects when used in pregnant women.
Glasdegib is contraindicated during breastfeeding.
The manufacturer states that breastfeeding is not recommended during treatment with glasdegib and for at least one week after the last dose. The presence and effects of glasdegib or its metabolites in human breast milk are unknown.
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: December 2020
Summary of Product Characteristics: Daurismo 25mg and 100mg film-coated tablets. Pfizer Limited. Revised June 2020.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 October 2021
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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