5

mg/m^2

Intravenous (IV)

5

days

daily infused over 3 hours, generally given in combination with daunorubicin and cytarabine

CLAG regimen:

5

mg/m^2

Intravenous (IV)

Over 2 hr

5

days

given in combination with cytarabine, filgrastim and mitoxantrone

300

mg

Orally 

once a day

14

days

for 28 days cycle

100

mg

Tablet

Oral

once a day

Continue the treatment until disease progression or unacceptable toxicity occurs    Patients without disease progression or unacceptable severe effects continue the treatment for six months to achieve clinical response

20

mg/m^2

Intravenous (IV)

over 1 hr

once daily for 5 days at 28-day cycle
For AML with TP53 mutation:
20 mg/m2 IV infused over 1 hour for 10 days for 28-day cycle
20 mg/m2 IV infused over 1 hour for 5 days for 28-days cycle in combination with venetoclax

Dose Adjustments

Require dose adjustment in case of renal dysfunction or hemodialysis
Terminate the use of docetaxel if total bilirubin > 2.5 times ULN
Administer 80% of the dose: AST/ALT > 2.5 to 5 times ULN
Discontinue the therapy with docetaxel: AST/ALT >5 times
Delay the treatment for 6 to 8 weeks: hematologic toxicity (ANC<1000/µl and platelets < 50,000/µl)

500

mg

Orally

once a day

continue the treatment until disease progression or unacceptable toxicity occurs
patients without disease progression or unacceptable toxicity, given the treatment for up to a minimum of 6 months for clinical response

Newly diagnosed CD33-positive acute myeloid leukemia (AML):
COMBINATION REGIMEN
Induction: 3 mg per m2 IV over 2hrs for Days 1, 4, and 7 given in combination with daunorubicin and cytarabine
the drug gemtuzumab during the second induction cycle gemtuzumab isn't encouraged for patients who require a second induction cycle
Consolidation: 3 mg per m2 IV over 2hrs on Day 1 in combination with daunorubicin and cytarabine

Newly diagnosed CD33-positive acute myeloid leukemia (AML):
SINGLE-AGENT REGIMEN:
Induction: 6 mg per m2 IV over 2hrs on Day 1 and 3 mg/m2 IV on Day 8
Continuation: 2 mg per m2 IV over 2hrs on Day 1 every four weeks
Relapsed or Refractory CD33-positive AML:
SINGLE-AGENT REGIMEN:
3 mg per m2 IV over 2hrs on Days 1, 4, and 7
a single course of gemtuzumab given for treatment in the relapsed or refractory setting

150

mg

Capsules

Orally 

twice a day

until the disease progresses

Dose Adjustments

Differentiation syndrome
Withhold REZLIDHIA if differentiation syndrome is suspected until signs and symptoms become improved
Systemic corticosteroids should be given; hemodynamic monitoring should start and continue for at least three days after symptom remission
Restart REZLIDHIA at 150 mg twice daily once the differentiation syndrome has subsided.

Indicated for Acute myeloid leukemia following induction therapy:

• This is a treatment regimen for administering medication (likely a form of chemotherapy) intravenously at a dose of 250 mcg/m2/day over 4 hours
• The treatment is to begin on or around day 11 of the treatment cycle, or four days after the completion of induction chemotherapy provided that the patient's bone marrow is hypoplastic (meaning that it has a reduced number of cells) and that the number of blasts (immature blood cells) is less than 5%. Suppose a second cycle of induction chemotherapy is needed
• In that case, the treatment is to be administered approximately four days after the completion of the chemotherapy, again provided that the bone marrow is hypoplastic with less than 5% blasts
• The treatment is to continue until the patient's absolute neutrophil count (ANC) is more significant than 1500 cells/mm3 for three consecutive days or a maximum of 42 days

100 mg orally four times daily on 1-28 days of 28 days cycle. It is given in combination with 20 mg of cytarabine subcutaneously, twice daily, for 1-10 days of the cycle

Dose Adjustments

In case of QT prolongation (separate ECGs ≥2)
QTc >480 to 500 milliseconds
Check the electrolyte levels and provide supplements as indicated
Review & adjust concomitant medications with QTc interval-prolonging effects
Weekly monitor the ECGs for 2 weeks after the QTc prolongation resolution ≤480 milliseconds
QT >500 milliseconds
Check the electrolyte levels and provide supplements as indicated
Review & adjust concomitant medications with QTc interval-prolonging effects
Check on glasdegib dosing; restart at a reduced dose of 50 mg per day when QTc interval returns to 30 milliseconds
Weekly monitor the ECGs for 2 weeks after the QTc prolongation resolution
Consider re-starting glasdegib dose to 100 mg per day if other causes are identified for QTc prolongation
If QTc prolongation occurs with life-threatening arrhythmia, discontinue the dosing permanently
In case of hematologic toxicity
If platelets are less than 10 Gi/L or neutrophil count is less than 0.5 Gi/L for more than 42 days in the absence of disease, discontinue cytarabine and glasdegib permanently.
In case of non-hematologic toxicity
Interrupt glasdegib until symptoms are reduced
Start glasdegib at the same dose or reduce the dose to 50 mg
In high-grade, non-hematologic toxicity, discontinue glasdegib permanently
In case of renal impairment
No dosage modifications are recommended if eGFR 15-89 mL/min (mild-to-severe)
Monitor the patients with severe renal impairment (when eGFR is 15-29 mL/min); there is an increased risk of adverse effects
No studies are performed in the case of hepatic impairment

120 mg orally each day, the response may get delayed Continue the dose for at least 6 months until the unacceptable toxicity or disease progression

Dose Adjustments

In case of adverse reactions
For PRES (posterior reversible encephalopathy syndrome), discontinue the treatment
If the QTc interval >500 milliseconds interrupt the treatment; start over at 80 mg when the QTc interval gets backs within 30 milliseconds
For pancreatitis, interrupt the treatment if the condition persists; start over the dose at 80 mg

Differentiation Syndrome
If differentiation syndrome is suspected, administer systemic corticosteroids, and start hemodynamic monitoring
Continue this process until symptoms are resolved for minimum 3 days
Interrupt dose if severe symptoms and signs persist for over 48 hours after initiating corticosteroids
Start over the previous dose if the symptoms improve
Hepatic or renal impairment
In the case of mild to moderate hepatic or renal impairment, the effect of meaningful pharmacokinetics is unknown
In case of severe hepatic or renal impairment, the effect of the drug is unknown

50 mg orally twice daily from the 8th to the 21st day of the cycle
Use the drug in combination with standard daunorubicin and cytarabine
The dose should be taken with food

Induction therapy: On days 1 through 3, administer 12 mg/m2 once a day (in addition to 100 mg/m2 of cytarabine given as a continuous intravenous infusion on days 1 through 7)

Second Induction Therapy: On days 1 and 2, inject 12 mg/m2 (combined with a continuous 24-hour intravenous infusion of cytarabine on days 1 through 5)

Consolidation: Day 1 and Day 2 IV administration of 12 mg/m2. The first course is typically delivered six weeks after the last introductory course, while the second is delivered four weeks later.

Indicated for Acute Nonlymphocytic Leukaemia:

2 mg/kg orally everyday
If there is no improvement after four weeks, gradually increase to 3 mg/kg/day
Consume on an empty stomach to avoid nausea and vomiting

Induction
First cycle: Administering liposomal daunorubicin at a dosage of 44 mg/m2 along with cytarabine at a dosage of 100 mg/m2 via intravenous infusion on days first third and fifth recommended
Second cycle: Exclusively intended for patients who do not experience a favorable outcome following the initial induction cycle
If there were no unacceptable toxicity, the second cycle can be administered within a time frame of 2-5 weeks following the initial cycle
If necessary, It involves the intravenous (IV) administration of liposomal daunorubicin at a dosage of 44 mg/m2 and cytarabine at a dosage of 100 mg/m2
This administration should be performed on the first and third days Consolidation
Consolidation: intravenous liposomal (daunorubicin 29 mg/m2/cytarabine 65 mg/m2) on days 1 and 3
begin the initial consolidation phase approximately 5-8 weeks following the commencement of the preceding induction phase

FDA approval pending for relapsed or resistant acute myeloid leukemia (AML).

To treat refractory or relapsed AML, administer 80–90 mg/m2 intravenously on days 1 and 4 (in combination with cytarabine).
AML newly diagnosed in elderly patients: 72 mg/m2 intravenously on days 1 and 8 twice daily.

Take an initial dose of 60 mg orally twice daily for 8 weeks

off-label:

120 mg/m2 amsacrine combined with cytarabine intravenously for an hour on the third, fifth, and seventh day of the induction cycle
or 120 mg/m2 intravenously combined with cytarabine for an hour on the fourth, fifth, and sixth day of the second induction cycle

Children and adolescents:

8.9

mg/m^2

Intravenous (IV)

once a day

5

days

Children > 2 years and adolescents:

75

mg/m^2

Subcutaneous (SC)

once a day

7

days

Or
300 mg/m^2 IV once a day for 2 days.

Children > 2 years and adolescents:

75

mg/m^2

Subcutaneous (SC)

once a day

7

days

Or
300 mg/m^2 IV once a day for 2 days.

off-label: If the child is less than three years, a dose :

3.3

mg/kg

once a day

IV given continuous infusion for four days If the child is more than three years, a dose of 100 mg per m² per day IV given continuous infusion for four days

Safety and efficacy are not studied

Newly Diagnosed De Novo CD33-positive AML:
Combination Regimen:
age: >1year
BSA< 0.6 m2: 0.1 mg per kg IV over 2hrs
BSA>0.6 m2: 0.3 mg per m2 IV over 2hrs
INDUCTION 1:
gemtuzumab is given for Induction 1 once in combination with standard chemotherapy
In the second induction cycle, gemtuzumab isn't encouraged
INTENSIFICATION:
in the first or third intensification cycles, gemtuzumab isn't encouraged gemtuzumab is given for Intensification 2 once in combination with standard chemotherapy
During Intensification 2, check for risks and potential benefits before giving gemtuzumab
Relapsed or Refractory CD33-positive AML:
SINGLE-AGENT REGIMEN:
age: > 2years
3 mg per m2 given IV over 2hrs on Days 1, 4, and 7
a single course of gemtuzumab for treatment in the relapsed or refractory setting

Indicated for Acute Nonlymphocytic Leukaemia:

2 mg/kg orally everyday
If there is no improvement after four weeks, gradually increase to 3 mg/kg/day
Consume on an empty stomach to avoid nausea and vomiting

Induction
First cycle: Intravenous administration of liposomal daunorubicin at a dosage of 44 mg/m2 in combination with cytarabine at a dosage of 100 mg/m2 on days first third and fifth
Second cycle: This is exclusively intended for patients who do not experience a response during their initial induction cycle
If there were no instances of unacceptable toxicity, the second cycle may be scheduled within a timeframe of 2-5 weeks following the initial cycle
In case it is required, the liposomal formulation of daunorubicin should be administered intravenously at a dose of 44 mg/m2, along with intravenous administration of cytarabine at a dose of 100 mg/m2 on the first and third days
Consolidation
Consolidation: intravenous liposomal (daunorubicin at a dosage of 29 mg/m2 and cytarabine at a dosage of 65 mg/m2) on days 1 and 3
begin the initial consolidation phase approximately 5-8 weeks following the commencement of the preceding induction phase

Refer adult dosing  

20

mg/m^2

Intravenous (IV)

over 1 hr

for 5 days for a 28-day cycle in combination with venetoclax
Terminate the therapy as soon as unacceptable adverse effects appear