Usual Adult Dose for Acute Myeloid Leukemia

100 mg orally once a day on days 1 to 28 in combination with cytarabine 20 mg subcutaneously 2 times a day on days 1 to 10 of each 28-day cycle in the absence of unacceptable toxicity or loss of disease control; for patients without unacceptable toxicity, treat for a minimum of 6 cycles to allow time for clinical response

Use: This drug, in combination with low-dose cytarabine, for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adult patients who are 75 years old or older or who have comorbidities that preclude use of intensive induction chemotherapy

Usual Geriatric Dose for Acute Myeloid Leukemia

75 years or older:
100 mg orally once a day on days 1 to 28 in combination with cytarabine 20 mg subcutaneously 2 times a day on days 1 to 10 of each 28-day cycle in the absence of unacceptable toxicity or loss of disease control; for patients without unacceptable toxicity, treat for a minimum of 6 cycles to allow time for clinical response

Use: This drug, in combination with low-dose cytarabine, for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adult patients who are 75 years old or older or who have comorbidities that preclude use of intensive induction chemotherapy

Renal Dose Adjustments

Mild to moderate renal impairment: No adjustment recommended.
Severe renal impairment: Data not available

Liver Dose Adjustments

Mild hepatic impairment: No adjustment recommended.
Moderate to severe hepatic impairment: Data not available

Dose Adjustments

Dose Modifications for Adverse Reactions:
QTC INTERVAL PROLONGATION ON AT LEAST 2 SEPARATE ELECTROCARDIOGRAMS (ECGS):

• QTc interval greater than 480 ms to 500 ms: Assess electrolyte levels as clinically indicated; review and adjust concomitant medications with known QTc interval-prolonging effects; monitor ECGs at least weekly for 2 weeks following resolution of QTc prolongation to less than or equal to 480 ms.
• QTc interval greater than 500 ms: Assess electrolyte levels and supplement as clinically indicated; review and adjust concomitant medications with known QTc interval-prolonging effects; interrupt therapy; resume therapy at a reduced dose of 50 mg once daily when QTc interval returns to within 30 ms of baseline or less than or equal to 480 ms; monitor ECGs at least weekly for 2 weeks following resolution of QTc prolongation; consider re-escalating the dose to 100 mg daily if an alternative etiology for the QTc prolongation can be identified.
• QTc interval prolongation with life-threatening arrhythmia: Permanently discontinue therapy.

• Platelets less than 10 GI/L for more than 42 days in the absence of disease: Discontinue this drug and low-dose cytarabine permanently.
• Neutrophil count less than 0.5 GI/L for more than 42 days in the absence of disease: Discontinue this drug and low-dose cytarabine permanently.

• Grade 3: Interrupt this drug and/or low-dose cytarabine until symptoms reduce to mild or return to baseline; resume this drug at the same dose level, or at a reduced dose of 50 mg; resume low-dose cytarabine at the same dose level, or at a reduced dose of 10 or 15 mg; if toxicity recurs, discontinue this drug and low-dose cytarabine; if toxicity is attributable to this drug only, low-dose cytarabine may be continued.
• Grade 4: Discontinue this drug and low-dose cytarabine permanently.

• Avoid concomitant use of this drug with moderate CYP450 3A4 inducers.
• If concomitant use cannot be avoided, increase the dose of this drug as tolerated as shown below:
• After the moderate CYP450 3A4 inducer has been discontinued for 7 days, resume this drug at the dose taken prior to initiating the moderate CYP450 3A4 inducer.

• If the current dose is 100 mg once a day: Increase to 200 mg orally once a day.
• If current dose is 50 mg orally once a day: Increase to 100 mg orally once a day.

Precautions

US BOXED WARNINGS:

• This drug is embryotoxic, fetotoxic, and teratogenic in animals; therefore, it is expected to cause severe birth defects and/or embryofetal death in humans.
• Verify pregnancy status in females of reproductive potential prior to initiating therapy.
• Advise females of reproductive potential to use effective contraception during therapy and for at least 30 days after.
• Advise males of the potential risk of exposure to this drug through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during therapy and for at least 30 days after.

• None

Dialysis

Data not available

Other Comments

Administration advice:

• This drug may be taken with or without food.
• Do not split, divide, or crush tablets.
• Administer at the same time each day.
• If a dose is vomited, do not administer a replacement dose; wait until the next scheduled dose is due.
• If a dose is missed or not taken at the usual time, administer the dose as soon as possible and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day.
• Do not administer 2 doses within 12 hours.

• Store at 20C to 25C (68F to 77F); excursions permitted between 15C to 30C (59F to 86F).

• Assess complete blood counts, electrolytes, renal, and hepatic function prior to the initiation of therapy and at least once a week for the first month.
• Monitor electrolytes and renal function once monthly for the duration of therapy.
• Obtain serum creatine kinase levels prior to initiating therapy and as indicated clinically thereafter (e.g., if muscle symptoms are reported).
• Monitor electrocardiograms (ECGs) prior to the initiation of therapy, approximately 1 week after initiation, and then once monthly for the next 2 months to assess for QTc prolongation. Repeat ECG if abnormal. Some patients may require more frequent and ongoing ECG monitoring.

• This drug can harm a developing fetus. Males and females of reproductive potential should use adequate contraception during therapy and for at least 30 days after the last dose.
• Do not breastfeed during therapy and for at least 30 days after the last dose.
• Do not donate blood or blood products during therapy and for at least 30 days after the last dose.
• Contact your healthcare provider immediately if you experience syncope, pre-syncopal symptoms, and cardiac palpitations.

Frequently asked questions

• What type of cancer is Daurismo (glasdegib) used to treat?