and as indicated
clinically thereafter (e.g., if muscle symptoms are reported). Monitor electrocardiograms (ECGs) prior to theinitiation of DAURISMO, approximately one week after initiation, and then once monthly for the next twomonths to assess for QTc prolongation. Repeat ECG if abnormal. Certain patients may require more frequent
and ongoing ECG monitoring [see Warnings and Precautions (5.2)]. Manage any abnormalities promptly [seeAdverse Reactions (6.1)].
See Table 1 for dose modification guidelines for patients who develop an adverse reaction.
Table 1. Recommended Dose Modifications for Adverse Reactions
Adverse Reaction Recommended Action
QTc interval
prolongation on at
least 2 separate
electrocardiograms
(ECGs)
QTc interval greater
than 480 ms to
500 ms
Assess electrolyte levels and supplement as clinically indicated.
Review and adjust concomitant medications with known QTcinterval-prolonging effects [see Drug Interactions (7)].
Monitor ECGs at least weekly for 2 weeks following resolution ofQTc prolongation to less than or equal to 480 ms.
QTc interval greater Assess electrolyte levels and supplement as clinically indicated.
than 500 ms
Review and adjust concomitant medications with known QTcinterval-prolonging effects [see Drug Interactions (7)].
Interrupt DAURISMO.
Resume DAURISMO at a reduced dose of 50 mg once dailywhen QTc interval returns to within 30 ms of baseline or less thanor equal to 480 ms.
Monitor ECGs at least weekly for 2 weeks following resolution ofQTc prolongation.
Consider re-escalating the dose of DAURISMO to 100 mg dailyif an alternative etiology for the QTc prolongation can beidentified.
QTc interval
prolongation with
life-threatening
arrhythmia
Discontinue DAURISMO permanently.
Hematologic
toxicity
Platelets less than
10 Gi/L for more
than 42 days in the
Discontinue DAURISMO and low-dose cytarabine permanently.
Table 1. Recommended Dose Modifications for Adverse ReactionsAdverse Reaction Recommended Actionabsence of disease
Neutrophil count
less than 0.5 Gi/L
for more than
42 days in the
absence of disease
Discontinue DAURISMO and low-dose cytarabine permanently.
Nonhematologic
toxicity
Grade 3* Interrupt DAURISMO and/or low-dose cytarabine untilsymptoms reduce to mild or return to baseline.
Resume DAURISMO at the same dose level, or at a reduced doseof 50 mg.
Resume low-dose cytarabine at the same dose level, or at a
reduced dose of 15 mg or 10mg.
If toxicity recurs, discontinue DAURISMO and low-dose
cytarabine.
If toxicity is attributable to DAURISMO only, low-dosecytarabine may be continued.
Grade 4* Discontinue DAURISMO and low-dose cytarabine permanently.
*Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening.
3 DOSAGE FORMS AND STRENGTHS
DAURISMO 100 mg tablets: round, pale orange film-coated tablet debossed with “Pfizer” on one side and“GLS 100” on the other.
DAURISMO 25 mg tablets: round, yellow film-coated tablet debossed with “Pfizer” on one side and “GLS 25”on the other.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Embryo-Fetal Toxicity
Based on its mechanism of action and findings from animal embryo-fetal developmental toxicity studies,DAURISMO can cause embryo-fetal death or severe birth defect |
