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The recommended starting dose of dasatinib for adult patients with chronic-phase (CP) CML is 100 mg orally once daily. For adult patients with accelerated-phase (AP) CML, myeloid or lymphoid blast-phase (BP) CML, or Ph+ ALL, the recommended starting dose is 140 mg orally once daily.Tablets should not be crushed, split, or chewed; they must be swallowed whole. Dasatinib can be taken with or without food, either in the morning or evening.
The recommended starting dose of dasatinib for pediatric patients is based on body weight. The dose is administered orally once daily, with or without food. The dose should be recalculated every 3 months based on changes in body weight, or more frequently if necessary.
Do not crush, split, or chew the tablets; swallow them whole. For pediatric patients who have difficulty swallowing whole tablets, additional administration considerations apply.
Dasatinib dosage for pediatric patients is as follows:
Body weight 10 kg to <20 kg: 40 mg daily.
Body weight 20 kg to <30 kg: 60 mg daily.
Body weight 30 kg to <45 kg: 70 mg daily.
Body weight ≥45 kg: 100 mg daily.
Tablet administration is not recommended for patients weighing less than 10 kg.
Concomitant use of strong CYP3A4 inducers and St. John’s Wort (Hypericum perforatum) should be avoided. If a patient must receive a strong CYP3A4 inducer, consider increasing the dasatinib dose. If the dasatinib dose is increased, closely monitor the patient for toxicity.
Concomitant use of strong CYP3A4 inhibitors and grapefruit juice should be avoided. Whenever possible, select alternative concomitant medications with no or minimal enzyme inhibitory potential. If dasatinib must be used concomitantly with a strong CYP3A4 inhibitor, consider reducing the dasatinib dose as follows:
Patients taking 140 mg dasatinib daily: Reduce to 40 mg daily.
Patients taking 100 mg dasatinib daily: Reduce to 20 mg daily.
Patients taking 70 mg dasatinib daily: Reduce to 20 mg daily.
For patients taking 60 mg or 40 mg dasatinib daily, consider interrupting dasatinib until the inhibitor is discontinued. After discontinuing the inhibitor, allow a washout period of approximately 1 week before restarting dasatinib treatment.
These reduced dasatinib doses are expected to adjust the area under the curve (AUC) to the range observed without CYP3A4 inhibitors; however, there are no clinical data supporting these dosage adjustments in patients receiving strong CYP3A4 inhibitors. If dasatinib remains intolerable after dose reduction, discontinue the strong CYP3A4 inhibitor or interrupt dasatinib until the inhibitor is discontinued. After discontinuing the inhibitor, allow a washout period of approximately 1 week before increasing the dasatinib dose.
For adult patients with CML or Ph+ ALL who do not achieve a hematologic or cytogenetic response at the recommended starting dose, consider escalating the dose to 140 mg once daily (for CP CML) or 180 mg once daily (for AP CML, BP CML, and Ph+ ALL).
For pediatric patients with CML who do not achieve a hematologic or cytogenetic response at the recommended starting dose, escalate the dasatinib dose as follows:
Starting dose 40 mg: Escalate to 50 mg.
Starting dose 60 mg: Escalate to 70 mg.
Starting dose 70 mg: Escalate to 90 mg.
Starting dose 100 mg: Escalate to 120 mg.
Dose escalation is not recommended for pediatric patients with Ph+ ALL, as dasatinib is administered in combination with chemotherapy.
In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation of study treatment. Hematopoietic growth factors were used in patients with refractory myelosuppression. Guidelines for dosage adjustments in adult and pediatric patients are summarized below.
Dosage Adjustments for Neutropenia and Thrombocytopenia in Adult Patients
If absolute neutrophil count (ANC) <0.5×10⁹/L or platelets <50×10⁹/L:
Discontinue dasatinib until ANC ≥1.0×10⁹/L and platelets ≥50×10⁹/L.
If recovery occurs within ≤7 days, restart dasatinib at the original starting dose.
If recurrence of platelets <25×10⁹/L or ANC <0.5×10⁹/L lasts >7 days, repeat Step 1. For the second event, restart dasatinib at a reduced dose of 80 mg once daily. For the third event, further reduce the dose to 50 mg once daily (for newly diagnosed patients) or discontinue dasatinib (for patients resistant or intolerant to prior therapy including imatinib).
If ANC <0.5×10⁹/L or platelets <10×10⁹/L:
Check if cytopenia is leukemia-related (via bone marrow aspiration or biopsy).
If cytopenia is not leukemia-related: Discontinue dasatinib until ANC ≥1.0×10⁹/L and platelets ≥20×10⁹/L, then restart at the original starting dose.
If cytopenia recurs: Repeat Step 1, then restart dasatinib at a reduced dose of 100 mg once daily (for the second event) or 80 mg once daily (for the third event).
If cytopenia is leukemia-related: Consider escalating the dose to 180 mg once daily.
If cytopenia persists for >3 weeks: Check if it is leukemia-related (via bone marrow aspiration or biopsy).
If cytopenia is not leukemia-related: Discontinue dasatinib until ANC ≥1.0×10⁹/L and platelets ≥75×10⁹/L, then restart at the original starting dose or a reduced dose.
If cytopenia recurs: Repeat bone marrow aspiration/biopsy, then restart dasatinib at a reduced dose.
Dose reduction levels are as follows:
Original starting dose 40 mg: Reduce to 20 mg.
Original starting dose 60 mg: Reduce to 40 mg, then further to 20 mg if needed.
Original starting dose 70 mg: Reduce to 60 mg, then further to 50 mg if needed.
Original starting dose 100 mg: Reduce to 80 mg, then further to 70 mg if needed.
Lower tablet doses are not available.
For pediatric patients with CP CML: If grade ≥3 neutropenia or thrombocytopenia recurs during complete hematologic remission, interrupt dasatinib and restart at a reduced dose. Implement temporary dose reductions as needed for moderate cytopenia and disease response.
For pediatric patients with Ph+ ALL: If neutropenia and/or thrombocytopenia delays the next treatment block by >14 days, interrupt dasatinib and restart at the same dose level when the next treatment block begins. If neutropenia and/or thrombocytopenia persists and delays the next treatment block by an additional 7 days, perform a bone marrow assessment to evaluate cellularity and blast percentage:
If bone marrow cellularity <10%: Interrupt dasatinib until ANC >500/μL, then restart full-dose treatment.
If bone marrow cellularity >10%: Consider restarting dasatinib treatment.
For adult patients with Ph+ CML/ALL and pediatric patients with Ph+ CML who experience severe non-hematologic adverse reactions to dasatinib: Interrupt treatment until the adverse reaction resolves or improves. Thereafter, restart treatment at an appropriately reduced dose based on the severity and recurrence of the reaction.
Interrupt treatment for grade ≥3 non-hematologic adverse reactions (except abnormal liver function tests), and restart at a reduced dose when the reaction resolves to grade ≤1.
Interrupt treatment for direct bilirubin elevation >5× the institutional upper limit of normal (ULN) until improvement to baseline or grade ≤1.
Interrupt treatment for AST/ALT elevation >15× ULN until improvement to baseline or grade ≤1.
For recurrent abnormal liver function tests: If the adverse reaction recurs after restarting dasatinib, reduce the dose.
Dose reduction recommendations for non-hematologic toxicities:
Grade 2 non-hematologic toxicity: If no recovery occurs despite symptomatic treatment, consider interrupting dasatinib. Once recovery to grade ≤1, restart at the original starting dose. For recurrent events, restart at a reduced dose.
Grade 3 non-hematologic toxicity: Discontinue dasatinib until recovery to grade ≤1, then restart at a reduced dose. The dose reduction levels are the same as those for cytopenia.
Direct bilirubin >5× ULN or AST/ALT >15× ULN: Interrupt dasatinib until recovery to grade ≤1, then restart at the original starting dose. For recurrent hepatotoxicity, restart at a reduced dose.
In clinical studies, adult and pediatric patients with CP CML continued dasatinib treatment until disease progression or loss of tolerability. The impact of treatment discontinuation on long-term disease outcomes after achieving a cytogenetic response (including complete cytogenetic response) or major molecular response has not been established.
In clinical studies, the maximum duration of dasatinib treatment for pediatric patients with Ph+ ALL was 2 years.
FDA，2024.07
