Dasatinib Dosage

Usual Adult Dose for Leukemia

Chronic phase CML:
Initial dose: 100 mg once daily

Accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL:
Initial dose: 140 mg orally once daily.

In clinical studies, treatment with dasatinib was continued until disease progression or until no longer tolerated by the patient. The effect of stopping treatment after the achievement of a complete cytogenetic response has not been investigated.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Dose increase or reduction of 20 mg increments per dose is recommended based on individual safety and tolerability.

If dasatinib must be administered with a CYP450 3A4 inducer, a dose increase should be considered. If the dose of dasatinib is increased, the patient should be monitored carefully for toxicity.

If dasatinib must be administered with a strong CYP450 3A4 inhibitor, a dose decrease to 20 mg daily should be considered for patients taking 100 mg daily and a dose decrease to 40 mg daily should be considered for patients taking 140 mg daily. Following dose reduction, if dasatinib is not tolerated, either the strong CYP450 3A4 inhibitor should be discontinued or dasatinib should be discontinued until treatment with the inhibitor is discontinued. After the strong inhibitor is discontinued, a washout period of approximately 1 week should be allowed to transpire prior to increasing the dasatinib dose.

Dose Escalation:
In clinical studies of adult CML and Ph+ ALL patients, dose escalation to 140 mg once daily (chronic phase CML) or 180 mg once daily (advanced phase CML and Ph+ ALL) was allowed in patients who did not achieve a hematologic or cytogenetic response at the recommended dosage.

Dose Adjustment for Adverse Reactions:
Myelosuppression:
In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation of study therapy. Hematopoietic growth factor has been used in patients with resistant myelosuppression. Guidelines for dose modifications are summarized below:

Dose Adjustments for Neutropenia and Thrombocytopenia:
For Chronic Phase CML (starting dose 100 mg once daily) with an Absolute Neutrophil Count (ANC) less than 0.5 x 10(9)/L and/or Platelets less than 50 x 10(9)/L:
1.) Stop dasatinib until the ANC is greater than or equal to 1.0 x 10(9)/L and platelets are greater than or equal to 50 x 10(9)/L.
2.) Resume treatment with dasatinib at the original starting dose if recovery occurs in less than or equal to 7 days.
3.) If platelets are less than 25 x 10(9)/L and/or recurrence of ANC less than 0.5 x 10(9)/L for greater than 7 days, repeat Step 1 and resume dasatinib at a reduced dose of 80 mg once a day (second episode) or for a third episode, further reduce dose to 50 mg once a day (for newly diagnosed patients) or discontinue dasatinib (for patients resistant or intolerant to prior therapy including imatinib).

For Accelerated Phase CML, Blast Phase CML and Ph+ ALL (starting dose 140 mg once daily) with an ANC less than 0.5 x 10(9)/L and/or Platelets less than 10 x 10(9)/L:
1.) Check if cytopenia is related to leukemia (marrow aspirate or biopsy).
2.) If cytopenia is unrelated to leukemia, stop dasatinib until the ANC is greater than or equal to 1.0 x 10(9)/L and platelets are greater than or equal to 20 x 10(9)/L and resume at the original starting dose.
3.) If recurrence of cytopenia, repeat Step 1 and resume dasatinib at a reduced dose of 100 mg once a day (second episode) or 80 mg once a day (third episode).
4. If cytopenia is related to leukemia, consider dose escalation to 180 mg once a day.

Nonhematologic adverse reactions:
If a severe nonhematologic adverse reaction develops with dasatinib use, treatment must be withheld until the event has resolved or improved. Thereafter, treatment can be resumed as appropriate at a reduced dose depending on the initial severity of the event.

Precautions

Treatment with dasatinib has been associated with severe thrombocytopenia, neutropenia, and anemia. Their occurrence has been more frequent in patients with advanced chronic myeloid leukemia (CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) than in chronic phase CML. Complete blood counts should be performed weekly for the first two months and then monthly thereafter, or as clinically indicated. Myelosuppression has generally been reversible. It may be managed by withholding dasatinib temporarily or by dose reduction. In patients with resistant myelosuppression, hematopoietic growth factor may be considered.

Severe CNS hemorrhages, including fatalities, have occurred in patients receiving dasatinib. Severe gastrointestinal hemorrhage occurred in patients and generally required treatment interruptions and transfusions. Other cases of severe hemorrhage have been reported in patients. Most bleeding events were associated with severe thrombocytopenia.

Exercise caution if patients are required to take medications that inhibit platelet function or anticoagulants.

In vitro data suggest that dasatinib has the potential to prolong cardiac ventricular repolarization (QT interval). Administer dasatinib with caution to patients who have or may develop prolongation of the QT interval. These include patients with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking antiarrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy. Correct hypokalemia or hypomagnesemia prior to dasatinib administration.

Use of dasatinib has been associated with adverse cardiac events including cardiomyopathy, congestive heart failure, diastolic dysfunction, fatal myocardial infarction, and left ventricular dysfunction. Patients should be monitored for signs and symptoms of cardiac dysfunction during treatment with dasatinib.

Dasatinib may increase the risk of developing pulmonary arterial hypertension (PAH) which may occur anytime after initiation, including after more than one year of treatment. Manifestations include dyspnea, fatigue, hypoxia, and fluid retention. PAH may be reversible on discontinuation of dasatinib. Evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to initiating dasatinib and during treatment. If PAH is confirmed, dasatinib should be permanently discontinued.

Fluid retention, in some cases severe, including severe ascites, generalized edema, severe pulmonary edema, pleural and pericardial effusion, has been reported.. Patients who develop symptoms suggestive of pleural effusion such as dyspnea or dry cough should be evaluated by chest X-ray. Severe pleural effusion may require thoracentesis and oxygen therapy. Fluid retention events have typically been managed by supportive care measures that have included diuretics or short courses of steroids.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Dialysis

Data not available

Other Comments

Dasatinib may be taken without regard to meals, either in the morning or in the evening.

Dasatinib oral tablets should be swallowed whole, and not crushed or cut.

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