Trade Names:Sprycel- Tablets 20 mg- Tablets 50 mg- Tablets 70 mg- Tablets 100 mg
Inhibits growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines that overexpress the kinase BCR-ABL.
T max is between 0.5 and 6 h.
Vd is 2,505 L, suggesting extensive distribution in extravascular space. Protein binding 96%; active metabolite 93%.
Extensively metabolized by CYP3A4 to an active metabolite, which is equipotent to dasatinib. Also metabolized by flavin-containing monooxygenase-3 and uridine diphosphate-glucuronosyltransferase enzymes.
Terminal half-life is 3 to 5 h. Excretion is primarily fecal (85%) and 4% in urine.
There are no studies in patients with impaired renal function; however, only 4% of the drug and its metabolites are excreted by the kidney.Hepatic Function Impairment
There are no studies in patients with impaired hepatic function.
Treatment of adults with chronic accelerated, or myeloid or lymphoid blast phase CML with resistance or intolerance to prior therapy including imatinib; treatment of adults with Philadelphia chromosome–positive (Ph+) ALL with resistance or intolerance to prior therapy.
PO Start with 100 mg once daily in the morning or evening. May escalate dosage to 140 mg once daily in patients who do not achieve a hematologic or cytogenetic response.Accelerated phase CML, myeloid, or lymphoid blast CML phase, or (Ph+) ALL Adults
Start with 70 mg in the morning and evening. May escalate dosage to 100 mg twice daily in patients who do not achieve a hematologic or cytogenetic response.Coadministration With Strong CYP3A4 InhibitorsAdults
PO Selection of an alternate drug with no or minimal enzyme inhibition potential is recommended. If a strong CYP3A4 inhibitor must be coadministered, consider decreasing the dosage of dasatinib to 20 mg daily.Coadministration With Strong CYP3A4 InducersAdults
PO Selection of an alternate drug with no or minimal enzyme induction potential is recommended. If a strong CYP3A4 inducer must be coadministered, consider increasing the dosage of dasatinib and carefully monitor the patient for toxicity.Dose Adjustments for Neutropenia and ThrombocytopeniaAdults Chronic phase CML
PO Starting dosage 100 mg once daily. If absolute neutrophil count (ANC) is less than 0.5 × 10 9 /L or platelet count is less than 50 × 10 9 /L, stop dasatinib until ANC is at least 1 × 10 9 /L and platelets are at least 50 × 10 9 /L. Then resume treatment at the original starting dose if recovery occurs in 7 days or less. If platelets are less than 25 × 10 9 /L and/or recurrence of ANC is less than 0.5 × 10 9 /L for more than 7 days, stop dasatinib until ANC is at least 1 × 10 9 /L and platelets are at least 50 × 10 9 /L. Then resume treatment at 80 mg twice daily (second episode) or discontinue (third episode).Accelerated phase CML, blast phase CML, and Ph+ ALL
PO Starting dosage 70 mg twice daily. If ANC is less than 0.5 × 10 9 /L or platelet count is less than 10 × 10 9 /L, check if cytopenia is related to leukemia. If unrelated to leukemia, stop dasatinib until ANC is at least 1 × 10 9 /L and platelets are at least 20 × 10 9 /L. Then, resume treatment at the original starting dose. If recurrence of cytopenia, check if cytopenia is related to leukemia, and resume dasatinib at a dosage of 50 mg twice daily (second episode) or 40 mg twice daily (third episode). If cytopenia is related to leukemia, consider escalating the dasatinib dosage to 100 mg twice daily.
Store between 59° and 86°F.
Based on nonclinical data, if antacid therapy cannot be avoided, administer the antacid at least 2 h before or after dasatinib.CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort)
May reduce dasatinib plasma levels, decreasing the therapeutic effect. When possible, use alternative therapy.CYP3A4 inhibitors (eg, atazanavir, clarithromycin, erythromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)
May elevate dasatinib plasma concentrations, increasing the risk of adverse reactions.CYP3A4 substrates (eg, alfentanil, astemizole, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, quinidine, simvastatin, sirolimus, tacrolimus, terfenadine)
Plasma levels may be altered by dasatinib; therefore, use with caution.H 2 antagonists (eg, famotidine), proton pump inhibitors (eg, omeprazole)
May reduce dasatinib plasma levels, decreasing the therapeutic effect. Concommitant use is not recommended.
None well documented.
CHF/cardiac dysfunction (4%); arrhythmia including tachycardia, flushing, hypertension, palpitations (1% to less than 10%).
Headache (24%); fatigue (21%); asthenia, depression, dizziness, dysgeusia, insomnia, neuropathy, somnolence (1% to less than 10%); CNS bleeding (1%).
Rash (22%); acne, alopecia, dermatitis, dry skin, hypertrichosis, pruritus, urticaria (1% to less than 10%).
Dry eyes, visual disorder (1% to less than 10%).
Diarrhea (37%); nausea (24%); vomiting (13%); abdominal pain (10%); GI bleeding (7%); abdominal distention, anorexia, appetite disturbance, colitis, constipation, dyspepsia, enterocolitis infection, gastritis, mucosal inflammation, oral soft tissue disorder (1% to less than 10%); ascites (1%).
Thrombocytopenia (81%); neutropenia (80%); anemia (75%); hemorrhage (21%); febrile neutropenia, pancytopenia (1% to less than 10%).
Hypophosphatemia (20%); hypocalcemia (16%); elevated ALT (7%); elevated AST, elevated bilirubin (5%); hyperuricemia (1% to less than 10%); elevated creatinine (3%).
Fluid retention (37%); weight decrease, weight increase (1% to less than 10%).
Musculoskeletal pain (14%); arthralgia, muscle inflammation, muscle weakness, myalgia (1% to less than 10%).
Dyspnea (20%); pulmonary edema (3%); cough; lung infiltration; pneumonia including bacterial, fungal, and viral; pneumonitis; upper respiratory tract infection/inflammation (1% to less than 10%).
Pleural effusion (23%); superficial localized edema (20%); pyrexia (13%); generalized edema, pericardial effusion (4%); chest pain; chills; contusion; herpes virus infection; infections, including bacterial, fungal, nonspecific, and viral pain (1% to less than 10%); pulmonary hypertension (1%).
Monitor CBC weekly for the first 2 mo, then monthly thereafter, or as clinically indicated.
Category D .
Safety and efficacy not established.
In most studies, safety and efficacy were similar in patients 65 yr of age and older compared with younger patients. However, in 2 studies in patients with chronic phase CML, the rates of major cytogenetic response were lower in patients 65 yr of age and older.
Use with caution.
Severe hemorrhage, including fatal CNS hemorrhages and GI hemorrhages, may occur. Use with caution in patients receiving anticoagulants or medications that may inhibit platelet function.
Fluid retention, possibly severe (eg, pleural and pericardial effusion), may occur.
A 140 mg daily dose contains 189 mg; a 100 mg daily dose contains 135 mg.
Severe thrombocytopenia, neutropenia, and anemia may occur and can usually be managed by withholding treatment or reducing the dose.
QTc prolongation has been reported; therefore, use with caution in patients who have or may develop QTc prolongation, including patients with hypokalemia or hypomagnesemia, patients with congenital QT syndrome, or patients taking high-dose anthracycline therapy, antiarrhythmic agents, or other medicines that prolong the QT interval. Correct hypokalemia or hypomagnesemia before administering dasatinib.
Bleeding and severe myelosuppression.
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