Dasatab

Approved Indications:

• Chronic Myeloid Leukemia (CML):
• Adults and pediatric patients with:
• Chronic phase CML (newly diagnosed or resistant/intolerant to prior therapy including imatinib)
• Accelerated or myeloid/lymphoid blast phase CML (resistant/intolerant to prior therapy)
• Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL):
• Adults and pediatric patients with Ph+ ALL resistant or intolerant to prior therapy.

Clinically Accepted Off-label Uses:

• Central Nervous System Leukemia (limited evidence; CNS penetration studied)
• Pre-transplant cytoreduction in patients with Ph+ leukemias
• Maintenance therapy post stem cell transplantation in Ph+ leukemias (under investigation)

Adults:

• Chronic Phase CML (Newly Diagnosed):
• 100 mg orally once daily.
• Accelerated Phase, Myeloid or Lymphoid Blast CML, and Ph+ ALL:
• 140 mg orally once daily.

Pediatric Patients (≥1 year):

• Based on body weight:
• 40–100 mg/m² orally once daily (maximum 100 mg/day for CP-CML; 140 mg/day for Ph+ ALL).
• Tablets must not be crushed; oral suspension available in some regions.

Renal Impairment:

• No adjustment required.

Hepatic Impairment:

• Use with caution in moderate to severe impairment; monitor hepatic function.

Administration Instructions:

• Take with or without food.
• Swallow tablets whole; do not crush, cut, or chew.
• Avoid antacids or proton pump inhibitors near dosing time.

Dasatinib is a potent oral multi-targeted tyrosine kinase inhibitor (TKI) that blocks the activity of BCR-ABL kinase, which results from the Philadelphia chromosome translocation in CML and Ph+ ALL. It binds both the active and inactive conformations of the BCR-ABL kinase domain, making it more potent than imatinib. Additionally, it inhibits several other kinases including members of the Src family, c-KIT, ephrin receptors, and PDGFR-β. Inhibition of these kinases disrupts downstream signaling required for leukemic cell proliferation and survival, inducing apoptosis in malignant hematopoietic cells.

Absorption:

• Rapidly absorbed; peak plasma concentration reached in 0.5–6 hours.
• Bioavailability may be reduced by concurrent antacid use.

Distribution:

• Widely distributed; protein binding ~96%.
• Volume of distribution: ~2500 L, indicating extensive tissue penetration.

Metabolism:

• Primarily metabolized by hepatic CYP3A4 enzyme.
• Also undergoes non-CYP-mediated hydrolysis.

Elimination:

• Terminal half-life: ~3–5 hours.
• Excreted mainly in feces (~85%); renal elimination <5%.

• Pregnancy:
• FDA Category D. Positive evidence of human fetal risk. Contraindicated unless potential benefits outweigh risks.
• Lactation:
• Excreted in animal milk; risk to nursing infants cannot be excluded. Breastfeeding is not recommended during treatment and for 2 weeks after the last dose.

• Primary Class: Antineoplastic agent
• Subclass: Tyrosine kinase inhibitor (BCR-ABL and multi-kinase inhibitor)

• Known hypersensitivity to dasatinib or any component of the formulation
• Use with strong CYP3A4 inducers (e.g., rifampin) due to reduced efficacy
• Use with caution in patients with severe fluid retention or uncontrolled cardiovascular conditions

• Myelosuppression: Common; monitor CBC regularly. May require dose interruptions or reductions.
• Fluid Retention and Pleural Effusion: May be severe; monitor for signs of edema, dyspnea.
• QT Prolongation: Caution in patients with cardiac disease or on QT-prolonging agents.
• Pulmonary Arterial Hypertension (PAH): Rare but potentially fatal. Discontinue if PAH is confirmed.
• Bleeding Risk: Inhibition of platelet function may increase bleeding risk.
• Hepatotoxicity: Monitor liver function tests periodically.
• Growth Retardation in Children: Monitor height and weight routinely.

Hematologic (Very Common):

• Neutropenia
• Thrombocytopenia
• Anemia

Non-Hematologic (Common):

• Headache
• Fatigue
• Diarrhea
• Nausea
• Rash
• Fever
• Arthralgia
• Pleural effusion
• Cough

Serious/Rare:

• QT interval prolongation
• Pulmonary arterial hypertension
• Severe fluid retention
• Pancreatitis
• Myelosuppression-related sepsis
• Cardiomyopathy

• CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir): Increase dasatinib exposure; avoid or monitor closely.
• CYP3A4 Inducers (e.g., rifampin, carbamazepine): Reduce dasatinib levels; avoid use.
• Antacids/PPIs (e.g., omeprazole): Reduce dasatinib absorption. Separate antacids by ≥2 hours before/after dosing.
• QT-Prolonging Drugs: Additive effect; use with caution.

• FDA/EMA (2023–2024): No major changes in indications or dosage.
• NCCN Guidelines: Dasatinib remains a recommended first-line and second-line option for CML in various phases, and for Ph+ ALL.
• Pediatric Use: Approved and recommended in CP-CML and Ph+ ALL based on positive efficacy and safety data.

• Temperature: Store at 20°C to 25°C (68°F to 77°F).
• Excursions: Permitted between 15°C and 30°C.
• Light/Humidity: Protect from light and moisture.
• Handling: Use gloves when handling tablets. Wash hands after handling.
• Disposal: Follow cytotoxic drug disposal procedures. Do not crush or chew tablets.