Dasaren 100 mg (Tablet)

Therapeutic Class

• Targeted Cancer Therapy

Indications

• Treatment of adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase
• Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including Imatinib
• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy
• Treatment of pediatric patients 1 year of age and older with Ph+ CML in chronic phase
• Newly diagnosed Ph+ ALL in combination with chemotherapy

Pharmacology

• Inhibition of BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ at nanomolar concentrations

Absorption

Maximum plasma concentrations (Cmax) observed between 0.5 hours and 6 hours following oral administration; food effect: high-fat meal increased the mean AUC by 14%

Distribution

Apparent volume of distribution is 2505 (CV% 93%); approximately 96% binding of Dasatinib to human plasma proteins in vitro

Elimination

Mean terminal half-life of Dasatinib is 3 to 5 hours; mean apparent oral clearance is 363.8 l/hr (CV% 81.3%); elimination primarily via the feces

Metabolism

Metabolized primarily by CYP3A4; exposure of active metabolite represents approximately 5% of the AUC of Dasatinib

Excretion

Primarily via the feces; 4% of the administered radioactivity recovered in urine and 85% in feces within 10 days

Dosage & Administration

• Recommended starting dosage for chronic phase CML in adults: 100 mg once daily
• Recommended starting dosage for accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL in adults: 140 mg once daily
• Recommended starting dosage for pediatric patients with CML or Ph+ ALL based on body weight
• Tablets should be swallowed whole and can be taken with or without a meal

Interaction

• Strong CYP3A4 Inhibitors: May increase Dasaren concentrations; concomitant use should be avoided or dose reduction should be considered
• Strong CYP3A4 Inducers: May decrease Dasaren concentrations; use alternative drugs with less enzyme induction potential or consider dose increase
• Gastric Acid Reducing Agents: May decrease the concentrations of Dasaren; H2 antagonists or proton pump inhibitors should not be administered with Dasaren

Contraindications

• Known hypersensitivity to Dasatinib or any component of the formulation

Side Effects

• Myelosuppression
• Bleeding-related events
• Fluid retention
• Cardiovascular events
• Pulmonary arterial hypertension
• QT prolongation
• Severe dermatologic reactions
• Tumor lysis syndrome
• Effects on growth and development in pediatric patients

Pregnancy & Lactation

• Fetal Harm: Can cause fetal harm when administered to a pregnant woman; females of reproductive potential should use effective contraceptive methods during treatment and avoid breastfeeding

Precautions & Warnings

• Myelosuppression associated with severe thrombocytopenia, neutropenia, and anemia
• Bleeding-related events
• Fluid retention
• Cardiovascular events
• Pulmonary arterial hypertension
• QT prolongation
• Severe dermatologic reactions
• Tumor lysis syndrome

Overdose Effects

Limited experience with overdose; reported severe myelosuppression and bleeding

Mode of Action

Dasatinib inhibits BCR-ABL, SRC family kinases, c-KIT, EPHA2, and PDGFRβ at nanomolar concentrations

Pediatric Use

Safety profile comparable to that reported in studies in adult subjects with chronic phase CML; bone growth and development should be monitored

Elemination

Mean terminal half-life of Dasatinib is 3 to 5 hours

Metabolites

• Inactive oxidative metabolites

Storage Conditions

• Below 30°C in a dry place
• Protected from light
• Keep out of the reach of children

Related Brands

• Dasaren 140 mg (Tablet) - renata-limited