Nurses Compass
Drug Guide
Dasatinib
Classification
Therapeutic: Antineoplastic Agent
Pharmacological: Tyrosine Kinase Inhibitor
FDA Approved Indications
- Chronic Phase Philadelphia chromosome-positive (Ph+) BCR-ABL positive CML in adults
- Accelerated Phase and Blast Crisis Ph+ CML
- Ph+ Acute Lymphoblastic Leukemia (ALL) in adults and pediatric patients
Mechanism of Action
Dasatinib inhibits BCR-ABL kinase activity, disrupting signals required for the proliferation and survival of leukemia cells. It also inhibits other kinases such as SRC family kinases, contributing to its antileukemic effects.
Dosage and Administration
Adult: The typical dose is 100 mg once daily, taken orally with or without food. Dose adjustments may be required based on response and tolerability.
Pediatric: Dosing in pediatric patients is based on body surface area and clinical response, typically starting at 60 mg/m² daily.
Geriatric: Use with caution; start at lower doses and adjust based on tolerability and response.
Renal Impairment: No initial dose adjustment necessary, but monitor closely.
Hepatic Impairment: Use with caution; no specific dose adjustment recommendations available.
Pharmacokinetics
Absorption: Rapidly absorbed, with peak plasma concentrations achieved in approximately 0.5-4 hours.
Distribution: Extensively bound to plasma proteins (~96%).
Metabolism: Primarily metabolized in the liver via CYP3A4.
Excretion: Excreted mainly in feces (~85%); renal excretion accounts for about 4%.
Half Life: Approximately 5-6 hours.
Contraindications
- Hypersensitivity to dasatinib or any component of the formulation.
Precautions
- Risk of bleeding, so caution in patients with bleeding disorders or on anticoagulants.
- Myelosuppression risk requires blood count monitoring.
- Pregnancy category: D – risk to fetus; use effective contraception during treatment and for at least 30 days after.
Adverse Reactions - Common
- Myelosuppression (neutropenia, anemia, thrombocytopenia) (Very common)
- Fluid retention, pleural effusion (Common)
- GI symptoms (nausea, diarrhea, abdominal pain) (Common)
Adverse Reactions - Serious
- QT prolongation, cardiac arrhythmias (Uncommon but serious)
- Bleeding complications (Uncommon)
- Pulmonary toxicities including pulmonary arterial hypertension (Rare)
Drug-Drug Interactions
- CYP3A4 inhibitors and inducers (affect dasatinib levels)
Drug-Food Interactions
- Grapefruit and Seville oranges may increase plasma levels of dasatinib.
Drug-Herb Interactions
- St. John’s Wort and other CYP3A4 inducers may decrease efficacy.
Nursing Implications
Assessment: Monitor complete blood counts, liver function tests, and cardiac status regularly. Watch for signs of bleeding, infection, or pulmonary issues.
Diagnoses:
- Risk for bleeding
- Impaired skin integrity
- Decreased cardiac output
Implementation: Administer as prescribed, monitor labs, manage side effects, educate patient on signs of adverse reactions.
Evaluation: Assess for hematologic response, tolerability, and adverse effects periodically.
Patient/Family Teaching
- Take medication exactly as prescribed, preferably at the same time daily.
- Report symptoms such as unusual bleeding, SOB, or swelling.
- Avoid grapefruit and Seville oranges.
- Use effective contraception during and after treatment as advised.
- Report any signs of infection or bleeding promptly.
Special Considerations
Black Box Warnings:
- Potential for severe and fatal bleeding, myocardial infarction, and pulmonary hypertension.
Genetic Factors: Pharmacogenetic variations in CYP3A4 may affect drug levels.
Lab Test Interference: May cause false increases in serum amylase and lipase levels.
Overdose Management
Signs/Symptoms: Bleeding, hypotension, arrhythmias, muscle weakness.
Treatment: Supportive care, discontinue dasatinib, manage symptoms, consider gastric lavage or activated charcoal if ingestion is recent.
Storage and Handling
Storage: Store at room temperature, 20-25°C (68-77°F).
Stability: Stable until expiration date when stored properly.