Drug Guide
Nilotinib Tartrate
Classification
Therapeutic: Antineoplastic agent (targeted therapy)
Pharmacological: Tyrosine kinase inhibitor
FDA Approved Indications
- Chronic myeloid leukemia (CML) Philadelphia chromosome-positive (Ph+)
Mechanism of Action
Nilotinib inhibits the BCR-ABL tyrosine kinase, which is produced by the Philadelphia chromosome abnormality in CML cells, thereby inhibiting tumor cell proliferation.
Dosage and Administration
Adult: Typically 300 mg twice daily on an empty stomach, at least 1 hour before or 2 hours after a meal.
Pediatric: Not generally used in pediatric patients.
Geriatric: Adjustments may be necessary based on renal and hepatic function.
Renal Impairment: Use with caution; dose adjustments may be required.
Hepatic Impairment: Use with caution; hepatic function should be monitored; dose adjustments may be necessary.
Pharmacokinetics
Absorption: Rapid absorption with peak plasma concentrations reached within 2 hours.
Distribution: High protein binding (~98%), primarily to plasma proteins.
Metabolism: Primarily metabolized in the liver via CYP3A4 enzyme.
Excretion: Excreted mainly in feces; minor amount in urine.
Half Life: Approximately 17 hours.
Contraindications
- Hypersensitivity to nilotinib or any component of the formulation.
Precautions
- Monitor for QT prolongation, hepatotoxicity, myelosuppression, and interactions with other drugs affecting QT interval. Caution in patients with cardiac history, electrolyte abnormalities, or hepatic impairment. Use during pregnancy only if clearly needed; maternal-fetal risk cannot be ruled out. Lactation is not recommended.
Adverse Reactions - Common
- Fluid retention, fatigue, rash (Frequent)
- Elevation of serum lipase or amylase (Less frequent)
Adverse Reactions - Serious
- QT prolongation, torsades de pointes (Serious and potentially life-threatening)
- Hepatotoxicity, including elevated liver enzymes and hepatic failure (Serious)
- Myelosuppression leading to anemia, neutropenia, thrombocytopenia (Serious)
Drug-Drug Interactions
- CYP3A4 inducers or inhibitors (e.g., ketoconazole, rifampin) which can alter nilotinib levels.
- Agents that prolong QT interval (e.g., certain antiarrhythmics, antipsychotics).
Drug-Food Interactions
- Grapefruit and grapefruit juice may increase plasma concentrations.
Drug-Herb Interactions
- St. John's Wort may reduce effectiveness.
Nursing Implications
Assessment: Monitor complete blood counts, liver function tests, and ECG for QT prolongation.
Diagnoses:
- Risk for infection, risk for bleeding, risk for cardiac arrhythmia.
Implementation: Administer on an empty stomach; monitor for adverse reactions; educate about symptoms of QT prolongation and hepatotoxicity.
Evaluation: Assess response to therapy through hematologic parameters and symptom control; monitor for adverse effects.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Report symptoms like palpitations, dizziness, jaundice, or unusual bleeding.
- Avoid grapefruit products.
- Attend regular blood tests and ECGs.
- Do not discontinue without consulting healthcare provider.
Special Considerations
Black Box Warnings:
- QT prolongation and sudden death.
- Hepatotoxicity.
Genetic Factors: Patients with CYP3A4 polymorphisms may have altered drug metabolism.
Lab Test Interference: May cause elevated serum lipases, liver enzymes, and electrolyte imbalances.
Overdose Management
Signs/Symptoms: Severe nausea, vomiting, diarrhea, signs of cardiac arrhythmia, or hepatotoxicity.
Treatment: Supportive care, continuous ECG monitoring, activated charcoal if ingestion occurred recently, and specific interventions as indicated.
Storage and Handling
Storage: Store at 20°C to 25°C (68°F to 77°F); protect from moisture.
Stability: Stable under recommended storage conditions; consult manufacturer for specific stability data.