Nurses Compass
Drug Guide
Lapatinib Ditosylate
Classification
Therapeutic: Antineoplastic agent
Pharmacological: Tyrosine kinase inhibitor
FDA Approved Indications
- Treatment of advanced or metastatic HER2-positive breast cancer
Mechanism of Action
Lapatinib inhibits both epidermal growth factor receptor (EGFR, HER1) and HER2 tyrosine kinases, blocking downstream signaling pathways involved in tumor cell proliferation and survival.
Dosage and Administration
Adult: Usually 1250 mg orally once daily, in combination with capecitabine or other agents, as per prescribing guidelines.
Pediatric: Not approved for pediatric use; safety and efficacy not established.
Geriatric: No specific dosage adjustments indicated, but caution advised due to potential comorbidities.
Renal Impairment: No dosage adjustment necessary for mild to moderate impairment.
Hepatic Impairment: Use with caution; patients with hepatic impairment may require dose adjustments based on liver function tests.
Pharmacokinetics
Absorption: Lapatinib has variable absorption, enhanced when taken with food.
Distribution: Extensively protein-bound (~99.5%).
Metabolism: Primarily metabolized by CYP3A4 and, to a lesser extent, CYP2C8.
Excretion: Primarily via feces; minimal renal excretion.
Half Life: Approximately 24 hours.
Contraindications
- Hypersensitivity to lapatinib or any component of the formulation.
Precautions
- Risk of hepatotoxicity; monitor liver function.
- QT prolongation; monitor EKG and electrolytes.
- Potential for cardiotoxicity; baseline and periodic cardiac function tests recommended.
- Pregnancy Category D: risk to fetus. Use effective contraception during treatment and for period after.
Adverse Reactions - Common
- Diarrhea (Common)
- Nausea (Common)
- Rash (Common)
- Hand-foot skin reaction (Common)
- Fatigue (Common)
Adverse Reactions - Serious
- Hepatotoxicity (elevated liver enzymes, hepatitis) (Uncommon to rare)
- QT prolongation, arrhythmias (Uncommon)
- Cardiotoxicity (heart failure) (Rare)
- Interstitial lung disease (Rare)
Drug-Drug Interactions
- Cyclosporine, which can increase lapatinib levels.
- Concurrent use with other QT prolonging drugs increases cardiac risk.
Drug-Food Interactions
- High-fat meals can increase absorption, but also increase risk of toxicity; should be taken consistently either with or without food.
Drug-Herb Interactions
- St. John’s Wort (CYP3A4 inducer) can decrease effectiveness.
Nursing Implications
Assessment: Monitor hepatic function, cardiac function (ECG), and evaluate for signs of toxicity.
Diagnoses:
- Risk for hepatotoxicity
- Risk for cardiac arrhythmias
Implementation: Administer as prescribed; monitor liver enzymes, ECG; counsel on signs of toxicity.
Evaluation: Assess for adverse effects, therapeutic response, and laboratory values.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Report symptoms of hepatotoxicity (yellowing skin or eyes, dark urine), cardiotoxicity (chest pain, palpitations), or severe diarrhea.
- Avoid grapefruit and grapefruit juice, which can increase drug levels.
- Use effective contraception during and after treatment as directed.
Special Considerations
Black Box Warnings:
- Fatal hepatotoxicity.
- Cardiac dysfunction including heart failure and QT prolongation.
Genetic Factors: No specific genetic testing mandated but be aware of pharmacogenomic implications for metabolism.
Lab Test Interference: May cause elevated liver function tests; monitor accordingly.
Overdose Management
Signs/Symptoms: Severe diarrhea, nausea, vomiting, hepatotoxicity, arrhythmias.
Treatment: Supportive care, discontinue lapatinib, monitor cardiac and hepatic function, provide symptomatic treatment.
Storage and Handling
Storage: Store at 20°C to 25°C (68°F to 77°F); protect from moisture.
Stability: Stable under standard conditions for storing pharmaceuticals.