Nurses Compass
Drug Guide
Pazopanib Hydrochloride
Classification
Therapeutic: Antineoplastic Agent (Cancer treatment)
Pharmacological: Tyrosine Kinase Inhibitor
FDA Approved Indications
- Renal cell carcinoma (advanced and metastatic)
- Soft tissue sarcoma (adults who have received prior chemotherapy)
Mechanism of Action
Pazopanib inhibits multiple receptor tyrosine kinases involved in tumor growth and angiogenesis, including VEGFR, PDGFR, and c-Kit, thereby reducing blood supply to tumors and inhibiting their growth.
Dosage and Administration
Adult: Typically 800 mg once daily, with or without food. Dose adjustments may be necessary based on tolerance and adverse effects.
Pediatric: Not approved for pediatric use; safety and efficacy not established.
Geriatric: No specific dosing adjustments, but cautious use due to potential increased sensitivity and comorbidities.
Renal Impairment: Adjustments may be needed; consult prescribing information.
Hepatic Impairment: Use with caution; dose adjustments are recommended, especially in mild to moderate impairment.
Pharmacokinetics
Absorption: Well absorbed orally, peak plasma levels in 3 hours.
Distribution: High plasma protein binding (~99.9%).
Metabolism: Metabolized primarily via CYP3A4; minor pathways include CYP1A2 and CYP2C8.
Excretion: Excreted mainly in feces (~61%) and urine (~13%).
Half Life: Approximately 31 hours.
Contraindications
- Hypersensitivity to pazopanib or any component of the formulation.
Precautions
- Use with caution in hepatic impairment, bleeding risk, hypertension, and during pregnancy. Regular monitoring of blood pressure, liver function, and blood counts is recommended.
Adverse Reactions - Common
- Hypertension (Very common)
- Diarrhea (Common)
- Nausea (Common)
- Fatigue (Common)
- Altered taste (Common)
Adverse Reactions - Serious
- Hepatotoxicity (Serious, requires monitoring)
- Bleeding and hemorrhage (Serious, use caution in patients at risk)
- Cardiac dysfunction, including Heart failure (Serious)
- Gastrointestinal perforation or fistulae (Serious)
- Hypertension, severe (Serious)
Drug-Drug Interactions
- CYP3A4 inhibitors (e.g., ketoconazole) increase pazopanib levels.
- CYP3A4 inducers (e.g., rifampin) decrease efficacy.
- Anticoagulants (e.g., warfarin) — increased bleeding risk.
Drug-Food Interactions
- High-fat meals may alter absorption.
- Avoid grapefruit juice and grape juice — may increase plasma concentrations.
Drug-Herb Interactions
- St. John’s wort can decrease pazopanib levels.
Nursing Implications
Assessment: Monitor blood pressure, liver function tests, complete blood counts, and signs of bleeding or adverse effects.
Diagnoses:
- Risk of bleeding
- Risk for hepatotoxicity
- Hypertension
Implementation: Administer as prescribed, monitor labs regularly, educate patient about adverse effects and adherence.
Evaluation: Assessment of adverse effects, efficacy in tumor control, and patient’s overall tolerance.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Report any signs of bleeding, severe abdominal pain, jaundice, or unusual fatigue.
- Typically taken once daily, with or without food.
- Avoid grapefruit juice and alcohol.
- Keep regular follow-up appointments for blood tests and monitoring.
Special Considerations
Black Box Warnings:
- Hepatotoxicity and severe hepatic failure (monitor liver function closely).
- Risk of arterial thromboembolic events.
Genetic Factors: None specific but consider genetic testing if relevant.
Lab Test Interference: May affect thyroid function tests and liver enzymes.
Overdose Management
Signs/Symptoms: Nausea, vomiting, diarrhea, hepatotoxicity, bleeding, hypertension.
Treatment: Supportive care, activated charcoal if ingestion was recent, symptomatic treatment, and monitoring for adverse effects.
Storage and Handling
Storage: Store at room temperature, 20°C to 25°C (68°F to 77°F).
Stability: Stable when kept in original container, away from moisture and light.