Nurses Compass
Drug Guide
Irinotecan Hydrochloride
Classification
Therapeutic: Antineoplastic agent
Pharmacological: Topoisomerase I inhibitor
FDA Approved Indications
- Colorectal cancer (metastatic)
- Pancreatic adenocarcinoma (Onivyde)
Mechanism of Action
Irinotecan inhibits topoisomerase I, an enzyme involved in DNA replication. By stabilizing the DNA-topoisomerase I complex, it prevents DNA unwinding and replication, leading to cell death.
Dosage and Administration
Adult: Dose varies by indication and regimen; typically administered IV every 3 weeks or weekly, with supportive medications.
Pediatric: Pregnancy category D; limited data in pediatrics, use with caution.
Geriatric: Adjust dose based on functional status and comorbidities.
Renal Impairment: Adjust dose in severe renal impairment.
Hepatic Impairment: Adjust dose; avoid in severe hepatic impairment.
Pharmacokinetics
Absorption: Administered IV, so absorption is complete.
Distribution: Wide distribution, crosses blood-brain barrier minimally.
Metabolism: Primarily hepatic via carboxylesterases to active metabolite SN-38.
Excretion: Fecal and renal routes.
Half Life: Approximately 3-4 days for the active metabolite SN-38.
Contraindications
- Hypersensitivity to irinotecan or mannitol (used in formulation).
- Severe urinary or hepatic impairment.
Precautions
- Use with caution in immunosuppressed patients, as it causes myelosuppression.
- Monitor for severe diarrhea, neutropenia, and hepatotoxicity.
- Pregnancy risk category D; use effective contraception during treatment.
Adverse Reactions - Common
- Neutropenia (Common)
- Diarrhea (Common)
- Alopecia (Common)
- Nausea and vomiting (Common)
Adverse Reactions - Serious
- Severe neutropenia leading to infection (Serious)
- Severe diarrhea leading to dehydration and electrolyte imbalance (Serious)
- Mucositis (Serious)
- Liver toxicity (Serious)
Drug-Drug Interactions
- Rifampin (may decrease irinotecan levels),
- Ciprofloxacin (may increase levels of SN-38)
- Other myelosuppressive agents
Drug-Food Interactions
- Grapefruit juice (may alter metabolism)
Drug-Herb Interactions
N/ANursing Implications
Assessment: Monitor complete blood counts, liver function tests, and renal function.
Diagnoses:
- Risk for infection (neutropenia)
- Fluid volume deficit (diarrhea)
- Imbalanced nutrition (anorexia)
Implementation: Administer IV as prescribed, premedicate with antiemetics, monitor for signs of toxicity, manage diarrhea proactively.
Evaluation: Assess blood counts, hepatic and renal function regularly, evaluate patient’s response and side effects.
Patient/Family Teaching
- Report any signs of infection, severe diarrhea, or dehydration.
- Use effective contraception during and for at least 6 months after treatment.
- Maintain hydration and nutritional support.
- Follow-up laboratory tests as scheduled.
Special Considerations
Black Box Warnings:
- Severe myelosuppression and diarrhea can be life-threatening.
- Monitor closely for early signs and intervene promptly.
Genetic Factors: UGT1A1 *28/*28 genotype increases risk of severe neutropenia and diarrhea.
Lab Test Interference: May cause transient elevations in liver enzymes; monitor accordingly.
Overdose Management
Signs/Symptoms: Severe myelosuppression, diarrhea, dehydration.
Treatment: Supportive care, including hospitalization, IV fluids, antibiotics for infection, and possibly use of hematopoietic growth factors.
Storage and Handling
Storage: Store at room temperature, protected from light.
Stability: Stable under recommended storage conditions for the duration specified in the package insert.