irinotecan hydrochloride

irinotecan hydrochloride Warning - Hazardous drug!

Campto (UK), Camptosar

Pharmacologic class: Topoisomerase inhibitor

Therapeutic class: Hormonal antineoplastic

Pregnancy risk category D

FDA Boxed Warning

• Give under supervision of physician experienced in using cancer chemotherapy, in facility with adequate diagnostic and treatment resources.
• Drug can cause both early and late forms of diarrhea that may be severe. Early diarrhea (arising during or shortly after drug infusion) may be accompanied by cholinergic symptoms; atropine may prevent or relieve it. Late diarrhea (generally arising more than 24 hours after administration) can be life-threatening and prolonged, and may lead to dehydration, electrolyte imbalance, or sepsis. For late diarrhea, give loperamide promptly.
• Drug may cause severe myelosuppression.

Action

Inhibits topoisomerase 1 (an enzyme that allows DNA replication) by binding to it. This action prevents religation of DNA strand, which results in breakage of double-stranded DNA and cell death.

Availability

Injection: 20 mg/ml in 2-ml and 5-ml vials

⊘Indications and dosages

➣ Metastatic colorectal cancer recurrence or progression after fluorouracil (5-FU) therapy

Adults: 125 mg/m² I.V. infused over 90 minutes on days 1, 8, 15, and 22, followed by a 2-week rest; given with leucovorin and 5-FU. Or, 180 mg/m² I.V. infused over 90 minutes on days 1, 15, and 29 with leucovorin, 5-FU bolus, and 5-FU infusion. Or as monotherapy, 125 mg/m² I.V. infused over 90 minutes weekly for 4 weeks, followed by a 2-week rest; or, 350 mg/m² I.V. infused over 90 minutes q 3 weeks as long as tolerable. Adjust dosage based on tolerance.

Off-label uses

• Most cancers

Contraindications

• Hypersensitivity to drug
• Concurrent atazanavir use
• Pregnancy or breastfeeding

Precautions

Use cautiously in:
• bone marrow depression, severe diarrhea
• patients undergoing radiation therapy
• elderly patients
• children.

Administration

☞ Follow facility policy for handling antineoplastics. If skin contact occurs, wash with soap and water immediately and thoroughly. If mucous membrane contact occurs, flush with water.
• Dilute in dextrose 5% in water or normal saline solution, to a concentration of 0.12 to 1.1 mg/ml.
• Infuse within 6 hours if drug is stored at room temperature or within 24 hours if refrigerated.
• Give single dose by I.V. infusion over 90 minutes.
• Administer antiemetic to ease nausea and vomiting, as needed and prescribed.

Route	Onset	Peak	Duration
I.V.	Immediate	1-2 hr	Unknown

Adverse reactions

CNS: insomnia, dizziness, asthenia, headache, akathisia

CV: vasodilation, orthostatic hypotension

EENT: rhinitis

GI: nausea, vomiting, constipation, diarrhea, flatulence, dyspepsia, abdominal pain or enlargement, stomatitis, anorexia

Hematologic: anemia, neutropenia, leukopenia, thrombocytopenia

Hepatic: hepatotoxicity

Metabolic: dehydration

Musculoskeletal: back pain

Respiratory: dyspnea, increased cough

Skin: alopecia, diaphoresis, rash

Other: weight loss, edema, fever, pain, chills, minor infections

Interactions

Drug-drug. Dexamethasone: increased risk of lymphocytopenia

Diuretics: increased risk of dehydration

Laxatives: increased risk of diarrhea

Other antineoplastics: additive adverse effects

Drug-diagnostic tests. Alkaline phosphatase: increased level

Hemoglobin, neutrophils, white blood cells: decreased values

Patient monitoring

☞ Assess CBC before each infusion. Withhold dose if neutrophil count is below 1,500 cells/mm³.
• Monitor infusion site for extravasation; if it occurs, flush with sterile water and apply ice.
• Assess fluid intake and output. Keep patient well hydrated.
• Monitor oral intake. Evaluate for nausea and vomiting.
• Assess for diarrhea. In severe diarrhea, expect to decrease dosage or withhold dose.
• Institute infection-control protocols to help prevent infection.
• Monitor liver function test results.

Patient teaching

• Inform patient that blood tests will be done before each dose.
• Instruct patient to report pain at infusion site; severe nausea or vomiting; severe, increased, or bloody diarrhea; infection; or injury.
☞ Instruct patient to immediately report unusual tiredness or yellowing of skin or eyes.
• Tell patient that drug increases his risk of infection. Advise him to avoid crowds and other potential infection sources.
• Caution female patient not to breastfeed or become pregnant during therapy. Recommend barrier contraception.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.