irinotecan hydrochloride

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 or recurrence or progression of metastatic colorectal cancer 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 followed by a 2-week rest. Or as monotherapy, 125 mg/m² I.V. infused over 90 minutes weekly for 4 weeks, followed by a 2-week rest period; or, 350 mg/m² I.V. infused over 90 minutes q 3 weeks as long as tolerable. Adjust dosage in increments based on tolerance and age.

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

See 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.

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

See 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.

See 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.