Irinotecan

A to Z Drug Facts

 Action Irinotecan is a derivative of camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks.

 Indications Metastatic cancer of the colon or rectum after standard treatment with fluorouracil. Unlabeled use(s): Cervical cancer, lung cancer (small cell or non-small cell), ovarian cancer.

 Contraindications Standard considerations.

 Route/Dosage

Colon or Rectal Cancer

ADULTS: IV Cycle 1: Irinotecan 125 mg/m² once weekly for 4 wk followed by 2 wk of rest. Subsequent cycles: Give irinotecan once weekly for 4 wk, followed by 2 wk of rest. Based on response and adverse effects, the dose may be adjusted in 25 to 50 mg/m² increments. The weekly dose may be increased to a max of 150 mg/m² or decreased to a min of 50 mg/m². Alternate schedule: Irinotecan 350 mg/m² IV once q 21 days. Give an initial dose of irinotecan 300 mg/m² IV q 21 days in patients at least 70 yr, patients with prior pelvic or abdominal radiation, or patients with a performance status of 2. Based on adverse effects, the dose may be decreased in 50 mg/m² increments to a min of 200 mg/m² (max, 350 mg/m²).

Dosage Adjustment for Hepatic Dysfunction

ADULTS: IV Once-daily regimen: Dosage should be 125 mg/m² if serum bilirubin is less than 1 mg/dL. If bilirubin concentration is 1 to 2 mg/dL, dosage should be 100 mg/m³. Irinotecan is not recommended if bilirubin is more than 2 mg/dL. Every 21-day regimen: Dosage should be 350 mg/m² if serum bilirubin is less than 1 mg/dL. If bilirubin concentration is 1 to 2 mg/dL, dosage should be 300 mg/m². Irinotecan is not recommended if bilirubin is more than 2 mg/dL.

 Interactions

Antineoplastics: Irinotecan adverse effects (eg, myelosuppresion, diarrhea) would possibly be exacerbated by other antineoplastics having similar adverse effects. Dexamethasone: It is possible that coadministration of dexamethasone and irinotecan may enhance the likelihood of lymphocytopenia. Dexamethasone given as emetic prophylaxis can contribute to hyperglycemia in some patients. Laxatives: Laxative therapy during irinotecan therapy may increase the severity of diarrhea, but this has not been studied. Prochloperazine: The incidence of akathesia in clinical trials was greater (8.5%) when prochlorperazine was administered on the same day as irinotecan than when these drugs were given on separate days (1.3%). Diuretics: The health care provider may wish to withhold diuretics during irinotecan dosing during periods of active vomiting or diarrhea because of the potential risk of dehydration secondary to irinotecan-induced vomiting and diarrhea.

 Lab Test Interferences None well documented.

 Adverse Reactions

CV: Flushing; edema. CNS: Insomnia; headache; dizziness. DERM: Alopecia; sweating; rash. GI: Diarrhea (“early” occurring within 24 hr after infusion or “late” occurring an average of 11 to 18 days after infusion); moderate to high potential for nausea and vomiting; anorexia; constipation; flatulence; stomatitis; dyspepsia; abdominal pain; increased LFTs. HEMA: Leukopenia; lymphocytopenia; anemia; moderate to severe neutropenia. Neutrophil nadir occurs between days 15 to 27 with once weekly dosing and at days 8 to 9 with 21-day cycles. RESP: Dyspnea; cough; rhinitis. OTHER: Fever; pain; chills.

 Precautions

Pregnancy: Category D. Lactation: Discontinue nursing when receiving therapy with irinotecan. Children: Safety and efficacy not established. Toxic deaths: Do not use in combination with the “Mayo Clinic” regimen of 5–FU/LV because of reports of increased toxicity, including toxic deaths. Use irinotecan as recommended. Diarrhea: Irinotecan injection can induce early and late forms of diarrhea, which may be severe and appear to be mediated by different mechanisms. Irradiation: Patients who have previously received pelvic/abdominal irradiation are at an increased risk of severe myelosuppression following irinotecan administration. Myelosuppression: Deaths caused by sepsis following severe meylosuppression have been reported in patients treated with irinotecan. Temporarily discontinue therapy if neutropenic fever occurs or if the absolute neutrophil count drops below 1000/mm³. Hypersensitivity reactions: Hypersensitivity reactions including severe anaphylactic or anaphylactoid reactions have been observed. Renal function impairment: Rare cases of renal impairment and acute renal failure have been identified, usually in patients who became volume-depleted from severe vomiting or diarrhea. Elderly: Exercise particular caution in monitoring the effects of irinotecan in the elderly (ie, at least 65 yr). Special risk: It has been noted that patients with modestly elevated baseline serum total bilirubin levels (1 to 2 mg/dL) have had a significantly greater likelihood of experiencing first-course grade 3 or 4 neutropenia than those with bilirubin levels that were less than 1 mg/dL. Extravasation: Local irritation or phlebitis may occur. Refer to the institution-specific protocol. Adverse effects requiring irinotecan dosage modification: See manufacturer's recommendations.

 Administration/Storage

• Store solution for injection at room temperature and protect from light. Store in the protective packaging until just before use.
• Dilute to a final irinotecan concentration of 0.12 to 2.8 mg/mL before administration. The preferred diluent is 5% Dextrose, although 0.9% Sodium Chloride is acceptable. In most clinical trials, doses were diluted in 250 to 500 mL of 5% Dextrose.
• Diluted in 5% Dextrose, the final product is stable for up to 24 hr at ambient room temperature under fluorescent light. When refrigerated, the solution is stable for up to 48 hr. These solutions are preservative-free and should be used within 24 hr.
• When diluted with 0.9% Sodium Chloride, solutions may develop visible particulate matter if refrigerated. The manufacturer recommends using such solutions within 6 hr of preparation.
• IV infusion over 90 min. Shorter infusions (30 min) are associated with a higher incidence of myelosuppression.
• Do not begin a new course of therapy until the granulocyte count has recovered to at least 1500/mm³ and the platelet count has recovered to at least 100,000/mm³ and treatment-related diarrhea is fully resolved. Delay treatment 1 to 2 wk to allow recovery from treatment-related toxicities. If the patient has not recovered after a 2-wk delay, consider discontinuing therapy.
• Premedicate patients with antiemetic agents.

 Assessment/Interventions

• Monitor the WBC with differential, hemoglobin, and platelet count before each irinotecan dose.

 Patient/Family Education

• Instruct patients to call the health care provider if experiencing more than 3 days of diarrhea.
• Inform patients and caregivers of the expected toxic effects of irinotecan, particularly of its GI manifestations, such as nausea, vomiting, and diarrhea. Instruct each patient to have loperamide readily available and to begin treatment for late diarrhea (generally occurring more than 24 hr after administration) at the first episode of poorly formed or loose stools or the earliest onset of bowel movements more frequent than normally expected for the patient. One dosage regimen for loperamide is 4 mg at the first onset of late diarrhea and then 2 mg q 2 hr until the patient is diarrhea-free for at least 12 hr. During the night, the patient may take 4 mg loperamide every 4 hr. Notify health care provider if diarrhea occurs. Premedication with loperamide is not recommended.
• Avoid the use of drugs with laxative properties because of the potential for exacerbation of diarrhea. Advise patients to contact the health care provider to discuss any laxative use.
• Consult health care provider if vomiting or fever occurs or evidence of infection develops, of if symptoms of dehydration, such as fainting, lightheadedness, or dizziness are noted following irinotecan therapy.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts