Irinotecan

FDA label

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Titration Weekly single-agent only: if no toxicity, may increase by 25 mg/m2 at start of next cycle up to 150 mg/m2

Renal Not evaluated — use caution in renal impairment; not recommended in patients on dialysis

Hepatic Use caution — clearance reduced and active metabolite SN-38 increased proportional to impairment; no dosing recommendation possible for bilirubin >2 mg/dL; consider 1-dose-level starting reduction for increased bilirubin; bilirubin 1-2 mg/dL (weekly regimen) carries higher grade 3-4 neutropenia risk

Do not use with the 4-5 consecutive-day 5-FU/LV regimen outside a clinical study

Instructions

• Premedicate with antiemetics (e.g., dexamethasone 10 mg + 5-HT3 antagonist) >=30 min before infusion; consider atropine 0.25-1 mg IV/SC prophylactically or for cholinergic symptoms
• Dilute in D5W (preferred) or NS to 0.12-2.8 mg/mL; infuse over 90 min; use ASAP (<=24 h at 2-8 C); single-use vial
• Do not begin a new cycle until granulocytes >=1500/mm3, platelets >=100,000/mm3, and treatment-related diarrhea fully resolved; delay 1-2 weeks for recovery; consider discontinuing if not recovered after 2-week delay
• Consider 1-dose-level starting reduction for prior pelvic/abdominal radiotherapy, performance status 2, or increased bilirubin
• UGT1A1*28/*28, *6/*6, or *6/*28 genotypes: reduce starting dose by at least one level
• Extensive dose-modification tables by toxicity grade (neutropenia, neutropenic fever, diarrhea, other) — see label
• Hazardous drug — special handling; avoid extravasation (flush with sterile water, apply ice if it occurs)

Cautions

• Early (cholinergic) and late diarrhea — late diarrhea can be life-threatening; treat with loperamide, replace fluids/electrolytes, antibiotics for ileus/fever/severe neutropenia
• Myelosuppression — interrupt and reduce dose; deaths from sepsis after severe neutropenia reported
• Reduced UGT1A1 activity (*28/*28, *6/*6, *6/*28) — increased risk of severe neutropenia
• Hypersensitivity including severe anaphylactic/anaphylactoid reactions — discontinue
• Renal impairment/acute renal failure — usually with volume depletion from vomiting/diarrhea
• Interstitial pulmonary disease-like events, including fatal — interrupt for new/progressive dyspnea, cough, fever; discontinue if confirmed
• Embryo-fetal toxicity — effective contraception (females 6 months, males/condoms 3 months after last dose)
• Patients >=65: greater risk of early and late diarrhea — monitor closely; >=70 on q3wk regimen: start 300 mg/m2

Adverse reactions

• Combination (>=30%): nausea, vomiting, abdominal pain, diarrhea, constipation, anorexia, mucositis, neutropenia, leukopenia, anemia, thrombocytopenia, asthenia, pain, fever, infection, abnormal bilirubin, alopecia
• Single agent (>=30%): nausea, vomiting, abdominal pain, diarrhea, constipation, anorexia, neutropenia, leukopenia, anemia, asthenia, fever, weight loss, alopecia

Pregnancy Can cause fetal harm (embryofetal mortality and teratogenicity in animals below clinical exposure); verify pregnancy status; effective contraception during treatment and 6 months after (females); condoms during and 3 months after (males)

Lactation Irinotecan and metabolites present in human milk — do not breastfeed during treatment and for 7 days after final dose