Irinotecan Hydrochloride Injection, USP is a topoisomerase inhibitor indicated for:

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First-line therapy in combination with 5-fluorouracil and leucovorin for patients with metastatic carcinoma of the colon or rectum. (1)

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Patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy. (1)

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Colorectal cancer combination regimen 1: Irinotecan Hydrochloride Injection, USP 125 mg/m2 intravenous infusion over 90 minutes on days 1, 8,15, 22 with LV 20 mg/m2 intravenous bolus infusion on days 1, 8, 15, 22 followed by 5-FU intravenous bolus infusion on days 1, 8, 15, 22 every 6 weeks. (2.1)

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Colorectal cancer combination regimen 2: Irinotecan Hydrochloride Injection, USP 180 mg/m2 intravenous infusion over 90 minutes on days 1, 15, 29 with LV 200 mg/m2 intravenous infusion over 2 hours on days 1, 2, 15, 16, 29, 30 followed by 5-FU 400 mg/m2 intravenous bolus infusion on days 1, 2, 15, 16, 29, 30 and 5-FU 600 mg/m2 intravenous infusion over 22 hours on days 1, 2, 15, 16, 29, 30. (2.1)

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Colorectal cancer single agent regimen 1: Irinotecan Hydrochloride Injection, USP 125 mg/m2 intravenous infusion over 90 minutes on days 1, 8, 15, 22 then 2-week rest. (2.2)

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Colorectal cancer single agent regimen 2: Irinotecan Hydrochloride Injection, USP 350 mg/m2 intravenous infusion over 90 minutes on day 1 every 3 weeks. (2.2)

Injection: 40 mg/2 mL (20 mg/mL), 100 mg/5 mL (20 mg/mL), and 500 mg/25 mL (20 mg/mL) solution in a single-dose vial. (3)

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Hypersensitivity to Irinotecan Hydrochloride Injection, USP or its excipients (4)

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Diarrhea and Cholinergic Reactions: Early diarrhea (occurring during or shortly after infusion of Irinotecan Hydrochloride Injection, USP) is usually transient and may be accompanied by cholinergic symptoms. Consider prophylactic or therapeutic administration of 0.25 mg to 1 mg of intravenous or subcutaneous atropine (unless clinically contraindicated). Late diarrhea (generally occurring more than 24 hours after administration of Irinotecan Hydrochloride Injection, USP) can occur. Monitor and replace fluid and electrolytes. Treat with loperamide. Use antibiotic support for ileus and fever. Interrupt Irinotecan Hydrochloride Injection, USP and reduce subsequent doses if severe diarrhea occurs. (5.1)

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Myelosuppression: Manage promptly with antibiotic support. Interrupt Irinotecan Hydrochloride Injection, USP and reduce subsequent doses if necessary. (5.2)

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Increased Risk of Neutropenia in Patients With Reduced UGT1A1 Activity: Individuals with UGT1A1*28/*28, or *6/*6, or *6/*28 genotypes are at increased risk for severe neutropenia during Irinotecan Hydrochloride Injection, USP treatment. (5.3)

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Hypersensitivity: Hypersensitivity reactions including severe anaphylactic or anaphylactoid reactions have been observed. Discontinue Irinotecan Hydrochloride Injection, USP if this occurs. (5.4)

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Renal Impairment/Renal Failure: Rare cases of renal impairment and acute renal failure have been identified, usually in patients who became volume depleted from severe vomiting and/or diarrhea. (5.5)

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Pulmonary Toxicity: Interstitial Pulmonary Disease (IPD)-like events, including fatalities, have occurred. Interrupt for new or progressive dyspnea, cough, and fever pending evaluation. If IPD diagnosed, discontinue and institute appropriate treatment as needed. (5.6)

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Toxicity of the 5 Day Regimen: Irinotecan Hydrochloride Injection, USP should not be used in combination with a regimen of 5-FU/LV administered for 4–5 consecutive days every 4 weeks outside of a clinical study. (5.7)

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Embryo-Fetal Toxicity: Irinotecan Hydrochloride Injection, USP can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. Advise male patients with female partners of reproductive potential to use condoms. (5.9, 8.1, 8.3)

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Patients With Hepatic Impairment: In clinical trials, Irinotecan Hydrochloride Injection, USP has not been administered to patients with serum bilirubin >2.0 mg/dL, or transaminases >3 times ULN if no liver metastases, or transaminases >5 times ULN if liver metastases. With the weekly dosage schedule, patients with total bilirubin levels 1.0–2.0 mg/dL had greater likelihood of grade 3–4 neutropenia. (5.10)

Common adverse reactions (≥30%) observed in combination therapy clinical studies are: nausea, vomiting, abdominal pain, diarrhea, constipation, anorexia, mucositis, neutropenia, leukopenia (including lymphocytopenia), anemia, thrombocytopenia, asthenia, pain, fever, infection, abnormal bilirubin, alopecia. (6.1)

Common adverse reactions (≥30%) observed in single agent therapy clinical studies are: nausea, vomiting, abdominal pain, diarrhea, constipation, anorexia, neutropenia, leukopenia (including lymphocytopenia), anemia, asthenia, fever, body weight decreasing, alopecia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc. at 1-800-441-4100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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Strong CYP3A4 Inducers: Do not administer strong CYP3A4 inducers with Irinotecan Hydrochloride Injection, USP. (7.2)

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Strong CYP3A4 Inhibitors: Do not administer strong CYP3A4 inhibitors with Irinotecan Hydrochloride Injection, USP. (7.3)

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Lactation: Advise not to breastfeed. (8.2)

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Geriatric Use: Closely monitor patients greater than 65 years of age because of a greater risk of early and late diarrhea in this population. (8.5)

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Patients With Renal Impairment: Use caution and do not use in patients on dialysis. (8.6)

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Patients With Hepatic Impairment: Use caution. (2.1, 5.10, 8.7, 12.3)