Irinotecan Hydrochloride

⛔ FDA Black Box Warning

WARNING: DIARRHEA and MYELOSUPPRESSION Early and late forms of diarrhea can occur. Early diarrhea may be accompanied by cholinergic symptoms which may be prevented or ameliorated by atropine. Late diarrhea can be life threatening and should be treated promptly with loperamide. Monitor patients with diarrhea and give fluid and electrolytes as needed. Institute antibiotic therapy if patients develop ileus, fever, or severe neutropenia. Interrupt irinotecan hydrochloride injection and reduce subsequent doses if severe diarrhea occurs [see Dosage and Administration ( 2.2 ) and Warnings and Precautions ( 5.1 )] . Severe myelosuppression may occur [see Warnings and Precautions ( 5.2 )] . WARNING: DIARRHEA and MYELOSUPPRESSION See full prescribing information for complete boxed warning. Early and late forms of diarrhea can occur. Early diarrhea may be accompanied by cholinergic symptoms which may be prevented or ameliorated by atropine. Late diarrhea can be life threatening and should be treated promptly with loperamide. Monitor patients with diarrhea and give fluid and electrolytes as needed. Institute antibiotic therapy if patients develop ileus, fever, or severe neutropenia. Interrupt irinotecan hydrochloride injection and reduce subsequent doses if severe diarrhea occurs. ( 2.2 , 5.1 ) Severe myelosuppression may occur. ( 5.2 )

Contraindications

4 CONTRAINDICATIONS Irinotecan Hydrochloride Injection is contraindicated in patients with a known hypersensitivity to the drug or its excipients. Hypersensitivity to Irinotecan Hydrochloride Injection or its excipients ( 4 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, irinotecan hydrochloride injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . Available postmarketing and published data reporting the use of irinotecan hydrochloride injection in pregnant women, are insufficient and confounded by the concomitant use of other cytotoxic drugs, to evaluate for any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, intravenous administration of irinotecan to rats and rabbits during the period of organogenesis resulted in embryo-fetal mortality and teratogenicity in pregnant animals at exposures lower than the human exposure based on AUC at the clinical dose of 125 mg/m 2 ( see Data ). Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Radioactivity related to 14 C-irinotecan crosses the placenta of rats following intravenous administration. Intravenous administration of irinotecan to rats at a dose of 6 mg/kg/day (approximately 0.2 times the clinical exposure (AUC) at the 125 mg/m 2 dose based on exposure data from a separate rat study) during the period of organogenesis resulted in increased post-implantation loss and decreased numbers of live fetuses; at doses ≥ 1.2 mg/kg/day (approximately 0.03 times the clinical exposure (AUC) at the 125 mg/m 2 dose based on exposure data from a separate rat study) there were increases in a variety of external, visceral, and skeletal abnormalities. Administration of irinotecan to pregnant rabbits at a dose of 6 mg/kg (approximately half of the clinical dose of 125 mg/m 2 based on BSA) resulted in similar findings to those in rats, with increased post-implantation loss, decreased live fetuses