Mechanism of effect
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 .
Pharmacodynamic
Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of Irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38. Mammalian cells cannot efficiently repair these doublestrand breaks.
Pharmacokinetics
After intravenous infusion of Irinotecan in humans, Irinotecan plasma concentrations decline in a multiexponential manner, with a mean terminal elimination half-life of about 6 to 12 hours.Irinotecan exhibits moderate plasma protein binding (30% to 68% bound). SN-38 is highly bound to human plasma proteins (approximately 95% bound).
Irinotecan is subject to extensive metabolic conversion by various enzyme systems, including esterases to form the active metabolite SN-38 and UGT1A1 mediating glucuronidation of SN-38 to form the inactive glucuronide metabolite SN-38G. The urinary excretion of Irinotecan is 11% to 20%; SN-38, <1%; and SN-38 glucuronide, 3%.
Dosage
Usual Adult Dose for Colorectal Cancer
Either as a single agent or in combination with fluorouracil and leucovorin :
125 mg/m2 intravenously over 90 minutes once a week for leucovorin
or
as a single agent :
350 mg/m2 intravenously over 90 minutes every three weeks
or
in combination with fluorouracil and leucovorin :
180 mg/m2 intravenously over 90 minutes every other week for three doses.
Drug contraindications
hypersensitivity to this drugSide effects
nausea , Headache , constipation , vomiting , vertigo , Diarrhea , edema , Cough , fever , weight decrease , Infections , anorexia , hemorrhage , itching , flatulence , sweating , stinging , Leukopenia , Infection , Mucositis , Rash , Back pain , rhinitisInteractions
Itraconazole , Rifampin , Succinylcholine , Phenobarbital , Phenytoin , Voriconazole , Ketoconazole , Lopinavir , Clarithromycin , Rifapentine , Fluorouracil , Nefazodone , ritonavir , saquinavir , Vitamin A , Vitamin E , Carbamazepine , Rifabutin , nelfinavir , mitotane , Zileuton , Idelalisib , Efavirenz , Tipranavir , Etravirine , Panitumumab , Mibefradil , cobicistat , Delavirdine , Adenovirus types 4 and 7 live, oral , Apalutamide , Crizotinib , oleandomycin , Cannabidiol , lasmiditan , Meningococcal conjugate vaccine , tucatinibAlerts
Early diarrhea (occurring during or shortly after infusion of Irinotecan hydrochloride injection) is usually transient and infrequently severe.
It may be accompanied by cholinergic symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, and intestinal hyperperistalsis that can cause abdominal cramping.
Bradycardia may also occur. Early diarrhea and other cholinergic symptoms may be prevented or treated.
Deaths due to sepsis following severe neutropenia have been reported in patients treated with Irinotecan hydrochloride injection.
Hypersensitivity reactions including severe anaphylactic or anaphylactoid reactions have been observed. Discontinue Irinotecan hydrochloride injection if anaphylactic reaction occurs.
Renal impairment and acute renal failure have been identified, usually in patients who became volume depleted from severe vomiting and/or diarrhea.
Interstitial Pulmonary Disease (IPD)-like events, including fatalities, have occurred in patients receiving Irinotecan (in combination and as monotherapy).
Risk factors include pre-existing lung disease, use of pneumotoxic drugs, radiation therapy, and colony stimulating factors.
Irinotecan hydrochloride injection can cause fetal harm when administered to a pregnant woman.
Points of recommendation
Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
• if you are pregnant, planning to become pregnant, or are breast-feeding
• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
• if you have allergies to medicines, foods, or other substances
• if you have liver disease; a blood disorder; bone marrow depression; diabetes or high blood sugar; kidney or lung disease; or herpes zoster, varicella, or another infection; or you cannot tolerate fructose
• if you have recently received or will be receiving a live vaccine (eg, measles, mumps)
• if you have recently had or will be having dental procedures or radiation therapy
Drink plenty of water and other clear liquids while using irinotecan .
If you miss a dose of irinotecan, contact your doctor right away.
Ask a Pharmacist