It is a topoisomerase inhibitor indicated for: ? First-line therapy in combination with 5-fluorouracil and leucovorin for patients with metastatic carcinoma of the colon or rectum. ? Patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy.
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. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks.
Colorectal cancer combination regimen 1: irinotecan 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) ? Colorectal cancer combination regimen 2: irinotecan 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) ? Colorectal cancer single agent regimen 1: irinotecan 125 mg/m2 intravenous infusion over 90 minutes on days 1,8,15,22 then 2-week rest. (2.2) ? Colorectal cancer single agent regimen 2: irinotecan 350 mg/m2 intravenous infusion over 90 minutes on day 1 every 3 weeks. (2.2)
Diuretics increase risks of dehydration secondary to vomiting/diarrhoea; prophylactic dexamethasone as an antiemetic may enhance lymphocytopenia; prochlorperazine may increase incidence of akathisia; antineoplastic agents (myelosuppression and diarrhoea). St John's wort, ketoconazole may reduce irinotecan exposure.
Diarrhea and Cholinergic Reactions: Early diarrhea (occurring during or shortly after infusion of irinotecan) 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) can occur. Monitor and replace fluid and electrolytes. Treat with loperamide. Use antibiotic support for ileus and fever.Interrupt irinotecan and reduce subsequent doses if severe diarrhea occurs. ? Myelosuppression: Manage promptly with antibiotic support. Interrupt irinotecan and reduce subsequent doses if necessary. ? Patients with Reduced UGT1A1 Activity: Individuals who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia following initiation of irinotecan treatment. ? Hypersensitivity: Hypersensitivity reactions including severe anaphylactic or anaphylactoid reactions have been observed. Discontinue irinotecan if this occurs. ? 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. ? Pulmonary Toxicity: Interstitial Pulmonary Disease (IPD)-like events,including fatalities,have occurred. Interrupt for new or progressive dysnpnea,cough,and fever pending evaluation. If IPD diagnosed,discontinue and institute appropriate treatment as needed. ? Toxicity of the 5 Day Regimen: irinotecan 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. ? Embryofetal Toxicity: irinotecan can cause fetal harm when administered to a pregnant woman. ? Patients with Hepatic Impairment: In clinical trials,irinotecan 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.
nausea,vomiting,abdominal pain,diarrhea,constipation,anorexia,mucositis,neutropenia,leukopenia (including lymphocytopenia),anemia,thrombocytopenia,asthenia,pain,fever,infection,abnormal bilirubin,alopecia.
Nursing Mothers: Discontinue nursing when receiving therapy with it.
In U.S. phase 1 trials, single doses of up to 345 mg/m2 of irinotecan were administered to
patients with various cancers. Single doses of up to 750 mg/m2 of irinotecan have been given in
non-U.S. trials. The adverse events in these patients were similar to those reported with the
recommended dosage and regimen. There have been reports of overdosage at doses up to
approximately twice the recommended therapeutic dose, which may be fatal. The most
significant adverse reactions reported were severe neutropenia and severe diarrhea. There is no
known antidote for overdosage of CAMPTOSAR. Maximum supportive care should be
instituted to prevent dehydration due to diarrhea and to treat any infectious complications.
Store at controlled room temperature 15° to 30°C. Protect from light. Keep the vial in the carton until the time of use.
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