[8] Common side effects include diarrhea, vomiting, bone marrow suppression, hair loss, shortness of breath, and fever.

[8] Other severe side effects include blood clots, colon inflammation, and allergic reactions.

[10] It is made from the natural compound camptothecin which is found in the Chinese ornamental tree Camptotheca acuminata.

[6] In February 2024, the US Food and Drug Administration (FDA) approved irinotecan liposome, in combination with oxaliplatin, fluorouracil, and leucovorin, for the first-line treatment of metastatic pancreatic adenocarcinoma.

[14][6] The most significant adverse effects of irinotecan include diarrhea, nausea and vomiting, neutropenia and fever, infections of blood or lungs (sepsis, pneumonia), shock, dehydration, kidney failure and thrombocytopenia (low levels of blood platelets).

Late diarrhea occurs more than 24 hours after administration of Irinotecan and can be life threatening, sometimes leading to severe dehydration requiring hospitalization or intensive care unit admission.

[15] The molecular action of irinotecan occurs by trapping a subset of topoisomerase-1-DNA cleavage complexes, those with a guanine +1 in the DNA sequence.

[19] One irinotecan molecule stacks against the base pairs flanking the topoisomerase-induced cleavage site and poisons (inactivates) the topoisomerase 1 enzyme.

[21] About 2–5% of the pro-drug irinotecan is hydrolyzed into its active metabolite SN-38 in the liver by two carboxylesterase converting enzymes (CES1 and CES2) and in plasma by butyrylcholinesterase (hBChE).

[21][22] SN-38 is inactivated by glucuronidation to SN-38G (β-glucuronide conjugate) by several uridine diphosphate glucuronosyltransferase enzymes (UGTs) in the liver (UGT1A1, UGT1A9) and extra-hepatic (UGT1A1, UGT1A7, UGT1A10) and excreted into the bile.

[21][22] Irinotecan elimination half-lives were reported between 5 and 18 h. SN-38 half-lives were reported between 6 and 32 h.[21] There is high (30%) interindividual variability in irinotecan pharmacokinetic parameters which can be altered by several factors including age, sex, dose, administration timing, hepatic function, enzyme activity or hematocrit levels.

During chemotherapy, they effectively receive a larger than expected dose because their bodies are not able to clear irinotecan as fast as others.

[24] In February 2024, the FDA approved irinotecan liposome, in combination with oxaliplatin, fluorouracil, and leucovorin, for the first-line treatment of metastatic pancreatic adenocarcinoma.

[26][27][28] A liposome encapsulated version of irinotecan sold under the brand name Onivyde, was approved by the FDA in October 2015, to treat metastatic pancreatic cancer.