IrinotecanClinical dataTrade namesCamptosar (US), Campto (EU), Onivyde (liposomal)AHFS\/Drugs.comMonographMedlinePlusa608043Pregnancycategory<\/p>\n
O=C7OCC=6C(=O)N2C(c1nc5c(c(c1C2)CC)cc(OC(=O)N4CCC(N3CCCCC3)CC4)cc5)=C\/C=6[C@@]7(O)CC<\/p>\n
Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer and small cell lung cancer.[1] For colon cancer it is used either alone or with fluorouracil.[1] For small cell lung cancer it is used with cisplatin.[1] It is given by slow injection into a vein.[1]<\/p>\n
Common side effects include diarrhea, vomiting, bone marrow suppression, hair loss, shortness of breath, and fever.[1] Other severe side effects include blood clots, colon inflammation, and allergic reactions.[1] Those with two copies of the UGT1A1*28 gene variant are at higher risk for side effects.[1] Use during pregnancy can result in harm to the baby.[1] Irinotecan is in topoisomerase inhibitor family of medication.[2] It works by blocking topoisomerase 1 which results in DNA damage and cell death.[1]<\/p>\n
Irinotecan was approved for medical use in the United States in 1996.[1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] In the United Kingdom it is available as a generic medication and costs the NHS about 114.00 pounds per 100mg.[2] It is made from the natural compound camptothecin.[1]<\/p>\n
Its main use is in colon cancer, in particular, in combination with other chemotherapy agents. This includes the regimen FOLFIRI, which consists of infusional 5-fluorouracil, leucovorin, and irinotecan. The regimen XELIRI consists of capecitabine and irinotecan.[4][5]<\/p>\n
The most significant adverse effects of irinotecan are severe diarrhea and extreme suppression of the immune system.[6]<\/p>\n
Irinotecan-associated diarrhea is severe and clinically significant, sometimes leading to severe dehydration requiring hospitalization or intensive care unit admission. This side-effect is managed with the aggressive use of antidiarrheals such as loperamide or co-phenotrope with the first loose bowel movement.<\/p>\n
The immune system is adversely impacted by irinotecan. This is reflected in dramatically lowered white blood cell counts in the blood, in particular the neutrophils. The patient may experience a period of neutropenia (a clinically significant decrease of neutrophils in the blood) while the bone marrow increases white cell production to compensate.<\/p>\n
Irinotecan is activated by hydrolysis to SN-38, an inhibitor of topoisomerase I. This is then inactivated by glucuronidation by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). The inhibition of topoisomerase I by the active metabolite SN-38 eventually leads to inhibition of both DNA replication and transcription.[6]<\/p>\n
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.[7] One irinotecan molecule stacks against the base pairs flanking the topoisomerase-induced cleavage site and poisons (inactivates) the topoisomerase 1 enzyme.[7]<\/p>\n
Click on genes, proteins and metabolites below to link to respective articles. [ 1]<\/p>\n
Irinotecan is converted by an enzyme into its active metabolite SN-38, which is in turn inactivated by the enzyme UGT1A1 by glucuronidation.<\/p>\n
People with variants of the UGT1A1 called TA7, also known as the \"*28 variant\", express fewer UGT1A1 enzymes in their liver and often have Gilbert's syndrome. During chemotherapy, they effectively receive a larger than expected dose because their bodies are not able to clear irinotecan as fast as others. In studies this corresponds to higher incidences of severe neutropenia and diarrhea.[8]<\/p>\n
In 2004, a clinical study was performed that both validated prospectively the association of the *28 variant with greater toxicity and the ability of genetic testing in predicting that toxicity before chemotherapy administration.[8]<\/p>\n
In 2005, the FDA made changes to the labeling of irinotecan to add pharmacogenomics recommendations, such that irinotecan recipients with a homozygous (both of the two gene copies) polymorphism in UGT1A1 gene, to be specific, the *28 variant, should be considered for reduced drug doses.[9] Irinotecan is one of the first widely used chemotherapy agents that is dosed according to the recipient's genotype.[10]<\/p>\n
Irinotecan received accelerated approval from the U.S. Food and Drug Administration (FDA) in 1996 and full approval in 1998.[11][12]<\/p>\n
During development, it was known as CPT-11.<\/p>\n
A liposome encapsulated version of irinotecan sold as Onivyde, was approved by FDA in October 2015 to treat metastatic pancreatic cancer.[13] It gained EU approval in October 2016.[14]<\/p>\n
<\/p>\n
Read more: IrinotecanClinical dataTrade namesCamptosar (US), Campto (EU), Onivyde (liposomal)AHFS\/Drugs.comMonographMedlinePlusa608043Pregnancycategory O=C7OCC=6C(=O)N2C(c1nc5c(c(c1C2)CC)cc(OC(=O)N4CCC(N3CCCCC3)CC4)cc5)=C\/C=6[C@@]7(O)CC Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer and small cell lung cancer.[1] For colon cancer it is used either alone or with fluorouracil.[1] For small cell lung cancer it is used with cisplatin.[1] It is given by slow injection into a vein.[1] Common side effects include diarrhea, vomiting, bone marrow suppression, hair loss, shortness of breath, and fever.[1] Other severe side effects include blood clots, colon inflammation, and allergic reactions.[1] Those with two copies of the UGT1A1*28 gene variant are at higher risk for side effects.[1] Use during pregnancy can result in harm to the baby.[1] Irinotecan is in topoisomerase inhibitor family of medication.[2] It works by blocking topoisomerase 1 which results in DNA damage and cell death.[1] Irinotecan was approved for medical use in the United States in 1996.[1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] In the United Kingdom it is available as a generic medication and costs the NHS about 114.00 pounds per 100mg.[2] It is made from the natural compound camptothecin.[1] Its main use is in colon cancer, in particular, in combination with other chemotherapy agents. This includes the regimen FOLFIRI, which consists of infusional 5-fluorouracil, leucovorin, and irinotecan. The regimen XELIRI consists of capecitabine and irinotecan.[4][5] The most significant adverse effects of irinotecan are severe diarrhea and extreme suppression of the immune system.[6] Irinotecan-associated diarrhea is severe and clinically significant, sometimes leading to severe dehydration requiring hospitalization or intensive care unit admission Continue reading
\nIrinotecan - Wikipedia<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"