Brands, Medical Use, Clinical Data
Drug Category
- Radiation-Sensitizing Agents
- Prodrugs
- Parasympathomimetics
- Antineoplastic Agents
- Enzyme Inhibitors
Dosage Forms
- Solution for IM injection
Brands / Synonyms
Camptosar; CP0; Irinotecan Hcl; Irinotecan Hydrochloride; Irinotecan Hydrochloride Trihydrate; IRINOTECAN, CPT-11; Irinotecanum [Inn-Latin]
Indications
For the treatment of metastatic colorectal cancer (first-line therapy when administered with 5-fluorouracil and leucovorin).
Pharmacology
Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. 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. 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 double-strand breaks. The precise contribution of SN-38 to the activity of Irinotecan in humans is not known. Irinotecan is cell cycle phase-specific (S-phase).
Mechanism of Action
Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death.
Absorption
100%
Toxicity
Gastrointestinal complications, such as nausea, vomiting, abdominal cramping, diarrhea, and infection.
Biotrnasformation / Drug Metabolism
Hepatic
Contraindications
CAMPTOSAR Injection is contraindicated in patients with a known hypersensitivity to the drug.
Drug Interactions
The adverse effects of CAMPTOSAR, such as myelosuppression and diarrhea, would be expected to be exacerbated by
other antineoplastic agents having similar adverse effects.
Patients who have previously received pelvic/ abdominal irradiation are at increased risk of severe
myelosuppression following the administration of CAMPTOSAR. The concurrent administration of CAMPTOSAR with
irradiation has not been adequately studied and is not recommended.
Lymphocytopenia has been reported in patients receiving CAMPTOSAR, and it is possible that the administration of
dexamethasone as antiemetic prophylaxis may have enhanced the likelihood of this effect. However, serious
opportunistic infections have not been observed, and no complications have specifically been attributed to
lymphocytopenia.
Hyperglycemia has also been reported in patients receiving CAMPTOSAR. Usually, this has been observed in patients
with a history of diabetes mellitus or evidence of glucose intolerance prior to administration of CAMPTOSAR. It is
probable that dexamethasone, given as antiemetic prophylaxis, contributed to hyperglycemia in some patients.
The incidence of akathisia in clinical trials of the weekly dosage schedule was greater (8.5%, 4/47 patients) when
prochlorperazine was administered on the same day as CAMPTOSAR than when these drugs were given on separate days
(1.3%, 1/80 patients). The 8.5% incidence of akathisia, however, is within the range reported for use of
prochlorperazine when given as a premedication for other chemotherapies.
It would be expected that laxative use during therapy with CAMPTOSAR would worsen the incidence or severity of
diarrhea, but this has not been studied.
In view of the potential risk of dehydration secondary to vomiting and/or diarrhea induced by CAMPTOSAR, the
physician may wish to withhold diuretics during dosing with CAMPTOSAR and, certainly, during periods of active
vomiting or diarrhea.
Drug-Laboratory Test Interactions
There are no known interactions between CAMPTOSAR and laboratory tests.
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