Why is atropine given before irinotecan?

The risk of cholinergic syndrome is increased when irinotecan is administered with oxaliplatin. Because of these unpleasant side effects, many practitioners prophylactically administer atropine as a premedication. Atropine sulfate injection is an anticholinergic agent and muscarinic antagonist.

What is irinotecan toxicity?

Unfortunately, the treatment with irinotecan is often associated with severe toxicities, especially neutropenia and diarrhea. The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of irinotecan active metabolite SN-38 by UGT1A enzyme.

Does irinotecan cause myelosuppression?

The main side-effects of irinotecan are myelosuppression and severe diarrhea. Initial studies of this drug in patients with recurrent malignant gliomas reported response rates of 15% and median overall survival of 43 weeks (Friedman et al., 1999).

How is irinotecan metabolized?

Irinotecan is delivered as a prodrug; the active drug is a potent topoisomerase-1 inhibitor, which causes breaks in double-stranded DNA, ultimately leading to cell death. Irinotecan is metabolized by carboxylesterases to the active 7-ethyl-10-hydroxycamptothecin (SN-38) (Figure 1).

What is irinotecan used for?

Irinotecan is used alone or in combination with other medications to treat colon or rectal cancer (cancer that begins in the large intestine). Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It works by stopping the growth of cancer cells.

How long does irinotecan diarrhea last?

The mean duration of symptoms is 30 minutes and they usually respond rapidly to atropine. Delayed-type diarrhea is defined as diarrhea occurring more than 24 hours after administration of irinotecan and is noncumulative and occurs at all dose levels.

When do you give atropine to irinotecan?

Subcutaneous atropine 250mcg immediately prior to irinotecan for the prevention of acute cholinergic syndrome. A further 250mcg subcutaneous dose may be given to relieve cholinergic symptoms if they develop.

Where is irinotecan metabolized?

IRI is metabolized in the liver and converted to SN-38, the active metabolite and Topoisomerase I inhibitor, by carboxylesterases (CES) mediated hydrolysis.

What is the half-life of 5-fluorouracil?

Following parenteral administration of 5-fluorouracil, there is rapid distribution of the drug and rapid elimination with an apparent terminal half-life of approximately 8 to 20 minutes.