Vaxcel Granisetron Drug Interactions

Granisetron did not induce or inhibit the cytochrome P450 drug metabolizing enzyme system in rodent studies or inhibit the activity of any well characterized P450 sub-families studied in in vitro investigations. In humans, hepatic enzyme induction with phenobarbital resulted in an increase in total plasma clearance of intravenous granisetron of approximately 25%. Ketoconazole inhibited ring oxidation of granisetron in in vitro human microsomal studies. However, given the absence of pK/pD relationship with granisetron, these changes are believed to have no clinical consequences. Granisetron has been safely administered in humans with benzodiazepines, neuroleptics and anti-ulcer medications, commonly prescribed with antiemetic treatments. Additionally, granisetron has shown no apparent drug interaction with emetogenic cancer chemotherapies. No specific interaction studies have been conducted in anesthetized patients, but granisetron has been safely administered with commonly used anesthetic and analgesic agents. In addition, the activity of the cytochrome P450 subfamily 3A4 (involved in the metabolism of some of the main narcotic analgesic agents) is not modified by granisetron. As for other 5-HT₃ antagonists, cases of ECG modifications including QT prolongation have been reported with granisetron. These ECG changes with granisetron were minor and generally not of clinical significance, specifically with no evidence of proarrhythmia. However, in patients concurrently treated with drugs known to prolong QT interval and/or which are arrhythmogenic, this may lead to clinical consequences.
Incompatibilities: Admixtures of granisetron hydrochloride and dexamethasone sodium phosphate are compatible at concentrations of 10 to 60 μg/ml granisetron and 80 to 480 μg/ml dexamethasone phosphate in either 0.9% sodium chloride or 5% glucose intravenous infusion fluids.