ABSTRACT
PURPOSE: Fosaprepitant dimeglumine for injection is the water-soluble phosphorylated prodrug of the neurokinin-1 receptor antagonist aprepitant. Both agents are approved (in combination with a 5-HT3 antagonist and a corticosteroid) for prevention of chemotherapy-induced nausea and vomiting. Because fosaprepitant is likely to be combined and stored in the same intravenous (IV) bag with 5-HT3 antagonists and corticosteroids, the in vitro compatibility of fosaprepitant with these agents and other IV diluents was assessed. METHODS: Fosaprepitant (1 mg/mL in 0.9 % sodium chloride injection solution) was combined in binary or tertiary fashion with therapeutic-dose preparations of a 5-HT3 antagonist (ondansetron, granisetron, palonosetron, or tropisetron) and/or a corticosteroid (dexamethasone sodium phosphate or methylprednisolone sodium succinate). For diluent compatibility assessment, fosaprepitant was also prepared 1 mg/mL in 0.9 % sodium chloride injection solution, water for injection, or 5 % dextrose injection solution. After 24-h storage under ambient conditions, samples were assayed for degradation. RESULTS: Fosaprepitant demonstrated compatibility when combined in the same IV infusion bag with common 5-HT3 antagonists and corticosteroids for storage and IV coadministration, with the exception of palonosetron (incompatible under all experimental conditions) and tropisetron (incompatible unless combined with a corticosteroid). No incompatibility was observed between fosaprepitant and any of the 3 diluents tested. CONCLUSIONS: Use of fosaprepitant in combination with other antiemetics may provide a flexible option for administration of antiemetics to patients receiving moderately or highly emetogenic chemotherapy.
Subject(s)
Antiemetics/chemistry , Glucocorticoids/chemistry , Morpholines/chemistry , Serotonin 5-HT3 Receptor Antagonists/chemistry , Antiemetics/administration & dosage , Aprepitant , Dexamethasone/administration & dosage , Dexamethasone/analogs & derivatives , Dexamethasone/chemistry , Drug Combinations , Drug Incompatibility , Drug Stability , Drug Storage , Glucocorticoids/administration & dosage , Glucose/chemistry , Infusions, Intravenous , Methylprednisolone Hemisuccinate/administration & dosage , Methylprednisolone Hemisuccinate/chemistry , Morpholines/administration & dosage , Serotonin 5-HT3 Receptor Antagonists/administration & dosage , Sodium Chloride/chemistryABSTRACT
The purpose of the present study is to apply and contrast several analytical techniques to understand the change in moisture content of 20 mm diameter bromobutyl rubber stoppers as a function of typical stopper processing conditions. Three separate methods were examined and Karl-Fischer titration and techniques based on capacitance measurements at a thin-film sensor were found to provide comparable results. Stopper moisture levels were examined in stoppers: (i) as received from the manufacturer, (ii) following steam sterilization, (iii) as a function of various drying cycles, and (iv) during simulated hold conditions prior to use. Finally, the transfer of moisture from stopper to an actual product is examined on storage and general agreement observed between stopper drying conditions and cake moisture levels.
