1733. Stability of Imipenem/Cilastatin/Relebactam under Different Temperature and Administration Conditions

Abstract

Abstract Background Imipenem/Cilastatin/Relebactam is an FDA-approved combination antibiotic indicated for resistant infections. There is a practical need to extend the shelf life of parenterals given to patients with such life-threatening infections in the hospital setting. The reconstituted drug's shelf life can be extended by storing at subzero temperatures to slow the degradation kinetics. Package insert indicate stability is 2 hrs at room temperature and refrigeration up to 24 hr. The study aims to determine the stability of the combination in polyvinyl chloride (PVC) infusion (IV) bags when stored at room temperature, refrigerated in addition to continuous infusion CADD pumps. Methods Drug vials (Merck & Co) were reconstituted to 5mg/mL (imipenem) in a 100mL normal saline. To avoid further degradation, samples were collected and mixed 1:1 with stabilizing buffer, then frozen at -80 °C within 5 minutes. For room temperature stability, 6 bags were prepared and stored at (24°C). 0.5ml samples were collected at 0, 2, 4, 6, 8, 12, 24 h from each bag at each time point. For refrigeration stability, 6 bags were prepared and refrigerated at 4 °C. At each time point (24, 36, 48, 60, 72, 84, 96,108, 120h), a sample of 0.5-mL is taken from each bag and frozen at −80 °C. For continuous ambulatory drug delivery (CADD) infusion devices stability, the reconstituted drug is loaded to 2g/200 mL cassettes (for 24-hr infusion) continuous infusion and 1g/100mL (for 12-hr infusion). The cassettes are immediately attached to the infusion pump and placed in a cold pouch with gel packs. After the initial 0.5 mL, 0-h samples from each pump, the pumps are sampled at 4, 8,12, 16, 20, and 24 hours for 2g/ 200mL cassettes and 2, 4, 8, 12 h for 1g/100 mL. Cut off for stability was set at 90% of the original concentration. Chemical assay was performed by a validated HPLC method. Results See tables Table 1:CADD pumps, concentrations are in mg/mL. Imi; imipenem, Rel; relebactam, Cil; Cilastatin, CADD; continuous ambulatory delivery device, SD; standard deviationTable 2:PCV bags, concentrations are in mg/mL. Imi; imipenem, Rel; relebactam, Cil; Cilastatin, PVC; polyvinyl chloride, SD; standard deviation Conclusion Imipenem/relebactam/cilastatin drug product was stable for 12 hrs in CADD pumps 100mL, 16 hrs in 200 mL, 108 hours in refrigerated PVC bags and 12 hrs at room temperature. The extended stability data will assistant pharmacy departments in optimizing drug preparation and storage, nursing time and minimize drug waste improving overall cost and efficiency of drug administration. Disclosures Islam Ghazi, PharmD, Merck And Co Inc: Grant/Research Support David Nicolau, PharmD, Marck and Co Inc: Advisor/Consultant|Marck and Co Inc: Grant/Research Support.