Compatibility of imipenem-cilastatin sodium with commonly used intravenous solutions

Bigley, F.P.; Forsyth, Richard J.; Henley, M W

doi:10.1093/ajhp/43.11.2803

Cited by 8 publications

(8 citation statements)

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“…Imipenem is known to be unstable in various solutions. Its degradation is pH, concentration, and temperature dependant (7). Based on our results, imipenem shows a rapid degradation: 10% degradation is reached in 2 hours at 37°C in Physioneal.…”

Section: Discussionsupporting

confidence: 51%

Stability and Compatibility of Antibiotics in Peritoneal Dialysis Solutions Applied to Automated Peritoneal Dialysis in the Pediatric Population

et al. 2016

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♦ OBJECTIVES: Assess the stability of several antibiotics in peritoneal dialysis (PD) solutions under common conditions of use in pediatrics, particularly in automated PD. ♦ METHODS: Amoxicillin, cefazolin, cefepime, ceftazidime, imipenem, cotrimoxazole, tobramycin, vancomycin, and the association of ceftazidime + vancomycin and ceftazidime + tobramycin, were tested in 3 different PD solutions: bicarbonate/lactate solution with 2 glucose concentrations (Physioneal 1.36 and 3.86%; Baxter Healthcare Corporation, Deerfield, IL, USA) and an icodextrin-containing solution (Extraneal; Baxter Healthcare Corporation, Deerfield, IL, USA). Concentrations were those recommended in guidelines for the treatment of peritonitis in pediatrics. Physioneal bags were incubated at 37°C for 24 hours, whereas Extraneal bags were stored 12 hours at room temperature (22 ± 2°C) and then 12 hours at 37°C. Drug concentrations were determined using high performance liquid chromatography (HPLC). Each measure was taken in triplicate. Stability of antibiotics was defined as less than 10% degradation of the drug over time. ♦ RESULTS: Cefazolin, cotrimoxazole, tobramycin, and vancomycin were stable under studied conditions. Ceftazidime was stable 24 hours in icodextrin, 12 hours in Physioneal 1.36% and 6 hours in Physioneal 3.86%. The association of tobramycin or vancomycin did not influence the stability of ceftazidime. Cefepime and amoxicillin were stable 6 h, 4 h, and 8 h in Physioneal 1.36%, 3.86% and Extraneal, respectively. The stability of imipenem was very low: 2 h in Physioneal and 6 h in Extraneal. Moreover, an increasingly yellow coloration was observed with the use of imipenem, whereas no color change or precipitation occurred in other bags. ♦ CONCLUSION: Cefazolin, tobramycin, cotrimoxazole, and vancomycin are stable in PD solutions up to 24 hours and can be administered in the PD bag for the treatment of peritonitis, even in automated PD under studied conditions. However, amoxicillin, cefepime, ceftazidime, and imipenem must be used with caution due to their lack of stability.

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Section: Discussionsupporting

confidence: 51%

Stability and Compatibility of Antibiotics in Peritoneal Dialysis Solutions Applied to Automated Peritoneal Dialysis in the Pediatric Population

et al. 2016

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“…In the present study, imipenem showed a tendency for greater degradation in glucose 5% infusion solutions (Table ), in accordance with the Bigley, Forsyth, and Henley (). These authors also reported imipenem to be more stable in 0.9% sodium chloride injection, as observed in our experiments, and the pH values generally decreased during the study period, which may be due the hydrolysis of the β ‐lactam ring and formation of carboxylic acid.…”

Section: Resultssupporting

confidence: 91%

Stability and degradation products of imipenem applying high‐resolution mass spectrometry: An analytical study focused on solutions for infusion

Barbosa

Pezzi

Tsao

et al. 2019

Biomedical Chromatography

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Carbapenems show recognized instability in aqueous solutions; therefore some care must be taken in their handling and preparation and their use in the hospital environment. The stability and degradation products of imipenem were investigated from conditions that simulate its clinical use. For this, a simple stability‐indicating method by HPLC‐DAD was validated with a focus on the quantitation of drug concentration remaining from infusion solutions (sodium chloride 0.9% and glucose 5%). The degradation products formed were identified by high‐resolution mass spectrometry (ESI‐Q‐TOF‐MS/MS), with detection of the [M + H]+ ions at m/z 318 (DP‐1), m/z 599 (DP‐2) and m/z 658 (DP‐3). The most probable elemental compositions were obtained with a high degree of confidence, where the error between the masses observed and calculated was 1.25 ppm for DP‐1, −0.33 ppm for DP‐2 and 1.82 ppm for DP‐3. The DP‐1 degradation product resulted from cleavage of the β‐lactam ring; DP‐2 corresponded to the drug dimer; and DP‐3 was generated from the interaction between imipenem and cilastatin. The proposed method provides a safe and reliable alternative for the quantitation of imipenem, and the stability data obtained by ESI‐Q‐TOF help in understanding the drug behavior under the conditions of clinical use.

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“…11,12 Other broad-spectrum antibiotics are grossly instable or incompatible (ceftriaxone and carbapenems) in lactated Ringer solution or have uncertain or variable stability (piperacillin-tazobactam). [13][14][15][16] Interestingly, Trissel's 2 Clinical Pharmaceutics Database states that there is no information to support cefepime administration with lactated Ringer solution. 17 According to prescribing information, cefepime is chemically stable in lactated Ringer solution at concentrations of 1 to 40 mg/L.…”

Section: Discussionmentioning

confidence: 99%

Chemical and Physical Stability of an Admixture Containing Cefepime and Vancomycin in Lactated Ringer Solution

et al. 2020

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Purpose: To evaluate the chemical and physical stability of an admixture containing cefepime and vancomycin in a single volume of lactated Ringer solution at refrigerated temperatures. Methods: Cefepime 2000 mg and vancomycin 1000 mg were, respectively, reconstituted with 10 and 20 mL of sterile water for injection (SWFI) per manufacturer instructions. This resulted in cefepime and vancomycin concentrations of 200 and 50 mg/mL, respectively. The resulting cefepime and vancomycin solutions at 10 and 20 mL, respectively, were drawn up and injected into 1000 mL lactated Ringer solution. Aliquot samples were obtained on days 0 to 9, visually inspected for gross incompatibility, and then stored at −80°C. Samples were thawed on the day of the analysis and run through ultraperformance liquid chromatography. Area under the concentration-time curve (AUC) on each day was compared with baseline AUC values. Chemical stability was defined as an AUC more than 93% of the baseline value. Results: No evidence of gross physical incompatibility was observed by visual inspection. Cefepime and vancomycin replicants were more than 94.5% and 98% of baseline AUC values. Therefore, all sample replicants were found to be more than 93% of their baseline AUC value. Conclusion: An admixture containing cefepime 2000 mg and vancomycin 1000 mg in 1000 mL lactated Ringer solution appears to be chemically and physically stable at refrigerated temperatures for up to 9 days.

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Compatibility of imipenem-cilastatin sodium with commonly used intravenous solutions

Cited by 8 publications

References 0 publications

Stability and Compatibility of Antibiotics in Peritoneal Dialysis Solutions Applied to Automated Peritoneal Dialysis in the Pediatric Population

Stability and Compatibility of Antibiotics in Peritoneal Dialysis Solutions Applied to Automated Peritoneal Dialysis in the Pediatric Population

Stability and degradation products of imipenem applying high‐resolution mass spectrometry: An analytical study focused on solutions for infusion

Chemical and Physical Stability of an Admixture Containing Cefepime and Vancomycin in Lactated Ringer Solution

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