Pdf solidstate stability study of meropenem solutions. Insights on stability of meropenem administered as a continuous infusion veena venugopalan1, kayihura manigaba2, samuel j borgert2, jessica cope2, charles a peloquin 1 and kenneth p klinker. Diminished renal function and central nervous system lesions may increase the risk of seizures. However, studies to date have shown that carbapanems and in particular, meropenem, are relatively unstable in solution. Stability of meropenem in saline and dextrose solutions. Meropenem fda prescribing information, side effects and uses.
The stability of broadspectrum antibiotic meropenem was studied in order to investigate the kinetics of degradation of this drug in powder for injection and reconstituted sample. Stability of meropenem in saline and dextrose solutions and. Stability of meropenem in polyvinyl chloride bags and an elastomeric infusion device. Until now we have had no data to evaluate the stability of this drug during continuous infusion in a tropical country. Tdmmonograph meropenem october 2015, concept version page 4 of 5 meropenem 500 mg every 8 hours, or 1 gram every 6 hours in patients with normal renal function. The aim of this work was to evaluate the stability profile of these 3 different medicines to investigate the possibility of using them interchangeably in. Meropenem stability has been shown to be influenced by temperature,7 ph10 11 and. Meropenem was subsequently assayed using highperformance liquid chromatography hplc. When multiple doses are administered 8hourly to subjects with normal renal function, accumulation of meropenem does not occur. Meropenem 20 mgml required immediate administration following preparation under ambient temperatures, whilst meropenem 25 mgml did not remain stable following 24 hrs storage at ambient temperatures.
Solidstate stability study of meropenem solutions based. When meropenem for injection is indicated in patients with these risk factors, caution is. Clinical efficacy, safety and stability, plos one, 2014. Dunn school of pharmacy, winchester, va 22601, usa. Meropenems stability was examined at two temperatures 22c and 33c to mimic average and high temperature in hospital wards. Merrem meropenem dose, indications, adverse effects.
Vabomere meropenem and vaborbactam for injection, for intravenous use initial u. The uv, ftir and raman spectra of meropenem were recorded during a solidstate stability study. Continuous infusions of meropenem in ambulatory care. The stability of the drug substance is first assessed in the preformulation stage. Dosage adjustments are necessary in patients with renal impairment see dosage, administration, storage, and stability section. The main objective of the present research was to develop analytical methods for the evaluation of changes in meropenem in the solid state during a stability study. If no reaction occurs, start the scheduled meropenem dose as follows 8 to 12 hours from the last desensitization dose as ordered by the treating physician. Stability, compatibility and microbiological activity. The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. To show the method was stabilityindicating, a forced degradation study was performed under the following conditions.
Stability and degradation kinetics of meropenem in powder for. No significant change in ph was observed during the study period. Degradation of meropenem was adequately modeled by specific equations for order rate. Jul 26, 2019 the study evaluated meropenem at doses of 500 mg administered intravenously every 8 hours and imipenemcilastatin at doses of 500 mg administered intravenously every 8 hours. A stability study of meropenem diluted to 1 mgml and 20 mgml with sterile water for injection or 0. Meropenem for injection, usp is a sterile, pyrogenfree, synthetic, carbapenem antibacterial for intravenous administration. Meropenem s stability was examined at two temperatures 22c and 33c to mimic average and high temperature in hospital wards. Meropenem for injection page 6 of 36 meropenem for injection, like all. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and raman scattering activities were calculated according to the densityfunctional theory dftb3lyp method with a 631gd,p basis set.
Fawaz, sarah, barton, stephen, whitney, laura, swinden. The objective of this study was to provide such data. Prediction of the stability of meropenem in intravenous mixtures. Frozen meropenem solutions displayed good stability in all concentrations but were physically unstable due to the formation of a precipitate. Highlights of prescribing information these highlights do not include all the information needed to use vabomere safely and effectively. Dec 23, 2019 when multiple doses are administered 8hourly to subjects with normal renal function, accumulation of meropenem does not occur. Research article open access solidstate stability study.
When meropenem for injection is indicated in patients with these risk factors, caution is advised. Aug 15, 2004 stability of meropenem in polyvinyl chloride bags and an elastomeric infusion device. Also, the drug has not been studied in pediatric patients aged 18 years and younger. Solidstate stability study of meropenem solutions based on. Solutions were prepared aseptically at the clinically relevant concentration. The presence of kcl did not affect the stability of meropenem. A retrospective observational study demonstrated that meropenem 1g iv every 8. Stability of meropenem in polyvinyl chloride bags and an. The objective of the study was to compare marketed generic and innovator product of meropenem for injectionnearing theshelf life. Stability of meropenem after reconstitution for administration by.
There are many published studies about meropenem stability, but this study compares the chemical and physical stability among the 3 different. Product monograph pr meropenem for injection sterile lyophilized powder for injection 500 mg and 1 g meropenem, usp vials for intravenous use usp antibiotic fresenius kabi canada ltd. Jun 16, 2006 the stability of broadspectrum antibiotic meropenem was studied in order to investigate the kinetics of degradation of this drug in powder for injection and reconstituted sample. Few studies have investigated meropenem stability in elastomeric infusion devices in prospect of opat. Full text an investigation of the stability of meropenem. The hydrolysis of meropenem in aqueous solution was found to be accelerated by ph, and by increasing concentrations of sodium bisulfite sbs and lcysteine. Investigation of meropenem stability after reconstitution. The study evaluated meropenem at doses of 500 mg administered intravenously every 8 hours and imipenemcilastatin at doses of 500 mg administered intravenously every 8 hours. The study compared the clinical response between treatment groups in the clinically evaluable population at the followup visit testofcure. Strains from bacterial strain bank as well as clinical isolates were used in the study. Meronem iv 500mg summary of product characteristics smpc. In vitro stability evaluation of different pharmaceutical. Carbapenem was submitted to conditions of accelerated thermal decomposition.
Stability and degradation kinetics of meropenem in powder. Stability of meropenem in normal saline solution after storage. Therefore, this study aimed to evaluate the stability of meropenem as the trihydrate in elastomeric infusion devices at a range of selected concentrations 6, 12, 20 and 25 mgml at ambient, refrigeration and freezing temperatures. However, the stability of meropenem reconstituted in solution is influenced by the storage temperature. In vitro stability evaluation of different pharmaceutical products. Data suggest that meropenem is less stable in phosphate buffer, even when the ph is maintained at 6. For the retrospective arm of the study, individual consent was not obtained, but all records were anonymised and deidentified prior to analysis. Long term stability studies study is performed at 25 0 c60% or 30 0 c 65%. Pharmaceutical product used as antibiotic agent details of the supplier of the safety data sheet 2. Meropenem is only found in individuals that have used or taken this drug. Drug stability the stability of pharmaceutical product is investigated throughout the various stages of the development process. The purpose of this study was to predict the stability of meropenem in a mixed infusion. This study demonstrates that at least three factors.
The method was developed and validated in compliance with international council for harmonisation ich guidelines. Pdf meropenem is a new carbapenem antibacterial agent with wide spectrum of activity against gramnegative, grampositive and anaerobic organisms. Jan 01, 2020 meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis. However, studies to date have shown that carbapenems and in particular, meropenem, are relatively unstable in solution. They confirmed that the only avail able european studies on the reconstituted meropenem product are those reported in the aic italian. Meropenem stability under simulated opat conditions meropenem trihydrate ranbaxy australia pty. This trial was designed to compare the effectiveness of colistin monotherapy versus colistinmeropenem combination therapy among patients with severe infections caused by carbapenemresistant gramnegative bacteria, targeting the patient population with carbapenemresistant gramnegative bacterial infections treated in clinical practice, in a. Stability of meropenem in solutions in polyvinyl chloride bags stored at 2126 and 45 c.
Pdf stability of generic brands of meropenem reconstituted in. Meronem iv 500mg summary of product characteristics. Investigation of meropenem stability after reconstitution european. Approximately 70% 50% to 75% of a meropenem dose administered intravenously is recovered unchanged in the urine over 12 hours 1. Meropenem has significant stability to hydrolysis by. Indications and usage merrem iv is a penem antibacterial indicated for the treatment of. There are many published studies about meropenem stability, 3,4,7,8 but this study compares the chemical and physical stability among the 3 different products present on the italian market. Meropenem is a parenteral carbapenem antibiotic which has excellent bactericidal activity in vitro. Pdf stability of meropenem in normal saline solution after storage. Stability of generic meropenem solutions for administration. Meropenem is a parenteral carbapenem antibiotic which has excellent bactericidal activity in vitro against almost all clinically significant aerobes and anaerobes. Meropenem was stable for the longest time in sterile water for injection and in 0.
A retrospective observational study demonstrated that meropenem 1g iv every 8 hours given. Cephalosporin antibiotic relevant identified uses of the substance or mixture and uses advised against intended use. Stability was also influenced by storage temperature. Stability of meropenem in intravenous solutions american. The results from the nmr study showed an increase in open ring methyl groups. Apr 12, 2019 meropenem 20 mgml required immediate administration following preparation under ambient temperatures, whilst meropenem 25 mgml did not remain stable following 24 hrs storage at ambient temperatures. Iv meropenem for injection, for intravenous use initial u. It is active against grampositive and gramnegative bacteria. Meropenem stability has been shown to be influenced by temperature,7 ph10 11.
Complicated skin and skin structure infections adult patients and pediatric patients 3 months of age and older only. Highlights of prescribing information see full prescribing. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and raman scattering activities. Full text an investigation of the stability of meropenem in. Research article open access solidstate stability study of. A study of 12 patients administered meropenem mg 8 hourly postsurgically for intraabdominal infections showed a comparable cmax and halflife to normal subjects but a greater volume of distribution 27 l. For mics greater than 2mgl, the probably of target attainment was near 99% with 1g q8h infused over 3hours. Degradation of generic meropenem was both time and temperature dependent, and the aqueous solutions were stable for up to 8 hours in the. Meropenem stability under simulated opat conditions meropenem trihydrate ranbaxy australia pty ltd, north. Meropenem was prepared in each of the three chemically forcing solution conditions, stored at 50c. Original article in vitro stability evaluation of different. Prediction of the stability of meropenem in intravenous. Meropenem is excreted in breast milk, but little is known about the excretion of vaborbactam. Manufacturer states data insufficient to make dosage recommendations in patients undergoing hemodialysis or peritoneal dialysis.