Long-Term Stability of Lorazepam in Sodium Chloride 0.9% Stored at Different Temperatures in Different Containers.

Background and Objective: Infusion containing lorazepam is used by geriatric department to limit anxiety disorders in the elderly. Currently, these infusions are prepared according to demand by the nursing staff, but the preparation in advance in a centralized service could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in polypropylene syringes stored at 5 ± 3°C. Then, results obtained were compared with stability data of lorazepam in syringes stored at room temperature, glass bottles at 5 ± 3°C, and glass bottles at room temperature. Method: Eight syringes and 6 bottles of infusion were prepared by diluting 1 mL lorazepam 4 mg in 23 mL of NaCl 0.9% under aseptic conditions. Five syringes and 3 bottles were stored at 5 ± 3°C and 3 syringes and 3 bottles were stored at room temperature for 30 days. During the storage period, particle appearance or color change were periodically checked by visual and microscope inspection. Turbidity was assessed by measurements of optical density (OD) at 3 wavelengths (350 nm, 410 nm, 550 nm). The stability of pH was also evaluated. The lorazepam concentrations were measured at each time point by high-performance liquid chromatography with ultraviolet detector at 220 nm. Results: Solutions were physically unstable in syringes at 5 ± 3°C after 4 days: crystals and a drop of OD at 350 nm were observed. However, pH was stable. After 2 days, solutions were considered as chemically unstable because a loss of lorazepam concentration higher than 10% was noticed: the lower 1-sided confidence limit at 95% was below 90% of the initial concentration. To assess temperature and polypropylene influence, results were compared with those obtained for syringes at room temperature and bottles at 5 ± 3°C and room temperature. Precipitation, drop of OD at 350 nm, and chemical instability were observed in all conditions. Conclusion: Solutions of lorazepam were unstable after 2 days in syringes at 5 ± 3°C. Preparation in advance appears, therefore, not possible for the clinical use. Storage conditions (temperature and form) do not improve the stability.

Development of clinical pharmacy in Belgian hospitals through pilot projects funded by the government.

Objectives The goal is to develop clinical pharmacy in the Belgian hospitals to improve drug efficacy and to reduce drug-related problems. Methods From 2007 to 2014, financial support was provided by the Belgian federal government for the development of clinical pharmacy in Belgian hospitals. This project was guided by a national Advisory Working Group. Each funded hospital was obliged to describe yearly its clinical pharmacy activities. Results In 2007, 20 pharmacists were funded in 28 pilot hospitals; this number was doubled in 2009 to 40 pharmacists over 54 institutions, representing more than half of all acute Belgian hospitals. Most projects (72%) considered patient-related activities, whereas some projects (28%) had a hospital-wide approach. The projects targeted patients at admission (30%), during hospital stay (52%) or at discharge (18%). During hospital stay, actions were mainly focused on geriatric patients (20%), surgical patients (15%), and oncology patients (9%). Experiences, methods, and tools were shared during meetings and workshops. Structure, process, and outcome indicators were reported and strengths, weaknesses, opportunities, and threats were described. The yearly reports revealed that the hospital board was engaged in the project in 87% of the cases, and developed a vision on clinical pharmacy in 75% of the hospitals. In 2014, the pilot phase was replaced by structural financing for clinical pharmacy in all acute Belgian hospitals. Conclusion The pilot projects in clinical pharmacy funded by the federal government provided a unique opportunity to launch clinical pharmacy activities on a broad scale in Belgium. The results of the pilot projects showed clear implementation through case reports, time registrations, and indicators. Tools for clinical pharmacy activities were developed to overcome identified barriers. The engagement of hospital boards and the results of clinical pharmacy activities persuaded the government to start structural financing of clinical pharmacy.

Physical stability of highly concentrated injectable drugs solutions used in intensive care units.

BACKGROUND: The intensive care department of the institution use drug solutions within higher concentration to avoid fluid overload. The purpose of the study is to prove the physical stability of different injectable drugs within high concentration (amiodarone 25mg/mL, isosorbide 0.60mg/mL, lorazepam 0.16mg/mL, noradrenalin 0.120 and 0.240mg/mL, salbutamol 0.06mg/mL and sodium valproate 12mg/mL) to ensure the patients safety. METHODS: Five of 30 or 50mL polypropylene syringes were prepared for each solution under aseptic conditions and stored at room temperature. Immediately after the preparation (hour 0) and after 1, 4, 8, 24 and 48hours, 2mL of each solution were withdrawn from each syringe and placed in glass tubes to proceed to the stability test. All specimens were visually inspected in front of a black and of a white background and aliquots of each solution were centrifuged to proceed to microscopic inspection with a ten-fold magnification. The pH of each solution was measured with glass electrode pH-meter (Inolab level 1, WTW Weilhem, Germany with biotrode electrode, Hamilton, Bonaduz, Switzerland) and spectrophotometric measurements (Genesys 10 series, New-York, USA) were performed at three wavelengths (350, 410 and 550nm) to avoid the apparition of turbidity. RESULTS: For all the drugs included in the study, there was no significant change in pH, no color change, no turbidity or opacity and no precipitation observed in the solutions during the storage at room temperature for 48hours. No microaggregates were detected by microscope neither revealed by a change of absorbance. CONCLUSION: Within these limits, the preparations of amiodarone in 5% glucose polypropylene syringes and isosorbide, lorazepam, noradrenalin, salbutamol, valproate in 0.9% sodium chloride polypropylene syringes are physically stable at room temperature for 48hours. These results allow us to consider a study of chemical stability by high-performance liquid chromatography (HPLC).

Does an interaction exist between ketamine hydrochloride and Becton Dickinson syringes?

INTRODUCTION: An international alert from Becton Dickinson (BD) has noted the possibility of interaction between several molecules and some syringes. The Centralized IntraVenous Additives Service of the institution was using 3 mL BD syringes to store ketamine HCl. This study evaluated the interaction between ketamine and these syringes. METHOD: A batch of BD syringes produced in Europe and left in quarantine from the day of the international alert has been tested at 22, 29, 36, 43 and 50 days of storage at room temperature. At each time, the pH of the solutions was measured. The solutions were inspected visually and by microscope, and spectrophotometric measurements were performed. The concentrations were measured by a validated ultra-high-performance liquid chromatography-diode array detector. RESULTS: Neither physical change nor pH modification was observed during the study. According to a lower limit of the 95% unilateral CI on the mean >90% of the theoretical concentration, the solutions remain stable for at least 50 days. CONCLUSION: In our study conditions, ketamine can be stored for at least 50 days without risk of sorption with syringes.

Long-term stability of dexamethasone and alizapride or ondansetron in sodium chloride 0.9% polyolefin bag at 5±3°C.

INTRODUCTION: The aim of the study was to investigate the long-term stability of dexamethasone 10mg associated with alizapride 100mg or ondansetron 8mg in 100mL of 0.9% sodium chloride solution stored at 5±3°C. METHOD: Solutions of 0.9% sodium chloride 100mL in polyolefin bags (n=5) containing approximately dexamethasone (DEX) 10mg associated with alizapride (ALI) 100mg or ondansetron (OND) 8mg were prepared under aseptic conditions and stored about 30 days at 5±3°C. ALI, DEX and OND concentrations were measured by high-performance liquid chromatography (HPLC). Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCL 5M and NaOH 5M before and after heating at 100°C was also performed. Solutions were considered stable if the 95% one-sided lower confidence limit of the concentration remains superior to 90% of the initial concentration or 95% of the initial concentration when any signs of physical instability exist as recently recommend. RESULTS: The calibration was linear over the following range from 20 to 1.25mg/100mL for DEX, from 200 to 12.5mg/100mL for ALI and from 20 to 1.25mg/100mL for OND with a calculated correlation coefficient (r2) of 0.998, 0.999 and 0.999, respectively. The inter- and intra-assay precision was below 10% for both mixtures. All formulations were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 30 days. CONCLUSION: The HPLC method is specific and reproducible and can easily be adopted for monitoring the quality control in the production of DEX-ALI and DEX-OND bags. Solutions of DEX-ALI and DEX-OND were physically and chemically stable for 30 days in polyolefin bags stored at 5±3°C and could therefore be prepared in advance.

Long-term stability of ketamine hydrochloride 50mg/ml injection in 3ml syringes.

INTRODUCTION: Ketamine hydrochloride (Ketalar(®)) injection is often used as a general anesthetic agent. It is particularly suited to short-term interventions. It can also be used as an inducer of anesthesia before the administration of other anesthetic agents. The aim of this study was to evaluate the stability of ketamine hydrochloride in 3ml polypropylene syringes after storage for up to 180days at room temperature. METHOD: Syringes containing ketamine hydrochloride (50mg/ml) were prepared and stored at room temperature (25°C) for 180days. The concentrations were measured by validated ultra-performance liquid chromatography-diode array detection at 0, 7, 14, 28, 60, 84, 112, 140 and 180days. A degradation test was performed to evaluate the specificity of the analysis. At each time point, the pH, color and visible particles of each solution were also assessed. RESULTS: Degradation tests proved no interfering peaks with ketamine. All solutions were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 180days (100%±2%). CONCLUSION: Solutions of ketamine (50mg/ml) were chemically stable for 180days in polypropylene syringes with storage at room temperature and could be prepared in advance by a centralized intravenous admixture service.

[Standardisation of methods for dilution of intravenous medications in hospital]. / Standardisation des méthods de dilution des medications injectables en unites de soins intensifs et unites conventionnelles.

Introduction The administration of intravenous medications in hospital is a common practice. Although it may seem almost insignificant, this practice remains no less an act which involves risks, due to many factors identified. It is therefore important to gather, clarify and communicate the updated information on the modalities of the administration of these injections in order to facilitate and secure the work of the teams of care with a view of an optimal and standardized administration of intravenous medications. Method The tables of standardization of injectable drugs have been made on several occasions in the past and distributed in the care units. The latest version of these documents was reviewed and updated in the light of the recent editions of several sources. The data concerning each individual injectable medicine have individual as well been systematically updates. The updated data have been integrated into the electronic prescription of medicines, a standardized dilution is now proposed by default to the prescriber. For some drugs, special modalities of administration have been planned to meet the specific needs of patients hospitalized in the Intensive Care Unit (ICU). Results The methods for dilution of injections in classical hospitalization have been integrated in the electronic prescribing software (238 "packages" in total. The specific dilutions used in the ICU (48 in total, have been validated but may not be used in the conventional care units. Conclusion All of the information relating to the methods of preparation and administration have been gathered and clarified in order to facilitate and secure the work of the teams of care and thus enable optimal administration of intravenous medications. The information is accessible on paper file and via the internal computer network, the PC of intensive care units and the software Computerized prescription.

[Preliminary study for the implementation of standardized rounded doses of cytotoxic druqs]. / Etude préliminaire pour l'implémentation d'un dose-banding de chimiothérapie anticancéreuse.

BACKGROUND: "Dose-banding" is a concept of cytotoxic drugs standardization allowing the preparation in advance of standardized rounded doses (SRD covering the most frequently prescribed doses rounded to +/-5%. Standard doses will be prepared in advance by batch in order to increase production capacity and at the same time to regulate pharmacy workflow as well as to reduce patient waiting time. PURPOSE: To identify anticancer drugs suitable for dose banding and to fix standardized doses. METHODS: The interesting molecules are first selected in accordance with several criteria: preparations frequency, long-term physicochemical stability after reconstitution, repetition of the prescribed doses and savings opportunity. The selected molecules were: Carboplatin, Cetuximab, Cisplatin, Cyclophosphamide, Doxorubicin, 5-Fluorouracil, Gemcitabine, Oxaliplatine, Paclitaxel, Rituximab, Trastuzumab and Vinorelbine. We established an inventory of the prescriptions retrospectively for a period of six months in order to highlight the most often prescribed doses. For the analysis, we fixed bands with a standard deviation of +/- 5%, 7% and +/- 10%. RESULTS: Standardization of doses of chemotherapy was deemed interesting if > or =60% of the doses were standardisable with a maximum of five SRD and a minimum of one delivery per week, in order to guarantee a good turnover of the batch. A maximum of 5% standard deviation is added to those three criteria, the deviation currently accepted among our medical staff. After analyzing 3506 prescriptions, 7 molecules are eligible: Doxorubicine, 5-Fluorouracil infusion, 5-Fluorouracil pump, Gemcitabine, Paclitaxel, Rituximab, Trastuzumab and Vinorelbine, with a percentage of standardisation of 77% [SRD: 30 mg), 61% [SRD: 700 mg, 750 mg, 800 mgl, 75% (SRD: 4000 mg, 4500 mg, 5000 mg), 72% [SRD: 1600 mg, 1800 mg, 2000 mg), 61% [SRD: 140 mg, 150 mg, 160 mgl, 64% (SRD: 600 mg, 700 mg, 750 mg], 71% (SRD: 350 mg, 400 mg. 450 mgl et 62% [SRD: 40 mg, 50 mg] respectively. CONCLUSION: This preliminary study allows us to consider implementing the dose banding concept in order to optimize the chemotherapy circuit at our institution.

[The long-term chemical stability of injectable drugs reconstituted in Hospital Pharmacy]. / Stabilité chimique à long terme de médications injectables reconstituées en Pharmacie Hospitaliére.

BACKGROUND: Other injectable preparations than parenteral nutrition admixture and injectable cytotoxic drugs could be prepared by Centralised IntraVenous Admixture Service (CIVAS) if the Long-term stability of the drugs is known. However, this information is not always available. PURPOSE: To develop a program of chemical drug stability analysis in collaboration between Hospital Pharmacy, Medical Laboratory and Scientific Support Unit to determine the long-term stability of largely used injectable anti-infectious and non-anti-infectious drugs. MATERIAL AND METHODS: After a setup of the High Performance Liquid Chromatography (HPLCI method, 28 drugs were reconstituted in laminar air flow hood, 17 of them stored directly at 5 +/- 3 degrees C and 19 stored in the freezer at -20 degrees C, thawed by microwave following a standardised procedure and stored at 5 +/- 3 degrees C before use. Concentration stability was evaluated by regression analysis. RESULTS: For each drug, long-term stability has varied from 11 days to 180 days. The freeze-thaw treatment by microwave may enhance the stability (from 30 to 120 days) and allow batch-scale production of intravenous drugs, less expensive in term of manpower and sterile device than a drug reconstitution at the ward. The results were published by 55 posters in international congress and by 36 publications in national and international pharmaceutical journals. CONCLUSIONS: Our findings contribute to enhance the scale of drugs that may be take on by a CIVAS.

Microwave freeze-thaw technique of injectable drugs. A review from 1980 to 2014.

OBJECTIVE: Microwave freeze-thaw treatment (MFTT) of injectable drugs can support the development of centralized intravenous admixtures services (CIVAS). The aim of the review is to collect information and results about this method. METHODS: A systematic review of the scientific literature about injectable drug stability studies was performed. The data are presented in a table and describe name of the drug, producer, final concentration, temperature and time of freezing storage, type of microwave oven, thawing power, method of dosage and results after treatment or final long-term storage at 5±3 °C. RESULTS: From 1980 to 2014, 59 drugs were studied by MFTT and the results were presented in 49 publications. Forty papers were presented by 8 teams (2 to 18 by team). The temperatures of freezing storage vary from -70 °C to -10 °C, the time storage from 4 hours to 12 months, the thaw from low to full power. Dosages are mainly made by high performance liquid chromatography. Most of the 59 drugs are stable during and after treatment. Only 3 teams have tested the long-term stability after MFTT, the first for ganciclovir after 7 days, the second for ceftizoxime after 30 days and the third for 19 drugs after 11 to 70 days. CONCLUSIONS: This review can help CIVAS to take in charge the productions of ready-to-use injectable drugs.

Long-term stability of acyclovir in 0.9% NaCl infusion polyolefin bags at 5±3°C after freeze-thaw treatment: a generic product versus the brand name.

INTRODUCTION: The aim of the study was to investigate the long-term stability of acyclovir 5 mg/mL (a generic product versus the brand name) in NaCl 0.9% after storage at 5±3°C and to evaluate the influence of initial freezing and microwave thawing on this stability. METHODS: Five bags of Acyclovir® Hospira 5 mg/mL (A) and five bags of Zovirax® GSK 5 mg/mL (B) were prepared under aseptic conditions and stored 3 months at -20°C, then thawed and stored 30 days at 4°C. Five bags of Acyclovir® 5 mg/mL (C) and five bags of Zovirax® 5 mg/mL (D) were also prepared under aseptic conditions and stored 30 days at 5±3°C. Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCl 12 M and NaOH 5 M before and after heating at 100°C was also performed. The concentrations were measured by HPLC-PDA. RESULTS: The only one forced degradation test that yielded chromatograms with degradation products peak was the test with the acid solution heated at 100°C without interference with the native product. No significant change in pH values or optic densities were seen during the study for both products. No crystals were seen with the optic microscope during the study. Acyclovir® and Zovirax® solutions were stable for at least 21 days according to the FDA recommendations. Moreover, there was no statistical difference between regression lines of those two products and two storage conditions. CONCLUSION: Under the conditions of this study, Acyclovir® 5 mg/mL in 100 mL of NaCl 0.9% infusion remains stable at least for 21 days at 5±3°C with or without freezing at -20°C during the three previous months. There is no statistical difference between the brand name and a generic product. Acyclovir may be prepared in advanced by a centralized intravenous additive service, frozen in polyolefin bags and microwave thawed before storage under refrigeration until 21 days.

Long-term stability of morphine hydrochloride in 0.9% NaCl infusion polyolefin bags after freeze-thaw treatment and in polypropylene syringes at 5 degrees C + 3 degrees C.

The aim of this study was to investigate the long-term stability of morphine hydrochloride in 0.9% NaCI infusion polyolefin bags and polypropylene syringes after storage at 5 degrees C + 3 degrees C and to evaluate the influence of initial freezing and microwave thawing on this stability. Ten polyolefin bags and five polypropylene syringes containing 100 mL of 1 mg/mL of morphine hydrochloride solution in 0.9% NaCI were prepared under aseptic conditions. Five polyolefin bags were frozen at -20 degrees C for 90 days before storage. Immediately after the preparation and after thawing, 2 mL of each bag were withdrawn for the initial concentration measurements. All polyolefin bags and polypropylene syringes were then refrigerated at 5 degrees C + 3 degrees C for 58 days during which the morphine concentrations were measured periodically by high-performance liquid chromatography using a reversed-phase column, naloxone as internal standard, a mobile phase consisting of 5% acetonitrile and 95% of KH2PO4 buffer (pH 3.50), and detection with diode array detector at 254 nm. Visual and microscopic observations and spectrophotometric and pH measurements were also performed. Solutions were considered stable if the concentration remained superior to 90% of the initial concentration. The degradation products peaks were not quantitatively significant and were resolved from the native drug. Polyolefin bag and polypropylene syringe solutions were stable when stored at 5 degrees C + 3 degrees C during these 58 days. No color change or precipitation in the solutions was observed. The physical stability was confirmed by visual, microscopic, and spectrophotometric inspection. There was no significant change in pH during storage. Freezing and microwave thawing didn't influence the infusion stability. Morphine hydrochloride infusions may be prepared in advance by centralized intravenous additive service, frozen in polyolefin bags, and microwave thawed before storage under refrigeration until 58 days either in polyolefin bags or polypropylene syringes. Such treatment could improve safety and management.

[Standard doses applied to preparations of injectable drugs and their reconstitution in the hospital: methodology and implementation]. / Présentation d'une démarche d'aide et de réflexion pour la mise en place de doses standards appliquée aux préparations et reconstitution d'injectables en milieu hospitalier.

INTRODUCTION: Improvement of healthcare quality and safety are two main goals for hospitals. High risk preparations of injectable drugs is one of the possible areas for improvement. In this context the production of batches of standard doses is a practical solution in response to the increased demand. Some toolkits exists to facilitate the implementation of dose banding, but, to our knowledge, no complete strategy was available until today. AIM AND PURPOSE: To propose a rational approach to analyse the possibility of implementing standard doses and choose the most relevant drugs for dose standardization. METHOD: The method is based on the analysis of literature focusing on different themes: safety, international guidelines, batch production regulation and stability studies. RESULTS: An approach on the strategies to develop is detailed for pharmacists willing to implement standard doses. All key stages are discussed: the needs of care units, the analysis and risk assessment, the stability studies and the practical implementation of the standard doses preparation and quality control. CONCLUSION: The implementation of standard doses seems a rational and necessary evolution of hospital pharmacy in response to the increase of compounding activity and the requirements of quality preparation. A global and all-inclusive approach is needed for this purpose. All parameters have to be considered to avoid errors. A process and a decision aid are suggested to facilitate the development of standard doses.

SFPO and ESOP recommendations for the practical stability of anticancer drugs: an update.

The recommendations for the practical stability of anticancer drugs published in 2010 by the French Society of Hospital Pharmacists (SFPO) and the European Society of Oncology Pharmacists (ESOP) have been updated. Ten new molecules have been included (asparaginase, azacitidine, bevacizumab, clofarabine, eribuline mesylate, folinate sodium, levofolinate calcium, nelarabine, rituximab, temsirolimus).

[Implementation of computerized phisician order entry in a hospital setting: what are the keys to success?]. / Implémentation de la prescription informatisée en milieu hospitalier: quelles sont les clés d'un déploiement réussi ?

INTRODUCTION: A software of computerized physician order entry [CPOE] was developed by a data-processing company in collaboration with the Mont-Godinne University Hospital By 2006, parallel to the evolution of the software, the progressive implementation of CPOE was carried out, and currently covers 16 wards, the emergency room, the recovery rooms and the center of medical care [day hospital] as well as the day surgical center OBJECTIVES: Complete computerization of the drug supply chain, including the regulation by the physician, the pharmaceutical validation, the delivery and the follow-up of stocks by pharmacy, the validation of the administration by the nurse and the tariffing of the drugs. METHOD AND RESULTS: In 2006, a working group was created in order to validate specifications allowing the development of a software of CPOE, Linked to the computerized medical record. A data-processing company was selected in order to develop this software. Two beds were computerized in the pneumology ward, in order to test and validate the software. From 2007 to 2009, 3 additional wards were computerized [geriatrics, neurosurgery, revalidation]. A steering committee of CPOE, composed of various members (direction, doctors, pharmacists, nurses, data processing specialistsl is created. This committee allows the installation of the means necessary to the deployment of CPOE in the Institution. Structured teams for the deployment are created: medical and nurse coaches. From 2009 to 2012, the deployment of the software is carried out, covering 16 wards, the emergency room, the recovery room and the day-hospitals. CONCLUSION: The computerization of the drug supply chain is a challenge which concerns the institutional level. The assets of our hospital and our project were: - a strong management committee, making of this project a priority entering the strategical planning of the institution; - a steering committee allowing each type of actor to express his needs, and of prioriser requests; - a closer medical coaching; - teams of nurses coaches, accompanying each ward, during and after the deployment; - a dynamic IT team allowing a relay between the Institution and the data-processing company. These points appeared essential and are as many keys for a successful deployment.

Microwave freeze-thaw treatment of dose-banded cytotoxics injectable drugs: a review of the literature from 1980 to 2011.

INTRODUCTION: Microwave freeze-thaw treatment (MFTT) of injectable drugs can support the development of centralized intravenous admixtures services (CIVAS). The aim of this review is to collect information about the stability of cytotoxic and hazardous drugs after this treatment. METHODS: The scientific literature about drug stability studies was reviewed. The data describe the name of the drug, the manufacturer, the final concentration, the temperature and time of freezing storage, type of microwave oven, the thawing power, the measurement, the method and the results after treatment and final long-term storage at 5±3°C. RESULTS: From 1980 to 2011, nine drugs (cyclophosphamide, cytarabine, daunorubicine, doxorubicine, epirubicine, fluorouracile, ganciclovir, methotrexate sodium, mitomycine C) were studied after MFTT and the results were presented in 10 publications. The storage freezing temperature ranged from -15°C to -30°C, the time storage from 14 to 364 days, the thaw from moderate to full power. High performance liquid chromatography is mainly used to measure drug concentrations. All drugs are stable during and after the treatment. However, mitomycine needs to be stored at -30°C. The long-term stability after MFTT was evaluated only for the ganciclovir after 7 days, and for fluorouracile after 28 days. The concentration of the seven drugs was measured after one to 11 freezing-thawing cycles with a loss below 5%. CONCLUSIONS: This review can help the hospital pharmacist to take in charge the productions of nine dose-banded ready-to-use injectable cytotoxic and hazardous drugs. Freezing enhances their long-term stability without altering their chemical stability. Validated microwave thawing reduces the time of defrosting of these drugs at the studied concentrations.