Safety of intrathecal route: focus to methylprednisolone acetate (Depo-Medrol) use.

PURPOSE: Complications of the intrathecal route may cause potential toxicity related to the medical device and properties of the administered drug and/or excipient. A description of clinical and histological effects of polyethylene glycol and miripirium after Depo-Medrol injection, and the adverse reactions of particulate methylprednisolone acetate was conducted. The safety of the intrathecal route with excipients, label and off-label drugs is discussed. METHODS: A bibliographic search in Medline, Google, and Cochrane database from 1940 to June 2016 was performed. The keywords included 'intrathecal methylprednisolone acetate', 'miripirium', 'myristyl-gamma-picolinium', 'side effects', 'intrathecal Depo-Medrol', 'polyethylene glycol', and 'intrathecal devices' used individually or in combination. RESULTS: Adverse reactions have been reported with this intrathecal administration route such as arachnoiditis, bladder dysfunction, headache, meningitis. Some pharmaceutical excipients have been associated with specific toxicity issues and with allergic and anaphylaxis reactions. Additives of methylprednisolone acetate formulations such as polyethylene glycol and miripirium chloride can be neurotoxic when injected intrathecally. Polyethylene glycol-an antimicrobial agent widely used in pharmaceutical drugs-has been associated with cardiovascular, hepatic, respiratory, and CNS toxicity. CONCLUSIONS: Intrathecal methylprednisolone acetate (Depo-Medrol) therapy seems not fully safe due to reported adverse events. The use of other forms of corticosteroid therapy free from excipients should be emphasized such as soluble methylprednisolone sodium succinate.

Preliminary hazard analysis applied to outsourcing sterile chemotherapy preparations.

Background Our hospital organization raised the possibilities of outsourcing their sterile pediatric chemotherapy preparations to another hospital conditional on analyzing the potential hazardous events that need to be anticipated. Methods The study was conducted by a multidisciplinary working group from September 2015 to January 2016 with the support of a risk manager. A list of hazardous situations that could occur during outsourcing process was assessed. First, a map of hazardous situations was developed by crossing outsourcing processes divided into phases classified as critical or not. Second, a map of risk was established by crossing potential consequences of these hazardous situations and elaborating corrective actions to reduce the initial risks. Results The map of hazardous situations identified 183 relevant hazardous situations, 78 of which were considered high priority and 154 scenarios were developed. Slightly more than half of these hazardous situations concerned information system (30%), human resources (14%), and management (11%). The generic hazards of information system and human generated 37 (24%) and 41 (27%) scenarios, respectively. To reduce critical risks, 33 corrective actions were proposed. Working time required was estimated at 35 days. The subcontractor personnel for this new organization included an estimated extra time of 0.7-pharmacist working day and 1.4-pharmacy dispenser working day. Conclusions The preliminary hazard analysis method appeared to apply to our system of outsourcing sterile cytotoxic preparations in another hospital. Regardless, this analysis is complex and requires time and expertise.

Performing a preliminary hazard analysis applied to administration of injectable drugs to infants.

RATIONALE, AIMS AND OBJECTIVES: Errors in hospitals during the preparation and administration of intravenous drugs to infants and children have been reported to a rate of 13% to 84%. This study aimed to investigate the potential for hazardous events that may lead to an accident for preparation and administration of drug injection in a pediatric department and to describe a reduction plan of risks. METHODS: The preliminary hazard analysis (PHA) method was implemented by a multidisciplinary working group over a period of 5 months (April-August 2014) in infants aged from 28 days to 2 years. The group identified required hazard controls and follow-up actions to reduce the error risk. To analyze the results, the STATCART APR software was used. RESULTS: During the analysis, 34 hazardous situations were identified, among 17 were quoted very critical and drawn 69 risk scenarios. After follow-up actions, the scenarios with unacceptable risk declined from 17.4% to 0%, and these with acceptable under control from 46.4% to 43.5%. CONCLUSION: The PHA can be used as an aid in the prioritization of corrective actions and the implementation of control measures to reduce risk. The PHA is a complement of the a posteriori risk management already exists.

Stability of Extemporaneously Prepared Hydroxycarbamide Oral Suspensions.

Hydroxycarbamide, available as tablets, is a pharmacological agent for fetal hemoglobin induction such as sickle cell anemia. The need for alternative dosage form options for patients unable to take tablets led hospital pharmacies to prepare solutions and suspensions. The objective of this study was to determine the stability of hydroxycarbamide in Ora-Plus in combination with either Ora-Sweet or Ora-Sweet SF, Ora-Blend, or Ora-Blend SF suspending agents. The studied samples were compounded into 100-mg/mL suspensions and stored in 60-mL amber glass bottles at room (22°C to 25°C) or refrigerated (4°C to 8°C) temperature. Samples were assayed at each time point out to 120 days by a stability-indicating high-performance liquid chromatography method. The samples were examined for any change in color, odor, visual microbiology, and pH on initial and final day of analysis. At least 90% of hydroxycarbamide concentration remained in all suspensions at the end of the 120-day study period in both conditions. There was no appreciable change in color, odor, or taste. The pH values of suspensions stored at 25°C changed by at least 1 unit at the end of the study period. Based on the data collected, the beyond-use date of these suspensions is 120 days when stored in 60-mL amber glass bottles at both temperature storage conditions.

Stability study of oral pediatric idebenone suspensions.

Adapted forms for administration to infants are limited. The proposed study was performed to propose oral liquid formulations of idebenone in Ora-Plus and either Ora-Sweet or Ora-Sweet SF, Ora-Blend, Ora-Blend SF and Inorpha. Each formulation was stored in 30 ml amber glass bottle at 5 or 25 °C for 90 days. Idebenone contents in these suspensions, determined by a stability-indicating high-performance liquid chromatography method, remained stable at least 90 days in Inorpha when stored at the two temperatures. In Ora-Blend, the stability was estimated at 14 days and in other suspensions at 20 days at the two temperatures. After 90 days storage, the pH of Ora-Plus and Ora-Sweet or Ora-Sweet SF changed between -0.10 and -0.25 units. For others suspensions, the pH changes were not significant (< -0.09 unit). No change was observed in color, odor or visual microbiology. To conclude, we recommended the use of idebenone in Inorpha vehicle stable for at least 90 days at 25 °C.

Stability of suxamethonium in pharmaceutical solution for injection by validated stability-indicating chromatographic method.

STUDY OBJECTIVE: To assess the stability of pharmaceutical suxamethonium (succinylcholine) solution for injection by validated stability-indicating chromatographic method in vials stored at room temperature. METHODS: The chromatographic assay was achieved by using a detector wavelength set at 218 nm, a C18 column, and an isocratic mobile phase (100% of water) at a flow rate of 0.6 mL/min for 5 minutes. The method was validated according to the International Conference on Harmonization guidelines with respect to the stability-indicating capacity of the method including linearity, limits of detection and quantitation, precision, accuracy, system suitability, robustness, and forced degradations. RESULTS: Linearity was achieved in the concentration range of 5 to 40 mg/mL with a correlation coefficient higher than 0.999. The limits of detection and quantification were 0.8 and 0.9 mg/mL, respectively. The percentage relative standard deviation for intraday (1.3-1.7) and interday (0.1-2.0) precision was found to be less than 2.1%. Accuracy was assessed by the recovery test of suxamethonium from solution for injection (99.5%-101.2%). CONCLUSION: Storage of suxamethonium solution for injection vials at ambient temperature (22°C-26°C) for 17 days demonstrated that at least 95% of original suxamethonium concentration remained stable.

Stability-Indicating High-Performance Liquid Chromatography Assay for the Determination of Sulthiame in Pharmaceutical Dosage Forms.

A stability-indicating assay by reversed-phase high performance liquid chromatography method was developed and validated for the determination of sulthiame (STM). The chromatographic separation was achieved on a reversed-phase NovaPack C18 column and an isocratic mobile phase consisting of deionized water:methanol (70:30, v/v). The flow rate was 1.0 mL/min (ultraviolet detection at 210 nm). The STM was separated within 2.83 min. The linearity of the method was demonstrated in the range of 20.0-200.0 µg/mL and a coefficient of determination of r (2) = 0.9999. The limits of detection and quantification were 4.2 and 9.5 µg/mL, respectively. The intraday and interday precisions were less than 1%. Accuracy of the method ranged from 98.3% to 101.7%, with a relative standard deviation of <1%. STM was degraded by accelerated breakdown in alkaline, acidic, or oxidative stress conditions. This method allows accurate and reliable determination of STM for drug stability assay in pharmaceutical studies.

Stability-Indicating HPLC Assay for Determination of Idebenone in Pharmaceutical Forms.

A stability-indicating method was validated for the determination in pharmaceutical forms of idebenone a coenzyme Q10-like compound. The assay was achieved by liquid chromatography analysis using a reversed-phase C18 column and a detector set at 480 nm. The optimized mobile phase consisted of isocratic flow rate at 1.0 mL/min for 3 min with methanol. The linearity of the assay was demonstrated in the range of 3.0 to 8.0 mg/mL with a correlation coefficient r (2) > 0.998. The limits of detection and quantification were 0.03 and 0.05 mg/mL, respectively. The intraday and interday precisions were less than 1.0%. Accuracy of the method ranged from 98.6 to 101.5% with RSD < 0.6%. Specificity of the assay showed no interference from tablets components and breakdown products formed by alkaline, acidic, oxidative, sunlight, and high temperature conditions. This method allows accurate and reliable determination of idebenone for drug stability assay in pharmaceutical studies.

Stability-Indicating Assay for the Determination of Pentobarbital Sodium in Liquid Formulations.

A stability-indicating assay by reversed-phase high performance liquid chromatography (RP-HPLC) method was developed for the determination of pentobarbital sodium in oral formulations: a drug used for infant sedation in computed tomography (CT) or magnetic resonance imaging (MRI) scan. The chromatographic separation was achieved on a reversed-phase C18 column, using isocratic elution and a detector set at 214 nm. The optimized mobile phase consisted of a 0.01 M potassium buffer pH 3 and methanol (40 : 60, v/v). The flow rate was 1.0 mL/min and the run time of analysis was 5 min. The linearity of the method was demonstrated in the range of 5 to 250 µg/mL pentobarbital sodium solution (r (2) = 0.999). The limit of detection and limit of quantification were 2.10 and 3.97 µg/mL, respectively. The intraday and interday precisions were less than 2.1%. Accuracy of the method ranged from 99.2 to 101.3%. Stability studies indicate that the drug is stable to sunlight and in aqueous solution. Accelerated pentobarbital sodium breakdown by strong alkaline, acidic, or oxidative stress produced noninterfering peaks. This method allows accurate and reliable determination of pentobarbital sodium for drug stability assay in pharmaceutical studies.