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Intrathecal analgesia has increased over the last 30 years. In oncology, it is a real alternative for the treatment of refractory pain. The diversity of the molecules alone or in combination that can be used, the risk related to the route of administration, and the cost of certain molecules are all arguments in favor of centralized preparation within the pharmacy. The purposes of this work are first of all to explain the reasons for centralization of these preparations, and in a second time to describe the circuit developed within our establishment.

The association of morphine and baclofen is used for the treatment of spasticity related pain. Moving these patients is sometimes difficult. In order to transport these syringes for pump refilling, it could be interesting to demonstrate the stability of the mixture, and so to be able to ensure the best transport conditions of syringes.

Intrathecal analgesia has increased over the past two decades based on high level proof of efficacy in patients with cancer. Morphine and Ziconotide remains the reference. Polyanalgesic Consensus Conference IT treatment algorithm recommends as the second line therapy opioids/ziconotide combination. Sufentanil and ziconotide combination can be used. The implantable pumps development helped to improve the comfort of the patient. The refills were prepared under a laminar airflow hood under strictly aseptic conditions, by the hospital pharmacist. In order to secure the process, a new analytical method by simple liquid chromatography ultraviolet spectrometry method was developed for the simultaneous quantification of two analgesic drugs (sufentanil, ziconotide). The method was validated according to the recommendation of the US Food and Drug Administration (FDA). The method was linear between 0.1 to 4 μg/mL for ziconotide and 3.125 to 50 µg/mL for sufentanil. This routine quality control analysis secures the production process.

Objective: The aim of this study was to investigate the physicochemical stability of morphine-bupivacaine-ziconotide mixtures used in intrathecal analgesia in polypropylene syringes and intrathecal pumps., Materials and Methods: The stability study method was conceived according to International Council for Harmonisation guidelines. For propylene syringes, six different mixtures of morphine-bupivacaine and ziconotide were assessed over seven days. Two storage temperatures were tested (5 °C ± 3 °C and 25 °C ± 2 °C). For implantable pumps, nine different mixtures were assessed over 60 days and stored at 37 °C. Assays were performed using ultrahigh-pressure liquid chromatography. Turbidity and pH also were measured throughout the study., Results: Results confirmed excellent physicochemical stability for morphine and bupivacaine in the study for all conditions investigated (pumps at 37 °C, polypropylene syringes at 5 °C ± 3 °C and 25 °C ± 2 °C). Concerning ziconotide, after seven days, our study showed that every 95% confidence interval calculated had lower bounds >90% for all mixtures stored in polypropylene syringes. In implantable pumps, a decrease of the concentration was observed in all the mixtures studied. Moreover, the appearance of a degradation product confirmed the ziconotide degradation., Conclusion: All results are in favor with a physicochemical stable preparation for six mixture profiles when stored in polypropylene syringes at 5 °C ± 3 °C and 25 °C ± 2 °C. For mixtures stored in implantable pumps, the efficacy should decrease over time owing to the degradation of ziconotide. A trade-off between high morphine concentration and increased refill interval will need to be found by clinicians., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

The pharmacotechnical expert group of the French Society of Oncological Pharmacy presents the results of its national survey carried out in 2021 in the form of an inventory of pharmaceutical compounding units dedicated to oncology. Premises, equipment, controls, production flows and trends are described in this article, providing an overview of the sector at a time when the new Good Manufacturing Practices (GMP) are applicable. This overview will allow us to better address the needs and expectations of production pharmacists regarding the application of GMP and the development of their units., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: This study aimed to investigate the physicochemical stability of morphine-ropivacaine-ziconotide mixtures used in intrathecal analgesia., Materials and Methods: Eight mixtures were studied to assess their stability profiles according to the initial drug concentrations used. The solutions obtained were put in implantable pumps and stored at 37 °C over a period of 60 days. Assays were performed using ultra high-pressure liquid chromatography. Turbidity and pH were also measured throughout the study., Results: Results confirmed excellent physicochemical stability for morphine and ropivacaine. Concerning ziconotide, three of the eight mixtures did not show any sign of chemical instability: average concentrations remained constant throughout the 60 days. A decrease of the concentration was observed for the five other mixtures. Moreover, the appearance of a degradation product linked to oxidation confirmed the ziconotide degradation., Conclusions: All these results are in favor of a physicochemical stable preparation for three of the mixture profiles when stored in implantable pumps at 37 °C up to 60 days. For the five others, the efficacy should decrease over time owing to the degradation of ziconotide. The decrease in kinetics of the ziconotide concentration depends on the mixing profile. One possibility is to adapt the filling intervals according to the profile of the mixture. Finally, the results show the period of stability ensuring maximum analgesic efficacy for the eight mixture profiles studied., (Copyright © 2021 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: Spinal analgesia is recommended for intractable cancer pain. Morphine-clonidine and sufentanil-clonidine are often used in association in intrathecal drug delivery systems, injected by intraabdominal pumps. To refill these pumps and to limit patient transport, it may be necessary to ship the mixtures in polypropylene syringes to peripheral establishments located near patient homes. The purpose of this study is to determine the stability of morphine-clonidine and sufentanil-clonidine mixtures in polypropylene syringes to ensure the best and safest transport conditions and in implantable pumps for intrathecal use., Materials and Methods: The stability study method was conceived according to the International Council for Harmonization guidelines. For polypropylene syringes, four different mixtures of morphine-clonidine and sufentanil-clonidine were assessed over seven days. Two storage temperatures were tested (5 ± 3 °C and 25 ± 2 °C). For implantable pumps, two different mixtures of morphine-clonidine and sufentanil-clonidine were assessed over 28 days and stored at 37 °C., Results: For the morphine-clonidine mixtures in polypropylene syringes, all mixtures remained stable for five days in both storage conditions (5 ± 3 °C and 25 ± 2 °C) because of relative concentrations systematically positioned between 90% and 110% (95% CIs of the mean of three samples). The two mixtures in implantable pumps remained stable for 28 days. For the sufentanil-clonidine mixtures in polypropylene syringes, cold conservation kept all the preparations stable for seven days, whereas a quick degradation was observed after only two days for ambient storage conditions. This result is similar to that with an implantable pump, in which the concentration is <90% on day 7 for low concentration mixtures. No visual modification, no significant pH modification, and no changes in turbidity assays were observed in either study., Conclusion: This study shows the stability of the morphine-clonidine mixtures in syringes stored at 5 °C for five days and in implantable pumps stored at 37 °C for 28 days. For the sufentanil-clonidine mixtures, the results show stability in syringes for seven days at 5 °C. Pump results show stability of seven days for low concentrations and 28 days for high concentrations., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Introduction: In 2018, according to the latest report from the French National Cancer Institute (INCa), approximately 400,000 new cases of cancer in France were identified. Fifty-four percent were represented by men and 46% by women. The number of new cases increased between 2010 and 2018 (+6,000 cases for men and 23,000 for women). Hospital pharmacies caring for cancer patients must absorb this flow without having additional human resources or without being able to increase the capacity of the chemotherapy reconstitution unit. And this always while ensuring a quality according to the legal requirements. This increase of activity and the centralization of chemotherapy preparations bring with it new problems: musculoskeletal disorders (MSDs). The objective of this work is, through the improvement of work quality, to prevent and monitor the appearance of MSDs in pharmacy technician team., Method: Initially, using the Nordic questionnaire, an inventory of the pain and genes felt by the staff according to location and duration was conducted with pharmacy technician team. Secondly, an assessment of the risk of occurrence of MSDs in the pharmacy technician team according to the tasks performed was carried out using the Borg CR10 scale and the Occupational Safety and Health Administration (OSHA) checklist., Results/discussion: The prevalence of musculoskeletal complaints over the last twelve months and the last seven days within the sample was highest for the wrists/hands (67% and 56%) and head/neck (56% and 33%). The severity index of musculoskeletal problems at work was 50% for the elbow region and 33% for the wrist/hand region. According to the OSHA checklist, the workstations for the preparation of cytotoxics and the workstations for the preparation of analgesics intended for the intrathecal route obtained a score greater than 5, which is equivalent to a risk of occurrence of MSDs. On the positions evaluated using Borg's CR10 scale, the following body regions saw a significant increase in the strain felt after a day of production: head/neck (P-value 0.04), upper back (P-value 0.03), lower back (P-value 0.03) and legs (0.04)., Conclusion: This work made it possible to produce a map of the body regions affected, to identify the positions at risk and to assess the level of risk. Several approaches have been defined to prevent MSDs for the pharmacy technician team. Staff training, by one of the physiotherapists, in muscle warm-ups before a production day is planned. In the continuity of this approach, an expertise by an ergonomist, which could not be carried out due to the health situation and the preventive measures would be essential in order to put in place additional preventive and curative actions., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background: The association of morphine ziconotide or sufentanil ziconotide was used to manage cancer pain. Moving these patients is sometimes difficult. In order to transport these syringes for pump refilling, it could be interesting to demonstrate the stability of the mixture and so to be able to ensure the best transport conditions of syringes., Materials and Methods: A stability indicating UPLC-DAD method was developed and validated according to the ICH guidelines. Fur mixtures of each association have been stored in 5 ± 3°C and 25 ± 2°C and were evaluated for seven days and compared to the initial observed concentrations., Results: The stability of these associations was demonstrated at 5°C for seven days thanks to relative concentrations (95% confidence intervals of the mean of three samples) systematically positioned between 95% and 105%. No degradation product was observed during the stability study., Conclusion: This study shows the stability of these association morphine ziconotide or sufentanil ziconotide at 5°C for seven days in polypropylen syringes. This result will allow the transport of the preparation under optimal conditions. Advance preparations for intrathecal pump refills could also be feasible., (© 2020 International Neuromodulation Society.)

Objective: To determine the physicochemical stability of ziconotide solutions for intrathecal administration in the Medication Cassette Reservoir (MCR)., Materials and Methods: A stability indicating UPLC-DAD method was developed and validated according to the ICH guidelines. Two mixtures of ziconotide (0.40 μg/mL and 0.60 μg/mL) stored in MCR stored at 25 ± 2°C were evaluated for 14 days and compared to the initial observed concentrations., Results: The physicochemical stability of the two solutions was demonstrated for two days thanks to relative concentrations, pH measurement, visual inspections, and turbidity assays. A degradation product was observed and increased during the study., Conclusion: This study showed a very low physicochemical stability of diluted ziconotide stored at 25 ± 2°C in the MCR. The intrathecal administration of ziconotide does not seem appropriate with this device for outpatients., (© 2020 International Neuromodulation Society.)

Intrathecal analgesia is a method using various molecules alone or in combination. Among these, a preparation of sufentanil-ropivacaine-baclofen is widely used. Instead of moving patients to the few expert centers taking charge of these specific preparations, it could be beneficial to transport syringes to peripheral centers who manage pump refills. The objective of this study was to determine the physicochemical compatibility and stability of a preparation of sufentanil, ropivacaine, and baclofen in polypropylene syringes. Drugs were mixed together at different concentrations and stored with light protection at 5°C ± 3°C and 25°C ± 2°C. The stabilities were determined by visual inspection, turbidity, pH measurement, and ultra-high-pressure liquid chromatography assay of drug concentrations. The concentrations of ropivacaine, baclofen, and sufentanil were stable after 7 days at 5°C ± 3°C and no degradation of product appeared. The drug mixtures were clear in appearance and no color change or precipitation was observed. Throughout this period, the absorbance and the pH value of samples remained stable. The preparations of sufentanil, baclofen, and ropivacaine remained stable for at least 7 days when stored in polypropylene syringes at 5°C ± 3°C., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Objectives: The oral route is becoming increasingly important in the panel of anti-cancer therapeutics, but it generates difficulties (adherence, management of adverse effects...). In order to secure medication management, the pharmaceutic team chose to set up pharmaceutical consultations. Its objectives are multiple: understanding of treatment for better adherence, pharmaceutical analysis, enhancement of the city-hospital link. This work presents the setting up of the pharmaceutical consultations and makes an assessment after one year., Methods: The initial step was a meeting with institutional health professionals who work with patients to define the place, the objectives, and the patients targeted by the pharmaceutical consultation. The targeted patients are all patients receiving temozolomide and some patients initiating oral chemotherapy, considered at risk, on medical solicitation. Documents were created to standardize practices in the team from the collection of information and pharmaceutical analysis until the conduct of the consultation and the consultation report (integrated into the computerized patient's medical file). Activity indicators were defined and collected., Results: Over one year, 65 pharmaceutical consultations were conducted, of which 23 % resulted in pharmaceutical interventions. The average duration of consultation was 34minutes. The whole team (four pharmacists and two residents) was involved in this activity., Conclusions: Pharmaceutical consultations help secure medical care of patients, providing tools, dedicated and personalized time, pharmaceutical analysis, etc. Ultimately, the goal is to accompany the patient throughout his treatment by having follow-up pharmaceutical consultations, in collaboration with community pharmacists thanks to the city-hospital link that we have established., (Copyright © 2019 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Based on nursing reports and interviews, a public health program was set up in the Paris region in order to respond to the health needs of thousands of refugees with the goal of steering them, if necessary toward medical care. Elaborated gradually and interfacing with refugee social policies, this organization seems effective. Although subject to certain conditions, this experience provides lessons that could be generalized to other areas of public health and other populations.

Pain is the most feared symptom amongst individuals living with cancer. In 15% to 20% of patients, conventional analgesic therapy either fails to relieve pain or induces adverse effects. Intrathecal drug delivery systems may present an effective alternative for pain management. The Cancerology Center Paul Papin protocol includes an admixture of morphine, ropivacaine, and ziconotide in intrathecal preparations. These drugs are administered by a fully implantable or an external pump. Syringes or polyolefin infusion bags are prepared for refill just before use. Few centers in France use the method of intrathecal analgesia. Therefore, for those patients receiving intrathecal preparations, each filling requires that the patients be transported from their local hospital (or their home) to a referral center where the patients are monitored. They sometimes must travel up to a hundred kilometers to have a pump filled. The preparation and the analytical control of the mixture are carried out only by those centers meeting the proper criteria, which includes the proper equipment. To spare the patient this travel, a peripheral center may be subcontracted to manage the patient's pump refill. No data are available concerning the chemical stability of admixtures in syringes or polyolefin infusion bags. The aim of this study was to evaluate, with a new analytical method using ultra high-performance liquid chromatography, the chemical stability of these admixtures in syringes or in polyolefin infusion bags. Ziconotide 1 µg/mL was combined with ropivacaine (7.5 mg/mL) and morphine (3.5 mg/mL) in syringes at 5°C, 21°C, and 31°C, and in polyolefin infusion bags at 21°C. Assays were performed using ultra high-pressure liquid chromatography. In syringes stored at 21°C and 31°C, concentrations after 6 hours were not in the acceptable criterion of 10% variability. When syringes were stored at 5°C, the residual concentration of ziconotide after 3 days was 100.5% +/- 2.6% [92.7% to 108.4%]. In polyolefin infusion bags, the residual concentration of ziconotide after 14 days was 96.9% +/- 2.2% [90.1% to 103.6%]. This study demonstrates the chemical stability of this admixture in syringes stored at 5°C for 3 days and in polyolefin plastibags stored at 21°C for 14 days., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Background: Use of intrathecal admixtures is widespread, but compounding these is sometimes challenging and may result in errors and complications causing super-potency or sub potency adverse events in patients or malfunctions in the pump itself., Objective: The purpose of this study is to evaluate the accuracy of compounding of intrathecal admixtures through a prospective, systematic quantitative analysis of each component of the mixture before delivery to patients., Study Design: Observational follow up prospective study of intrathecal mixtures components concentrations before refills., Settings: Assays were performed on all intrathecal admixtures produced by the ICO-Paul Papin compounding pharmacy between January 2013 and October 2014 using Ultra High Performance Liquid Chromatography (U.H.P.L.C.). In addition, pH levels of admixtures have been measured since June 2014. When measured concentrations were 15% above or below the required concentrations, the mixture was excluded and compounded again., Results: 1729 mixtures were analyzed. Mean deviation from theoretical values was -1.17% ± 0.28% for morphine, -0.95% ± 1.07% for ropivacaine, and 4.82% ± 0.6% for ziconotide. Exclusion rates were 8.33% overall, but fell from 11.67% in 2013 to 4.97% in 2014. Most exclusions were caused by inaccuracy in the dose of ziconotide. Average mixture pH of the 603 tested admixtures was 4.83 ± 0.6%., Limitations: This study is monocentric and limitations include also its non-randomized nature with no clinical comparison of the rate of adverse events with a refill process without control of each component concentrations., Conclusion: Prospective assays provide benefits in ensuring accuracy of intrathecal mixture compounding and in preventing overdosing or sub dosing, most notably concerning Ziconotide.

Objectives: Ziconotide is often administered in combination with other analgesics via an intrathecal pump. Studies have established that ziconotide is stable when delivered alone in high concentrations. No stability data are available, however, for ziconotide given in low concentrations and/or with other analgesics as usually occurs in clinical oncology practice. The objective of this study was to assess the in vitro stability of ziconotide alone and combined with other analgesics in intrathecal pumps at 37 °C, as well as in syringes at 5 °C, to evaluate conditions for storing and transporting preparations., Materials and Methods: Various ziconotide concentrations (0.1, 0.25, 0.5, and 0.75 μg/mL) were combined with an admixture of ropivacaine (7.5 mg/mL), morphine (7.5 mg/mL), and clonidine (15 μg/mL) in 20-mL intrathecal pumps at 37 °C and in syringes at 5 °C. Solutions of ziconotide alone in concentrations of 0.25, 0.5, 0.75, and 1 μg/mL were introduced into pumps at 37 °C and syringes at 5 °C. Assays were performed using ultra high pressure liquid chromatography., Results: In admixtures, mean ziconotide concentrations decreased linearly to 53.4% (± 3.33%) of baseline after 35 days. When ziconotide was introduced alone in pumps at 37 °C, the residual concentration on day 31 was 35.54% (± 0.04%) with 0.25 μg/mL, 39.37% (± 0.15%) with 0.5 μg/mL, and 44.49% (± 0.18%) with 1 μg/mL. Ziconotide alone or combined with the other analgesics was stable in syringes stored at 5 °C. The preparations complied with the prescriptions, with a mean error of less than 10%, except with the lowest ziconotide concentration (0.1 μg/mL)., Conclusions: At the low ziconotide concentrations studied, the degradation of ziconotide admixed with other drugs was linear and only weakly influenced by the baseline concentration. Linear regression with intrapolation to 30 days showed that the degradation of ziconotide admixed with other drugs was consistent with previously published data., (© 2014 International Neuromodulation Society.)