Self-application of aminoglycoside-based creams to treat cutaneous leishmaniasis in travelers.

BACKGROUND: In endemic foci, the use of an aquaphilic cream containing paromomycin with/without gentamicin to treat cutaneous leishmaniasis (CL) is safe, painless and cures 78-82% of patients with New and Old World CL. Self-application in travelers requires evaluation. METHODS: Travelers with 1-10 lesions of confirmed CL were prospectively treated with the paromomycin-gentamicin formulation (WR279396, 2012-2017, Group 1) and carefully follow up, or treated with a locally produced paromomycin-only cream (2018-2022, Group 2). The cream was applied once under supervision, then self-applied daily for 20-30 days. A cured lesion was defined as 100% re-epithelialization at day 42 without relapse at three months. RESULTS: Medical features were similar in Group 1 (17 patients), and Group 2 (23 patients). Patients were infected with either Leishmania major, L. infantum, L. killicki, L. guyanensis, L. braziliensis, or L. naiffi. Intention-to-treat and per-protocol cure rates were 82% (95% confidence interval (CI) [64.23;100.00]) and 87% (95% CI [71,29;100.00]) in Group 1, and 69% (95% CI [50.76; 88.37]) and 76% (95% CI [57.97; 94.41]) in Group 2. In the pooled Group 1&2, 75% (95% CI [61.58;88.42]) (30/40) and 81% (95% CI [68,46;93.6]) (30/37) of patients were cured in intention-to-treat and per-protocol, respectively. There were no significant differences observed in the success rates between Old World and New World CL (83.3% vs. 60%, p = 0.14). Prospective observations in Group 1 showed that adverse events were mainly pruritus (24%) and pain (18%) on lesions (all mild or moderate). No mucosal involvement was observed in either group. DISCUSSION: In this representative population of travelers who acquired CL either in the Old or New World, the 81% per-protocol cure rate of a self-applied aminoglycoside cream was similar to that observed in clinical trials.

Pharmaceutical Oral Formulation of Methionine as a Pediatric Treatment in Inherited Metabolic Disease.

L-Methionine (Met) is an essential alpha-amino acid playing a key role in several metabolic pathways. Rare inherited metabolic diseases such as mutations affecting the MARS1 gene encoding methionine tRNA synthetase (MetRS) can cause severe lung and liver disease before the age of two years. Oral Met therapy has been shown to restore MetRS activity and improve clinical health in children. As a sulfur-containing compound, Met has a strongly unpleasant odor and taste. The objective of this study was to develop an optimized pediatric pharmaceutical formulation of Met powder, to be reconstituted with water, to obtain a stable oral suspension. Organoleptic characteristics and physicochemical stability of the powdered Met formulation and suspension were evaluated at three storage temperatures. Met quantification was assessed by a stability-indicating chromatographic method as well as microbial stability. The use of a specific fruit flavor (e.g., strawberry) with sweeteners (e.g., sucralose) was considered acceptable. No drug loss, pH changes, microbiological growth, or visual changes were observed at 23 ± 2 °C and 4 ± 2 °C with the powder formulation for 92 days, and the reconstituted suspension for at least 45 days. The developed formulation facilitates the preparation, administration, the dose adjustment and palatability of Met treatment in children.

Setting up of a hospital Covid-19 vaccination center: A descriptive study.

Background and Aims: The coronavirus pandemic challenged countries worldwide in a race against contaminations and variants. Vaccination campaigns were the answer to such an infectious spread. This descriptive study presents the organizational process of the setting up of a Covid-19 vaccination center in a French University Hospital in January 2021, the issues encountered along the way and assessment of adaptability. Methods: Three major stakeholders: SARS CoV-2 crisis referent, referring vaccination medical doctor and referring vaccination pharmacist retraced key moments and identified issues encountered during the setting up of the vaccination center and its long term maintenance, threw a series of meetings. Records of crisis and periodic meetings that took place threw out the vaccination campaign were consulted. Results: A multidisciplinary crisis steering committee with nine different professionals was created January 3. Logistics for the vaccination center opening were discussed: location, informatics, appointment-scheduling, pharmaceutical circuit, internal circuit, human resources, and information communication. The vaccination center was ready to welcome healthcare workers in less than 24 h on January 4. The first month, 2757 1st shots were administered, leading up to a total of 9167 1st shots during 6 months of activity. From January to June 2021, the multidisciplinary group dealt and adapted its processes to challenging and unexpected situations. Indeed, issues encountered with Pfizer BioNTech's and AstraZeneca's vaccine, were: supply shortages, vaccine manipulation, targeted populations, pharmacovigilance, and general communication. Conclusion: This descriptive study provides an exclusive insight on how a hospital vaccination center was organized and adapted during Covid-19 pandemic to ensure healthcare workers' security and resilience, and to protect high risk patients of severe Covid-19 infection.

Indications and Safety of Rituximab in Pediatric Neurology: A 10-Year Retrospective Study.

BACKGROUND: RTX is used off-label in several neurological inflammatory diseases in adults children patients. We conducted a study to assess indications and safety of rituximab (RTX) for children and to identify risk factors for early B-cell repopulation. METHODS: A single-center retrospective study of children treated with RTX for a neurological disease between May 31, 2010, and May 31, 2020, was performed. RESULTS: A total of 77 children (median age, 8.9 years) were included. RTX was mostly used as second-line therapy in all groups of diseases (68%). Median dose was 1500 mg/m2 for each patient. There were 13 clinical relapses (17%), 5 when B-cell depletion was complete. Adverse events were present in 6% of the cases. The factors influencing early B-cell repopulation were the recent infusion of intravenous Ig (P < 0.01) and the administration of less than 1500 mg/m2 during the first RTX treatment (P = 0.04). The median time to B-cell repopulation seemed to be shorter (160 vs 186 days) when patients had plasmapheresis even when a 48-hour delay was observed with RTX infusions. CONCLUSIONS: This study confirms the good tolerance of RTX in the treatment of specific neurological disorders in a pediatric population. It also highlights risk factors for early B-cell repopulation and underlines the importance of B-cell monitoring.

Subcontracting sterile pediatric and adult chemotherapy preparations activity: A global risk analysis.

Objective: The main purpose of this study was to carry out a global risk analysis (GRA) on the subcontracting circuit to determine and evaluate the risks linked to the future subcontracting process and to propose corrective actions for the most critical risks to ensure safety. This study must allow to conclude in an objective way to the feasibility or not of this project. Methods: A GRA was performed, conducted by a multidisciplinary working group that met in 20 meetings, corresponding to about 50 h of work. Results: We identified 92 scenarios: 13% of scenarios had an initial criticality C1, 40% C2, and 47% C3. The GRA shows that the riskiest scenarios concern the management, material, and equipment with IT system and logistics with transport. The working group identified 25 corrective actions. After implementing those actions, 85% of scenarios had residual criticality C1, 8.5% C2, and 6.5% had residual criticality C3. The working group chose that it was impossible to subcontract part of the activity. Conclusion: The GRA conducted in this study highlighted the risks related to outsourcing this activity, evaluated and prioritized them, and recommended corrective actions. Therefore, we conclude that subcontracting the totality of sterile preparations would be harmful to patient care quality and reactivity for vital medical emergencies, such as macrophage activation syndrome, preparation of clinical trials, graft rejection therapies, preparation of very short stability chemotherapy, and the pediatric graft conditioning chemotherapy.

Physicochemical Stability Study of Oral Suspension Containing Ruxolitinib in Children with Steroid-Refractory Acute Graft-Versus-Host Disease.

Ruxolitinib, used in children with steroid-refractory acute graft-versus-host (GVH) disease, is currently commercially available only as a tablet adult dosage. For the paediatric population, an oral liquid would be an adapted dosage formulation. The aim of this study was to develop ruxolitinib compounded oral suspensions at 2 mg/mL by using commercial tablets in available aqueous vehicle (Inorpha) and to measure its stability at both room temperature and under refrigeration. Chemical stability of suspensions containing ruxolitinib was evaluated for 60 days based on pH, degradation, and drug content. Physical stability of the drug suspension was evaluated by visual aspect and odour. The remaining ruxolitinib concentration of the suspension was at least 95% of the initial concentration after 60 days at both temperatures. The pH, colour, and odour of the suspensions throughout the study remained unchanged with respect to the initial time point.

Stability and Formulation of Erlotinib in Skin Creams.

Recent studies have highlighted the benefit of repurposing oral erlotinib (ERL) treatment in some rare skin diseases such as Olmsted syndrome. The use of a topical ERL skin treatment instead of the currently available ERL tablets may be appealing to treat skin disorders while reducing adverse systemic effects and exposure. A method to prepare 0.2% ERL cream, without resorting to a pure active pharmaceutical ingredient, was developed and the formulation was optimized to improve ERL stability over time. Erlotinib extraction from tablets was incomplete with Transcutol, whereas dimethyl sulfoxide (DMSO) allowed 100% erlotinib recovery. During preliminary studies, ERL was shown to be sensitive to oxidation and acidic pH in solution and when added to selected creams (i.e., Excipial, Nourivan Antiox, Pentravan, and Versatile). The results also showed that use of DMSO (5% v/w), neutral pH, as well as a topical agent containing antioxidant substances (Nourivan Antiox) were key factors to maintain the initial erlotinib concentration. The proposed ERL cream formulation at neutral pH contains a homogeneous amount of ERL and is stable for at least 42 days at room temperature in Nourivan cream with antioxidant properties.

External contamination of antineoplastic drug vials: an occupational risk to consider.

Risk management for workers involved in the handling and preparation of cytotoxic drugs is challenging. This study aims to investigate drug contamination of the exterior surfaces of cytotoxic drug vials. Two batches of commercially available cytotoxic drugs in unprotected vials (ifosfamide, etoposide phosphate and cyclophosphamide) and plastic shrink wrap vials (doxorubicin, cytarabine and busulfan) were tested without removing the flip-off cap or the plastic wrap, and without prewashing. The results showed significant trace amounts of cytotoxic drugs on the exterior surfaces in both unprotected (eg, cyclophosphamide, ifosfamide) and protected plastic shrink wrap vials (eg, cytarabine), indicating that the secondary packaging of protected vials does not systematically prevent exposure to the handlers. These results focus on the need for guidelines to prevent cytotoxic vial contamination and safety recommendations for staff in the handling and storage of these vials.

Stability of pemetrexed diarginine concentrates for solution in vials and diluted in 0.9% sodium chloride and dextrose 5% polyolefin infusion bags.

OBJECTIVES: To determine the physicochemical stability of pemetrexed diarginine in original vials, and after dilution in two commonly used infusion fluids (0.9% sodium chloride, 5% dextrose) in polyolefin bags, stored under refrigeration (2-8°C) or at ambient temperature (22-25°C) exposed to light. METHODS: Stability of pemetrexed diarginine injection concentrate was determined in the original glass vials with closed-system transfer device. Diluted pemetrexed diarginine infusion solutions were aseptically prepared by dilution of pemetrexed diarginine concentrate with either 0.9% sodium chloride or dextrose 5% in polyolefin bags, in amounts yielding pemetrexed diarginine concentrations of 4, 9 and 12 mg/mL. Test solutions were stored under refrigeration (2-8°C) or at ambient temperature (22-25°C) exposed to light. Pemetrexed diarginine concentrations were determined throughout a 14-day storage period using a stability-indicating HPLC assay. In addition, test solutions were visually examined for colour change and precipitation. RESULTS: Pemetrexed diarginine injection concentrate with closed-system transfer device is shown to be physicochemically stable for up to 4 days when stored under refrigeration and for 1 day at room temperature. A browning of the pemetrexed diarginine concentrate solutions appeared 0n day 2 when stored at ambient temperature and on day 5 under refrigeration. Pemetrexed diarginine diluted in dextrose 5% and 0.9% sodium chloride was physicochemically stable for up to 4 days when stored under refrigeration and for 1 day at room temperature. A browning of the diluted solutions appeared on day 2 when stored at room temperature and on day 5 when stored under refrigeration. CONCLUSIONS: Pemetrexed diarginine concentrate for solution stored under refrigeration with closed-system transfer device can be retained as a residual to reduce product losses. The analytical stability of pemetrexed diarginine in dextrose 5% and 0.9% sodium chloride under refrigeration enables our centralised unit to prepare this drug in advance.

Impact of a pharmacist-led programme on biologics knowledge and adherence in patients with spondyloarthritis.

OBJECTIVES: In spondyloarthritis (SpA), improving patients' knowledge on their biologics is a key factor to enhance adherence. The information given to the patient has to ensure the acquisition of safety skills regarding their treatment. The aims of this trial were to evaluate the impact of a pharmacist's educational interview on knowledge and adherence to biologics in these patients. METHODS: Consecutive adult patients with well-controlled axial SpA, stable on biologics were enrolled in a randomised, controlled, single-centre, open-label, 6-month trial. A pharmacist's educational interview provided information on biologics management at baseline in the intervention group and at month 6 in the control group. The changes in a weighted knowledge score concerning the management of biologics and the change in the Medication Possession Ratio (MPR) at month-6 were primary outcomes. The changes in disease activity (BASDAI) and patients' satisfaction regarding the pharmacists' interview were secondary outcomes. RESULTS: Patients' characteristics at baseline were comparable among the 89 included patients (46 in the intervention group, 43 in the control group). The patient's knowledge score concerning biologics management improved at a greater magnitude in the educational group (+11.0±11.5 vs. +3.0 ±10.6 in the intervention versus the control group, respectively, p<0.0001). There was also a trend in a better adherence (+2.2±13.9 vs. -0.6±18.9 in the intervention versus the control group, respectively, p=0.691). The disease activity remained stable in both groups. CONCLUSIONS: This study is strongly in favour of the benefit of a pharmacist's educational interview in the management of patients with axial SpA.

Severe hypersensitivity reaction to etoposide phosphate: A case report.

Hypersensitivity to etoposide phosphate has rarely been documented. We report a case of severe hypersensitivity reaction to etoposide phosphate in an old man. The patient experienced anaphylactic shock and has been hospitalized in intensive care unit. Vigilance is required regarding potential severe reactions with etoposide phosphate formulation.

Maternal ABVD chemotherapy for Hodgkin lymphoma in a dichorionic diamniotic pregnancy: a case report.

BACKGROUND: Hodgkin lymphoma (HL) is the most common hematological malignancy during pregnancy. The first-line treatment for HL in pregnancy is the standard ABVD regimen without any drug and/or dose adjustment. However, data on chemotherapy during twin pregnancies are sparse, and a better understanding of the mechanisms involved in exposure to and the toxic effects of anticancer drugs in the fetuses is needed. CASE PRESENTATION: A 41-year-old dichorionic diamniotic pregnant patient was given ABVD treatment for HL at a gestational age of 28 weeks and 3 days. The patient received 2 cycles of chemotherapy with a 15-day therapeutic window including an actual 25 mg/m2 dose of doxorubicin per cycle. Unlike the female twin, the male twin presented four days after birth a left cardiac dysfunction. Doxorubicin cardiotoxicity in the male newborn was also supported by high blood levels of troponin. At one month of age, echocardiography findings were normal. We investigated literature data on physiological aspects of pregnancy that may influence doxorubicin pharmacokinetics, and pharmacodynamic and pharmacokinetic data on the use of doxorubicin in pregnancy. We detailed the role of the transporters in doxorubicin placenta distribution, and tried to understand why only one fetus was affected. CONCLUSIONS: Fetal safety depends at least on maternal doxorubicin pharmacokinetics.Because of drug interactions (i.e. drug metabolism and drug transport), care should always be taken to avoid maternal pharmacokinetic variability. The toxic effects were discrepant between the dizygotic twins, suggesting additional fetus-specific pharmacokinetic/pharmacodynamic factors in doxorubicin toxicity.

Infliximab biosimilar for treating neurosarcoidosis: tolerance and efficacy in a retrospective study including switch from the originator and initiation of treatment.

OBJECTIVES: Infliximab is increasingly used to treat neurosarcoidosis. We aimed to determine the efficacy and tolerance of an infliximab biosimilar for treating neurosarcoidosis. METHODS: We conducted a retrospective single-center study to describe the efficacy, safety and immunogenicity of an infliximab biosimilar in neurosarcoidosis patients. We compared the survival time without relapse while receiving the biosimilar or previous originator-infliximab treatment. RESULTS: Twenty patients with histologically documented neurosarcoidosis were treated with an infliximab biosimilar (initiation of treatment in 12 and switch from the originator drug in 8) between February 2016 and August 2018. All patients presenting with neurological involvement of one or more areas, including meningeal (n = 15), cerebral (n = 10), spinal cord (n = 9), and/or cranial nerves (n = 5); epilepsy (n = 3); and/or intracranial hypertension (n = 3) were enrolled. Eighteen patients received glucocorticoids during infliximab treatment, and 16 had methotrexate or azathioprine concomitant treatment. The median duration of follow-up was 25 months (19-28). Six patients relapsed during biosimilar treatment. Relapse rates and time-to-relapse did not differ between the infliximab originator previously received and biosimilar treatment groups (p = 0.40 and 0.51, respectively). Nine patients experienced 11 adverse events with the infliximab biosimilar, including infections (n = 5), urticaria (n = 4), headache (n = 1), and diarrhea (n = 1). All side effects were grade 2 or less using the WHO classification. CONCLUSIONS: In this retrospective study, the infliximab biosimilar was efficacious and safe for treating neurosarcoidosis.

A virtual centralized cytotoxic preparation unit simulation to evaluate the pharmacy staff knowledge.

BACKGROUND: The risk of medication errors related to drug preparation unit cannot be totally avoided because of human interference. The aim of this study is to investigate the background and knowledge of the pharmacy staff by replicating the cytotoxic preparation unit with potential errors. METHODS: A 10-m2 room was provided to duplicate the centralized chemotherapy unit with three areas reproducing virtually the equipment preparation bench, the isolator, and the dispensing bench. The 14 situations selected by experts were integrated to each corresponded area. For each participant, a form was given and answers were analyzed by two independent experts. Statistical processing data were performed using GraphPad Prism® software. RESULTS: A total of 19 professionals participated in error simulation workshop over a one-month period. The overall rate of correct responses was 58 ± 19%. In five situations, correct responses rate was lower than 50%: wrong drug batch related to the preparation sheet (40%), inappropriate sterilizing conditions (15%), the time on the preparation sheet provides an expired expiry date for melphalan preparation (45%), a maximum drug dose exceeded (25%), the dispensing form not corresponds to the preparation sheet and final product label (30%). The rate of correct responses was 45 ± 25% for professionals not specifically dedicated to chemotherapy preparation. The overall satisfaction workshop rate was 8.7 ± 1.0 out of 10. CONCLUSION: This study showed the importance of training programs to sensitize personal staff to the risks of chemotherapy preparation and prevent errors.

Program to Manage New and Expensive Drugs in Pediatrics: Profile of a New Drug Policy and a 12-Month Descriptive Study.

BACKGROUND: With growing financial pressure and the range of new and expensive drugs, hospital administrators, clinicians, and pharmacy directors are facing tough decisions on how to manage drug budgets. At a Canadian mother-child hospital, a policy for new and expensive drugs was developed, with the goal of managing their use and costs. OBJECTIVES: To describe the development and implementation of a policy for new and expensive drugs in a mother-child teaching hospital and to describe the profile of requests for these therapies over a 12-month period. METHODS: A brainstorming session was conducted with members of the pharmacy and therapeutics committee to define the criteria for new and expensive drugs at the study hospital and a new process to evaluate requests for these drugs. Over the 12-month period following implementation of the policy, all requests for new and expensive drugs were evaluated through collection and analysis of relevant data. RESULTS: The new drug policy was launched on October 1, 2014. Over the following 12-month period, a total of 58 requests for new and expensive drugs were discussed, but only 47 request forms were completed and signed by a physician and a clinical pharmacist. CONCLUSIONS: New and expensive drugs represent a challenge for clinicians and hospital stakeholders. This study illustrates the implementation of a new policy for these drugs in a mother-child teaching hospital over a 12-month period.

CONTEXTE: Les budgets de plus en plus serrés et la gamme de médicaments nouveaux ou coûteux placent les administrateurs, les cliniciens et les directeurs de pharmacie des hôpitaux devant des décisions difficiles en ce qui touche la gestion des dépenses en médicaments. On a mis au point, dans un hôpital canadien mère-enfant, une politique concernant les médicaments nouveaux ou coûteux avec pour objectif de gérer leur utilisation et leurs coûts. OBJECTIFS: Décrire l'élaboration et la mise en place d'une politique sur les médicaments nouveaux ou coûteux dans un hôpital universitaire mère-enfant et décrire le profil des demandes pour ces pharmacothérapies sur une période de 12 mois. MÉTHODES: Les membres du comité de pharmacologie ont procédé à une séance de remue-méninges dans le but de définir les critères pour les médicaments nouveaux ou coûteux dans l'hôpital à l'étude et un nouveau processus servant à évaluer les demandes pour ces médicaments. Au cours des 12 mois suivant la mise en place de la politique, toutes les demandes pour des médicaments nouveaux ou coûteux ont été évaluées à l'aide d'une cueillette et d'une analyse de données pertinentes. RÉSULTATS: La nouvelle politique sur les médicaments a été lancée le 1er octobre 2014. Au cours des 12 mois suivants, un total de 58 demandes pour des médicaments nouveaux ou coûteux ont été analysées, mais seulement 47 formulaires de demande ont été remplis et signés par un médecin et un pharmacien clinicien. CONCLUSIONS: Les médicaments nouveaux ou coûteux représentent un défi pour les cliniciens et les parties prenantes des hôpitaux. La présente étude décrit la mise en place d'une nouvelle politique pour ces médicaments dans un hôpital universitaire mère-enfant sur une période de 12 mois.