Chemical Stability of Epinephrine 10 mcg/mL Diluted in 0.9% Sodium Chloride and Stored in Polypropylene Syringes at 4 degrees C and 25 degrees C.

Studies have evaluated epinephrine stability in higher concentrations and shorter durations than we require. The objective of this study was to evaluate the chemical stability of epinephrine in syringes at concentrations of 10 mcg/mL in 0.9% sodium chloride at 4°C and 25°C. Solutions of 10 mcg/mL epinephrine in 0.9% sodium chloride were prepared and stored in 10-mL Becton, Dickinson and Company syringes. Three units of each container were stored at 4°C and 25°C. Concentration analysis was completed on study days 0, 2, 7, 14, 21, 28, 42, 56, 72, and 91 using a validated stability-indicating liquid chromatographic method with ultraviolet detection. Chemical stability was based on the intersection of the lower limit of the 95% confidence interval of the observed degradation rate and the time to achieve 90% of the initial concentration (T-90). The analytical method separated degradation products from epinephrine to measure concentration specifically, accurately, and reproducibly. During the study period, all solutions at 4°C retained more than 89.62% of the initial concentration for 91 days. Solutions stored at 25°C retained more than 90% for 21 days. Multiple linear regression revealed significant differences in percent remaining due to study day (P<0.001) and temperature (P=0.002). The calculated T-90, with 95% confidence, was 71.40 days for solutions stored at 4°C but only 12.77 days for solutions stored at 25°C. We conclude that 10 mcg/mL epinephrine solution diluted in 0.9% sodium chloride stored at 4°C is chemically and physically stable for 64 days, with 95% confidence. The syringe may be held at room temperature for up to 24 hours during this period and still retain more than 90% of the initial concentration.

Stability of Compounded Clozapine 25 mg/mL and 50 mg/mL Suspensions in Plastic Bottles.

BACKGROUND: Clozapine oral suspension is not commercially available in Canada but is required for administration to patients who cannot swallow intact tablets. OBJECTIVE: To evaluate the stability of 25 mg/mL and 50 mg/mL clozapine suspensions prepared in a 50:50 mixture of methylcellulose gel 1% and Oral Syrup (flavoured syrup vehicle, Medisca Pharmaceutique Inc) and stored in amber glycol-modified polyethylene terephthalate (PET-G) bottles over 120 days at 4°C and 25°C. METHODS: This study used a validated reverse-phase stability-indicating liquid chromatographic method capable of quantifying clozapine, 3 known degradation compounds, a known impurity, and an unknown compound. Three separate batches of 25 mg/mL and 50 mg/mL clozapine suspensions were prepared, divided into 100-mL aliquots, and stored in 120-mL PET-G bottles. Half of the bottles from each concentration were stored at room temperature (20°C to 25°C) and the other half were stored in the refrigerator (2°C to 8°C). On study days 0, 28, 60, 90, and 120, concentrations of clozapine, each of the 3 known clozapine degradation products, a known impurity, and an unknown compound were determined. RESULTS: When suspensions were stored in PET-G containers at room temperature or under refrigeration for 120 days, the concentration of clozapine remained above 95% of initial concentration, and the measured concentration of degradation products and impurities did not exceed the 0.5% limits set by regulatory authorities worldwide. The proportion of the initial concentration of clozapine remaining on day 120, based on fastest degradation rate with 95% confidence (1-sided), exceeded 92%, and the only degradation product found (clozapine lactam, 0.2%) and an unknown impurity (0.2%) also did not exceed allowable limits. CONCLUSIONS: Compounded clozapine suspensions of 25 mg/mL and 50 mg/mL can be stored in amber PET-G containers for up to 120 days after preparation with storage at room temperature or under refrigeration.

CONTEXTE: La clozapine en suspension orale n'est pas disponible sur le marché canadien, mais elle est nécessaire pour les patients qui ne peuvent l'avaler sous forme de comprimé intact. OBJECTIF: Évaluer la stabilité des suspensions de clozapine de 25 mg/mL et de 50 mg/mL, préparées dans un mélange 50:50 de gel méthylcellulose à 1 % et de Sirop Oral (véhicule de sirop aromatisé, MEDISCA) et conservées dans des flacons ambrés en polytéréphtalate d'éthylène modifié au glycol (PET-G) pendant 120 jours à des températures de 4°C et 25°C. MÉTHODE: Cette étude a utilisé une méthode validée par chromatographie liquide indicatrice de stabilité en phase inverse pouvant quantifier la clozapine, trois composés de dégradation connus, une impureté connue et un composé inconnu. Trois lots séparés de suspensions de clozapine de 25 mg/mL et de 50 mg/mL ont été préparés, divisés dans des aliquotes de 100-mL et stockés dans des flacons en PET-G de 120-mL. La moitié des flacons de chaque concentration a été conservée à température ambiante (de 20°C à 25°C), et l'autre moitié au réfrigérateur (de 2°C à 8°C). Aux jours 0, 28, 60, 90 et 120 de l'étude, on a déterminé les concentrations de clozapine, celles de chacun des trois produits de dégradation de la clozapine, celles d'une impureté connue et d'un complexe inconnu. RÉSULTATS: Lorsque les suspensions étaient stockées dans des contenants en PET-G à température ambiante et réfrigérées pendant 120 jours, la concentration de clozapine demeurait au-dessus de 95 % de la concentration initiale; la concentration mesurée des produits de dégradation et des impuretés ne dépassait pas la limite de 0,5 % fixée par les autorités de règlementation mondiales. La proportion de concentration initiale de clozapine restante au 120e jour, sur la base du taux de dégradation le plus rapide avec un intervalle de confiance de 95 % (unilatéral), dépassait 92 %, et le seul produit de dégradation trouvé (clozapine lactam, 0,2 %) ainsi qu'une impureté inconnue (0,2 %) ne dépassaient pas non plus les limites autorisées. CONCLUSIONS: Les suspensions de clozapine composées de 25 mg/mL et de 50 mg/mL peuvent être conservées dans des contenants ambrés PET-G jusqu'à 120 jours après leur préparation, soit à température ambiante, soit dans un réfrigérateur.

Stability of Extemporaneously Compounded Nadolol 10-mg/mL Suspension in Oral Mix in Glass and Plastic Bottles and Plastic Syringes.

An oral liquid formulation of nadolol, which is required for administration to patients who cannot swallow intact tablets, is not commercially available. The objective of this study was to evaluate the stability of nadolol 10 mg/mL prepared in Oral Mix vehicle and stored in amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride for 91 days at 4ÆC and 25ÆC; and polypropylene oral plastic syringes at 25ÆC only. Three separate batches of nadolol suspension 10 mg/mL were prepared with Oral Mix. Of the suspension, 50-mL aliquots were stored in 100-mL bottles (amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride). Half of the bottles from each container type were stored at 25ÆC and the other half at 4ÆC. On study days 0, 2, 7, 14, 21, 28, 42, 56, 72, and 91, nadolol concentration was determined using a reverse-phase, stability-indicating liquid chromatographic method from samples drawn from each type of container at each temperature. Oral syringes (3 mL), filled with 2 mL of suspension, were stored at 25ÆC and tested on days 0, 2, 7, 21, 42, and 91. The concentration of nadolol 10 mg/mL in Oral Mix in all study samples from bottles and oral syringes remained within 3.5% of the initial concentration. Based on the fastest degradation rate with 95% confidence, on day 91, between 99% to 100% and 98% to 100% remained in suspensions stored in bottles at 25ÆC and 4ÆC, respectively. Oral syringes at 25ÆC had 94% remaining on day 91. Multiple linear regression analysis demonstrated that the percent remaining was related to study day and container, but not temperature. On day 91, nadolol 10 mg/mL oral suspensions prepared with Oral Mix and stored in all bottle types at 4ÆC will retain more than 98% of the initial concentration compared to 99% at 25ÆC and only 94% when stored in oral syringes.

Stability of Generic Formulations of Bortezomib 1.0 and 2.5 mg/mL in Vials and Syringes Stored at 4°C and Room Temperature (23°C or 25°C).

BACKGROUND: The availability of generic versions of bortezomib raises questions about the reliability of extrapolating stability data from one brand to another. OBJECTIVE: To evaluate the stability of bortezomib formulations available from Janssen, Teva Canada, Actavis Pharma, Dr. Reddy's Laboratories, Apotex, and MDA, reconstituted with 0.9% sodium chloride (normal saline) to produce solutions of either 1.0 or 2.5 mg/mL and stored over at least 21 days under refrigeration (4°C) or at room temperature (either 23°C or 25°C) in the manufacturer's original glass vials or in polypropylene syringes. METHODS: On study day 0, solutions with concentration 1.0 mg/mL or 2.5 mg/mL of the Teva, Actavis, Dr. Reddy's, Apotex, and MDA generic formulations were prepared. Three units of each type of container (glass vials and syringes) were stored at 4°C and 3 units at room temperature. Concentration and physical inspection were completed on at least 8 study days (including day 0) over a 21- to 84-day study period. Bortezomib concentrations were determined by a validated stability-indicating liquid chromatographic method with ultraviolet detection. The end point of these studies was the time to reach 90% of the initial concentration (T-90) with 95% confidence, which is expressed as "T-9095%CI", where CI refers to the confidence interval. In addition to estimating the T-9095%CI, differences in stability among products from all manufacturers were compared using multiple linear regression. Previously published data for the Janssen product were included in the overall comparisons. RESULTS: In all of the studies, the analytical method separated degradation products from bortezomib, such that the concentration of bortezomib was measured specifically, accurately (deviations < 2.5%), and reproducibly (average replicate error 2.5%). During all studies, solutions retained more than 94% of the initial concentration at 4°C. The T-9095%CI exceeded the study period for all formulations under all combinations of concentration, container, and temperature, except the 84-day study for the MDA product. Multiple linear regression showed no significant differences among manufacturers (p = 0.57). CONCLUSIONS: In this study, formulations of bortezomib currently marketed in Canada (by Janssen, Teva Canada, Actavis Pharma, Dr. Reddy's Laboratories, Apotex, and MDA) were pharmaceutically equivalent and interchangeable. Given that there was no difference in stability related to manufacturer, nominal concentration, or container, we conclude that these formulations are physically and chemically stable for at least 35 days under refrigeration and at least 25 days at room temperature.

CONTEXTE: La disponibilité de versions génériques de bortezomib soulève des questions relatives à la fiabilité de l'extrapolation des données concernant la stabilité d'une marque à l'autre. OBJECTIF: Évaluer la stabilité des formules de bortezomib de Janssen, de Teva Canada, d'Actavis Pharma, des Laboratoires du Dr Reddy, d'Apotex et de MDA, reconstituées avec 0,9 % de chlorure de sodium (solution saline normale) pour produire des solutions de 1 ou de 2,5 mg/mL et réfrigérées au moins 21 jours à 4 °C ou à température ambiante (23 °C ou 25 °C), dans des fioles en verre du fabricant ou dans des seringues en polypropylène. MÉTHODES: La préparation des solutions avec une concentration de 1 mg/mL ou 2,5 mg/mL des formules génériques de Teva, d'Actavis, du Dr Reddy, d'Apotex et de MDA a eu lieu le jour 0 de l'étude. Trois unités de chaque contenant (fioles en verre et seringues) étaient stockées à 4 °C et 3 unités, à température ambiante. L'inspection de la concentration et l'inspection physique ont été réalisées pendant au moins 8 jours (y compris le jour 0) de l'étude qui a duré de 21 à 84 jours. Les concentrations de bortezomib ont été déterminées par une méthode chromatographique liquide validée, indiquant la stabilité à l'aide d'une détection par rayons ultraviolets. Le point final de ces études était le temps nécessaire pour que le produit atteigne 90 % de la concentration initiale (T-90) avec un seuil de confiance de 95 %, exprimé par T-90IC 95 %, IC indiquant l'intervalle de confiance. En plus de l'estimation du T-90IC 95 %, les différences de stabilité des produits de tous les fabricants ont été comparées à l'aide d'une régression linéaire multiple. Les données publiées précédemment sur le produit Jansen sont incluses dans les comparaisons globales. RÉSULTATS: La méthode analytique de toutes les études qui ont été menées a séparé les produits de dégradation du bortezomib de telle manière que la concentration était mesurée de manière spécifique, précise (déviations < 2,5 %) et reproductible (erreur de réplique 2,5 %). Tout au long des études, les solutions ont retenu plus de 94 % de la concentration initiale à 4 °C. Le T-90IC 95 % de toutes les formules dans toutes les combinaisons de concentration, de contenant et de température, dépassait la durée des études, à l'exception du produit MDA dans l'étude de 84 jours. La régression linéaire multiple n'a indiqué aucune différence importante parmi les fabricants (p = 0,57). CONCLUSIONS: Dans cette étude, les formules de bortezomib actuellement commercialisées au Canada (par Janssen, Teva Canada, Actavis Pharma, les Laboratoires du Dr Reddy, Apotex et MDA) étaient équivalentes et interchangeables d'un point de vue pharmaceutique. Puisqu'aucune différence de stabilité, de concentration nominale ou de contenant liée à l'un ou l'autre des fabricants n'a été révélée, nous concluons que ces formules sont physiquement et chimiquement stables pendant au moins 35 jours sous réfrigération et au moins 25 jours à température ambiante.

Stability of extemporaneously compounded temozolomide 10 mg/mL suspensions in Oral Mix SF® in glass and plastic bottles and plastic syringes.

BACKGROUND: Temozolomide oral suspension is not commercially available. OBJECTIVE: To evaluate the stability of three temozolomide 10 mg/mL suspensions prepared in Oral Mix SF® in three container types stored at 4°C and 23°C. METHODS: Using commercial capsules, three separate batches of three different temozolomide 10 mg/mL formulations (Oral Mix SF® with PK-30; PK-30 and citric acid; and neither PK-30 nor citric acid) were made and stored in three container types (amber glass bottles, amber polyethylene terephthalate bottles, and polypropylene oral syringes). The aliquots in each container type were stored protected from light, half at 25°C and half at 4°C. On study days 0, 5, 8, 14, 21, 28, 35, 42, and 56, physical properties of samples from each container type at each temperature were assessed, and the temozolomide concentration was determined using a stability-indicating method. The beyond-use-date (time to achieve 90% of initial concentration calculated using the lower limit of the 95% confidence interval of the observed degradation rate) was calculated. RESULTS: Samples stored at 25°C turned from white to orange within seven days. Temozolomide crystals were observed in all samples. Concentration changes due to study day and temperature (p < 0.001) were observed but not due to container (p = 0.991) or formulation (p = 0.987). The beyond-use-date of all formulations in all container types was 56 days at 4°C and 6 days at 23°C. CONCLUSIONS: We recommend that these temozolomide 10 mg/mL formulations be stored at 4°C and be assigned a beyond-use-date of 30 days.

Impact of a Comprehensive Antimicrobial Stewardship Program on Institutional Burden of Antimicrobial Resistance: A 14-Year Controlled Interrupted Time-series Study.

BACKGROUND: Antimicrobial resistance (AMR) constitutes an international public health threat widely believed to result from excessive antimicrobial use (AMU). Numerous authorities have recommended antimicrobial stewardship programs (ASPs) to curb the selection of AMR, but there is a lack of data confirming this benefit. METHODS: A controlled interrupted time-series study spanning 14 years was performed to assess impact of a comprehensive hospital-based ASP that included pharmacist-led audit and feedback on institutional AMR. Patient-level microbiologic and AMU data were obtained from October 2002 to September 2016. Poisson regression models were used to identify changes in the incidence and trend of hospital-acquired (HA) antibiotic-resistant organisms (AROs) and multidrug-resistant organisms (MDROs). Changes in community-acquired (CA)-ARO, CA-MDRO, and inpatient AMU were assessed as controls and process outcomes. RESULTS: Statistically significant shifts in AMU, HA-ARO, and HA-MDRO trends coinciding with ASP implementation were observed, corresponding with a 9% reduction in HA-ARO burden (incidence rate ratio [IRR], 0.91 [95% confidence interval {CI}, .83-.99]; P = .03) and a 13% reduction in HA-MDRO burden (IRR, 0.87 [95% CI, .73-1.04]; P = .13) in the intervention period. In contrast, CA-ARO and CA-MDRO incidence continued to rise, with 40% (IRR, 1.40 [95% CI, 1.28-1.54]; P < .0001) and 68% (IRR, 1.68 [95% CI, 1.57-1.82]; P < .0001) increases in burden found, respectively. CONCLUSIONS: Implementation of a comprehensive ASP resulting in reduced AMU was associated with a significant reduction in institutional AMR, even though community AMR increased during the same period. These results confirm that ASPs play an important role in the fight against AMR.

Relative bioavailability of an extemporaneously prepared aprepitant oral suspension in healthy adults.

PURPOSE: Use of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in patients unable to swallow capsules is hindered by the lack of a commercially available oral liquid formulation in many jurisdictions. A stable oral suspension can be extemporaneously prepared using commercially available capsules. We aimed to determine the bioavailability of this aprepitant suspension relative to the capsule. METHODS: This two-period crossover study enrolled 17 healthy adult volunteers. Volunteers received a single 125 mg aprepitant dose during each study period. Order of formulation presentation (capsule vs suspension first) was randomized. Thirteen blood samples were collected over a 48-h period. Aprepitant plasma concentrations were determined using liquid chromatography-mass spectroscopy. Relative bioavailability was defined as the geometric least squares mean ratio for area under the concentration versus time curve (AUC) from time zero to infinity of the aprepitant suspension versus the capsule. Bioequivalence, defined as per Health Canada guidelines, was assessed as a secondary aim. RESULTS: Relative bioavailability of the aprepitant suspension was 82.3% (90% CI: 69.09-98.00%). Bioequivalence was not established: geometric least squares mean ratios (suspension/capsule) for AUC time zero to 48 h and maximum concentration were 87.8% (90% CI: 75.48-102.16%) and 86.1% (90% CI: 75.59-98.16%), respectively. No serious adverse events were observed. CONCLUSIONS: With a relative bioavailability of 82.3%, the extemporaneous aprepitant oral suspension was well-absorbed relative to the capsule. Though not bioequivalent to the oral capsule, the clinical use of this aprepitant oral suspension in adult and pediatric patients unable to swallow capsules is likely to be effective and safe.

Administration of Intravenous Ascorbic Acid-Practical Considerations for Clinicians.

Emerging data suggest that intravenous ascorbic acid (AA) may be beneficial in patients with sepsis. Clinicians require data on stability of diluted AA for safe administration. We evaluated the stability of AA diluted in normal saline (NS) or 5% dextrose in water (D5W) solutions over 14 days at 25 °C and at 4 °C, protected from light, using concentrations of 37 mg/mL and 77 mg/mL (Sandoz) and 40 mg/mL and 92 mg/mL (Mylan). We also assessed stability of a 40 mg/mL solution (Mylan) at 25 °C exposed to light for 75 h. Concentrations were measured using liquid chromatographic separation with ultraviolet light detection on days 0, 0.33, 1, 1.33, 2, 3, 4, 7, 10 and 14. By day 14, solutions at 4 °C retained >97.72% of the initial concentration; at 25 °C, solutions retained >88.02% of the initial concentration, but visual changes were evident after day 2. Multiple linear regression demonstrated that study day and temperature (p < 0.001) but not solution type (p = 0.519), concentration (p = 0.677) or manufacturer (p = 0.808) were associated with the percentage remaining. At 75 h, degradation rates were similar in solutions protected from vs. exposed to light. In conclusion, AA solutions are stable for at least 14 days at 4 °C, with protection from light.

Stability of Extemporaneously Compounded Domperidone 5 mg/mL Suspension in Oral Mix in Plastic and Glass Bottles and Plastic Syringes.

BACKGROUND: Domperidone liquid for oral administration is not commercially available in Canada, but is needed for patients who cannot swallow intact tablets. OBJECTIVE: To evaluate the stability of domperidone 5 mg/mL suspensions prepared in Oral Mix vehicle and stored, for up to 91 days, in amber polyvinylchloride (PVC) bottles, amber glass bottles, or amber polyethylene terephthalate (PET) bottles at 4°C or 25°C or in polypropylene oral syringes at 25°C. METHODS: Three separate 300-mL batches of domperidone suspension 5 mg/mL were prepared with Oral Mix vehicle. Fifty-millilitre aliquots of the suspension were stored in 100-mL bottles (amber PVC, amber glass, or amber PET). Half of the bottles of each type were stored at 25°C and half at 4°C. On study days 0, 1, 2, 4, 7, 10, 14, 21, 28, 35, 42, 49, 63, 77, and 91, domperidone concentration was determined, with a validated reverse-phase, stability-indicating liquid chromatographic method, in samples drawn from each type of container stored at each temperature. In addition, 1.5-mL aliquots of a fourth 100-mL batch of suspension were stored in 3-mL oral syringes at 25°C and were tested on the same study days. RESULTS: The concentration of domperidone in all study samples remained above 93% of initial concentration after storage for 91 days. The percent remaining on day 91, based on fastest degradation rate (as represented by the lower limit of the 95% confidence interval [CI]), was at least 92.3% for suspensions stored at 4°C in PVC, glass, and PET bottles. With storage at 25°C, suspensions in PVC and glass bottles retained more than 90% of initial concentration, whereas suspensions in PET bottles and plastic syringes retained 88.9% and 88.0% of initial concentration, respectively. CONCLUSIONS: Because suspensions of domperidone in PET bottles and oral syringes retained less than 90% of their initial concentration on day 91 (based on the 95% CI), it is suggested that such suspensions be stored at 4°C or 25°C in any bottle type or syringe with an assigned beyond-use date not exceeding 75 days.

CONTEXTE: La dompéridone sous forme liquide pour administration orale n'est pas disponible sur le marché au Canada, mais elle est nécessaire pour les patients incapables d'avaler des comprimés entiers. OBJECTIF: Évaluer la stabilité de suspensions de dompéridone de 5 mg/mL préparées dans l'excipient Oral Mix et conservées jusqu'à 91 jours dans des flacons de polychlorure de vinyle (PVC) ambré, de verre ambré ou de polyéthylène téréphtalate (PET) ambré à 4 °C ou à 25 °C ou dans des seringues orales de polypropylène à 25 °C. MÉTHODES: Trois différents lots de 300 mL de suspension de dompéridone de 5 mg/mL ont été préparés à l'aide de l'excipient Oral Mix. Des aliquotes de 50 mL de la suspension ont été entreposées dans des flacons de 100 mL de PVC ambré, de verre ambré ou de PET ambré. La moitié des flacons de chaque type était conservée à 25 °C et l'autre moitié était conservée à 4 °C. Aux jours 0, 1, 2, 4, 7, 10, 14, 21, 28, 35, 42, 49, 63, 77 et 91 de l'étude, les concentrations de dompéridone ont été évaluées sur des échantillons tirés de chaque type de flacons conservés aux deux températures à l'aide d'une épreuve validée mesurant la stabilité par chromatographie liquide en phase inverse. De plus, des aliquotes de 1,5 mL provenant d'un quatrième lot de suspension ont été entreposées dans des seringues orales de 3 mL à 25 °C et ont été analysées aux mêmes jours. RÉSULTATS: Les concentrations de dompéridone dans l'ensemble des échantillons de l'étude conservaient plus de 93 % de la concentration initiale après un entreposage de 91 jours. Le pourcentage restant au jour 91, selon le taux de dégradation le plus rapide (correspondant à la limite inférieure de l'intervalle de confiance (IC) de 95 %), atteignait au moins 92,3 % pour les suspensions entreposées à 4 °C dans les flacons de PVC, de verre et de PET. Lorsqu'elles étaient entreposées à 25 °C, les suspensions contenues dans les flacons de PVC ou de verre conservaient plus de 90 % de la concentration initiale alors que les suspensions contenues dans les flacons de PET ou les seringues de plastique conservaient respectivement 88,9 % et 88,0 % de la concentration initiale. CONCLUSIONS: Comme les suspensions entreposées dans les flacons de PET et les seringues orales conservaient moins de 90 % de leur concentration initiale au jour 91 (selon l'IC de 95 %), on suggère d'entreposer les suspensions de dompéridone à 4 °C ou à 25 °C dans n'importe lequel contenant en l'accompagnant d'une date limite d'utilisation ne dépassant pas 75 jours.

Steady-State Pharmacokinetics of Oral Ciprofloxacin in Continuous Cycling Peritoneal Dialysis Patients: Brief Report.

Steady-state pharmacokinetics of oral ciprofloxacin in 3 continuous cycling peritoneal dialysis (CCPD) outpatients given ciprofloxacin 750 mg b.i.d. for 5 doses was determined. Mean steady-state maximum serum concentration and half-life were 4.4 ± 1.5 mg/L and 10.3 ± 2.6 hours, respectively. Mean maximum dialysate concentration in the daytime long dwell and overnight continuous cycling dwell were 7.4 ± 1.2 mg/L and 3.3 ± 1.2 mg/L, respectively. Oral ciprofloxacin 750 mg b.i.d. may be reasonable for bloodstream and peritoneal infections caused by susceptible bacteria in CCPD patients.

A prospective study evaluating tobramycin pharmacokinetics and optimal once daily dosing in burn patients.

BACKGROUND: Once-daily aminoglycoside dosing (ODA) is used in most patient populations to optimize antibacterial activity and reduce toxicity. Unfortunately, burn patients are excluded from ODA due to concerns over altered pharmacokinetics resulting in a shortened half-life and low peak aminoglycoside concentrations. Retrospective studies suggest that ODA may be appropriate if higher milligram/kilogram doses are used. However, no prospective clinical trials in burn patients exist to confirm these findings. OBJECTIVE: To determine the adequacy of once daily tobramycin dosed at 10mg/kg in adult burn patients. METHODS: This prospective single dose pharmacokinetic clinical trial was conducted at the Ross Tilley Burn Centre. Patients with a total burn surface area (TBSA) of <20% and creatinine clearance ≥50mL/min were eligible. A first-order one compartment model was used to determine the pharmacokinetic profile from 3 or 5 tobramycin levels over a 24h period per patient. Monte Carlo simulation (MCS) was performed to determine the probability of target level attainment. RESULTS: The mean percent TBSA, partial, and full thickness burn were 10%, 6%, and 4%, respectively. Nine of the ten patients recruited achieved peak concentrations of ≥20mg/L (mean of 29.4±5.7mg/L) and all patients had a trough level ≤0.5mg/L. The mean half-life, volume of distribution, and clearance were 2.58h, 0.33L/kg, and 7.40L/h, respectively. The MCS determined probability of attaining target peak concentrations with the 10mg/kg dose was 97%, which almost doubled that predicted with the usual 7mg/kg dose. CONCLUSION: Burn patients with adequate renal function and <20% TBSA are candidates for ODA. Tobramycin half-life was similar to healthy, non-burn patients. The larger than normal volume of distribution supports the use of the higher empiric dose of 10mg/kg total body or adjusted weight in non-obese and obese patients, respectively, with further dose adjustment based on therapeutic drug monitoring.

Extended Stability of Sodium Phosphate Solutions in Polyvinyl Chloride Bags.

BACKGROUND: Sodium phosphate injection is used to treat moderate to severe hypophosphatemia. There have been no published reports documenting the physical compatibility or chemical stability of sodium phosphate injection in IV solutions. OBJECTIVE: To evaluate the physical compatibility and chemical stability of 30 and 150 mmol/L solutions of phosphate, prepared from sodium phosphate injection, in 5% dextrose in water (D5W) and in 0.9% sodium chloride (normal saline [NS]) and stored in polyvinyl chloride (PVC) bags at 23°C or 4°C over 63 days. METHODS: On study day 0, solutions of phosphate 30 and 150 mmol/L in D5W or NS were prepared in PVC bags and stored at 4°C and 23°C. On prespecified days during the 63-day study period, the concentrations of sodium and phosphate were determined, and admixture weight was checked to assess moisture loss during storage without a plastic overwrap. Chemical stability was calculated from the intersection of the lower 95% confidence limit of the degradation rate and the lower limit of acceptability (90%) for concentration remaining. RESULTS: The analytical methods for both sodium and phosphate were found to be precise (coefficient of variation averaging less than 1% for pre-study validation samples). Both sodium and phosphate retained more than 94% of the initial concentration over the 63-day study period. With 95% confidence, the time to achieve 90% of the initial concentration of both sodium and phosphate approached or exceeded the 63-day study period, regardless of temperature, concentration, or base solution. CONCLUSIONS: Sodium phosphate solutions at a phosphate concentration of 30 or 150 mmol/L in either NS or D5W retained more than 94% of the initial concentration of both sodium and phosphate over 63 days when stored at 23°C or 4°C. In compliance with United States Pharmacopeia General Chapter <797> recommendations, a beyond-use date of 14 days (with refrigeration) or 48 h (room temperature) may be applied. Extending the beyond-use date beyond these limits may be considered, if a validated sterility test is performed.

CONTEXTE: Le phosphate de sodium injectable est employé pour traiter l'hypophosphatémie modérée et grave. À ce jour, aucun rapport portant sur la compatibilité physique ou la stabilité chimique du phosphate de sodium injectable contenu dans les solutions intraveineuses n'a été publié. OBJECTIF: Évaluer la compatibilité physique et la stabilité chimique de solutions de phosphate à des concentrations de 30 et de 150 mmol/L préparées à partir de phosphate de sodium injectable dilué dans du dextrose à 5 % dans l'eau (D5E) ou du chlorure de sodium à 0,9 % (solution physiologique salée [SP]) puis rangées dans des sacs de polychlorure de vinyle (PVC) à des températures de 4 °C ou de 23 °C pendant 63 jours. MÉTHODES: Au jour 0 de l'étude, les solutions de phosphate à des concentrations de 30 et de 150 mmol/L ont été préparées avec du D5E ou de la SP dans des sacs de PVC, puis entreposées à des températures de 4 °C ou de 23 °C. À des jours donnés pendant la période de 63 jours de l'étude, on a évalué les concentrations de sodium et de phosphate et l'on a pesé les mélanges pour vérifier la perte d'humidité pendant un entre-posage n'utilisant pas de suremballage de plastique. La stabilité chimique était calculée au point d'intersection entre la limite inférieure de confiance à 95 % du taux de dégradation et la limite inférieure d'acceptabilité (90 %) de la concentration restante. RÉSULTATS: Les méthodes analytiques employées pour évaluer le sodium et le phosphate se sont révélées précises (coefficient de variation moyen inférieur à 1 % pour les échantillons aux fins de validation avant l'étude). Le sodium et le phosphate conservaient chacun plus de 94 % de leurs concentrations initiales pendant la période d'étude de 63 jours. Avec un niveau de confiance de 95 %, le temps nécessaire pour atteindre 90 % de la concentration initiale pour le sodium et pour le phosphate approchait ou dépassait les 63 jours de la période d'étude, peu importe la température, la concentration ou la solution de base. CONCLUSIONS: Les solutions de phosphate de sodium dont la concentration en phosphate est de 30 ou de 150 mmol/L, qu'elles soient à base de D5E ou de SP, conservaient plus de 94 % des concentrations initiales de sodium et de phosphate pendant 63 jours, qu'elles soient entreposées à des températures de 4 °C ou de 23 °C. Conformément aux recommandations contenues dans le chapitre <797> de la United States Pharmacopeia, une date limite d'utilisation de 14 jours (sous réfrigération) ou de 48 heures (à température ambiante) peut être utilisée. Allonger la date limite d'utilisation au-delà des bornes fixées par l'organisme américain peut être envisageable si une épreuve validée de stérilité est réalisée.

Stability of Ertapenem 100 mg/mL in Manufacturer's Glass Vials or Syringes at 4°C and 23°C.

BACKGROUND: Prophylactic administration of ertapenem as a single 1-g IV dose has been shown to reduce sepsis after prostate biopsy. OBJECTIVE: To evaluate the stability of ertapenem after reconstitution with 0.9% sodium chloride to a final concentration of 100 mg/mL and storage in the manufacturer's original glass vials or polypropylene syringes. METHODS: On study day 0, 100 mg/mL solutions of ertapenem were retained in the manufacturer's glass vials or packaged in polypropylene syringes and stored at 4°C or 23°C without protection from fluorescent room light. Samples were assayed periodically over 18 days using a validated, stability-indicating liquid chromatographic method with ultra-violet detection. A beyond-use date was determined as the time for the concentration to decline to 90% of the initial (day 0) concentration, based on the fastest degradation rate, with 95% confidence. RESULTS: Reconstituted solutions stored in the manufacturer's glass vials or polypropylene syringes exhibited a first-order degradation rate, such that 10% of the initial concentration was lost in the first 2.5 days when stored at 4°C or within the first 6.75 h when stored at room temperature (23°C). Analysis of variance showed differences in the percentage remaining due to temperature (p < 0.001) and study day (p < 0.001) but not type of container (p = 0.98). When a 95% CI for the degradation rate was calculated and used to determine a beyond-use date, it was established that more than 90% of the initial concentration would remain for 2.35 days at 4°C and for 0.23 day (about 5 h, 30 min) at room temperature. CONCLUSIONS: A 100 mg/mL ertapenem solution stored in the manufacturer's glass vial or a polypropylene syringe will retain more than 90.5% of the initial concentration when stored for 48 h at 4°C and for an additional 1 h at 23°C.

CONTEXTE: Il a été démontré que l'administration prophylactique d'une dose unique de 1 g d'ertapénem par voie intraveineuse réduit les risques de sepsis après une biopsie de la prostate. OBJECTIF: Évaluer la stabilité de l'ertapénem reconstitué avec une solution de chlorure de sodium à 0,9 % pour atteindre une concentration finale de 100 mg/mL et placé dans les fioles de verre d'origine du fabricant ou dans des seringues de polypropylène. MÉTHODES: Au jour 0 de l'étude, des solutions de 100 mg/mL d'ertapénem ont été conservées dans les fioles de verre d'origine du fabricant ou conditionnées dans des seringues de polypropylène. Elles ont ensuite été entreposées à des températures de 4 °C ou de 23 °C sans protection contre la lumière des lampes fluorescentes de la pièce. Les échantillons ont été dosés périodiquement pendant 18 jours à l'aide d'une épreuve validée mesurant la stabilité par chromatographie liquide avec détection ultraviolette. Une date limite d'utilisation a été établie comme étant le temps nécessaire pour atteindre 90 % de la concentration initiale (jour 0), et ce, en fonction du taux de dégradation le plus rapide, avec un niveau de confiance de 95 %. RÉSULTATS: Les solutions reconstituées placées dans les fioles de verre du fabricant ou dans les seringues de polypropylène ont présenté un taux de dégradation de premier ordre, de sorte que la concentration initiale avait chuté de 10 % après les 2,5 premiers jours d'entreposage à 4 °C ou après les 6,75 premières heures d'entreposage à température ambiante (23 °C). L'analyse de variance a montré des différences dans le pourcentage restant qui étaient associées à la température (p < 0,001) et au jour de l'étude (p < 0,001), mais pas au type de contenant (p = 0,98). Lorsqu'un intervalle de confiance de 95 % pour le taux de dégradation a été calculé et utilisé pour déterminer la date limite d'utilisation, on a établi qu'il resterait plus de 90 % de la concentration initiale pendant 2,35 jours à 4 °C et pendant 0,23 jour (environ 5 heures 30 minutes) à température ambiante. CONCLUSIONS: Une solution de 100 mg/mL d'ertapénem placée dans la fiole de verre du fabricant ou dans une seringue de polypropylène conserve plus de 90,5 % de sa concentration initiale après avoir été entreposée pendant 48 heures à 4 °C et pendant 1 heure additionnelle lorsqu'elle est entreposée à 23 °C.

Trimethoprim and sulfamethoxazole transmembrane clearance during modeled continuous renal replacement therapy.

BACKGROUND/AIMS: There is limited data regarding trimethoprim (TMP)/sulfamethoxazole (SMX) continuous renal replacement therapy (CRRT) dosing. We aimed to estimate TMP/SMX transmembrane clearance (CLtm) during continuous hemofiltration (CH) and continuous hemodialysis (CD) to guide dosing. METHODS: Using an in vitro model, TMP/SMX sieving coefficients (SC) and saturation coefficients (SA) were determined with high-flux polyarylethersulfone and polyacrylonitrile-sodium methallyl sulfonate copolymer hemodiafilters at ultrafiltration/dialysate rates of 1, 2, 3, and 6 l/h. TMP/SMX CLtm was calculated using measured SC and SA. TMP/SMX CRRT doses were modeled using CLtm and published TMP/SMX pharmacokinetic parameters. RESULTS: TMP SC/SA during CH/CD were significantly higher than SMX SC/SA. During modeling, TMP 10 mg/kg/day and its corresponding SMX dose, 50 mg/kg/day, resulted in steady state TMP/SMX peak concentrations associated with efficacy against Pneumocystis jirovecii. CONCLUSIONS: CRRT resulted in greater TMP CLtm than SMX. TMP 10 mg/kg/day divided q12h may be an appropriate initial dose to consider in patients undergoing CRRT.

Stability of Bortezomib 2.5 mg/mL in Vials and Syringes Stored at 4°C and Room Temperature (23°C).

BACKGROUND: Solutions of bortezomib 1.0 mg/mL for IV administration are reportedly stable for up to 42 days. Recent publications have reported that the safety profile of bortezomib is better with subcutaneous administration than with IV administration. OBJECTIVE: To evaluate the stability of higher-concentration bortezomib solutions for subcutaneous administration (i.e., 2.5 mg/mL in 0.9% sodium chloride [normal saline or NS]). METHODS: On study day 0, twelve 3.5-mg vials of powdered bortezomib were each reconstituted with 1.4 mL of NS to prepare solutions with concentration 2.5 mg/mL. Half of the solutions were subsequently stored in the original vials and half were transferred to syringes. Three of each type of container were stored in the refrigerator (4°C) and the other 3 of each type were stored at room temperature (23°C). Concentration analysis and physical inspection were completed on study days 0, 1, 2, 8, 12, 14, 19, and 21. The concentration of bortezomib was determined by a validated liquid chromatographic method with ultraviolet detection. The expiry date was determined according to the time to achieve 90% of the initial concentration, based on the fastest degradation rate calculated from the 95% confidence interval of the observed degradation rate. RESULTS: The analytical method separated degradation products from bortezomib such that the concentration was measured specifically and accurately (with absolute deviations from known concentration averaging 2.99%), with intraday and interday reproducibility averaging 1.51% and 2.51%, respectively. During the study period, all solutions were observed to retain at least 95.26% of the initial concentration in both types of containers at both temperatures. CONCLUSIONS: Bortezomib (3.5 mg in manufacturer's vial) reconstituted with 1.4 mL NS is physically and chemically stable for up to 21 days at 4°C or 23°C when stored in either the manufacturer's original glass vial or a syringe. Subcutaneous injection of bortezomib represents a change in practice, and there is a potential safety concern if a solution of the increased concentration used for subcutaneous administration (2.5 mg/mL) is inadvertently used to prepare a dose intended for IV administration. Therefore, it is recommended that sites switching to subcutaneous administration of bortezomib eliminate 1.0 mg/mL IV solutions altogether or institute substantial barriers to prevent IV administration of the higher concentration of bortezomib.

CONTEXTE: Les solutions de bortézomib de 1,0 mg/mL pour administration intraveineuse sont jugées stables pour une période allant jusqu'à 42 jours. Des publications récentes indiquent que le profil d'innocuité du bortézomib est meilleur par administration sous-cutanée que par administration intraveineuse. OBJECTIF: Évaluer la stabilité de solutions de bortézomib à concentration plus élevée pour l'administration sous-cutanée (c.-à-d., 2,5 mg/mL dans du chlorure de sodium à 0,9 % [solution physiologique salée ou SP]). MÉTHODES: Au jour 0 de l'étude, on a reconstitué douze fioles de 3,5 mg de bortézomib sous forme de poudre avec 1,4 mL de SP par fiole afin d'obtenir des solutions d'une concentration de 2,5 mg/mL. La moitié de ces solutions a ensuite été entreposée dans les fioles d'origine et l'autre moitié a été placée dans des seringues. Trois seringues et trois fioles ont été entreposées au réfrigérateur (4 °C) alors que trois fioles et trois seringues ont été entreposées à la température ambiante (23 °C). Une analyse de la concentration ainsi qu'une inspection physique ont été effectuées aux jours 0, 1, 2, 8, 12, 14, 19 et 21 de l'étude. La concentration de bortézomib a été déterminée à l'aide d'une épreuve validée par chromatographie liquide avec détection ultraviolette. La durée de conservation a été établie en fonction du temps nécessaire pour atteindre 90 % de la concentration initiale, selon le taux de dégradation le plus rapide calculé grâce à l'intervalle de confiance à 95 % du taux de dégradation observé. RÉSULTATS: La méthode analytique a séparé le bortézomib de ses produits de dégradation de manière que la concentration a été mesurée de façon spécifique et précise (l'écart absolu par rapport à la concentration connue était en moyenne de 2,99 %), avec une reproductibilité moyenne intrajournalière et interjournalière respectivement de 1.51 % et de 2.51 %. Pendant l'étude, toutes les solutions conservaient au moins 95,26 % de la concentration initiale aux deux températures dans les fioles et les seringues. CONCLUSIONS: La solution obtenue à partir de la reconstitution du contenu d'une fiole de 3,5 mg de bortézomib (fiole du fabricant) avec 1,4 mL de SP est physiquement et chimiquement stable pendant une période allant jusqu'à 21 jours à des températures de 4 °C ou 23 °C lorsqu'elle est entreposée dans la fiole de verre d'origine du fabricant ou dans une seringue. L'injection sous-cutanée de bortézomib représente un changement dans la pratique. Une inquiétude demeure à propos d'un risque possible pour la sécurité des patients si une solution à concentration plus élevée (2,5 mg/mL), destinée à l'administration sous-cutanée, est utilisée par mégarde pour la préparation d'une dose à administrer par voie intraveineuse. Il est donc recommandé que les établissements qui se tournent vers l'administration sous-cutanée de bortézomib éliminent toutes les solutions de 1,0 mg/mL destinées à l'administration intraveineuse ou qu'ils mettent en place des obstacles importants pour éviter l'administration intraveineuse de solutions de bortézomib à concentration élevée. [Traduction par l'éditeur].

Determination of vancomycin pharmacokinetics in neonates to develop practical initial dosing recommendations.

Variability in neonatal vancomycin pharmacokinetics and the lack of consensus for optimal trough concentrations in neonatal intensive care units pose challenges to dosing vancomycin in neonates. Our objective was to determine vancomycin pharmacokinetics in neonates and evaluate dosing regimens to identify whether practical initial recommendations that targeted trough concentrations most commonly used in neonatal intensive care units could be determined. Fifty neonates who received vancomycin with at least one set of steady-state levels were evaluated retrospectively. Mean pharmacokinetic values were determined using first-order pharmacokinetic equations, and Monte Carlo simulation was used to evaluate initial dosing recommendations for target trough concentrations of 15 to 20 mg/liter, 5 to 20 mg/liter, and ≤20 mg/liter. Monte Carlo simulation revealed that dosing by mg/kg of body weight was optimal where intermittent dosing of 9 to 12 mg/kg intravenously (i.v.) every 8 h (q8h) had the highest probability of attaining a target trough concentration of 15 to 20 mg/liter. However, continuous infusion with a loading dose of 10 mg/kg followed by 25 to 30 mg/kg per day infused over 24 h had the best overall probability of target attainment. Initial intermittent dosing of 9 to 15 mg/kg i.v. q12h was optimal for target trough concentrations of 5 to 20 mg/liter and ≤20 mg/liter. In conclusion, we determined that the practical initial vancomycin dose of 10 mg/kg vancomycin i.v. q12h was optimal for vancomycin trough concentrations of either 5 to 20 mg/liter or ≤20 mg/liter and that the same initial dose q8h was optimal for target trough concentrations of 15 to 20 mg/liter. However, due to large interpatient vancomycin pharmacokinetic variability in neonates, monitoring of serum concentrations is recommended when trough concentrations between 15 and 20 mg/liter or 5 and 20 mg/liter are desired.

Determination of tobramycin pharmacokinetics in burn patients to evaluate the potential utility of once-daily dosing in this population.

The objective was to determine the pharmacokinetics of tobramycin in critically ill adult burn patients and evaluate a variety of milligram per kilogram (mg/kg) total body weight (TBW) regimens to determine whether practical initial once-daily administration recommendations to attain desired plasma levels could be identified. A retrospective study was conducted in 58 eligible patients who received tobramycin and had at least one set of steady-state levels from which pharmacokinetic parameters could be determined using standard first-order pharmacokinetic equations. Classification and Regression Tree analysis was used to identify whether tobramycin clearance changed with time postburn. Monte Carlo Simulation was used to evaluate initial mg/kg TBW dosing regimens to determine whether a clinically useful once-daily tobramycin recommendation could be made. Tobramycin clearance was significantly greater for patients ≤45 days postburn vs patients >45 days postburn. Once-daily tobramycin dosing for patients ≤45 days postburn of 10 to 13 mg/kg TBW and for patients >45 days postburn of 8 to 10 mg/kg TBW provided levels similar to those known to be effective in nonburn injury patients. Once-daily tobramycin dosing recommendations for burn patients were determined. Variability in pharmacokinetics in this population and change in pharmacokinetics with time postburn injury necessitate monitoring of tobramycin levels to ensure targets are met and maintained.

Current place of monoamine oxidase inhibitors in the treatment of depression.

This paper reviews the discovery and history of the use of irreversible monoamine oxidase (MAO) inhibitors (MAOIs) such as phenelzine, tranylcypromine and isocarboxazid, as well as the second generation selective and reversible MAOIs such as the MAO-A inhibitor, moclobemide and the MAO-B inhibitor, selegiline. Data for review were identified from a literature search of OvidSP Medline and PsycInfo performed in July 2012, using the subject terms and keywords of 'monoamine oxidase inhibitors', 'major depression', 'depressive disorder' and 'depression (emotion)'. The search was limited to papers published in the English language and from 2007 onward only. Irreversible MAOIs have the potential to treat the most challenging mood disorder patients including those with treatment-resistant depression, atypical depression and bipolar depression. Unfortunately, the use of irreversible MAOIs has been declining sharply due to lack of marketing and the excessive fears of clinicians. Moreover, few clinicians now have any experience, let alone comfort, in prescribing this class of antidepressants. The newer MAOIs are available as another option for the treatment of major depression but have not replaced the irreversible MAOIs for the specific sub-types of depression for which they are now recommended in most consensus guidelines and treatment algorithms. The pharmacology, drug interactions and dietary recommendations associated with the use of MAOIs are reviewed. With the appropriate dietary restrictions and attention to potential drug interactions with serotonin and noradrenaline agents this class of drugs can be used effectively and safely. The MAOIs still represent an important element in our therapeutic armamentarium. Despite recommendations by opinion leaders and consensus guidelines for the use of MAOIs in specific sub-types of depression, the prescription rate of MAOIs is far less than expected and is decreasing. The "bad reputation" and the lack of industry support for this class of agents (especially the irreversible MAOIs) must be overcome in order to continue to provide a potentially useful treatment for a very vulnerable yet substantial sub-population of mood disorder patients.

Identification of predictors of early infection in acute burn patients.

Burn patients are at high risk for infections; however, common indicators of infection are unreliable in this population and can lead to unnecessary use of antibiotics. The study objective was to determine if predictors of early infection in adult acute burn patients are identified to provide clinicians with a practical tool to aid in the diagnosis of infection, thereby minimizing unnecessary exposure to antimicrobials. A retrospective chart review of all adult acute burn injury patients admitted over a 1 year period to the burn centre at Sunnybrook Health Sciences Centre was conducted. Early infection was defined as one that occurred within the first 10 days after injury and in accordance with American Burn Association guidelines. Those without infection were compared to patients with infection generally and also to patients with sepsis specifically. The period prevalence of early infection and sepsis in our patients was 50% (56/111) and 16% (18/111), respectively. It was determined that heart rate ≥110 bpm, systolic blood pressure ≤100 mmHg and intubation were the best predictors of sepsis (p<0.05); and fraction of inhaled oxygen >25% and maximum temperature ≥39 °C were the best predictors of infection (p<0.05). This pilot project identified significant predictors of early infection and sepsis in acute burns and will be validated in a prospective study.

Eliciting patients' preferences for outpatient treatment of febrile neutropenia: a discrete choice experiment.

BACKGROUND: Studies have demonstrated that patients at low risk for febrile neutropenia (FN) complications can be treated safely and effectively at home. Information on patient preferences for outpatient treatment of this condition will help to optimize health care delivery to these patients. The purpose of this study was to elicit non-Hodgkin lymphoma patients' preferences on attributes related to outpatient treatment of FN. METHODS: We used a self-administered discrete choice experiment questionnaire based on the attributes of out-of-pocket costs, unpaid caregiver time required daily, and probability of return to the hospital. Ten paired scenarios in which levels of the attributes were varied were presented to study patients. For each pair, patients indicated the scenario they preferred. Adjusted odds ratios (ORs) of accepting a scenario that described outpatient care for FN were estimated. RESULTS: Eighty-eight patients completed the questionnaire. Adjusted ORs [95 % confidence intervals] of accepting outpatient care for FN were 0.84 [0.75, 0.95] for each $10 increase in out-of-pocket cost; 0.82 [0.68, 0.99] for each 1 h increase in daily unpaid caregiver time; and 0.53 [0.50, 0.57] for each 5 % increase in probability of return to the hospital. CONCLUSIONS: Probability of return to the hospital was the most important attribute to patients when considering home-based care for FN. Patients considered out-of-pocket costs and unpaid caregiver time to be less important than probability of return to the hospital. This study identifies factors that could be incorporated into outpatient delivery systems for FN care to ensure adequate patient uptake and satisfaction with such programs.