Annals of Pharmacotherapy最新文献

Background: Rasburicase is used to prevent and treat tumor lysis syndrome (TLS) by breaking down uric acid. Administration methods vary, including fixed, weight-based (0.15-0.2 mg/kg), single and multiple doses. Our primary objective is to describe rasburicase use in both adults and children for TLS prevention and treatment. Secondary objectives are to describe the efficacy and safety of different regimens inventoried. Exploratory objective is to estimate savings associated with use of a single fixed dose.

Methods: Retrospective descriptive study conducted among patients who received rasburicase for TLS prevention or treatment between January 2014 and April 2024 in 3 oncology services of the Hospital Center.

Results: A total of 133 adults and 60 children were included, of which 42.9% and 5.0%, respectively, presented biochemical TLS pre-rasburicase. A single 6 mg dose was administered in 86.5% of adults and 21.7% of children. Multiple daily doses were used in 24.8% of adults and 76.7% of children. Few adults (1.5%) received weight-based doses, contrary to children (76.7%). Normalized uric acid (< 476 μmol/L) was observed in 97.9% of patients 24 hours after a first dose, with no serious adverse events. Estimated savings were 86 542.92 CA$ if all patients included (n = 193) received a single 0.15 mg/kg dose, capped at 6 mg.

Conclusion and relevance: In the adult and pediatric population, a single rasburicase dose of 0.15 to 0.2 mg/kg, capped at 6 mg, represents an effective, safe, and more cost-effective option for both the prevention and treatment of TLS. Further studies are warranted to compare single versus multiple dosing in pediatric population and to identify potential risk factors for nonresponders.

Background: There is a lack of information regarding the combination therapy of phenobarbital (PB) and benzodiazepine (BZD) for the symptomatic management of patients in or at risk of severe alcohol withdrawal syndrome (AWS).

Objective: The objective of this study was to assess the safety and efficacy of a PB loading dose in addition to symptom-triggered BZD treatment for patients in or at risk of severe AWS.

Methods: Between January 2024 and May 2025, patients treated for AWS were screened for inclusion. Criteria for inclusion were age of at least 18 years old, a Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score of 4 or higher, and a record of receiving treatment for AWS. Patients were excluded from the study if they were directly admitted to the intensive care unit (ICU) or psychiatric service, transferred to the ICU within 12 hours of admission, or with a length of stay less than 24 hours. The primary endpoint was the difference in cumulative BZD requirements. Secondary endpoints included the need for adjunct therapies, incidence of adverse events, and escalation of care.

Results: The final analysis included 75 patients in the BZD group and 63 patients in the PB group. There was a statistically significant decrease in the cumulative BZD utilization in the PB loading group. Patients who exclusively received BZD therapy for AWS used an average of 148 mg of diazepam equivalents versus 112 mg in the PB group (P = 0.002). The PB group was also associated with a statistically significant reduction in the incidence of hypotension, respiratory depression, and the need for adjunct therapies.

Conclusions and relevance: The addition of a weight-based PB loading dose showed a significant reduction in BZD utilization for patients in or at risk of severe AWS and was associated with fewer adverse events. Application of this information may aid in enhancing treatment for patients in or at risk of severe AWS.

Background: Patients with substance use disorders (SUD) are at an increased risk of admission to intensive care units (ICUs) and the relationship between SUD and commonly used sedative and analgesic medications remains understudied.

Objective: The objective of this study was to describe associations between substance use disorder (SUD) and medication dose requirements in patients with critical illness requiring invasive mechanical ventilation (IMV).

Methods: This was a single center, retrospective study of adult patients admitted to an ICU between January 1, 2017, to October 31, 2022 who were initiated on IMV within 48 hours. The primary outcome was median total daily dose of each sedative and analgesic medication received, grouped as follows: parenteral opioids, benzodiazepines, propofol, and dexmedetomidine. Multivariable median regression was used to determine associations between SUD and median daily dose after adjustment for demographic and clinical covariables.

Results: Of 1290 included patients, 358 (27.8%) had a documented SUD present on admission. In unadjusted analyses, patients with SUD received higher median daily doses of parenteral opioids (197.5 MME [IQR 61.9-344.3] vs 162.2 MME [IQR 60.3-324.6]) and propofol (26 640 µg/kg [IQR 11 659-43 518] vs 23 248 µg/kg [IQR 10 510-38 870). No differences in median daily dose were noted for parenteral benzodiazepines or dexmedetomidine. In adjusted analyses, associations between SUD and median daily dose of parenteral opioids (β, 18.1 MME; 95% CI, -13.6 to 49.4) or propofol (β, 1699.9 µg/kg; 95% CI, -2477.1 to 5882.8) were no longer present.

Conclusion and relevance: Results of unadjusted analyses aligned with prior studies reporting increased dose requirements of sedation and analgesia in patients with SUD; however, associations were diminished after adjustment for clinical and demographic covariables. Our results suggest the presence of SUD alone may not necessitate empirically higher medication doses in patients with SUD receiving IMV during critical illness.

Background: Ivabradine is a hyperpolarization-activated cyclic nucleotide-gated channel blocker that has an off-label indication for arrhythmias in pediatric patients.

Objectives: The primary objective was identification of the line of therapy and type of arrhythmia for which ivabradine was initiated. The secondary objective was to evaluate the initial and peak ivabradine doses, tolerance in partially fed patients (i.e., patients not receiving full feeds at the time of ivabradine initiation), number of patients continued home on ivabradine, concomitant drug interactions with a class C, D, or X classification, and adverse effects.

Methods: A retrospective study of hospitalized patients <18 years of age receiving ivabradine for arrhythmias between January 1, 2021 and November 30, 2023. Data variables included demographics, ivabradine dosing regimens, concomitant anti-arrhythmic medications, percentage of ivabradine course while receiving full enteral feeds, concomitant medications with drug-drug interactions, and adverse effects (bradycardia [defined as <100 beats/min in neonates and <50 beats/min in infants and children], atrial fibrillation, vision changes, and emesis attributed to ivabradine).

Results: Seventeen patients were included. The most frequent arrhythmia indication was atrial tachycardia and ivabradine was most frequently used as a third-line anti-arrhythmic. Ten (58.8%) received ivabradine despite not being on full enteral feeds. The median initial and peak ivabradine doses were 0.05 mg/kg/dose and 0.07 mg/kg/dose, respectively, and it was most frequently administered every 12 hours. Only 1 patient required a dose decrease for a noted adverse effect. Most patients (94.1%) had a Class C drug-drug interaction, and 3 had a Class X interaction. Ten (58.8%) were discharged home on ivabradine.

Conclusions and relevance: Ivabradine was safe and effective as additive therapy for the treatment of pediatric arrhythmias. Larger studies of ivabradine use in pediatric arrhythmias are needed.