Hospital Pharmacy最新文献

Background: Acute bacterial skin and skin structure infections (ABSSSI) are serious infections predominantly caused by Gram-positive pathogens such as Staphylococcus aureus and Streptococcus pyogenes. Oritavancin, a lipoglycopeptide antibiotic, has emerged as a treatment alternative to vancomycin, especially in light of rising resistance. It is available in two formulations: oritavancin diphosphate (OD) and oritavancin complexed with 2-hydroxypropyl-β-cyclodextrin (OC), which differ in preparation, infusion time, and excipients.

Objective: To compare the safety profiles of OD and OC by analyzing adverse drug reactions (ADRs) reported in the U.S. FDA Adverse Event Reporting System (FAERS), with a focus on differences potentially attributable to the HPβCD excipient in the OC formulation.

Methods: This was a retrospective observational study evaluating ADRs associated with OD and OC reported in FAERS between January 2014 and June 2024. Reports were filtered to distinguish the two formulations explicitly, excluding generic "oritavancin" entries. Data were categorized by seriousness, gender, age group, source of report, and clinical outcome.

Results: A total of 761 reports were retrieved for oritavancin diphosphate (OD) and 245 for oritavancin-HPβCD (OC). For both formulations, the peak in reporting occurred about 3 years after market introduction. The majority of events were classified as non-serious, accounting for 70.4% of OD and 71.8% of OC cases. Sex distribution differed slightly, with OD showing a predominance of female reports (38.2% vs 25.7% in OC), whereas OC presented more cases among males (34.7% vs 34.8% in OD). Clinical outcomes were largely comparable, though OD showed higher proportions of death (2.2% vs 0.8%), hospitalization (13.2% vs 10.7%), and life-threatening events (3.2% vs 0.8%). Age distribution indicated broader use of OD, including pediatric patients and a higher proportion of adults aged 18 to 64 years, while OC was more frequently reported in elderly patients (65-85 years). In both groups, most reports originated from healthcare professionals (>93%). Analysis of specific ADRs highlighted distinct patterns: infusion-related reactions, particularly chills, tremor, and flushing, were more frequent with OC, while OD was associated with higher rates of dermatological manifestations such as pruritus, urticaria, rash, and erythema. OC also showed a markedly higher proportion of errors related to multiple use of the single-use vial (9.9% vs 0.8%), whereas off-label use was more common with OD (9.6% vs 4.9%).

Conclusions: Although both contain the same active ingredient, OD and OC differ in safety profiles due to their formulation and administration. Both formulations are considered safe, consistent with their product information. These findings highlight the need for formulation-specific safety consideratio

Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally. Recent advancements in systemic therapy, particularly the combination of durvalumab and tremelimumab - dual immune checkpoint inhibitors - have redefined first-line treatment for advanced or unresectable HCC. However, limited real-world data are available on their safety profile outside clinical trials.

Objective: This study aimed to compare adverse drug reactions (ADRs) related to durvalumab and tremelimumab reported in the European EudraVigilance (EV) pharmacovigilance database with safety data from the Phase III HIMALAYA trial. The purpose of this study was not to perform a definitive quantitative or causal comparison between HIMALAYA and EudraVigilance - which would require reliable denominators and proper adjustment - but rather to integrate controlled trial data with spontaneous post-marketing reports to obtain a broader view of the safety profile and to highlight signals that may inform pharmacovigilance priorities and future observational studies.

Methods: A retrospective observational analysis was conducted on suspected ADRs related to durvalumab plus tremelimumab in advanced HCC patients. Data were collected from EV reports submitted in 2023 and compared with ADRs recorded in the HIMALAYA trial. Events were categorized by System Organ Class (SOC) and Preferred Terms (PTs) using MedDRA Version 26.1 terminology.

Results: A total of 236 EV reports encompassing 434 ADRs were analyzed. Most reports (97.5%) were classified as serious and originated from healthcare professionals. The most commonly reported SOCs in EV were gastrointestinal disorders (25.1%), skin disorders (11.8%), and hepatobiliary disorders (9.4%). The most frequent PTs included diarrhea (8.5%), interstitial lung disease (4.6%), and colitis (4.1%). In contrast, HIMALAYA data (n = 1722 ADRs) showed a similar prevalence of gastrointestinal disorders (25.6%) but higher frequencies of laboratory abnormalities and general systemic symptoms. Key discrepancies included higher reporting of immune-related and hepatic toxicities in EV and more systemic symptoms like fatigue and pyrexia in HIMALAYA.

Conclusions: Real-world data from EV reveal a distinct ADR profile for durvalumab plus tremelimumab compared to clinical trial data, particularly highlighting a greater incidence of severe immune-related events in routine practice. However, it is important to note that incidence rates could not be estimated because the total number of patients exposed in EV is unknown, which limits the ability to quantify absolute risks. These findings underscore the importance of pharmacovigilance in capturing rare or delayed toxicities not fully observed in trials, and reinforce the need for continuous post-marketing monitoring to optimize patient safety in immunotherapy.

Background: The variability in propranolol dose significantly impacts its effectiveness in preventing variceal hemorrhage (VH) in cirrhotic patients. This study aimed to determine an effective prophylactic dose of propranolol for both primary and secondary VH prophylaxis to optimizing treatment.

Methods: A retrospective study was conducted on cirrhotic patients treated with propranolol for primary and secondary VH prophylaxis from 2008 to 2023. Patients were categorized into two groups: those receiving ≥80 mg/day and those receiving <80 mg/day. The primary outcome was VH incidence. A multivariable Cox-proportional hazard model with propensity score-inverse probability of treatment weighting (PS-IPTW) was used to assess the association between propranolol dose and VH incidence.

Results: Of 215 patients on primary prophylaxis, 104 (48.4%) received propranolol ≥80 mg/day and 111 (51.6%) propranolol <80 mg/day. In secondary prophylaxis, 157 patients were included, with 83 (52.9%) of propranolol ≥80 mg/day group and 74 (47.1%) of propranolol <80 mg/day group. In the PS-IPTW Cox-proportional hazard model, the propranolol dose of ≥80 mg/day was significantly associated with reduced VH incidence for both primary and secondary prophylaxis. The adjusted hazard ratio (HR) was 0.37 (95%CI; 0.17-0.81, P = 0.01) for primary prophylaxis, and the adjusted HR was 0.51 (95%CI; 0.27-0.96, P = 0.04) for secondary prophylaxis.

Conclusion: Achieving ≥80 mg/day of propranolol is associated with significantly reduced VH incidence in both primary and secondary prophylaxis in patients with cirrhosis. This dose should be considered as the target dose for enhancing the effectiveness of propranolol on VH prophylaxis.

Depression, projected to be the leading cause of global disability by 2030, affects up to 19.62% of Pakistan's population. Treatment-resistant depression (TRD), characterized by poor response to at least two antidepressants, poses a major clinical challenge. Although interventions like ECT exist, their use is limited by systemic barriers. Esketamine, an NMDA receptor antagonist, offers a rapid-onset antidepressant effect and has shown higher remission rates compared to quetiapine in TRD trials. Despite promising evidence, esketamine is not currently available in Pakistan, and cost-related barriers hinder its adoption. Local studies suggest ketamine infusions are effective in TRD, including among ECT non-responders. Pakistan's centralized, specialist-dependent mental health system limits access to such novel treatments, particularly for rural and marginalized populations. Integrating esketamine requires addressing regulatory, infrastructural, and economic challenges while leveraging digital solutions and expanding community-based mental health services.

Background: Ketamine is a commonly used sedative agent for procedural sedation and rapid sequence intubation. Ketamine can also be administered via continuous infusion as an adjunct agent for sedation and analgesia in mechanically ventilated patients requiring high levels of sedation. In individuals who are not catecholamine-depleted, ketamine induces the release of norepinephrine, epinephrine, and dopamine, leading to transient increases in cardiovascular function. This mechanism suggests that ketamine, when used as a sedative agent, could potentially reduce vasopressor requirements in patients undergoing vasopressor therapy to maintain stable hemodynamics while needing high levels of sedation. The existing literature on continuous infusion ketamine's effect on vasopressor requirements is conflicting, with some studies reporting potential benefit and others showing no clinical difference.

Methods: This retrospective cohort study was conducted at Saint Joseph Hospital, a 433 bed community hospital located in Lexington, KY. The study included mechanically ventilated patients admitted between August 7, 2018, and December 31, 2024 who received a vasopressor agent for at least 3 hours for hemodynamic support prior to the initiation of continuous infusion ketamine, and received both ketamine and vasopressors concomitantly for at least 3 hours. To be included, patients must have also been receiving vasopressors at a dose ≥0.1 mcg/kg/min norepinephrine equivalents (NEE). The primary outcome was change in vasopressor requirements in critically ill patients at 6, 12, 24 hours after initiation of a continuous ketamine infusion as an adjunct sedative.

Purpose: The purpose of this research is to investigate whether the use of ketamine as an adjunct sedative and analgesic agent can decrease vasopressor requirements in critically ill patients.

Results: Forty-one patients met inclusion criteria. There was a difference in mean vasopressor requirements from baseline to 6, 12, 24, hours after continuous ketamine infusion initiation (P = .035). Mean vasopressor requirements decreased from 0.218 NEE at baseline to 0.186 NEE at 6 hours (P = .002), 0.145 NEE at 24 hours (P = .022).

Conclusion: Based on the results of this study, continuous infusion ketamine can reduce mean vasopressor requirements when used as an adjunct sedative in mechanically ventilated patients.

Background: Irbesartan is widely used for hypertension management, but its relationship with erectile dysfunction (ED) is unclear. This study combines real-world data from the FAERS database with Mendelian randomization to explore this potential association. Methods: We conducted multiple pharmacovigilance analyses, including odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Gamma-Poisson Shrinker (GPS), to assess the association between irbesartan and ED. Additionally, Mendelian randomization was applied to investigate the causal relationship. Results: The pharmacovigilance analyses indicated a significant association between irbesartan and ED: ROR = 3.38 (95% CI: 2.36-4.84), PRR = 3.38 (95% CI: 2.36-4.83), IC = 1.75 (95% CI: 1.13-2.17), and EBGM = 3.37 (95% CI: 2.36-4.83). Mendelian randomization analysis also showed a significant correlation using the inverse variance weighting method (P = .01, β = 10.06, SE = 3.91), with other methods yielding consistent directional results. Conclusion: Our study reveals a significant association and potential causal link between irbesartan use and ED. These findings highlight the need to consider ED as a possible adverse effect when prescribing irbesartan. Further research and clinical monitoring are essential to understand the underlying mechanisms and develop strategies to mitigate this side effect.