Annals of Pharmacotherapy最新文献

The Food and Drug Administration (FDA) has long suffered from a lack of resources limiting their inspection capacity. They have fallen behind on proactive surveillance inspections of foreign manufacturing sites, relying instead on for-cause inspections after a problem has been discovered. Over-the-counter (OTC) products are especially vulnerable because the FDA considers them lower priority. This issue recently made big news after improperly manufactured OTC eye drops harmed users across the country, in some cases causing blindness. To prevent future harm to Americans, it is imperative that the FDA receives enough resources to keep up with their routine inspections.

Background: Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed agents to treat depression. Considering the growth in antidepressant prescription rates, SSRI-induced adverse events (AEs) need to be comprehensively clarified.

Objective: This study was to investigate safety profiles and potential AEs associated with SSRIs using the Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: A retrospective pharmacovigilance analysis was conducted using the FAERS database, with Open Vigil 2.1 used for data extraction. The study included cases from the marketing date of each SSRI (ie, citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) to April 30, 2023. We employed the reporting odds ratio and Bayesian confidence propagation neural network as analytical tools to assess the association between SSRIs and AEs. The Medical Dictionary for Regulatory Activities was used to standardize the definition of AEs. AE classification was achieved using system organ classes (SOCs).

Results: Overall, 427 655 AE reports were identified for the 6 SSRIs, primarily associated with 25 SOCs, including psychiatric, nervous system, congenital, familial, genetic, cardiac, and reproductive disorders. Notably, sertraline (n = 967) and fluvoxamine (n = 169) exhibited the highest and lowest signal frequencies, respectively. All SSRIs had relatively strong signals related to congenital, psychiatric, and nervous disorders.

Conclusions and relevance: Most of our findings are consistent with those reported previously, but some AEs were not previously identified. However, AEs attributed to SSRIs remain ambiguous, warranting further validation. Applying data-mining methods to the FAERS database can provide additional insights that can assist in appropriately utilizing SSRIs.

Objective: To review the pharmacologic and clinical profile of mirikizumab in the treatment of moderate to severe ulcerative colitis (UC).

Data sources: A PubMed search was performed from inception to December 2023 using keywords mirikizumab, interleukin-23 inhibitor, and UC. Information was also obtained from package inserts as well as published abstracts.

Study selection and data extraction: Phase 3 studies plus relevant literature on mirikizumab pharmacologic and clinical profile were reviewed.

Data synthesis: Mirikizumab approval was based on LUCENT-1 and LUCENT-2. In the phase 3 studies involving patients with moderate to severe UC, mirikizumab, when compared to placebo, resulted in clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. In addition, mirikizumab met the secondary endpoints of alternate definition of clinical remission, endoscopic remission, glucocorticoid-free clinical remission, histologic-endoscopic mucosal remission, and improvement in bowel urgency status, bowel-urgency remission, and maintenance of clinical remission. Common adverse events noted include infection (15.1%), injection-site reaction (8.7%), nasopharyngitis (7.2%), and headache (3.3%).

Relevance to patient care and clinical practice in comparison to existing agents: Mirikizumab is the first selective interleukin 23 (IL-23) inhibitor approved for UC. Additional studies are required to determine how to position mirikizumab in both biologic-naïve and biologic-experienced patients with moderate to severe UC.

Conclusion: Mirikizumab provides a novel mechanism of action for the treatment of moderate to severe UC and is another welcomed treatment advance in the treatment arsenal, providing a more selective mechanism of action while maintaining a comparable safety profile.

Background: People with gender dysphoria are treated with hormone therapy for gender reassignment. The indication of this therapy was initially for the opposite sex, and information on potential adverse drug reaction (ADR) is lacking.

Objective: To describe ADR associated with gender transition medication in transgender individuals reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: Data from the FAERS database up to June 2023 were examined, focusing on reports of gender transition medication use in the context of gender dysphoria. The ADRs were categorized using the Medical Dictionary for Regulatory Activities at both Preferred Term and System Organ Class (SOC) levels. Descriptive statistics summarized report counts, medication types, indications, and ADR severity.

Results: For individuals assigned female at birth undergoing gender transition to male (transgender men), 82 reports (230 ADRs) were analyzed, with an average age of 29.5 years. Transgender hormonal therapy was cited in 72% of reports, predominantly from the United States (67.1%). A striking 88% were categorized as serious ADRs, primarily SOC injury, poisoning, and procedural complications (26.5%), followed by psychiatric disorders (14.8%) and nervous system disorders (12.2%). Among those assigned sex male at birth transitioning to female (transgender women) (81 reports, 237 ADRs), mean age was 33.3 years, with 58% indicating use for gender dysphoria. A significant proportion (53.6%) were serious ADRs, primarily SOC: injury, poisoning, and procedural complications (26.6%).

Conclusions and relevance: The FAERS data reveal significant ADRs in transgender individuals using hormone therapy, sometimes unintended for their recipient gender. Population-level studies are crucial to enhance transgender health care. Spontaneous surveillance databases like FAERS illuminate off-label ADRs, urging health care providers to approach hormone therapies with informed caution.

Background: Preoperative amiodarone effects on postorthotopic heart transplant (OHT) outcomes remain controversial.

Objective: The purpose of this study was to determine the effect of cumulative pre-OHT amiodarone exposure on severe primary graft dysfunction (PGD).

Methods: We retrospectively reviewed adult OHT recipients between August 2012 and June 2018. Primary outcome was severe PGD in patients receiving amiodarone at 3, 6, and 12 months prior to OHT compared with those not receiving amiodarone. Secondary outcomes included intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, early graft failure (EGF), mortality at 3, 6, and 12 months post-OHT, and 30-day incidence of postoperative tachyarrhythmias, bradycardia, permanent pacemaker implantation, and rejection.

Results: Incidence of severe PGD was 12.5% in those who received amiodarone compared to 6.8% in those who did not (14 vs 6, P = 0.18). Cumulative preoperative amiodarone significantly increased the odds of severe PGD at 3 months (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.001-1.06; P = 0.044) and 6 months (OR: 1.02, 95% CI: 1.003-1.044; P = 0.024) in a multivariate logistic regression. Patients on amiodarone had significantly higher rates of postoperative bradycardia (13.4% vs 4.5%, P = 0.03).

Conclusion and relevance: A trend toward increased PGD was present in patients receiving preoperative amiodarone. This finding combined with the regression showing significantly increased odds of PGD with increasing 3 and 6 month cumulative amiodarone dose is clinically concerning. Escalation of care with pacemaker implantation was required more frequently in patients on pre-OHT amiodarone.

Background: Sugammadex rapidly reverses the nondepolarizing neuromuscular blocking agents (NMBAs) rocuronium and vecuronium. The role of sugammadex is not well-defined outside of the postoperative setting.

Objective: This study aims to describe sugammadex use outside the postoperative setting for the reversal of nondepolarizing NMBAs.

Methods: This was a single-center, retrospective cohort study conducted in patients who received sugammadex outside of the postoperative setting at an academic medical center between June 2016 and November 2022. The primary outcome was the effect of sugammadex use for rocuronium reversal, defined as any increase in train-of-four (TOF) after sugammadex administration and/or progress note documentation if TOF was unavailable. Secondary outcomes included adverse events and documentation of contraceptive counseling in patients taking hormonal contraceptives with child-bearing ability.

Results: A total of 14 383 patients received sugammadex during the study period. Of those patients, 39 (0.3%) were outside of the postoperative setting for the reversal of rocuronium and included in the study. Twenty-nine (74%) patients had an increase in TOF after sugammadex administration and/or progress note documentation if TOF was unavailable. Ten (26%) patients lacked documentation regarding the effect of sugammadex. No adverse reactions were reported. Three (8%) patients included in the study were of child-bearing ability, and 1 of the 3 patients was counseled on using an alternative method of contraception following sugammadex administration.

Conclusion and relevance: There is a paucity of literature for the use of sugammadex outside of the postoperative setting. This study found that while the use of sugammadex was rare, overall, it was safe and well-tolerated.

Objective: The aims of this article are to review the clinical aspects of rozanolixizumab, to describe clinical trial results that led to the drug's approval, and to examine the impact on patient care to aid clinical decision making.

Data sources: A PubMed search was conducted using the terms Rystiggo™, rozanolixizumab, rozanolixizumab therapy, and myasthenia gravis. The most recent prescribing information was also used for information relating to the drug and for identification of pertinent studies.

Study selection/data extraction: Phase I, II, and III randomized controlled trials were all eligible for inclusion. Meeting abstracts and articles focusing on the use of rozanolixizumab or any indication other than generalized myasthenia gravis were excluded from this article.

Data synthesis: Food and Drug Administration approval of rozanolixizumab is based on the phase III MycarinG study in patients with generalized myasthenia gravis. A phase II trial explored initial clinical efficacy and safety pertaining to the dose and frequency of rozanolixizumab across 2 treatment periods in patients with moderate to severe myasthenia gravis.

Relevance to patient care and clinical practice in comparison to existing agents: Rozanolixizumab is the first therapy approved to treat patients positive for both types of antibodies, anti-acetylcholine receptor or anti-muscle-specific tyrosine kinase, in generalized myasthenia gravis.

Conclusion/relevance: The approval of rozanolixizumab represents an advancement in therapy for generalized myasthenia gravis. The provision of individualized, targeted, and well-tolerated treatment is valuable for the patients whose myasthenia gravis is not well controlled and who are seeking a medication with a rapid onset of action to improve their symptoms and overall quality of life.

Objective: The article reviews the safety and efficacy of treatments for cytomegalovirus (CMV) in solid organ transplantation.

Data sources: A literature review was conducted in PubMed, MEDLINE, and Clinicaltrials.gov from database inception through January 2024, using terms CMV, therapy, and solid organ transplantation.

Study selection and data extraction: Clinical trials, meta-analyses, cohort studies, case reports, and guidelines were included. Letters to the editor, reviews, and commentaries were excluded.

Data synthesis: After abstract screening and full-text review of 728 citations for eligibility, 53 were included. Valganciclovir and intravenous ganciclovir are drugs of choice for CMV management and, until recently, the availability of alternative options has been restricted due to toxicity. For instance, foscarnet and cidofovir serve as second-line agents due to potential bone marrow and renal toxicity. In patients with refractory or resistant CMV, maribavir, a novel oral agent, has proven efficacy and a lower adverse effect profile. However, in refractory or resistant CMV, foscarnet and cidofovir are preferred in invasive disease (CMV gastritis, CMV retinitis, and CMV encephalitis), high viral loads, and inability to tolerate oral preparations.

Relevance to patient care and clinical practice: Consensus guidelines have not been revised since approval of novel antivirals in solid organ transplantation. Valganciclovir and ganciclovir remain drugs of choice for initial CMV therapy. Foscarnet, cidofovir, and maribavir are treatments for refractory or resistant-CMV.

Conclusions: Selection of CMV antiviral treatment should be determined by patient-specific factors, including severity of illness, resistant or refractory disease, dose-limiting adverse effects, and the preferred route of administration.

Background: Short courses of antibiotics (7-10 days) are effective for uncomplicated gram-negative bloodstream infections (GN-BSI). However, prior studies have been limited to small cohorts of critically ill patients.

Objective: The objective of this study was to evaluate the safety and efficacy of short courses of therapy compared with longer courses in patients admitted to the intensive care unit (ICU) with GN-BSI.

Methods: Propensity-matched, retrospective cohort study of critically ill patients with GN-BSI. The primary outcome was a composite of 30-day mortality or 60-day relapse. Secondary endpoints were components of the composite, 30-day relapse, cure with or without adverse drug events (ADE), and ADEs. Regression analysis was performed to identify factors predictive of the composite outcome.

Results: 225 patients were included in the propensity analysis, 145 in the long cohort and 80 in the short cohort. The primary outcome occurred in 3.8% of patients in the short group and 9.0% of patients in the long group (P = 0.24). There was no difference in 30-day mortality (3.8% vs 5.5%, P = 0.79), 60-day relapse (0% vs 3.4%, P = 0.23), or 30-day readmission (20% vs 22.8%, P = 0.76). ADEs were more common in the long group (47.2% vs 34.1%, OR 1.7, 95% CI 1.04-2.9), primarily attributable to diarrhea.

Conclusion and relevance: In critically ill patients with GN-BSI, there were no efficacy outcome differences in patients treated with a short course of antibiotics compared with longer. However, patients in the short group were less likely to experience ADE. These findings suggest that short courses of antibiotics are effective for GN-BSI in critically ill patients.