Objectives: This evaluation assesses the quantity, uniqueness, and innovative nature of the past 20 years of Rx-to-OTC (RTO) switches, where a current prescription (Rx) product is reclassified for over-the-counter (OTC) status. Broadening access to more OTC drugs with well-established safety and efficacy could help to reduce healthcare expenditure and address public health challenges. Methods: The FDA-maintained RTO switch list website was accessed to generate the primary dataset. Each product listed was assessed for the current OTC availability in the United States of its active ingredient, pharmacological class, and indication to determine its innovative quality. Descriptive statistics were employed in this study. Results: From January 2002 through August 2022 there were 45 RTO switches. Among these, 51.1% involved a new to OTC active ingredient, 22.2% involved a new pharmacological class, 6.6% involved a new indication, and 82.2% were considered follow-on products that introduced a new to OTC active ingredient or new dosage form of an already marketed active ingredient to treat an existing OTC indication. A small minority (6.6%) were considered an exceptional innovation that would offer US consumers a genuinely novel OTC product, providing a new to OTC active pharmaceutical ingredient, pharmacological class, and indication. Overall, there was 1 exceptional innovation every 6.7 years. Conclusions: Over 40 RTO switches have come to the OTC market in the past 20 years; however, exceptional innovations that expand access to new to OTC active ingredients for new indications are rare. Policies and strategies that result in more innovative switches that can benefit consumers and public health should be evaluated.

Introduction Most pharmacologic treatments with clinical data for insomnia symptoms are controlled substances. An exception is doxepin, an antihistamine that has shown efficacy for the treatment of difficulties with sleep maintenance. This analysis assessed the utility of doxepin 3 mg in the treatment of difficulties with sleep onset. Patients and methods A pooled analysis of two phase 3, randomized, controlled trials was conducted. Patients with primary insomnia received doxepin 3 mg or placebo 30 min before bedtime. Latency to persistent sleep (LPS) was assessed by polysomnography at screening (baseline), night 1 following a single dose (the main outcome of interest), and nights 15 and 29. Patient-reported latency to sleep onset (LSO) was recorded in a diary the following morning. Results A total of 310 patients, 153 randomized to placebo and 157 randomized to doxepin 3 mg, were included. Doxepin 3 mg resulted in a small but statistically significant 22% improvement in LPS compared with placebo on night 1 following a single dose (risk ratio: 0.78; 95% CI: 0.64, 0.94). A similar improvement was seen in a subgroup of patients with baseline LPS > 35 min. This subgroup had an 11-min reduction in LPS, compared with a 6.4-min reduction for the overall population. There was a nonsignificant 12% reduction in LSO in the overall population (risk ratio: 0.88; 95% CI: 0.73, 1.05). Conclusions Doxepin 3 mg has a statistically significant effect on sleep latency on the first night of treatment in adults with insomnia that did not reach the clinical significance threshold.

A variety of pharmacologic treatments are approved for insomnia, encompassing a range of mechanisms of action, including some treatments with published data in models of acute insomnia. However, most studies are conducted in individuals with chronic insomnia. Thus, it is unclear whether data from studies in individuals with chronic insomnia apply to individuals with acute insomnia symptoms. In this review, we discuss the generalizability of pharmacologic treatment data from chronic insomnia studies to individuals experiencing acute insomnia. Data from chronic insomnia treatment trials can be generalized to those with acute insomnia based on 1) the pathophysiology and evolution of insomnia and 2) data indicating medications effective for chronic insomnia are also effective for acute/induced insomnia. The pharmacologic management of acute insomnia should be based on a careful benefit-risk evaluation of each treatment option, data for acute insomnia or acute relief of chronic insomnia symptoms, and clinical practice guideline considerations. Given the limitations of available self-treatment options for acute insomnia symptoms, proven pharmacologic approaches are needed. Based on the available information, and the indications outlined in the United States (US) prescribing information, certain pharmacologic treatments are reasonable recommendations for treatment of acute insomnia.

OBJECTIVE: To assess risk of major adverse cardiovascular events associated with acute antimigraine treatments in patients with preexisting cardiovascular conditions. PATIENTS AND METHODS: In this retrospective, longitudinal, observational cohort study, we examined data from the Mass General Brigham Research Patient Data Registry on adults who received one or more prescriptions for acute migraine (index date) between January 2006 and December 2020 and who had one or more diagnoses of a cardiovascular condition during 12 months prior to index date. Study endpoints were nonfatal myocardial infarction, nonfatal stroke, and in-facility all-cause mortality, assessed separately and together as a composite major adverse cardiovascular events–proxy endpoint. RESULTS: Prescriptions were identified for 4016 oral triptans, 6084 opioids/butalbital, and 2021 NSAIDs. Hazard ratios (HRs) for major adverse cardiovascular events were 0.38 (95% CI: 0.22, 0.67; P =.001) comparing oral triptans with opioids/butalbital and 0.46 (95% CI: 0.29, 0.71; P <.001) with NSAIDs. There was no increased risk of nonfatal stroke comparing oral triptans with opioids/butalbital (HR 0.39; 95% CI 0.22, 0.69; P =.001) and with NSAIDs (HR 0.44; 95% CI 0.26, 0.76; P =.003). In a subgroup analysis of patients taking sumatriptan, HRs for major adverse cardiovascular events were 0.34 (95% CI: 0.21, 0.56; P <.001) when comparing oral sumatriptan with opioids/butalbital and 0.47 (95% CI: 0.28, 0.79; P =.004) with NSAIDs. CONCLUSIONS: The risk of adverse cardiovascular events observed with oral triptans is not greater than opioids/butalbital and NSAIDs in patients with migraine and preexisting cardiovascular conditions.

Introduction Patients are seeking greater involvement in their healthcare. It therefore may be beneficial to provide guidance on initial oral sumatriptan dose selection for the treatment of acute migraine in nontraditional settings, such as telehealth and other remote forms of medical care. We sought to determine whether clinical or demographic factors are predictive of oral sumatriptan dose preference. Methods This was a post hoc analysis of two clinical studies designed to determine preference for 25, 50, or 100 mg oral sumatriptan. Patients were aged 18–65 years with at least a 1 year history of migraine and experienced, on average, between one and six severe or moderately severe migraine attacks per month, with or without aura. Predictive factors were demographic measures, medical history, and migraine characteristics. Possibly predictive factors were identified using three analyses: classification and regression tree analysis, marginal significance (P < 0.1) within a full-model logistic regression, and/or selection within a forward-selection procedure in a logistic regression. A reduced model containing the variables identified in the preliminary analyses was developed. Due to differences in study design, data were not combined. Results A dose preference was expressed by 167 patients in Study 1 and 222 patients in Study 2. Gender and medical history of urologic and/or psychological conditions in Study 1 and duration of migraine history, height, and medical history of endocrine or neurologic disease and headache severity in Study 2 were identified as possibly predictive. The predictive model showed low positive predictive value (PPV; 23.8%) and low sensitivity (21.7%) for Study 1. For Study 2, the model showed moderate PPV (60.0%) but low sensitivity (10.9%). Conclusions No clinical or demographic characteristics alone or in combination were consistently or strongly associated with preference for oral sumatriptan dose level. Trial Registration The studies on which this paper is based were conducted before trial registration indexes were introduced.

Background/Objectives : Initially approved for the treatment of major depressive disorder, doxepin’s clinical applications have expanded to include pruritus and insomnia due to its receptor-specific activities at varying doses. This narrative review highlights the pharmacokinetics of doxepin, emphasizing its metabolism via CYP2D6 and CYP2C19 enzymes and the clinical implication of enzyme inhibition or induction. Methods: A literature search was performed using databases including PubMed, Embase, and Google Scholar, with no restrictions on publication date Results: Doxepin is primarily metabolized by CYP2D6 and CYP2C19, with inhibitors like fluoxetine, sertraline, cimetidine, and fluvoxamine increasing its plasma levels. Pharmacogenomic variations in CYP2D6 and CYP2C19 can also impact metabolism Conclusions Findings from this review suggest that while high-dose doxepin therapy may present notable interaction risks, low doses for insomnia are generally well-tolerated with minimal clinical consequences.