Improvement in sleep latency with extended-release once-nightly sodium oxybate for the treatment of adults with narcolepsy: Analysis from the phase 3 REST-ON clinical trial.

Background: In the REST-ON clinical trial (NCT02720744), mean sleep latency on the Maintenance of Wakefulness Test (MWT) was significantly improved with extended-release once-nightly sodium oxybate (ON-SXB) vs placebo (P < 0.001) in participants with narcolepsy. This post hoc analysis assessed response to treatment and improvement in excessive daytime sleepiness. Methods: Participants with narcolepsy aged ≥16 years were randomized 1:1 to receive ON-SXB (4.5 g, week 1; 6 g, weeks 2-3; 7.5 g, weeks 3-8; and 9 g, weeks 9-13) or placebo. Mean sleep latency on the MWT was measured across 5 trials of ≤30 min each. Post hoc assessments included percentage of participants whose sleep latency improved ≥5, ≥10, ≥15, and ≥20 min and with a mean sleep latency of 30 min. Results: Significantly more participants receiving ON-SXB vs placebo experienced increased mean sleep latency ≥5 min (all doses P < 0.001), ≥10 min (all doses P < 0.001), ≥15 min (6 and 7.5 g, P < 0.001; 9 g, P < 0.01), and ≥20 min (6 g, P < 0.01; 7.5 g, P < 0.001; 9 g, P < 0.05). More participants receiving ON-SXB had mean sleep latency of 30 min vs placebo (6 g, 5.7 % vs 0 %, respectively [P < 0.05]; 7.5 g, 10.5 % vs 1.3 % [P < 0.05]; 9 g, 13.2 % vs 5.1 % [P = 0.143]). Conclusions: Significantly more participants who received ON-SXB experienced increased mean sleep latency ≥5 to ≥20 min; at the 2 highest doses, >10 % remained awake for the entirety of the MWT. ON-SXB offers a once-at-bedtime treatment option for adults with narcolepsy.

Cataplexy response with extended-release once-nightly sodium oxybate: Post hoc responder analyses from the phase 3 REST-ON clinical trial.

Background: Once-nightly sodium oxybate (ON-SXB), an extended-release oxybate formulation, yielded significant (P < 0.001 at 6 g, 7.5 g, and 9 g) reductions in cataplexy episodes in participants in the phase 3 REST-ON clinical trial (NCT02720744). This post hoc analysis from REST-ON further characterized changes in cataplexy episodes in participants with narcolepsy type 1 (NT1). Methods: Participants with narcolepsy aged ≥16 years received ON-SXB (1 wk, 4.5 g; 2 wk, 6 g; 5 wk, 7.5 g; 5 wk, 9 g) or placebo. Percentages of participants with NT1 who had ≥25%, ≥50%, ≥75%, and 100% reductions from baseline in mean number of weekly cataplexy episodes were determined. Two-sided P values comparing ON-SXB vs placebo were calculated with Fisher exact test. Results: Participants with NT1 (ON-SXB, n = 73; placebo, n = 72; modified intent-to-treat population) had a baseline mean number of weekly cataplexy episodes of 18.9 (ON-SXB) and 19.8 (placebo). Of participants receiving the highest doses of ON-SXB (7.5 and 9 g), approximately half had a 50% reduction, one-third had a 75% reduction, and one-tenth had a 100% reduction in their cataplexy episodes vs placebo. Significantly greater proportions of participants receiving ON-SXB vs placebo had respective reductions in weekly cataplexy episodes of ≥25% at weeks 1 (4.5 g; P < 0.05), 3 (6 g; P < 0.001), 8 (7.5 g; P < 0.001), and 13 (9 g; P = 0.001). Conclusions: A significantly greater proportion of participants receiving ON-SXB vs placebo experienced reductions in weekly cataplexy episodes at all tested doses. Approximately 10% of participants taking the 2 highest ON-SXB doses had complete elimination of their cataplexy.

Once-nightly sodium oxybate (FT218) improved symptoms of disrupted nighttime sleep in people with narcolepsy: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a published article in the journal CNS Drugs. Narcolepsy is a rare sleep condition. Most people with narcolepsy experience disrupted nighttime sleep and have poor quality of sleep. Sometimes these symptoms are not easily diagnosed as a symptom of narcolepsy. Sodium oxybate is an approved treatment for narcolepsy. The only version of sodium oxybate that was available until 2023 required people to take their sodium oxybate at bedtime and then again in the middle of the night. The US Food and Drug Administration (FDA for short) has approved a once-nightly bedtime dose of sodium oxybate (ON-SXB for short, also known as FT218 or LUMRYZ™) to treat symptoms of narcolepsy in adults. These symptoms are daytime sleepiness and cataplexy, which is an episode of sudden muscle weakness. The once-nightly bedtime dose of ON-SXB removes the need for a middle-of-the-night dose of sodium oxybate. The REST-ON clinical study compared ON-SXB to a placebo (a substance that contains no medicine) to determine if it was better at treating symptoms of disrupted nighttime sleep associated with narcolepsy. This summary looks at whether; ON-SXB was better than placebo at treating symptoms of disrupted nighttime sleep. WHAT WERE THE RESULTS?: Compared to people who took placebo, people who took ON-SXB had fewer number of changes from deeper to lighter sleep stages and woke up less during the night. They also reported that they slept better at night and felt more refreshed when waking up in the morning. People with narcolepsy sometimes take alerting agents to help with sleepiness during the day, but alerting agents can cause difficulty sleeping at night. This study showed that people who took ON-SXB had better nighttime sleep even if they were taking alerting agents during the day. The most common side effects of ON-SXB included dizziness, nausea (feeling sick to your stomach), vomiting, headache, and bedwetting. WHAT DO THE RESULTS MEAN?: A once-nightly bedtime dose of ON-SXB is a narcolepsy treatment option for people without the need for a middle-of-the-night dose of sodium oxybate.

Clinician Preferences for Oxybate Treatment for Narcolepsy: Survey and Discrete Choice Experiment.

INTRODUCTION: Immediate-release sodium oxybate (SXB) has been Food and Drug Administration (FDA)-approved to treat narcolepsy since 2002; in 2020, a mixed-salt oxybates formulation was also approved. Both are taken at bedtime with a second dose taken 2.5-4 h later. A third oxybate option, an investigational extended-release SXB, may soon be available. This study was undertaken to understand clinicians' preferences between these 3 different oxybate treatments. METHODS: Clinicians in active clinical practice for 3-35 years and experience treating patients with narcolepsy were recruited. A 30-min web-based survey quantified narcolepsy disease-state attitudes, treatment perceptions, and satisfaction with oxybates on 9-point scales. A discrete choice experiment (DCE) of 12 choice sets, with 2 hypothetical treatment profiles in each, was used to capture clinician preferences about overall oxybate therapy preference, impact on patient quality of life (QoL), and patient anxiety/stress. Attributes associated with current therapies and those expected to be available in the near future were included in the design. RESULTS: The clinicians surveyed (n = 100) indicated that narcolepsy has a negative impact on patient QoL (mean rating, 7.7) and rated impact on QoL and treatment efficacy as the most important aspects of a narcolepsy treatment (mean rating, 7.3-7.7). Clinicians with experience prescribing oxybates had moderately high satisfaction with SXB and mixed-salt oxybates efficacy (mean ratings, 6.5-6.9) and safety (mean ratings, 6.1-6.7) and lower satisfaction with nightly dosing frequency (mean rating, 5.9 and 6.3, respectively). In the DCE, dosing frequency was the most important attribute driving overall product choice, patient QoL, and reducing patient anxiety/stress (relative attribute importance, 46.1, 41.7, and 44.0, respectively), with once nightly preferred over twice nightly. CONCLUSION: Clinicians indicated a significantly higher preference for the once-at-bedtime dosing schedule versus twice nightly in selecting oxybate therapies overall and when aiming to improve patient QoL or reduce patient anxiety.

Current medications for narcolepsy include immediate-release sodium oxybate and mixed-salt oxybates. People taking these oxybates for narcolepsy take 1 dose at bedtime and must wake up 2.5­4 h later for the second dose. An investigational sodium oxybate, designed as a single bedtime dose, has been tentatively approved by the US Food and Drug Administration. This study used a 30-min web-based survey to learn what clinicians think about narcolepsy and narcolepsy medicines. A discrete choice experiment was used to identify which properties of current/future oxybate medicines are most important in a narcolepsy treatment. In this exercise, relevant properties of current/future oxybate medicines were mixed and matched to create hypothetical medicine profiles. Clinicians selected from these profiles which medication they preferred overall, which would improve patient quality of life, and which would reduce patient anxiety when thinking about taking the treatment. Clinicians were moderately satisfied with the effectiveness and safety of current narcolepsy medications. They strongly preferred oxybate treatments with fewer nightly doses and agreed that waking up for the second oxybate dose causes stress for patients. In the discrete choice experiment, the number of doses each night was the product characteristic that had the biggest impact on clinicians picking a medicine for narcolepsy. This was true for overall medicine choice, choosing a medicine that would improve patient quality of life, and choosing one that would reduce patient anxiety/stress. If granted marketing approval, extended-release sodium oxybate will be a once-at-bedtime option that may overcome challenges with current oxybate therapies.

Efficacy of once-nightly sodium oxybate (FT218) in narcolepsy type 1 and type 2: post hoc analysis from the Phase 3 REST-ON Trial.

STUDY OBJECTIVES: Post hoc analyses from the phase 3 REST-ON trial evaluated efficacy of extended-release once-nightly sodium oxybate (ON-SXB; FT218) vs placebo for daytime sleepiness and disrupted nighttime sleep in narcolepsy type 1 (NT1) and 2 (NT2). METHODS: Participants were stratified by narcolepsy type and randomized 1:1 to ON-SXB (4.5 g, week 1; 6 g, weeks 2-3; 7.5 g, weeks 4-8; and 9 g, weeks 9-13) or placebo. Assessments included mean sleep latency on Maintenance of Wakefulness Test (MWT) and Clinical Global Impression-Improvement (CGI-I) rating (coprimary endpoints) and sleep stage shifts, nocturnal arousals, and patient-reported sleep quality, refreshing nature of sleep, and Epworth Sleepiness Scale (ESS) score (secondary endpoints) separately in NT1 and NT2 subgroups. RESULTS: The modified intent-to-treat population comprised 190 participants (NT1, n = 145; NT2, n = 45). Significant improvements were demonstrated with ON-SXB vs placebo in sleep latency for NT1 (all doses, p < .001) and NT2 (6 and 9 g, p < .05) subgroups. Greater proportions of participants in both subgroups had CGI-I ratings of much/very much improved with ON-SXB vs placebo. Sleep stage shifts and sleep quality significantly improved in both subgroups (all doses vs placebo, p < .001). Significant improvements with all ON-SXB doses vs placebo in refreshing nature of sleep (p < .001), nocturnal arousals (p < .05), and ESS scores (p ≤ .001) were reported for NT1 with directional improvements for NT2. CONCLUSIONS: Clinically meaningful improvements of a single ON-SXB bedtime dose were shown for daytime sleepiness and DNS in NT1 and NT2, with less power for the limited NT2 subgroup.

Evidence of Accidental Dosing Errors with Immediate-Release Sodium Oxybate: Data from the US Food and Drug Administration Adverse Event Reporting System.

INTRODUCTION: Sodium oxybate has been approved by the US Food and Drug Administration (FDA) to treat narcolepsy for 20 years; however, the only available products have been immediate-release (IR) formulations given twice nightly-once at bedtime and a second dose 2.5-4 h later-creating inherent risks with dosing administration errors. OBJECTIVES: Evidence and risks associated with accidental ingestion of the second IR oxybate dose < 2.5 h after the first dose were examined. METHODS: The FDA Adverse Event Reporting System database was searched for "inappropriate schedule of product administration" with IR sodium oxybate or calcium/magnesium/potassium/sodium oxybates; reports classified as serious and with IR oxybate as the suspect product were further analyzed. RESULTS: Of 541 reports meeting the search criteria, 178 were classified as serious: accidental early administration of the second dose resulting in adverse events (AEs; n = 41); "near miss" (no harm reported following early dosing; n = 9); intentionally taking second dose early (n = 25); other inappropriate use (late dosing/not taking daily; n = 102); and one duplicate report. Of the 41 reports of taking the second dose too early resulting in AEs, 22% (9/41) used emergency services and 27% (11/41) resulted in hospitalizations. AEs reported with accidentally taking the second dose too early included CNS depression, bradycardia, respiratory depression, dizziness, seizure, confusion, delirium, difficulty awakening, drowsiness, falls, nausea, vomiting, and enuresis. CONCLUSIONS: Patients, caregivers, clinicians, and Poison Control Centers should be aware of the risk of accidentally dosing twice-nightly IR oxybates earlier than 2.5 h after the first dose and the subsequent harm that may occur with early dosing.

Sodium oxybate and calcium, magnesium, potassium, and sodium oxybates (both medicines are called "oxybates") are medicines used to treat narcolepsy. People with narcolepsy need to take these medicines twice every night. They take one dose at bedtime and then wake up 2.5­4 h later to take the second dose. People could make mistakes taking their oxybate medicine because of this schedule. We looked in the US Food and Drug Administration's (FDA's) database called the FDA Adverse Event Reporting System to learn if there were reports of people accidentally taking the second dose of their oxybate medicine earlier than 2.5 h after taking the first dose. People who accidentally took the second dose too early experienced side effects like slowing down of the brain, breathing, and heart; feeling dizzy; having a seizure; being confused; having trouble waking up; being sleepy; falling down; feeling sick to their stomach; throwing up; and wetting the bed. Some people used emergency help and some went to the hospital. We found that harm may occur if people take the second dose of these oxybates too soon after the first dose. These risks were not previously reported. People with narcolepsy, their families, and their doctors need to know about these risks with the oxybates that are taken twice every night.

Randomized, crossover, open-label study of the relative bioavailability and safety of FT218, a once-nightly sodium oxybate formulation: Phase 1 study in healthy volunteers.

OBJECTIVES: Treatment for narcolepsy with sodium oxybate (SXB) has required twice-nightly dosing, at bedtime and 2.5-4 h later. This study evaluated the pharmacokinetics of FT218, an investigational, extended-release, once-nightly formulation of SXB (ON-SXB), vs twice-nightly SXB. METHODS: In this phase 1, open-label study, healthy volunteers were randomized (1:1) to ON-SXB 6 g or twice-nightly SXB (two 3-g doses administered 4 h apart); minimum 3-day washout before crossover. Doses were administered 2 h post-evening meal. Blood samples for pharmacokinetic assessments were collected predose and up to 14 h after the first dose during each treatment period. RESULTS: Twenty-eight participants were enrolled (mean age, 39.6 years; 54% women; 93% white). Mean ± SEM area under the concentration-time curve for ON-SXB was 282.7 ± 30.2  µg·h/mL vs 273.3 ± 27.8 µg·h/mL for twice-nightly SXB. Geometric mean ratio (GMR; 90% CI) was 102.9 (98.0-108.0). Maximum γ-hydroxybutyrate (GHB) plasma concentration (Cmax) was 65.8 ± 4.0 µg/mL for ON-SXB vs 77.1 ± 4.9 µg/mL for twice-nightly SXB (GMR [90% CI], 88.3 [80.5-97.0]). The GMR (90% CI) for GHB plasma concentrations 8 h post dose (C8h) for ON-SXB vs twice-nightly SXB was 61.7 (45.8-83.0). The most frequently reported adverse events were the same for ON-SXB and twice-nightly SXB (nausea, dizziness, somnolence, vomiting). CONCLUSIONS: GHB exposure and Cmax with one 6-g dose of ON-SXB were bioequivalent to those with two 3-g doses of twice-nightly SXB, whereas C8h was lower with ON-SXB. If approved, ON-SXB will provide a single bedtime oxybate option, with clinically relevant pharmacologic exposure during the entire sleep period.

Safety review of hydroxyprogesterone caproate in women with a history of spontaneous preterm birth.

17-alpha-hydroxyprogesterone caproate (17P) has been in use for prevention of recurrent preterm birth since 2003 when the Meis trial was published. A requirement for Food and Drug Administration approval of 17P was a confirmatory trial, called "PROLONG", which was recently completed, but did not replicate the efficacy demonstrated in the Meis trial. This review analyzes the safety data from each trial, as well as integrated data from the two trials. The relative risks (95% CI) with 17P versus placebo in the integrated dataset were 0.66 (0.25-1.78) for miscarriage, 1.83 (0.68-4.91) for stillbirth, and 0.86 (0.53-1.41) for all fetal and neonatal death. The rate of gestational diabetes in the integrated dataset was 3.6% for 17P vs. 3.8% for placebo. Similar findings with low and comparable rates between 17P and placebo were also found for other adverse events. The integrated safety data demonstrate a favorable safety profile that was comparable to placebo.

FDA approved vs. Pharmacy compounded 17-OHPC-current issues for obstetricians to consider in reducing recurrent preterm birth.

17α-hydroxyprogesterone caproate (17-OHPC; MAKENA and generic equivalents) is the only FDA-approved medicine available to reduce the risk of preterm birth (PTB) in pregnant women with a singleton pregnancy who have a history of singleton spontaneous PTB. The FDA held an Advisory Committee meeting in October 2019 to review conflicting data between one positive U.S.-based study and one international study that failed to confirm the benefit. At this meeting, the key vote as to whether the FDA should pursue withdrawal of Makena resulted in a split; 9 members voted that the FDA pursue withdrawal and 7 members voted to leave Makena on the market and require that additional effectiveness data be generated. Removal of FDA-approved formulations of 17-OHPC-both brand name Makena and the generic equivalents-would foreseeably result in clinicians administering compounded 17-OHPC to prevent PTB in their patients. Unlike FDA-approved products, compounded drugs are not approved by the FDA and, thus, have not undergone any FDA scrutiny with regard to safety, effectiveness, or quality (as designated by good manufacturing practices; GMP) before they are marketed. Compounded drugs may be associated with significant safety risks, as poor compounding practices have resulted in serious problems with drug quality (lack of sterility or stability) and potency. Given the markedly higher rates of PTB in the U.S. compared with other industrialized nations, it is imperative that FDA-approved, GMP-produced 17-OHPC (FDA-approved brand and generic formulations) is available while additional research on its optimal use is conducted, without providers and patients resorting to pharmacist-compounded formulations for their high-risk pregnant patients.

Correction to: Communicating with African-American Women Who Have Had a Preterm Birth about Risks for Future Preterm Births.

The article [Communicating with African-American Women Who Have Had a Preterm Birth About Risks for Future Preterm Births], written by [Allison S. Bryant, Laura E. Riley, Donna Neale, Washington Hill, Theodore B. Jones, Noelene K. Jeffers, Patricia O. Loftman, Camille A. Clare, and Jennifer Gudeman], was originally published electronically on the publisher's internet portal on January 16, 2020 without open access.

Communicating with African-American Women Who Have Had a Preterm Birth About Risks for Future Preterm Births.

PURPOSE: African-American women are at higher risk of preterm birth (PTB) compared with other racial/ethnic groups in the USA. The primary objective was to evaluate the level of understanding among a group of African-American women concerning risks of PTB in future pregnancies. Secondary objectives were to evaluate how some women obtain information about PTB and to identify ways to raise their awareness. METHODS: Six focus groups were conducted in three locations in the USA during 2016 with women (N = 60) who had experienced ≥ 1 PTB (< 37 weeks of gestation) during the last 5 years. The population was geographically, economically, and educationally diverse. RESULTS: We observed a tendency to normalize PTB. Knowledge about potential complications for the infant was lacking and birth weight was prioritized over gestational age as an indicator of PTB. Participants were largely unaware of factors associated with increased PTB risk, such as a previous PTB and race/ethnicity. The most trusted information source was the obstetrical care provider, although participants reported relying on mobile apps, websites, and chat rooms. The optimal time to receive information about PTB risk in subsequent pregnancies was identified as the postpartum visit in the provider's office. CONCLUSIONS: Awareness of the risks of recurrent PTB was limited in this diverse population. Educational programs on the late-stage development of neonates may strengthen knowledge on the relationship between gestational age and PTB and associated health/developmental implications. For educational efforts to be successful, a strong nonjudgmental, positive, solutions-oriented message focused on PTB risk factors is crucial.

17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial.

BACKGROUND: Women with a history of spontaneous preterm birth (SPTB) are at a significantly increased risk for recurrent preterm birth (PTB). To date, only one large U.S. clinical trial comparing 17-OHPC (17-α-hydroxyprogesterone caproate or "17P") to placebo has been published, and this trial was stopped early due to a large treatment benefit. OBJECTIVE: This study aimed to assess whether 17-OHPC decreases recurrent PTB and neonatal morbidity in women with a prior SPTB in a singleton gestation. STUDY DESIGN: This was a double-blind, placebo-controlled international trial involving women with a previous singleton SPTB (clinicaltrials.gov: NCT01004029). Women were enrolled at 93 clinical centers (41 in the United States and 52 outside the United States) between 160/7 to 206/7 weeks in a 2:1 ratio, to receive either weekly intramuscular (IM) injections of 250 mg of 17-OHPC or an inert oil placebo; treatment was continued until delivery or 36 weeks. Co-primary outcomes were PTB < 35 weeks and a neonatal morbidity composite index. The composite included any of the following: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, or proven sepsis. A planned sample size of 1,707 patients was estimated to provide 98% power to detect a 30% reduction in PTB < 35 weeks (30% to 21%) and 90% power to detect a 35% reduction in neonatal composite index (17%-11%) using a two-sided type-I error of 5%. Finally, this sample size would also provide 82.8% power to rule out a doubling in the risk of fetal/early infant death assuming a 4% fetal/early infant death rate. Analysis was performed according to the intention-to-treat principle. RESULTS: Baseline characteristics between the 1,130 women who received 17-OHPC and 578 women who received placebo were similar. Overall, 87% of enrolled women were Caucasian, 12% had >1 prior SPTB, 7% smoked cigarettes, and 89% were married/lived with partner. Prior to receiving study drug, 73% women had a transvaginal cervical length measurement performed and <2% had cervical shortening <25 mm. There were no significant differences in the frequency of PTB < 35 weeks (17-OHPC 11.0% vs. placebo 11.5%; relative risk = 0.95 [95% confidence interval (CI): 0.71-1.26]) or neonatal morbidity index (17-OHPC 5.6% vs. placebo 5.0%; relative risk = 1.12 [95% CI: 0.68-1.61]). There were also no differences in frequency of fetal/early infant death (17-OHPC 1.7% vs. placebo 1.9%; relative risk = 0.87 [95% CI: 0.4-1.81]. Maternal outcomes were also similar. In the subgroup of women enrolled in the United States (n = 391; 23% of all patients), although the rate of PTB < 35 weeks was higher than the overall study population, there were no statistically significant differences between groups (15.6% vs. 17.6%; relative risk = 0.88 [95% CI: 0.55, 1.40]. CONCLUSION: In this study population, 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death.

Mode of injection and treatment adherence: results of a survey characterizing the perspectives of health care providers and US women 18-45 years old.

PURPOSE: A market research study was conducted to characterize perceptions of intramuscular (IM) and subcutaneous (SC) routes of injection, including use of autoinjectors, and how these perceptions affect adherence to injection regimens. The perspectives were from women of childbearing age (18-45 years old; consumers) and health care providers (HCPs) involved in women's health care. METHODS: Two telephone surveys, one of HCPs and the other of consumers, were conducted by KRC Research (New York, NY, USA) between May and July 2017. HCPs were recruited across the US; the consumer survey was administered to a nationally representative sample. Survey questions identified potential challenges of IM and SC administration, their impact on treatment adherence, and perceptions of autoinjectors. Results are reported using descriptive statistics and reflect an unweighted sample; margin of error is ±3% for the consumer survey. RESULTS: HCP respondents included 100 generalist OB/GYNs, 101 maternal-fetal medicine specialists, and 519 nurses; there were 1,012 female consumer respondents. Nurses reported more experience than physicians in administering injections, including with autoinjectors. Consumers reported having received treatments via both IM and SC injections; 26% had received treatment with injections at regular intervals. Most HCPs (58%) said they preferred to administer SC injections, which was also the preference for receiving injections among consumers, who reported needle size as a concern regardless of administration mode. Other major concerns were perceptions of pain and fear/anxiety, and seeing the needle, all of which were greater for IM than for SC injections. HCPs and consumers both reported greater likelihood of adherence to therapy administered SC using an autoinjector because they believe that this method provides substantial HCP and patient benefits. CONCLUSION: HCPs and consumers identified similar challenges with adherence to injections. However, there was consistently higher preference for SC relative to IM. HCPs and consumers believe that autoinjectors may increase adherence.

Female Sexual Health: Barriers to Optimal Outcomes and a Roadmap for Improved Patient-Clinician Communications.

BACKGROUND: Although sexual health can be considered a vital sign for overall health, several barriers prevent women from receiving proper medical counseling, support, and/or care for their sexual health needs and concerns. METHODS: Experts in sexual health compiled research and experience on the impediments to women receiving adequate assessment and treatment for their sexual health. Specific solutions and a roadmap for overcoming such barriers and improving patient-clinician communication are presented. RESULTS: Social stigma around female sexuality remains in Western culture and as a result, women often avoid and/or are embarrassed to discuss their sexual health with their health care professionals (HCPs). Moreover, midlife women are typically unaware or have misconceptions about conditions that may adversely impact their sexual life, such as genitourinary syndrome of menopause and hypoactive sexual desire disorder. Without understanding there may be underlying medical conditions, there is also a lack of awareness that safe and effective treatments are available. Lack of training, tools, time, and limited treatment options impede HCPs from providing women with necessary sexual health support. Educating women, training HCPs, and providing communication tools to HCPs can facilitate effective dialog between patients and HCPs. More specifically, HCPs can be trained to initiate and maintain a sexual health conversation in a manner that is comfortable for women to convey sexual health needs and concerns, and for HCPs to correctly identify, diagnose, and treat the sexual problems of their female patients. CONCLUSIONS: Solutions exist to address the barriers currently impeding patient-clinician interactions around sexual health.

Understanding if, How, and Why Women with Prior Spontaneous Preterm Births are Treated with Progestogens: A National Survey of Obstetrician Practice Patterns.

Objective In 2017, the Society for Maternal-Fetal Medicine (SMFM) Guideline Committee reaffirmed that 17 α -hydroxyprogesterone caproate (17-OHPC) to prevent preterm birth (PTB) is underutilized. We sought to determine what drove progestogen treatment choice of obstetricians managing pregnant women with histories of 1+ singleton spontaneous PTBs (< 37 weeks) who then delivered singleton gestations within the previous 12 months. Subjects We recruited a nationally representative random sample of obstetricians to abstract medical records of study-qualified patients. Of the 423 study-qualified physicians contacted, 358 (85%) participated; 56 (16%) maternal fetal medicine specialists and 302 (84%) general obstetrician/gynecologists (OB/GYNs) extracted data from 991 eligible patient charts. Results Almost three-fourths of patients (73.6%) were treated with 17-OHPC; 18.6% received vaginal progesterone, and 11.8% were not treated. Key drivers of physicians' choice to (1) prescribe branded 17-OHPC were "FDA (Food and Drug Administration) approval" (52% relative influence [RI]) and "SMFM guidelines" (24% RI); (2) prescribe vaginal progesterone were "ease of administration" (32% RI) and "shortened cervix" (16% RI); and (3) not provide prophylaxis were "patient not informed of risk" (35% RI) and "no shortened cervix" (29% RI). Conclusion Study findings support SMFM's contention of continued 17-OHPC underutilization to prevent PTB. Need for additional physician education merits assessment along with appropriate follow-up actions.

Potential risks of pharmacy compounding.

Pharmacy compounding involves the preparation of customized medications that are not commercially available for individual patients with specialized medical needs. Traditional pharmacy compounding is appropriate when done on a small scale by pharmacists who prepare the medication based on an individual prescription. However, the regulatory oversight of pharmacy compounding is significantly less rigorous than that required for Food and Drug Administration (FDA)-approved drugs; as such, compounded drugs may pose additional risks to patients. FDA-approved drugs are made and tested in accordance with good manufacturing practice regulations (GMPs), which are federal statutes that govern the production and testing of pharmaceutical products. In contrast, compounded drugs are exempt from GMPs, and testing to assess product quality is inconsistent. Unlike FDA-approved drugs, pharmacy-compounded products are not clinically evaluated for safety or efficacy. In addition, compounded preparations do not have standard product labeling or prescribing information with instructions for safe use. Compounding pharmacies are not required to report adverse events to the FDA, which is mandatory for manufacturers of FDA-regulated medications. Some pharmacies engage in activities that extend beyond the boundaries of traditional pharmacy compounding, such as large-scale production of compounded medications without individual patient prescriptions, compounding drugs that have not been approved for use in the US, and creating copies of FDA-approved drugs. Compounding drugs in the absence of GMPs increases the potential for preparation errors. When compounding is performed on a large scale, such errors may adversely affect many patients. Published reports of independent testing by the FDA, state agencies, and others consistently show that compounded drugs fail to meet specifications at a considerably higher rate than FDA-approved drugs. Compounded sterile preparations pose the additional risk of microbial contamination to patients. In the last 11 years, three separate meningitis outbreaks have been traced to purportedly 'sterile' steroid injections contaminated with fungus or bacteria, which were made by compounding pharmacies. The most recent 2012 outbreak has resulted in intense scrutiny of pharmacy compounding practices and increased recognition of the need to ensure that compounding is limited to appropriate circumstances. Patients and healthcare practitioners need to be aware that compounded drugs are not the same as generic drugs, which are approved by the FDA. The risk-benefit ratio of using traditionally compounded medicines is favorable for patients who require specialized medications that are not commercially available, as they would otherwise not have access to suitable treatment. However, if an FDA-approved drug is commercially available, the use of an unapproved compounded drug confers additional risk with no commensurate benefit.

Transdermal hormone therapy in postmenopausal women: a review of metabolic effects and drug delivery technologies.

Vasomotor symptoms (VMS) associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT) is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch) products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.