zaleplon / Generic mfg. - LARVOL DELTA

Inter-Brand Price Variation of Z-Drugs Available in India: A Pharmacoeconomic Analysis (WFSBP 2026) - "Available brands of zolpidem, zopiclone, eszopiclone, and zaleplon were identified. Substantial inter-brand price variation exists among Z-drugs marketed in India. Given the widespread use of these medications in psychiatric practice, this variation may affect affordability, treatment adherence, and continuity of care. Greater awareness of medication costs among prescribers and consideration of cost-effective alternatives may help promote rational prescribing and improve access to treatment."

HEOR • Omic analysis • CNS Disorders • Insomnia • Sleep Disorder

Radical Fluoroacylation of Pyrazolo[1,5-a]pyrimidines: A Gateway to Zaleplon and Reversan Drugs. (PubMed, J Org Chem) - "This method entails a free radical-directed C-H functionalization, delivering a broad range of fluorinated pyrazolo[1,5-a]pyrimidine frameworks, which are valuable key intermediates in pharmaceutical APIs. In addition, this protocol was also applied in the concise synthesis of the zaleplon and reversan drugs."

Journal

Association between regular hypnotic use and age-related macular degeneration. (PubMed, Adv Ophthalmol Pract Res) - "Regular use of hypnotics, including benzodiazepines or Z-meds (non-benzodiazepine hypnotics such as zolpidem and zaleplon) were assessed at baseline...Prolonged use of Z-meds may elevate the risk of developing AMD. Given the increasing prescription of Z-meds for the treatment of insomnia, these findings underscore the necessity of considering potential ocular risks and requiring more frequent monitoring."

Journal • Age-related Macular Degeneration • CNS Disorders • Insomnia • Macular Degeneration • Ophthalmology • Retinal Disorders • Sleep Disorder

A rapid regioselective C3-functionalization of 7-phenylpyrazolo[1,5-a]pyrimidines: en route to the synthesis of zaleplon and reversan drugs. (PubMed, Org Biomol Chem) - "A diverse array of synthetic transformations is divulged via amidation, hydrolysis, reduction and esterification, emphasizing the method's utility in the post-functionalization process and in building organic frameworks. In addition, this method is also applied for the concise synthesis of the hypnotic drug zaleplon and the MRP1 inhibitor reversan."

Journal

Z-Drugs in the Environment: A Review. (PubMed, Molecules) - "This review paper focuses on summarizing data on these topics. To the best of our knowledge, such a comprehensive review has not yet been published."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Infectious Disease • Insomnia • Mood Disorders • Novel Coronavirus Disease • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia • Sleep Disorder

Z-Drug Use and All-Cause Mortality: A Meta-Analysis of Observational Cohort Studies. (PubMed, Neuropsychiatr Dis Treat) - "Non-benzodiazepine hypnotic drugs known as z-drugs (including zolpidem, eszopiclone, zopiclone, zaleplon) are commonly prescribed for insomnia patients worldwide. This meta-analysis showed a positive association between z-drug use and all-cause mortality; however, the substantial between-study heterogeneity (I2 = 99.6%) warrants cautious interpretation of these findings. Clinicians should exercise caution when prescribing z-drugs to high-risk patients."

Journal • Observational data • Retrospective data • CNS Disorders • Insomnia • Sleep Disorder

Benzodiazepines Prescribed to Hospitalized Patients with Major Depressive Disorder: A 3-year Retrospective Observational Study. (PubMed, Neuropsychiatr Dis Treat) - "For non-selective benzodiazepines at baseline, the most commonly prescribed were lorazepam (39.6%, n=110), oxazepam (23.7%, n=66), and clonazepam (16.2%, n=45)...However, the use of clonazepam, estazolam, and alprazolam remained comparable (P > 0.05)...While its use varied significantly over time (P 0.05)...It is advisable to limit benzodiazepine prescriptions for MDD patients to within 12 months. Discontinuing benzodiazepines becomes more challenging after prolonged use beyond this period."

Journal • Observational data • Retrospective data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Comparative effects of hypnotic agents on sleep architecture and respiratory outcomes in obstructive sleep apnea: A systematic review and network meta-analysis. (PubMed, Psychiatry Clin Neurosci) - "Our network meta-analysis identified different effects of various hypnotics on sleep architecture and respiratory parameters; however, the lack of data prevented a formal synthesis of subjective outcomes. Therefore, these results should be interpreted with caution in clinical practice."

Journal • Retrospective data • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Valorization of recycled waste in green/white purification and LC-QToF/MS analysis of beverages adulterated with incapacitating drugs. (PubMed, Talanta) - "A validated eco-friendly/economical purification/analysis kit prototype, along with an LC-QToF/MS method has been developed in coke and mixed fruit-juice, for simultaneous determination of 10 drugs used for incapacitating victims (zaleplone, zolpidem, zopiclone, mephedrone, fentanyl, phenytoin, thiopental, sertraline, ketamine and GHB). The validated method in fruit-juice and coke, extraordinarily gave successful results also in urine and saliva. Assessment tools for greenness/whiteness and pictograms confirmed the environmental friendliness of the method kit."

Journal

Evaluating the Safety of Prescription Sleep Medications in Patients Undergoing Total Knee Arthroplasty: A Propensity Matched Analysis. (PubMed, J Am Acad Orthop Surg) - "Use of any prescription sleep medication or only standard sleep medications is associated with increased surgical complications. Additional research is needed to find medications that may be safer for routine postoperative use."

Journal • CNS Disorders • Musculoskeletal Diseases • Orthopedics • Pain • Psychiatry • Sleep Disorder

Z-Drug Use in the First Trimester of Pregnancy and Risk of Congenital Malformations. (PubMed, JAMA Psychiatry) - "At least 1 dispensing of Z-drugs (zaleplon, eszopiclone, or zolpidem) in the first trimester of pregnancy compared with no dispensing. Results were consistent across multiple sensitivity analyses. These findings suggest that Z-drug exposure in the first trimester of pregnancy is not associated with a meaningful elevation in the risk of congenital malformations overall, nor was there a consistent signal observed for organ-specific or uncommon, individual malformations examined."

Journal • CNS Disorders • Sleep Disorder

Zaleplon nanospanlastics loaded transdermal patches: formulation, optimization, ex-vivo permeation, and in-vivo studies. (PubMed, J Pharm Pharm Sci) - "The in-vivo studies have shown that the pharmacokinetic parameters of ZLP oral suspension and ZLP-SP1 are significantly different, with the relative bioavailability of ZLP-SP1 being 2.681%. Therefore, these fabricated transdermal patches could be effectively used to treat insomnia."

Journal • Preclinical • CNS Disorders • Insomnia • Sleep Disorder

Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis. (PubMed, Sleep Med) - "Comprehensively considering the efficacy effect size, time windows (follow-up period, age, and types of insomnia), PV, severity of imperative adverse events, we propose prioritizing the use of daridorexant 25 mg/d for insomnia characterized by difficulty maintaining sleep and insufficient sleep duration. For insomnia characterized by difficulty falling asleep, we recommend prioritizing the use of lemborexant 10 mg/day or zolpidem 10 mg/day. For overall poor sleep efficiency, we recommend using lemborexant. Drug selection should be based on the types of insomnia and drug safety. More head-to-head clinical trials are needed to confirm those findings."

Journal • Review • CNS Disorders • Insomnia • Pulmonary Disease • Sleep Disorder

Real-World Treatment Patterns of Sleep Medications in the United States Veterans Affairs Health System (WSS 2025) - "Overall, an estimated 2.6% were prescribed zolpidem, 0.7% temazepam, 0.28% eszopiclone, 0.12% ramelteon, 0.6% zaleplon, 0.5% suvorexant, 0.4% triazolam, 0.006 lemborexant, 0.005% estazolam, and 0.0001% daridorexant. The Z-drug zolpidem was the most commonly prescribed medication indicated for insomnia. Sedative antidepressants were also frequently utilized, likely due to their affordability and the lack of widely accepted, cost-effective alternatives for managing insomnia. This reliance on off-label agents such as trazodone suggests a potential gap between clinical guidelines and real-world practice, possibly reflecting formulary constraints, prescriber familiarity, or patient comorbidities."

Clinical • HEOR • Real-world • Real-world evidence • CNS Disorders • Insomnia • Sleep Disorder

Effect of zaleplon on Cognitive Function of Insomnia Patients: a randomized, controlled multi-centre study (ChiCTR) - P=N/A | N=250 | Not yet recruiting | Sponsor: Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences); Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences

New trial • CNS Disorders • Insomnia • Sleep Disorder

Divergent synthesis of 3-formylpyrazolo[1,5-a]pyrimidines and methylene-bridged bis(pyrazolo[1,5-a]pyrimidines) using DMSO as a single carbon synthon. (PubMed, Org Biomol Chem) - "The reaction progressed through a radical pathway. The usefulness of 3-formylpyrazolo[1,5-a]pyrimidines in synthesizing a zaleplon derivative has been demonstrated."

Journal

Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis. (PubMed, Front Psychiatry) - "Compared with placebo, zolpidem (somnolence: relative risk [RR] 1.85; dizziness: RR 2.33; headache: RR 1.26), zopiclone (somnolence: RR 2.02; dizziness: RR 2.33; dysgeusia: RR 7.84), indiplon (somnolence: RR 3.46; dizziness: RR 2.30; headache: RR 1.63), gaboxadol (dizziness: RR 3.44), eszopiclone (somnolence: RR 2.00; dizziness: RR 3.18; dysgeusia: RR 10.54), estazolam (somnolence: RR 2.08), flunitrazepam (somnolence: RR 3.04), flurazepam (somnolence: RR 2.52), lemborexant (somnolence: RR 6.57), nitrazepam (somnolence: RR 3.80), Ramelteon (somnolence: RR 2.19), suvorexant (somnolence: RR 3.32), Temazepam (somnolence: RR 3.77), trazodone (somnolence: RR 2.86), triazolam (somnolence: RR 2.35), and esmirtazapine (somnolence: RR 4.63; dizziness: RR 2.87) had the most harmful profile in nervous system disorders...Data on some drugs like flurazepam, nitrazepam, triazolam, and zaleplon in some outcomes were mainly based on limited study with rare event and thus was highly..."

Adverse events • Journal • Retrospective data • Review • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Insomnia • Otorhinolaryngology • Pain • Psychiatry • Respiratory Diseases • Sinusitis • Sleep Disorder • Xerostomia

Physiologically based pharmacokinetic modeling of aldehyde oxidase drug-drug interactions mediated by erlotinib. (PubMed, Drug Metab Dispos) - "Recently, we characterized the epidermal growth factor receptor inhibitor erlotinib as a clinical AO inhibitor and proposed, through mechanistic metabolism studies and static modeling, that AO inhibition was responsible for its observed DDI with the investigational drug OSI-930...Additional simulations were also conducted to investigate untested clinical DDI scenarios between erlotinib and other known AO substrates-O6-benzylguanine, zaleplon, ziprasidone, and zoniporide...Additionally, our erlotinib model also predicts clinically significant DDIs would occur when dosing erlotinib with high fm,AO AO substrates. These findings highlight the need to consider AO inhibition in DDI risk assessments and may help inform future drug development and regulatory strategies."

Journal • PK/PD data • EGFR • SLCO2B1

Impact of cytosolic aldehyde oxidase contamination in liver microsomes on intrinsic clearance estimations. (PubMed, Drug Metab Dispos) - "Our results suggest that cytosolic AO contamination primarily impacts substrate depletion intrinsic clearance estimates for substrates with high AO clearance, but not those with moderate or low AO clearance, due to the apparent lack of turnover of O6-benzylguanine and zaleplon across all 3 batches of liver microsomes. SIGNIFICANCE STATEMENT: Our study underscores interindividual variability in hepatic aldehyde oxidase (AO) activity as the key determinant underlying residual AO activity in liver microsomes and illuminated the potential impact of cytosolic AO contamination on the reliability of intrinsic clearance estimates-emphasizing the need for substrate-specific strategies and refined in vitro methodologies in drug metabolism studies."

Journal

Sex Differences in Adverse Events Reported With Concomitant Buprenorphine and Insomnia Medications Use (CPDD 2025) - "Secondary search terms included commonly prescribed medications for insomnia: “temazepam”, “triazolam”, “estazolam”, “lorazepam”, “clonazepam”, “alprazolam”, “ramelteon”, “doxepin”, “trazodone”, “mirtazapine”, “suvorexant”, “lemborexant”, “daridorexant”, “quetiapine”, “hydroxyzine”, “gabapentin”, “eszopiclone”, “zaleplon”, “zolpidem”, “zolpidem ER”. Contrary to previous research demonstrating that females are involved in more AE reports across pharmacovigilance databases (Brabete et al., 2022), and that females taking 1 buprenorphine had an increased likelihood of insomnia medications prescription receipt, compared to their male counterparts (Martin et al., 2023), we did not find sex differences in the number of AE reports. However, the data suggest that males taking concomitant buprenorphine and insomnia medications, specifically benzodiazepines and DORAs, may experience more serious AEs than females."

Adverse events • CNS Disorders • Insomnia • Sleep Disorder

Treatment Patterns for Sleep Disorders in the United States Veterans Affairs Healthcare System (ISPOR 2025) - "Other treatments may include the melatonin receptor agonist (ramelteon) or sedating antidepressants (trazodone, off label)...Overall, an estimated 2.6% were prescribed zolpidem, 0.7% temazepam, 0.28% eszopiclone, 0.12% ramelteon, 0.06% zaleplon, 0.05% suvorexant, 0.04% triazolam, 0.006% lemborexant, 0.005% estazolam, and 0.001% daridorexant... The Z-drug zolpidem was the most commonly prescribed medication indicated for insomnia. Sedative antidepressants were also frequently utilized, likely due to their affordability and the lack of widely accepted, cost-effective alternatives for managing insomnia. Lemborexant and daridorexant, more recently approved for insomnia, were prescribed less frequently and have not yet become mainstream frontline treatments."

CNS Disorders • Insomnia • Sleep Disorder

Advances in Z-drug detection. (PubMed, Clin Chim Acta) - "The use of Z-drugs (zolpidem, zaleplon, zopiclone, and eszopiclone) has increased in recent years, leading to a growing need for analytical methods to accurately and reliably detect these compounds in biological samples. Recent studies have shown that these methods are effective in routine toxicological analysis and forensic detection of drug abuse. This review aims to provide a valuable resource for researchers and practitioners involved in the detection and analysis of Z-drugs, contributing to a better understanding and management of both therapeutic and illicit use of these compounds."

Journal • Review

A multicenter, open-label, randomized controlled study of the efficacy and safety of zaleplon in combination with escitalopram in the treatment of mild to moderate depression with insomnia (ChiCTR) - P4 | N=202 | Not yet recruiting | Sponsor: First Hospital of Shanxi Medical University; First Hospital of Shanxi Medical University

New P4 trial • CNS Disorders • Depression • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder

Improved clearance predictions for aldehyde oxidase substrates using a novel triculture human hepatocyte model. (PubMed, Drug Metab Dispos) - "CLh predictions generated using TruVivo for the reference compounds carbazeran, zoniporide, zaleplon, and O6-benzylguanine were within 2-fold of reported in vivo CL values...SIGNIFICANCE STATEMENT: The TruVivo in vitro primary human hepatocyte model maintains high levels of aldehyde oxidase (AO) activity for at least 14 days in culture, making the system suitable for evaluating slowly metabolized compounds, particularly those metabolized by AO. This novel system may therefore be useful for improving human clearance predictions for AO substrates."

Journal

Impact of Postoperative Sleep Medication Use on 90-Day Complications Following Total Knee Arthroplasty (AAOS 2025) - "We further analyzed the effects of standard prescription sleep medications (Daridorexant, Eszopiclone, Lemborexant, Suvorexant, Temazepam, Triazolam, Zaleplon, Zolpidem) and less potent prescription sleep medications (Doxepin, Ramelteon). Both standard and less potent prescription sleep medication use is associated with surgical complications. Post-operative sleep disturbance remains a major problem following TKA, but prescription sleep medications may be unsafe for routine postoperative use."

Insomnia • Musculoskeletal Diseases • Orthopedics • Pain • Sleep Disorder