Estazolam
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Estazolam: From Sedative-Hypnotic (Original Indication Not Recorded) to Insomnia
One-Sentence Summary
Estazolam is a benzodiazepine sedative-hypnotic sold in the US as generic tablets, but the US license records supplied here contain no indication text. The TxGNN model predicts it may be effective for insomnia, with 12 clinical trials and 18 publications retrieved for this direction. Insomnia is already a recognized use of estazolam, so this is closer to confirming an existing use than to true repurposing. Only one completed Phase 3 trial was found, and estazolam’s role in it (test drug or comparator) is unconfirmed.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (no indication text in the US license records) |
| Predicted New Indication | Insomnia |
| TxGNN Prediction Score | 99.48% |
| Evidence Level | L2 (see note below) |
| US Market Status | ✓ Marketed |
| Number of NDAs | 6 licenses reported (all ANDA generics; only 3 unique ANDA numbers appear in the list) |
| Recommended Decision | Proceed with Guardrails |
Note on evidence level: The pack’s scoring section labels this L1. Under the L1–L5 rules, L1 needs at least 2 completed Phase 3 RCTs. Only one completed Phase 3 trial was found (NCT00347295), and its estazolam role is unconfirmed. I have therefore assigned L2 here.
Why is This Prediction Reasonable?
Estazolam is a triazolo-benzodiazepine. It acts as a positive allosteric modulator of GABA-A receptors, which produces sedative-hypnotic effects. This drug-mechanism-disease link is direct and well established. Detailed mechanism data were not supplied in the pack’s MOA field; the mechanism described here comes from the pack’s repurposing rationale.
Insomnia is an established use of the drug, and an older US clinical review (PMID 1968721) reports that estazolam 1 mg and 2 mg improved sleep latency, total sleep time and sleep quality in adults with chronic insomnia. The empty “original indication” field is a gap in the input data, not evidence against the prediction.
Clinical Trial Evidence
Only trials with a plausible estazolam link are listed. Several are trials of acupuncture or herbal products in which estazolam is only a comparator or background therapy.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00347295 | Phase 3 | Completed | 253 | Randomized, double-blind, double-dummy, multicenter trial of brotizolam vs estazolam in insomnia outpatients. No results summary in the pack. |
| NCT00956319 | Phase 4 | Completed | 42 | Zolpidem modified release vs estazolam (Eurodin) as the comparator in primary insomnia. |
| NCT06859190 | Phase 3 | Recruiting | 60 | Auricular pressure beans plus electroacupuncture combined with estazolam for cancer-related insomnia. The test intervention is the non-drug therapy. |
| NCT03997058 | Phase 4 | Unknown | 120 | Auricular acupoint pressing vs oral estazolam for insomnia in maintenance hemodialysis patients. |
| NCT07306494 | Phase 4 | Not yet recruiting | 1200 | Compound Ciwujia Granules vs estazolam (double-dummy) in chronic insomnia. Estazolam is a comparator. |
| NCT06212934 | N/A | Unknown | 96 | Acupuncture at “Chou’s Tiaoshen” acupoints, tested for non-inferiority to estazolam in short-term insomnia. |
| NCT06258226 | N/A | Unknown | 108 | Auricular acupressure to reduce estazolam use in drug-dependent insomnia. |
| NCT02648776 | N/A | Unknown | 1400 | Prospective cohort of hypnotic use, efficacy and safety in elderly patients at a Taiwanese medical center. |
| NCT03420105 | N/A | Completed | 75 | Prospective memory and sleep in breast cancer. No direct estazolam efficacy question. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1968721 | 1990 | Clinical review | Am J Med | US clinical experience: estazolam 1 mg and 2 mg improved sleep latency, total sleep time, awakenings and sleep quality in chronic insomnia. The 2 mg dose remained effective for at least 6 weeks of nightly use. |
| 36571227 | 2022 | RCT | Zhen Ci Yan Jiu | Shallow-needle therapy combined with estazolam in insomnia (liver stagnation transforming into fire pattern), with ACTH and cortisol measured. |
| 37697875 | 2023 | Clinical study | Zhongguo Zhen Jiu | Syndrome-differentiation acupuncture vs estazolam in chronic insomnia, including effects on cognitive function. |
| 33798303 | 2021 | Clinical observation | Zhongguo Zhen Jiu | Baduanjin plus auricular point sticking vs oral estazolam for COVID-19-related insomnia. |
| 30625122 | 2018 | Review | Med Lett Drugs Ther | “Drugs for chronic insomnia” (no abstract available). |
| 31013432 | 2019 | Systematic review | J Altern Complement Med | Updated systematic review of RCTs on acupuncture for primary insomnia. Not estazolam-specific. |
| 40896345 | 2025 | Scoping review | Integr Med Res | Chinese herbal medicine and acupuncture for insomnia comorbid with chronic pain. Not estazolam-specific. |
| 25532388 | 2014 | Real-world analysis | Zhongguo Zhong Yao Za Zhi | Concurrent diseases and medicine use among insomnia patients in 20 hospitals (1,067 cases). |
| 40827342 | 2025 | Cross-sectional | Psychiatry Clin Psychopharmacol | Drug use for insomnia in a Chinese medicine hospital in Shenzhen. |
| 38007723 | 2023 | Preclinical | Stud Health Technol Inform | Flos Daturae sedative-hypnotic effects in mice, with estazolam as the positive control. |
US Market Information
Three unique ANDA numbers appear in the license list, and two of them are listed twice. All products are oral tablets. No approved-indication text was provided for any license.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA074818 | Estazolam | Tablet | Actavis Pharma, Inc. |
| ANDA074921 | Estazolam | Tablet | Dr. Reddy’s Laboratories Inc. |
| ANDA074826 | Estazolam | Tablet | Novitium Pharma LLC |
Safety Considerations
The package insert warnings and contraindications were not retrieved, so please refer to the package insert for safety information. No drug-interaction records were found.
The pack’s repurposing rationale lists these guardrails:
- Estazolam is a controlled substance.
- Risks include dependence, tolerance, next-day impairment and falls, especially in elderly patients.
- Short-term use is preferred.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The mechanism is direct and the insomnia use is long established. However, the trial evidence is weaker than it looks. Only one Phase 3 trial is completed, and most other trials test acupuncture or herbal products with estazolam as a comparator. Controlled-substance risks also call for guardrails.
To proceed, the following is needed:
- The US package insert (warnings, contraindications, labeled indication) to close the safety and indication gaps.
- Confirmation of estazolam’s role (test drug or comparator) in NCT00347295 and NCT00956319, and retrieval of their results.
- A short-term-use and elderly-patient monitoring plan covering dependence, next-day impairment and fall risk.
The other nine predicted indications (ranks 2–10) are all seizure, withdrawal, restless legs and pain conditions. They rest on class-level or preclinical evidence only and are not recommended for advancement at this stage.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.