Temazepam

證據等級: L5

預測適應症: 1 個

Temazepam: From Established Global Hypnotic to Sleep Disorder, Initiating and Maintaining Sleep

One-Sentence Summary

Temazepam is a benzodiazepine hypnotic with decades of established global use for insomnia, but is not currently registered in the Netherlands under a CBG-MEB marketing authorisation. The TxGNN model predicts — and strongly confirms — its efficacy for sleep disorder, initiating and maintaining sleep, with no registered clinical trials but 20 publications (including at least one Phase III RCT) supporting this direction. Notably, TxGNN is here validating a well-known indication rather than identifying a novel one, making this effectively a market-entry evaluation for the Dutch healthcare system.

Quick Overview

Item	Content
Original Indication	Not registered in the Netherlands; globally established for insomnia / sleep initiation and maintenance
Predicted New Indication	Sleep disorder, initiating and maintaining sleep
TxGNN Prediction Score	99.82%
Evidence Level	L1 (multiple completed RCTs including ≥1 Phase III)
NL Market Status	Not marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data was not retrieved from DrugBank (a data gap flagged in this Evidence Pack). Based on well-established pharmacological knowledge, Temazepam is a short-to-intermediate half-life benzodiazepine belonging to the GABA-A receptor positive allosteric modulator class. By enhancing GABAergic inhibitory neurotransmission in the CNS — particularly in sleep-regulating circuits of the hypothalamus and limbic system — it reduces sleep latency and nocturnal awakenings. Its half-life of approximately 8–20 hours makes it particularly suited for sleep maintenance insomnia compared to ultra-short agents such as triazolam.

The predicted indication, “sleep disorder, initiating and maintaining sleep,” is the canonical indication for which Temazepam holds regulatory approval in the United States (FDA), the United Kingdom, Australia, and numerous other jurisdictions. The TxGNN model’s high confidence score (99.82%, rank 501 of all drug–disease pairs) is therefore unsurprising: the knowledge graph correctly captures decades of clinical evidence linking this compound to insomnia pharmacotherapy.

The clinical relevance for the Netherlands is precisely the absence of a CBG-MEB authorisation. Whether this reflects a deliberate formulary policy, historical market withdrawal, or an unmet regulatory filing is outside the scope of this Evidence Pack and warrants investigation. Regardless, the evidence base is mature: from 1978 sleep-laboratory dose-finding studies through a 2024 multicenter Phase III RCT, Temazepam has been consistently evaluated for this indication.

Clinical Trial Evidence

No clinical trials were retrieved from ClinicalTrials.gov or ICTRP for the Temazepam × sleep disorder query.

Currently no related clinical trials registered in ClinicalTrials.gov or ICTRP against this specific query. Note: historical trials predating online registration systems (pre-2000) would not appear in these registries; substantive RCT evidence is captured in the literature table below.

Literature Evidence

Prioritised by study design (RCT > systematic review/meta-analysis > review/guideline > clinical study). Showing top 10 of 20 retrieved publications.

PMID	Year	Type	Journal	Key Findings
39304187	2024	Phase III RCT	Journal of Palliative Medicine	Three-arm double-blind multicenter RCT: Temazepam vs melatonin PR vs placebo for insomnia in advanced cancer (prevalence 30–78%); directly evaluates temazepam efficacy and safety as a pharmacologic hypnotic
39374004	2024	RCT	JAMA Internal Medicine	Masked taper + CBTI vs standard taper for benzodiazepine receptor agonist (BZRA) discontinuation; informs safe de-prescribing protocols for temazepam in older adults
2859305	1985	RCT	Journal of Clinical Psychopharmacology	Multicenter double-blind crossover study: Temazepam 30 mg vs midazolam 15 mg vs placebo for sleep maintenance insomnia; demonstrates hypnotic efficacy with acceptable next-day residual effects
6149491	1984	RCT	Neuropsychobiology	Comparative RCT of temazepam 40 mg vs flurazepam 30 mg: both produced significant improvements in sleep quality and duration; temazepam showed less next-morning performance impairment
342551	1978	Clinical Study	Journal of Clinical Pharmacology	Sleep-laboratory evaluation of temazepam 30 mg under short-, intermediate-, and long-term administration; foundational dose-finding study establishing the 30 mg standard dose
33249496	2021	Systematic Review / NMA	Sleep	Network meta-analysis comparing hypnotics for insomnia in older adults; positions temazepam relative to newer agents (z-drugs, orexin antagonists) in terms of efficacy and safety profile
27998379	2017	Clinical Practice Guideline	Journal of Clinical Sleep Medicine	AASM guideline on pharmacologic treatment of chronic insomnia in adults; evaluates temazepam as an individual agent with drug-specific evidence review
30058034	2018	Review	Drugs & Aging	Pharmacological management of insomnia in the elderly (57% prevalence); discusses benzodiazepines including temazepam with risk–benefit analysis for geriatric populations
27751669	2016	Review	Clinical Therapeutics	Safety and efficacy review of sleep medicines in older adults, including pharmacokinetic changes with ageing relevant to temazepam dosing
1319429	1992	Review	Journal of Clinical Psychiatry	Historical pharmacology review of benzodiazepine hypnotics; charts temazepam’s emergence as the preferred short half-life agent replacing flurazepam in the 1980s

Netherlands Market Information

Temazepam currently holds no CBG-MEB marketing authorisation in the Netherlands. There are no registered RVG numbers, no approved indications on file, and no active product licences in the dataset.

RVG Number	Product Name	Dosage Form	Approved Indication
—	—	—	No authorisations on record

Note for reviewers: The absence of a Dutch registration does not reflect a lack of global evidence. Temazepam is authorised in the US (DEA Schedule IV), UK, Australia, and other jurisdictions under brand names such as Restoril, Normison, and Euhypnos. A CBG-MEB application or a request for inclusion in the Dutch national formulary (Farmacotherapeutisch Kompas) would require a formal marketing authorisation dossier.

Safety Considerations

Formal safety data (SmPC warnings, contraindications, DDI data) was not retrieved for this Evidence Pack. The following applies:

No SmPC, PIL, or DDI data was available from the sources queried. Please refer to the EMA/MHRA product information for authorised temazepam products, or the DrugBank entry for DB00231, for a full safety profile.

As a benzodiazepine class alert, prescribers and pharmacists in the Netherlands should be aware that temazepam carries class-level risks including dependence and tolerance (critical for chronic insomnia management), CNS depression, risk of falls and fractures in older adults, and potential for rebound insomnia on discontinuation — all of which are relevant to the predicted indication and should be addressed in any market authorisation or formulary review.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The TxGNN prediction is confirmed by a robust and mature evidence base (Phase III RCT, multiple earlier RCTs, systematic reviews, and clinical guidelines), and the indication is Temazepam’s globally established primary use — this is not a speculative repurposing scenario but rather a market-entry question for the Netherlands. However, the complete absence of a CBG-MEB authorisation, combined with well-known benzodiazepine class safety concerns (dependence, elderly fall risk), warrants a structured regulatory and clinical safety review before any formulary recommendation.

To proceed, the following is needed:

Regulatory clarification: Determine why Temazepam lacks a Dutch/EMA centralised authorisation — historical withdrawal, patent expiry, or never-filed; assess whether a CBG-MEB MRP/DCP application is feasible
SmPC retrieval: Obtain and parse the UK MHRA or Australian TGA SmPC for warnings, contraindications, and DDI data (remediation for DG001)
DrugBank MOA data: Retrieve formal mechanism-of-action, pharmacokinetics, and toxicity data via DrugBank API (remediation for DG002)
Dutch clinical context: Review Farmacotherapeutisch Kompas and NHG-standaard Slaapproblemen en slaapmiddelen to understand current NL prescribing landscape and whether alternative agents have displaced temazepam
Elderly population safety plan: Given that most literature highlights geriatric concerns, a risk management plan addressing Beers Criteria alignment and deprescribing protocols is required
Controlled substance classification: Confirm Opiumwet (Dutch Opium Act) scheduling for temazepam and its implications for dispensing and monitoring
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.