Estazolam.

The adverse effect profile is the benzodiazepine profile. The United States safety experience across 1,320 volunteers and insomnia patients found somnolence, dizziness, hypokinesia and abnormal coordination as the drug related effects, all extensions of benzodiazepine pharmacology, with no clinically significant changes in vital signs or laboratory values; no consistent effects on psychomotor performance or memory were seen at recommended hypnotic doses in insomniacs ^[5]. In a geriatric sleep laboratory pilot, 1 mg nightly for four weeks improved sleep without marked daytime performance or memory deficits, though the sample was only ten patients ^[7]. Respiratory safety is comparatively well studied: single doses of 4 and 6 mg, two to three times the recommended dose, did not blunt the ventilatory response to carbon dioxide in sixty healthy subjects ^[6], and in 29 patients with chronic obstructive pulmonary disease, 2 mg nightly did not differ from placebo on ventilatory response or mouth occlusion pressure, with no clinical respiratory depression ^[8]. Tolerance, physical dependence and withdrawal are the defining hazards of the class: discontinuation after regular use can produce rebound insomnia, anxiety and, in severe cases, seizures, and estazolam dependent insomnia is a recognized clinical entity, the target of a dedicated withdrawal trial protocol ^[15]. Use is meant to be short term; the pivotal trials ran seven nights ^{[1] [2]}. Alcohol, opioids and other central nervous system depressants multiply sedation and respiratory risk and must be avoided. IARC reviewed estazolam in 1996 and classified it as not classifiable as to its carcinogenicity in humans, Group 3 ^[16]. Pregnancy use is discouraged on class grounds, and no estazolam specific human teratology data exist. Older adults face elevated risk of falls, confusion and next day sedation, and the hypnotic should be started at 1 mg or lower. Chronic insomnia trials in China, including a randomized comparison with acupuncture that tracked episodic memory and sleep structure, use estazolam as the standard active comparator ^[14]. This is research information, not medical advice.

Estazolam was synthesized at Takeda in Japan in 1970 and introduced there in 1975 as Eurodin. It was approved in the United States as ProSom in 1990. In China, the active pharmaceutical ingredient and tablet were developed by the Hubei Pharmaceutical Factory in the early 1980s and marketed as Sule Anding, and it became one of the most prescribed hypnotics in Chinese primary care.

Modest and clinical. Estazolam never acquired the notoriety of alprazolam or flunitrazepam; it is remembered as a workhorse hypnotic, the ProSom of the 1990s and the Sule Anding of Chinese primary care, where it doubles as the standard active comparator in traditional medicine insomnia research. It surfaces occasionally in forensic and toxicology case work, including confirmed poisonings in Australia.