테마제팜

DEA NFLIS-Drug Category -> Benzodiazepines

DEA Schedule IV Controlled Substance -> Depressants

Pharmaceuticals

Pharmaceuticals -> Hypnotic

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

Breast Feeding; Lactation; Milk, Human; Hypnotics and Sedatives; Anti-Anxiety Agents; Benzodiazepines

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

119-121 °C

119 - 121 °C

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 52 reports by companies from 7 notifications to the ECHA C&L Inventory.

Hazard Traits - Developmental Toxicity

DEA schedule IV controlled substance

Temazepam: Does not have an individual approval but may be used under an appropriate group standard

If the patient is conscious, vomiting should be induced mechanically or with emetics. Gastric lavage should be employed utilizing concurrently a cuffed endotracheal tube if the patient is unconscious to prevent aspiration and pulmonary complications. Maintenance of adequate pulmonary ventilation is essential. The use of pressor agents intravenously may be necessary to combat hypotension. Fluids should be administered intravenously to encourage diuresis. (L1712)

Temazepam, like other benzodiazepines, is rarely associated with serum ALT elevations, and clinically apparent liver injury from temazepam is extremely rare, if it occurs at all. There have been no case reports of symptomatic, acute liver injury from temazepam. Isolated single cases of clinically apparent liver injury have been reported with other benzodiazepines including alprazolam, chlordiazepoxide, clonazepam, diazepam, flurazepam, lorazepam, and triazolam. The clinical pattern of acute liver injury from benzodiazepines is typically cholestatic and mild-to-moderate in severity with a latency of 1 to 6 months and rapid resolution with discontinuation. Fever and rash are uncommon as is autoantibody formation.

Signs and Symptoms of Overdose

Benzodiazepines bind nonspecifically to benzodiazepine receptors, which affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABA_A) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

Temazepam

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 66: (1996) Some Pharmaceutical Drugs

1996

1996

3, not classifiable as to its carcinogenicity to humans. (L135)

Drug Induced Liver Injury Rank (DILIrank 2.0)

Temazepam

Ambiguous-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

◉ Summary of Use during Lactation

◈ What is temazepam?

Temazepam

Pharmaceutical

Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

N - Nervous system

QN - Nervous system

Temazepam is a benzodiazepine used as a hypnotic agent in the management of insomnia. Temazepam produces CNS depression at limbic, thalamic, and hypothalamic levels of the CNS. Temazepam increases the affinity of the neurotransmitter gamma-aminobutyric acid (GABA) for GABA receptors by binding to benzodiazepine receptors. Results are sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action. In sleep laboratory studies, the effect of temazepam was compared to placebo during a two week period. The studies demonstrated a linear dose-response improvement in total sleep time and sleep latency with substantial drug-placebo differences apparent for total sleep time and for sleep latency at higher doses of temazepam. Regardless, REM sleep was ultimately unchanged but slow wave sleep was decreased. Moreover, a transient syndrome, known as "rebound insomnia", wherein the symptoms that led to treatment with temazepam in the first place recur in an enhanced form, may happen on withdrawal of temazepam treatment. The possibility of this occurrence is in part why long term use of temazepam is not recommended due to worries over tolerance and dependence wherein patients' bodies become physiologically accustomed to the regular presence and pharmacological effect of higher and higher doses of the benzodiazepine used. The duration of hypnotic effect and the profile of unwanted adverse effects may be influenced by the distribution and elimination half-lives of the administered temazepam and any active metabolites that may be formed. When such half-lives are long, the drug or its metabolite(s) may accumulate during periods of nightly administration and be associated with impairments of cognitive and motor performance during waking hours. Conversely, if half-lives are short, the drug and metabolites would be cleared before the next dose is ingested, and carry-over effects related to sedation or CNS depression should be minimal or not present at all. However, during nightly use and for an extended period, pharmacodynamic tolerance or adaptation to some effects of benzodiazepine hypnotics may develop - which may also contribute to the possibility of 'rebound insomnia'. Consequently, if the drug has a very short elimination half-life, it is possible that a relative deficiency (for example, in relation to benzodiazepine GABA(a) receptor sites) may occur at some point in the interval between each night's use. This sequence of events may account for certain clinical findings reported happening after several weeks of nightly use of rapidly eliminated benzodiazepine hypnotics, including increased wakefulness during the last third of the night and the appearance of increased daytime anxiety.

Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons. Subsequently, benzodiazepines like temazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action.

First-pass metabolism of temazepam is minimal at approximately 5-8% of an administered dose. Nevertheless, temazepam is principally metabolized in the liver where most of the unchanged drug is directly conjugated to glucuronide and excreted in the urine. In particular, the primary metabolite present in the blood is the O-conjugate of temazepam. Less than 5% of the drug is demethylated to oxazepam and subsequently eliminated as the glucuronide. Regardless, the glucuronides of temazepam have no demonstrable CNS activity and it is believed that no active metabolites are formed in general. Since temazepam mainly undergoes Phase II conjugation reactions, it is proposed that it is devoid of CYP450 interactions.

Temazepam is a known human metabolite of diazepam.

Hepatic. Temazepam is completely metabolized through conjugation prior to excretion. The major metabolite is the O-conjugate of temazepam (90%). Route of Elimination: Temazepam was completely metabolized through conjugation prior to excretion; 80% to 90% of the dose appeared in the urine. Half Life: 10-20 hours

CHB1QD2QSS

TEMAZEPAM

Established Pharmacologic Class [EPC] - Benzodiazepine

Chemical Structure [CS] - Benzodiazepines

Temazepam is a Benzodiazepine.

TEMAZEPAM

Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.

Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.

Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.

Studies demonstrate that between 90 to 100% of an orally administered temazepam dose is absorbed, making the medication very well absorbed. The oral administration of 15 to 45 mg temazepam resulted in rapid absorption with significant blood levels achieved in 30 minutes and peak levels at 2-3 hours. In particular, direct studies following the oral ingestion of 30 mg of temazepam revealed measurable plasma concentrations were obtained 10-20 minutes after dosing with peak plasma levels ranging between 666-982 ng/mL (with a mean of 865 ng/mL) presenting approximately 1.2-1.6 hours (with a mean of 1.5 hours) after the dosing. Finally, a dose-proportional relationship was established for the area under the plasma concentration/time curve over the 15 to 30 mg dose range.

Following a single dose, 80-90% of the dose appears in the urine, predominantly as the O-conjugate metabolite, and 3-13% of the dose appears in the faeces. Less than 2% of the dose is excreted unchanged or as N-desmethyltemazepam in the urine.

The volume of distribution documented for temazepam is 1.3-1.5 L/kg body weight - and in particular, 43-68 L/kg for the unbound fraction.

Studies regarding the clearance of temazepam have recorded the values of 1.03 ml/min/kg and 31 ml/min/kg for the clearance of total temazepam and the clearance of unbound temazepam, respectively.

Use (kg; approx.) in Germany (2009): >250

Officially indicated for severe insomnia and other severe or disabling sleep disorders. For the short-term treatment of insomnia (generally 7-10 days).