트리아졸람

2.42

log Kow = 2.42

5.5

Tan crystals from 2-propanol

A white or pale yellow crystalline powder

4.53

Poorly soluble in water and soluble in alcohol.

In water, 4.53 mg/L @ 25 °C /Estimated/

1.83e-02 g/L

233-235 °C

233-235 °C

233 - 235 °C

3017；3017；3008；3008；2992；3025；3007；3025；3017；2992；3000；3010；3017；3018；3020；3020；3023；3043

3187；3036.1；3034.2；3041.6；3025；3031.5

172.4 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

173.8 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated]

This chemical does not meet GHS hazard criteria for 3% (1 of 33) of reports.

Danger

H360 (90.9%): May damage fertility or the unborn child [Danger Reproductive toxicity]；H362 (93.9%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]

P203, P260, P263, P264, P270, P280, P318, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 33 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 1 of 33 reports by companies.；There are 4 notifications provided by 32 of 33 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Hazard Traits - Developmental Toxicity；Authoritative List - Prop 65；Report - regardless of intended function of ingredient in the product

DEA schedule IV controlled substance

Triazolam: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule IV depressants includes any material, compound, mixture, or preparation which contains any quantity of triazolam, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation. DEA Code Number: 2887.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl triazolam, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Flumazenil, a specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation and intravenous access. (L1712)

Nefazodone increases the AUC of triazolam fourfold, resulting in impairment of psychomotor function; a 75% reduction in triazolam dosage is recommended during concurrent use.

Isoniazid may inhibit the elimination of triazolam, resulting in increased plasma concentrations.

Concurrent administration of disulfiram and benzodiazepines may result in inhibition of metabolism of some benzodiazepines. Disulfiram has reduce the plasma clearance and increased the plasma half-lives of chlordiazepoxide and diazepam during concomitant administration. It is likely that other benzodiazepines that undergo oxidative metabolism (eg, alprazolam, clonazepam, clorazepate, flurazepam, halazepam, prazepam, triazolam) would also interact with disulfiram. /Benzodiazepines/

Additive CNS depression may occur when benzodiazepines are administered concomitantly with other CNS depressants, including other anticonvulsants and alcohol. /Benzodiazepines/

For more Interactions (Complete) data for TRIAZOLAM (9 total), please visit the HSDB record page.

Following acute overdose, clinical symptoms or manifestations may include sleepiness, which, following larger overdose can range from stage zero to stage one coma. Initially, excitement may be seen as a result of the disinhibition effects of these drugs, which then progresses to central nervous system depression, hypotension, respiratory depression, and coma (A629).

Triazolam, like other benzodiazepines, is rarely associated with serum ALT and alkaline phosphatase elevations, and clinically apparent liver injury from triazolam is rare. There have been no well described case reports of acute liver injury from triazolam, except for a single report of severe and prolonged cholestatic liver injury ultimately leading to death from hepatic failure. Isolated single cases of clinically apparent cholestatic 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 self-limited in course, mild-to-moderate in severity and with a latency of 1 to 6 months. Fever and rash are uncommon as is autoantibody formation.；Likelihood score: D (possible rare cause of clinically apparent liver injury).

Benzodiazepines bind nonspecifically to bezodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects 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 GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

/SIGNS AND SYMPTOMS/ Following acute overdose, clinical symptoms or manifestations may include sleepiness, which, following larger overdose can range from stage zero to stage one coma. Initially, excitement may be seen as a result of the disinhibition effects of these drugs, which then progresses to central nervous system depression, hypotension, respiratory depression, and coma ... . On occasion, anticholinergic symptoms such as dry mouth, tachycardia, dilated pupils, and absent bowel sounds may be seen. Patients who have been receiving or ingesting benzodiazepines on a chronic basis (40 to 80 mg or more per day for one to two months or more) may exhibit mild to moderate symptoms of withdrawal, with severe withdrawal symptoms seen in patients taking the drug for many months to years. Symptoms may include jitteriness, nervousness, anxiety, agitation, confusion, hallucinations, and seizures. Patients exhibiting withdrawal symptoms should be restarted on benzodiazepine and slowly withdrawn over a period of several months ... . In most cases, ingestion of a benzodiazepine agent of up to 1.5 g results in only minor toxicity, ie, CNS depression. Fatality, following oral ingestion, is rare unless a combination of drugs is taken with the benzodiazepine ... . /Benzodiazepines/

/SIGNS AND SYMPTOMS/ Triazolam frequently has been noted to produce psychosis, delirium, coma, and complete, transient global amnesia when taken in normal oral doses or in minimal overdose.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Triazolam

Ambiguous-DILI-concern

4

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ No evidence of carcinogenic potential was observed in mice receiving triazolam doses up to 4000 times the human dose for 24 mo.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ... /Triazolam was given/ by gastric gavage to rats and rabbits in maximum total daily doses of 300 and 50 mg/kg respectively. Given during organogenesis, there was no teratogenic effect in either species. In the rabbit, doses of 3 and 50 mg/kg daily caused a decrease in implantations, viable fetuses, and fetal weight.

Hazard Traits - Developmental Toxicity；Authoritative List - Prop 65；Report - regardless of intended function of ingredient in the product

DEA schedule IV controlled substance

Triazolam: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule IV depressants includes any material, compound, mixture, or preparation which contains any quantity of triazolam, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation. DEA Code Number: 2887.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl triazolam, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

N05CD05

N - Nervous system；N05 - Psycholeptics；N05C - Hypnotics and sedatives；N05CD - Benzodiazepine derivatives；N05CD05 - Triazolam

QN - Nervous system；QN05 - Psycholeptics；QN05C - Hypnotics and sedatives；QN05CD - Benzodiazepine derivatives；QN05CD05 - Triazolam

A short-acting benzodiazepine used as a hypnotic agent in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. Triazolam has a shorter half-life than chlordiazepoxide, flurazepam, and prazepam and does not generate active metabolites.

Benzodiazepines bind nonspecifically to bezodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects 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 GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

In animals, benzodiazepines protect against seizures induced by electrical stimulation and by pentylenetetrazol; benzodiazepines appear to act, at least partly, by augmenting presynaptic inhibition. The drugs suppress the spread of seizure activity but do not abolish the abnormal discharge from a focus in experimental models of epilepsy. In usual doses, benzodiazepines appear to have very little effect on the autonomic nervous system, respiration, or the cardiovascular system. /Benzodiazepines/

... /Benzodiazepines/ appear to act at the limbic, thalamic, and hypothalamic levels of the CNS, producing anxiolytic, sedative, hypnotic, skeletal muscle relaxant, and anticonvulsant effects. The effects of benzodiazepines may be mediated through the inhibitory neurotransmitter gamma-aminobutyric acid. Benzodiazepines are capable of producing all levels of CNS depression from mild sedation to hypnosis to coma. /Benzodiazepines/

Anxiolytic and possibly paradoxical CNS stimulatory effects of benzodiazepines are postulated to result from release of previously suppressed responses (disinhibition). After usual doses of benzodiazepines for several days, the drugs cause a moderate decrease in rapid eye movement (REM) sleep. REM rebound does not occur when the drugs are withdrawn. Stage 3 and 4 sleep are markedly reduced by usual doses of the drugs; the clinical importance of these sleep stage alterations has not been established. /Benzodiazepines/

Benzodiazepines appear to produce skeletal muscle relaxation predominantly by inhibiting spinal polysynaptic afferent pathways, but the drugs may also inhibit monosynaptic afferent pathways. The drugs may inhibit monosynaptic and polysynaptic reflexes by acting as inhibitory neuronal transmitters or by blocking exitatory synaptic transmission. The drugs may also directly depress motor nerve and muscle function. /Benzodiazepines/

1.5-5.5 hours

It has a biphasic half-life with a reported mean apparent half-life of 3.4 hr for the initial phase and 7.8 hr for the terminal phase.

Elimination half-life for triazolam is 1.6-5.4 hr. /From table/

Hepatic. Small amounts of unmetabolized triazolam appear in the urine.

Triazolam undergoes hepatic microsomal oxidation to inactive hydroxylated metabolites that are eliminated primarily as glucuronide conjugates.

Triazolam has known human metabolites that include 4-Hydroxytriazolam and alpha-Hydroxytriazolam.

Hepatic. Small amounts of unmetabolized triazolam appear in the urine. Triazolam undergoes hepatic microsomal oxidation to inactive hydroxylated metabolites that are eliminated primarily as glucuronide conjugates (A630). Route of Elimination: Triazolam and its metabolites, principally as conjugated glucuronides, which are presumably inactive, are excreted primarily in the urine. Only small amounts of unmetabolized triazolam appear in the urine. The two primary metabolites accounted for 79.9% of urinary excretion. Half Life: 1.5-5.5 hours

1HM943223R

TRIAZOLAM

Established Pharmacologic Class [EPC] - Benzodiazepine

Chemical Structure [CS] - Benzodiazepines

Triazolam is a Benzodiazepine.

TRIAZOLAM

Agents that are administered in association with anesthetics to increase effectiveness, improve delivery, or decrease required dosage.

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.

Bioavailability is 44% (oral) and 53% (sublingual).

Triazolam and its metabolites, principally as conjugated glucuronides, which are presumably inactive, are excreted primarily in the urine. Only small amounts of unmetabolized triazolam appear in the urine. The two primary metabolites accounted for 79.9% of urinary excretion.

Plasma half-life, elimination coefficient, concentration, and apparent volume of distribution were calculated at steady state and mean values were 53 hr, 0.0147/hr, 884 ng/mL, & 1.13 l/kg /respectively/.

Triazolam is rapidly and nearly completely absorbed from the GI tract. It has a biphasic half-life with a reported mean apparent half-life of 3.4 hr for the initial phase and 7.8 hr for the terminal phase. It is reported to be extensively bound to plasma proteins. It is excreted in the urine in the form of its metabolites with only small amounts appearing unchanged.

In a study of triazolam tablets and a liquid formulation in healthy subjects, the bioavailability of the tablets was rapid and, relative to the liquid formulation, complete. The average half-life for absorption was 8 minutes with peak concentrations being achieved an average of 42 minutes after dosing.

It is not known whether triazolam is distributed into milk in humans; however, the drug and its metabolites are distributed into milk in rats.

Sedative, hypnotic

MEDICATION

For the short-term treatment of insomnia (A308).

Oral: Tablets: 0.125 mg Halcion (C-IV) )Pfizer), 0.125 mg Halcion (C-IV; scored) (Pfizer)

Trade Names: Halcion (Upjohn, USA), Novidorm (Syntial, Argentina), Novodorm (Rubio, Spain), Nuctane (Bago, Argentina).