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| Clinical data | |
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| Trade names | Halcion, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a684004 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 44% (oral route), 53% (sublingual) |
| Metabolism | Liver |
| Onset of action | 15–30 minutes[4] |
| Eliminationhalf-life | 1.5–5.5 hours |
| Excretion | Kidney |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.044.811 |
| Chemical and physical data | |
| Formula | C17H12Cl2N4 |
| Molar mass | 343.21 g·mol−1 |
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Triazolam, sold under the brand nameHalcion among others, is acentral nervous system (CNS)depressant tranquilizer of thetriazolobenzodiazepine (TBZD) class, which arebenzodiazepine (BZD) derivatives.[5] It possesses pharmacological properties similar to those of other benzodiazepines, but it is generally only used as asedative to treatsevere insomnia.[6][unreliable medical source?] In addition to thehypnotic properties, triazolam'samnesic,anxiolytic, sedative,anticonvulsant, andmuscle relaxant properties are pronounced as well.[7]
Triazolam was initially patented in 1970 and went on sale in the United States in 1982.[8] In 2017, it was the 289th most commonly prescribed medication in the United States, with more than one million prescriptions.[9]
Triazolam is usually used for short-term treatment of acuteinsomnia andcircadian rhythm sleep disorders, includingjet lag. It is an ideal benzodiazepine for this use because of its fast onset of action and shorthalf-life. It puts a person to sleep for about 1.5 hours, allowing its user to avoidmorning drowsiness. Triazolam is also sometimes used as anadjuvant in medical procedures requiringanesthesia[6][unreliable medical source?] or toreduce anxiety during brief events, such asMRI scans and nonsurgical dental procedures. Triazolam is ineffective in maintaining sleep due to its short half-life, withquazepam showing superiority.[10]
Triazolam is frequently prescribed as a sleep aid for passengers travelling on short- to medium-duration flights. If this use is contemplated, the user avoiding the consumption ofalcohol is especially important, as is trying a ground-based "rehearsal" of the medication to ensure that the side effects and potency of this medication are understood by the user prior to using it in a relatively more public environment (asdisinhibition can be a common side effect, with potentially severe consequences).[citation needed] Triazolam causesanterograde amnesia, which is why so many dentists administer it to patients undergoing even minor dental procedures. This practice is known as sedation dentistry.[11]
Adverse drug reactions associated with the use of triazolam include:
Triazolam, although a short-acting benzodiazepine, may cause residual impairment into the next day, especially the next morning. Ameta-analysis demonstrated that residual "hangover" effects after nighttime administration of triazolam such as sleepiness, psychomotor impairment, and diminishedcognitive functions may persist into the next day, which may impair the ability of users to drive safely and increase risks offalls andhip fractures.[13]Confusion andamnesia have been reported.[14]
In September 2020, the USFood and Drug Administration (FDA) required theboxed warning be updated for all benzodiazepine medicines to describe the risks ofabuse, misuse,addiction,physical dependence, andwithdrawal reactions consistently across all the medicines in the class.[15]
A review of the literature found that long-term use ofbenzodiazepines, including triazolam, is associated withdrug tolerance,drug dependence,rebound insomnia, and CNS-related adverse effects. Benzodiazepinehypnotics should be used at their lowest possible dose and for a short period of time. Nonpharmacological treatment options were found to yield sustained improvements in sleep quality.[16] A worsening of insomnia (rebound insomnia) compared to baseline may occur afterdiscontinuation of triazolam, even following short-term, single-dose therapy.[17]
Other withdrawal symptoms can range from mild unpleasant feelings to a major withdrawal syndrome, including stomach cramps,vomiting, muscle cramps, sweating,tremor, and in rare cases,convulsions.[12]
Benzodiazepines require special precautions if used in the elderly, during pregnancy, in children, inalcoholics, or in other drug-dependent individuals and individuals withcomorbidpsychiatric disorders.[18] Triazolam belongs to the Pregnancy Category X of the FDA.[19][1] It is known to have the potential to causebirth defects.
Triazolam, similar to other benzodiazepines andnonbenzodiazepines, causes impairments in body balance and standing steadiness in individuals who wake up at night or the next morning. Falls and hip fractures are frequently reported. The combination with alcohol increases these impairments. Partial, but incomplete tolerance develops to these impairments.[20] Daytime withdrawal effects can occur.[21]
An extensive review of the medical literature regarding the management of insomnia and the elderly found considerable evidence of the effectiveness and durability of nondrug treatments for insomnia in adults of all ages and that these interventions are underused. Compared with the benzodiazepines including triazolam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. Newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment, anterograde amnesia, daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls.[21] One study found no evidence of sustained hypnotic efficacy throughout the 9 weeks of treatment for triazolam.[21]
In addition, the effectiveness and safety of long-term use of these agents remain to be determined. More research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.[22]
Ketoconazole anditraconazole have a profound effect on thepharmacokinetics of triazolam, leading to greatly enhanced effects.[23] Anxiety, tremor, and depression have been documented in a case report following administration ofnitrazepam and triazolam.Following administration oferythromycin, repetitive hallucinations and abnormal bodily sensations developed. The patient had, however, acute pneumonia, andkidney failure.[citation needed] Co-administration of benzodiazepine drugs at therapeutic doses with erythromycin may cause serious psychotic symptoms, especially in those with other physical complications.[24]Caffeine reduces the effectiveness of triazolam.[25] Other important interactions includecimetidine,diltiazem,fluconazole,grapefruit juice,isoniazid,itraconazole,nefazodone,rifampicin,ritonavir, andtroleandomycin.[26][27] Triazolam should not be administered to patients onefavirenz/emtricitabine/tenofovir (Atripla).[28]
Symptoms of an overdose[6][unreliable medical source?] include:
Death can occur from triazolam overdose, but is more likely to occur in combination with other depressant drugs such asopioids,alcohol, ortricyclic antidepressants.[29]
Like other benzodiazepines, triazolam enhances the inhibitory effects of the neurotransmitter GABA by binding to the allostericbenzodiazepine receptor on GABAA receptor complexes.[30]
Triazolam is short-acting, islipophilic, and is metabolized hepatically via oxidative pathways. Triazolam produces one short-acting active metabolite, alpha-hydroxytriazolam, which is suspected to be of minor clinical significance.[31] The half-life of triazolam is only 2 hours making it a very short acting benzodiazepine drug.[32] It hasanticonvulsant effects on brain function.[33]
Triazolam, like other benzodiazepines, is susceptible to misuse and abuse. Its rapid onset of action and short half life contribute to its abuse potential, but its relative obscurity compared to other fast-acting benzodiazepines (such asalprazolam orlorazepam) prevent its abuse from becoming particularly commonplace. Likewise, because it is not prescribed as often or as readily as alprazolam or lorazepam, there is less triazolam available to be diverted for recreational use.[34]
Its use at low doses has been deemed acceptable by the US FDA and in several other countries.[6][unreliable medical source?]
Triazolam is aSchedule IV drug under theConvention on Psychotropic Substances[35] and the USControlled Substances Act.[citation needed]
The drug is marketed in English-speaking countries under the brand namesApo-Triazo,Halcion,Hypam, andTrilam. Other names include 2'-chloroxanax, chloroxanax, triclazolam, and chlorotriazolam.[citation needed]
This article incorporates text from this source, which is in thepublic domain.
