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Halcion

Generic Name: Triazolam
Class: Benzodiazepines
VA Class: CN302
CAS Number: 28911-01-5

Medically reviewed on Dec 11, 2017

Warning

    Concomitant Use with Opiates
  • Concomitant use of benzodiazepines and opiates may result in profound sedation, respiratory depression, coma, and death.700 701 703 705 706 707

  • Reserve concomitant use for patients in whom alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy and monitor closely for respiratory depression and sedation.700 703 (See Specific Drugs and Foods under Interactions.)

Introduction

Benzodiazepine; sedative and hypnotic.a b c

Uses for Halcion

Insomnia

Short-term (generally 7–10 days) management of insomnia.100 121

Decreases sleep latency, increases the duration of sleep, and decreases the number of nocturnal awakenings.a

Has been used for the prevention or short-term treatment of transient insomnia associated with sleep-wake schedule changes (e.g., rapid travel across time zones [“jet lag”], rotating shift work).225 226 227 228 229 230 231 232 233 234 235 236 276 277 280 May be useful for this purpose in some patients;227 228 229 230 however, consider the possibility of transient impairment of cognitive function (e.g., anterograde amnesia [“traveler’s amnesia”]).207 233 234 235 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 278 280 281 282 283 288 290 291 292 293 294 295 296 298 377 (See Amnesia under Cautions.)

Halcion Dosage and Administration

General

  • Use only when able to get 7–8 hours of sleep before being active again.a

  • Avoid prolonged administration.100 Generally limit hypnotic therapy to 7–10 days.100 121

  • Write prescriptions for short-term (7–10 days) use only; the quantity dispensed to the patient should not exceed a 1-month supply.100 121 a

  • Reevaluate patient if triazolam is to be used for more than 2–3 weeks.100 121 a

  • Avoid abrupt discontinuance in patients who have received prolonged therapy (because of potential for precipitating withdrawal manifestations);100 after therapy with more than the lowest dose for longer than a few weeks, taper dosage gradually, particularly in patients with a seizure history.100

  • Consider gradual dosage reduction (e.g., over several nights) when discontinuing short-term triazolam therapy (because of potential for rebound insomnia).100 101 120

Administration

Oral Administration

Administer at bedtime.a b

Avoid concomitant oral administration with grapefruit juice.129 509 510 516

Dosage

Individualize dosage; use the smallest effective dose.a

Some adverse effects (e.g., amnesia, dizziness, drowsiness, lightheadedness) appear to be dose related.a Inconclusive whether other effects (e.g., confusion, bizarre or abnormal behavior, agitation, hallucinations) are dose related.a

Adults

Insomnia
Oral

Usual dose is 0.25 mg.100

In some patients (e.g., those with low body weight), 0.125 mg may be adequate.100

Reserve 0.5-mg dose for exceptional cases in which the patient does not respond adequately to a lower dose.100 121

Prescribing Limits

Adults

Insomnia
Oral

Maximum 0.5 mg daily.100 121

Special Populations

Hepatic Impairment

No specific dosage recommendations.a

Renal Impairment

No specific dosage recommendations.a

Geriatric or Debilitated Patients

Usual dosages in healthy geriatric patients should be approximately half those in younger adults.102 103 122 123 124 125 126 127 128

Initially, 0.125 mg daily.100 Increased risk of adverse (e.g., behavioral) effects if therapy is initiated at doses >0.125 mg.106

Reserve 0.25-mg dose for exceptional cases in which the patient does not respond adequately to a lower dose.100 121

Cautions for Halcion

Contraindications

  • Concomitant use of itraconazole,a ketoconazole,a nefazodone,a delavirdine,139 141 efavirenz,140 141 or HIV protease inhibitors.130 132 133 134 135 136 137 138 141 627

  • Pregnancy.a

  • Known hypersensitivity to benzodiazepines or any ingredient in the formulation.a

Warnings/Precautions

Warnings

Concomitant Use with Opiates

Concomitant use of benzodiazepines, including triazolam, and opiates may result in profound sedation, respiratory depression, coma, and death.700 701 703 705 706 707 Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.700 701 705 706 707 711

Reserve concomitant use of triazolam and opiates for patients in whom alternative treatment options are inadequate.700 703 (See Specific Drugs and Foods under Interactions.)

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; avoid use of benzodiazepines as hypnotics during pregnancy.a c If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.a c

Adequate Patient Evaluation

Insomnia may be a manifestation of an underlying physical and/or psychiatric disorder; carefully evaluate patient before providing symptomatic treatment.a

Failure of insomnia to remit after 7–10 days of treatment, worsening of insomnia, or emergence of new abnormal thinking or behavior may indicate the presence of an underlying psychiatric and/or medical condition.a

Complex Sleep-related Behaviors

Potential risk of complex sleep-related behaviors such as sleep-driving (i.e., driving while not fully awake after ingesting a sedative-hypnotic drug, with no memory of the event), making phone calls, or preparing and eating food, while asleep.629

Adverse Psychiatric Events

Abnormal thinking and behavioral changes (e.g., aggressiveness, uncharacteristic extroversion, bizarre behavior, agitation, hallucinations, depersonalization, amnesia) may occur unpredictably in patients receiving benzodiazepines.a

Some evidence suggests that some such behavioral effects may occur more frequently with triazolam than with other hypnotic benzodiazepines.106 107 108 109 110 111 112 113 114 115 117 118 119 480 483 484 485 486 b

Immediately evaluate any new behavioral sign or symptom.a

Amnesia

Anterograde amnesia of varying degrees of severity reported following therapeutic doses.a Frequency may be greater with triazolam than with other benzodiazepines.a 112 217 234 235 262 263 265 266 267 268 269 270 271 272 276 277 278 279 280 298 480 481 482 486 491 May be particularly disturbing with triazolam,217 234 235 262 263 270 271 272 273 276 277 278 279 280 480 481 486 487 490 especially when high doses (e.g., 0.5 mg) are used.217 234 263 270 271 276 277 279 280 488 489

Anterograde amnesia (“traveler’s amnesia”) that occurred upon awakening and persisted for several hours has been reported by individuals who took triazolam to induce sleep while traveling (e.g., during airplane flights).a 122 234 235 280 Concomitant use of alcohol may have been a contributory factor in some cases.a 234 280

Bizarre behavior has been associated with the period of amnesia in some patients.235 277 279 280

Consider the risk of anterograde amnesia in patients receiving triazolam, particularly when relatively high doses are considered (e.g., for transient insomnia associated with sleep-wake schedule changes)207 217 234 235 276 277 278 279 280 281 283 284 or when the duration of drug effect is likely to exceed the intended period of sleep (e.g., when taken to induce sleep while traveling).207 234

CNS Depression

Performance of activities requiring mental alertness and physical coordination may be impaired.a b

Concurrent use of other CNS depressants may potentiate CNS depression.a b (See Concomitant Use with Opiates under Cautions and also see Specific Drugs and Foods under Interactions.)

Dependence and Abuse Potential

Psychologic and physical dependence may occur following prolonged use.a c

Patients with a history of drug or alcohol dependence or abuse are at risk of habituation or dependence; use only with careful surveillance in such patients.a

Tolerance and Withdrawal Effects

Tolerance and adaptation to the hypnotic effect may occur after several weeks of therapy, resulting in diminished effectiveness during the end of each night’s use (early morning insomnia) and, possibly, increased daytime anxiety.207 215 216 218 219 241 245 258 267 297 299 302 312 317 318 320 321 323 337 338 341 348

Increase in daytime anxiety reported after as few as 10 days of continuous use; daytime anxiety also may occur between nightly doses as a manifestation of interdose withdrawal.a If increased daytime anxiety occurs, discontinuance may be advisable.a

Potential for rebound insomnia for 1 or 2 nights after drug discontinuance.a 101 215 216 217 218 219 241 242 243 244 245 246 247 248 249 250 251 262 267 338 341 342 345 425 429

Rapid dosage reduction or abrupt discontinuance may result in signs and symptoms of withdrawal (similar to barbiturates or alcohol).a c

CYP3A-mediated Drug Interactions

Concomitant use with drugs that are potent inhibitors of CYP3A (e.g., itraconazole, ketoconazole, nefazodone, delavirdine, efavirenz, HIV protease inhibitors) is contraindicated.130 132 133 134 135 136 137 138 139 140 141 627 a Less potent inhibitors of CYP3A should be used concomitantly with caution; consider possible need for reduction of triazolam dosage.a (See Interactions.)

Sensitivity Reactions

Potential risk of anaphylaxis and angioedema; may occur even with the first dose of drug.629

General Precautions

Suicide

Use with caution in depressed patients; potential for suicidal tendencies.a Prescribe and dispense drug in the smallest feasible quantity.a b

Respiratory Effects

Use with caution in patients with compromised respiratory function (e.g., chronic pulmonary insufficiency, sleep apnea).a Respiratory depression and apnea reported infrequently in these patients.a

Specific Populations

Pregnancy

Category X.a (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

If used during the last weeks of pregnancy, potential for neonatal CNS depression.a

Lactation

Distributed into milk in rats; not known whether distributed into human milk.a Use not recommended.a

Pediatric Use

Safety and efficacy not established in children <18 years of age.a

Geriatric Use

Increased sensitivity to dose-related adverse effects.100 121 Clearance is reduced and plasma concentrations are increased by about 50%.a Use reduced dosages (see Geriatric or Debilitated Patients under Dosage and Administration); use the smallest effective dose.a

Hepatic Impairment

Use with caution.a

Renal Impairment

Use with caution.a

Common Adverse Effects

Drowsiness, headache, dizziness, nervousness, lightheadedness, coordination disorders or ataxia, nausea or vomiting.a

Interactions for Halcion

Metabolized by CYP3A.a b c

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interaction (increased plasma triazolam concentrations) with inhibitors of CYP3A.a b Concomitant use with potent CYP3A inhibitors is contraindicated.a b Use less potent CYP3A inhibitors with caution; triazolam dosage reduction may be indicated (see table).a b

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Amiodarone

Possible increased plasma concentrations of triazolama

Use with cautiona

Antidepressants, SSRIs (fluvoxamine, paroxetine, sertraline)

Possible increased plasma concentrations of triazolama

Use with cautiona

Antifungals, azoles (itraconazole, ketoconazole)

Increased plasma concentrations and decreased clearance of triazolama 562

Concomitant use of itraconazole or ketoconazole is contraindicated; avoid concomitant use of other azole antifungals that are potent CYP3A inhibitorsa

Calcium-channel blocking agents (diltiazem, nicardipine, nifedipine, verapamil)

Possible increased plasma concentrations of triazolama

Use with cautiona

Cimetidine

Increased plasma concentrations and decreased clearance of triazolama

Use with caution; consider triazolam dosage reductiona

CNS depressants (e.g., psychotropic agents, anticonvulsants, antihistamines, alcohol)

Additive CNS depressant effectsa c

Avoid concomitant use of alcohol;700 a use other CNS depressants with cautionc

Cyclosporine

Possible increased plasma concentrations of triazolama

Use with cautiona

Delavirdine

Decreased metabolism and clearance of triazolam; potential for intense and prolonged sedation and respiratory depression139 141

Concomitant use contraindicated139 141

Efavirenz

Decreased metabolism and clearance of triazolam; potential for intense and prolonged sedation and respiratory depression140 141

Concomitant use contraindicated140 141

Ergotamine

Possible increased plasma concentrations of triazolama

Use with cautiona

Grapefruit juice

Increased triazolam bioavailability with concomitant oral administration129 a

Avoid concomitant administration129 129 509 510 516

HIV protease inhibitors (atazanavir, darunavir, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir, tipranavir)

Decreased metabolism and clearance of triazolam; potential for intense and prolonged sedation and respiratory depression130 132 133 134 135 136 137 138 141 627

Concomitant use contraindicated130 132 133 134 135 136 137 138 141 627

Isoniazid

Increased plasma concentrations and decreased clearance of triazolama

Use with cautiona

Macrolide antibiotics (clarithromycin, erythromycin)

Increased plasma concentrations and decreased clearance of triazolama 212 213 562

Use with caution; consider triazolam dosage reductiona

Nefazodone

Increased plasma concentrations and decreased clearance of triazolama

Concomitant use contraindicateda

Opiate agonists and partial agonists

Risk of profound sedation, respiratory depression, coma, or death700 701 703 705 706 707

Whenever possible, avoid concomitant use708 709 710 711

Opiate analgesics: Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy; monitor closely for respiratory depression and sedation700 703

In patients receiving triazolam, initiate opiate analgesic, if required, at reduced dosage and titrate based on clinical response700

In patients receiving an opiate analgesic, initiate triazolam, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700

Opiate antitussives: Avoid concomitant use700 704

Consider offering naloxone to patients receiving benzodiazepines and opiates concomitantly709 712

Oral contraceptives

Increased plasma concentrations and decreased clearance of triazolama

Use with cautiona

Ranitidine

Increased plasma concentrations of triazolama

Use with cautiona

Warfarin

Effect on warfarin pharmacokinetics or PT unlikelya

Halcion Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentration usually attained within 2 hours after oral administration.a

Special Populations

In healthy geriatric patients, peak plasma concentration and AUC are increased by about 50% compared with younger adults.102

Distribution

Extent

Benzodiazepines are widely distributed into body tissues and cross the blood-brain barrier.c

Benzodiazepines generally cross the placenta and are distributed into milk; not known whether triazolam distributes into milk.c

Elimination

Metabolism

Extensively metabolized in the liver.a b c Hydroxylated by CYP3A and subsequently conjugated to form inactive metabolites.a b c

Elimination Route

Excreted principally in urine as inactive glucuronide conjugates.a c

Half-life

1.5–5.5 hours.a c

Special Populations

In healthy geriatric patients, clearance is decreased by about 50% compared with younger adults.102

Stability

Storage

Oral

Tablets

20–25°C.a

Actions

  • Effects appear to be mediated through the inhibitory neurotransmitter GABA; the sites and mechanisms of action within the CNS appear to involve a macromolecular complex (GABAA-receptor-chloride ionophore complex) that includes GABAA receptors, high-affinity benzodiazepine receptors, and chloride channels.313 320 358 359 360 361 362 363 364 365 366 367 368 369 370

Advice to Patients

  • Provide patient with a copy of the manufacturer's patient information.a

  • Importance of taking only as prescribed; do not increase dosage or duration of therapy unless otherwise instructed by a clinician.a

  • Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with opiates either therapeutically or illicitly.700 703 Avoid concomitant use of opiate antitussives;700 704 also avoid concomitant use of opiate analgesics unless use is supervised by clinician.700 703

  • Importance of informing clinicians of any behavioral or mental changes, memory impairment, tolerance, or dependence/withdrawal symptoms.a

  • Importance of taking only when able to get a full night’s sleep (i.e., 7–8 hours) before being active again.a

  • Potential for drug to impair mental alertness or physical coordination; use caution when operating machinery or performing hazardous tasks until effects on individual are known.a

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and of concomitant illnesses, particularly depression.a

  • Importance of not consuming alcoholic beverages.a

  • Risk of rebound insomnia for 1 or 2 nights after discontinuance.a

  • Importance of women informing their clinician if they are or plan to become pregnant or to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy.a

  • Importance of informing patients of other important precautionary information.a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Triazolam

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

0.125 mg*

Halcion ( C-IV)

Pfizer

Triazolam Tablets (C-IV)

0.25 mg*

Halcion ( C-IV; scored)

Pfizer

Triazolam Tablets (C-IV)

AHFS DI Essentials. © Copyright 2018, Selected Revisions December 11, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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