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Estazolam (Monograph)

Drug class: Benzodiazepines
VA class: CN302
Chemical name: 8-Chloro-6-phenyl-4H -[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
Molecular formula: C16H11ClN4
CAS number: 29975-16-4

Medically reviewed by Drugs.com on Sep 26, 2022. Written by ASHP.

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 under Interactions.)

    Potential for Abuse, Addiction, and Other Serious Risks

  • A boxed warning has been included in the prescribing information for all benzodiazepines describing risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions.900

  • Abuse and misuse can result in overdose or death, especially when benzodiazepines are combined with other medicines, such as opioid pain relievers, alcohol, or illicit drugs.900

  • Assess a patient’s risk of abuse, misuse, and addiction.900 Standardized screening tools are available ([Web]).900

  • To reduce risk of acute withdrawal reactions, use a gradual dose taper when reducing dosage or discontinuing benzodiazepines.900 Take precautions when benzodiazepines are used in combination with opioid medications.900

Introduction

Benzodiazepine, sedative and hypnotic.400 402 407 412 e

Uses for Estazolam

Insomnia

Short-term management of insomnia characterized by difficulty in falling asleep, nocturnal awakenings, and/or early morning awakening.e Has been used effectively for periods of up to 12 weeks in duration.400 405 409 417 418 419 420 421 422 423 447

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

Estazolam Dosage and Administration

General

Administration

Oral Administration

Administer at bedtime.400 416 417 418 419 420 421 422 423 e

Dosage

Individualize dosage; use smallest effective dosage.400

Adults

Insomnia
Oral

Initially, 1 mg at bedtime.416 417 418 419 420 421 422 423 e

If drug is well-tolerated, gradually increase dosage to 2 mg if needed.401 e

Special Populations

Hepatic Impairment

No specific dosage recommendations.e

Renal Impairment

No specific dosage recommendations.e

Geriatric or Debilitated Patients

Use smallest effective dosage.400 405 In small or debilitated geriatric patients, initially, 0.5 mg at bedtime.e

Detailed Estazolam dosage information

Cautions for Estazolam

Contraindications

Warnings/Precautions

Warnings

Concomitant Use with Opiates

Concomitant use of benzodiazepines, including estazolam, 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 estazolam and opiates for patients in whom alternative treatment options are inadequate.700 703 (See Specific Drugs under Interactions.)

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; use contraindicated during pregnancy.428 b e f If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.b e f

Adequate Patient Evaluation

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

Worsening of insomnia or emergence of new abnormal thinking or behavior may indicate the presence of an underlying psychiatric and/or medical condition.b

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.c e

CNS Depression

Performance of activities requiring mental alertness and physical coordination may be impaired.e Risk of residual daytime sedation and impaired performance.e

Concurrent use of other CNS depressants may cause additive or potentiated CNS depression.e (See Concomitant Use with Opiates under Cautions and also see Specific Drugs under Interactions.)

Adverse Psychiatric Events

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

Some adverse effects appear to be dose related; use the lowest effective dose.a

Withdrawal Effects

Abrupt discontinuance may result in symptoms of withdrawal (similar to barbiturates or alcohol).b e

CYP3A-mediated Drug Interactions

Concomitant use with drugs that are potent inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole) is contraindicated.e Concomitant use with lesser inhibitors of CYP3A4 (e.g., nefazodone, fluvoxamine, cimetidine, diltiazem, isoniazid, macrolide antibiotics) requires particular caution.e (See Specific Drugs under Interactions.)

Sensitivity Reactions

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

General Precautions

Respiratory Effects

Possible dose-related respiratory depression, especially in patients with compromised respiratory function.b e Monitor patients with compromised respiratory function.e

Suicide

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

Specific Populations

Pregnancy

Category X. 428 e f (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Benzodiazepines generally are distributed into milk.b Estazolam is distributed into milk in rats; not known whether the drug is distributed into human milk.400 e f Use not recommended in nursing women.e

Pediatric Use

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

Geriatric Use

Potential increased sensitivity to dose related adverse effects (e.g., oversedation, dizziness, confusion, ataxia); use low initial dosage and monitor closely, especially in small or debilitated elderly patients.215 221 222 224 252 253 256 259 297 400 405 427 e

Hepatic Impairment

Potential increased sensitivity to adverse CNS effects (e.g., oversedation, dizziness, confusion, ataxia); use with caution and monitor closely.b e

Renal Impairment

Potential increased sensitivity to adverse CNS effects (e.g., oversedation, dizziness, confusion, ataxia); use with caution and monitor closely.b e

Common Adverse Effects

Somnolence, hypokinesia, dizziness, abnormal coordination.e

Drug Interactions

Metabolized principally by CYP3A4.625 e

Does not inhibit CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A in vitro.e Pharmacokinetic interactions with drugs metabolized by these isoenzymes unlikely.e Not known whether estazolam induces drug metabolizing enzymes.e

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: potential pharmacokinetic interaction (increased plasma estazolam concentrations).625 e Concomitant use with potent CYP3A inhibitors is contraindicated.e Use less potent CYP3A inhibitors with caution; estazolam dosage reduction may be indicated (see table).e

Inducers of CYP3A4: potential pharmacokinetic interaction (decreased plasma estazolam concentrations).e

Specific Drugs

Drug

Interaction

Comments

Antifungals, azoles (fluconazole, itraconazole, ketoconazole)

Increased estazolam plasma concentrations625 b e

Concomitant use of itraconazole and ketoconazole contraindicated625 e

Barbiturates

Possible decreased plasma estazolam concentrationsc

Additive CNS depressant effectse

Use concomitantly with cautionb

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

Possible decreased clearance of estazolam and increased plasma estazolam concentrations 625 e

Use with caution; consider estazolam dosage reduction625 e

Carbamazepine

Possible decreased plasma estazolam concentrationsb e

Cigarette smoking

Possible decreased sedative effect due to increased clearance of estazolame

Cimetidine

Possible decreased clearance of estazolam and increased plasma estazolam concentrations 625 e

Use with caution; consider estazolam dosage reduction625 e

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

Additive CNS depressant effectse

Avoid concomitant use of alcohol;700 e use other CNS depressants with cautionb

Fluoxetine

Pharmacokinetic interactions unlikelye

Fluvoxamine

Possible decreased clearance of estazolam and increased plasma estazolam concentrations 625 e

Use with caution; consider estazolam dosage reduction625 e

Isoniazid

Possible decreased clearance of estazolam and increased plasma estazolam concentrations 625 e

Use with caution; consider estazolam dosage reduction625 e

Macrolide antibiotics

Possible decreased clearance of estazolam and increased plasma estazolam concentrations 625 e

Use with caution; consider estazolam dosage reduction625 e

MAO inhibitors

Additive CNS depressant effectse

Nefazodone

Possible decreased clearance of estazolam and increased plasma estazolam concentrations 625 e

Use with caution; consider estazolam dosage reduction625 e

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 estazolam, initiate opiate analgesic, if required, at reduced dosage and titrate based on clinical response700

In patients receiving an opiate analgesic, initiate estazolam, 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

Phenytoin

Possible decreased plasma estazolam concentrationsb e

Rifampin

Possible decreased plasma estazolam concentrationsb e
Estazolam drug interactions (more detail)

Estazolam Pharmacokinetics

Absorption

Bioavailability

Rapidly and well absorbed following oral administration, 400 402 403 404 407 with peak plasma concentration achieved within 2 hours.e

Food

Effect of food on GI absorption not determined.447

Distribution

Extent

Benzodiazepines are widely distributed into body tissues and cross the blood-brain barrier.401 b

Benzodiazepines generally cross the placenta and are distributed into milk;b f not known whether estazolam crosses the placenta or distributes into milk.400 450 f

Plasma Protein Binding

93%.401 447 e

Elimination

Metabolism

Rapidly and extensively metabolized in the liver, principally to 4-hydroxy-estazolam and 1-oxo-estazolam.400 401 402 403 404 e

Elimination Route

Excreted in urine (91%) mainly as inactive metabolites and in feces (4%).400 403 404

Half-life

14–19 hours (range: 10–24 hours) following single or multiple doses.401 402 403 404 407 e f

Special Population

In smokers, clearance of estazolam is increased compared with nonsmokers.e

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 20–25°C. e

Actions

Advice to Patients

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.400 e

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

Estazolam

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

1 mg*

Estazolam Tablets (C-IV)

2 mg*

Estazolam Tablets (C-IV)

AHFS DI Essentials™. © Copyright 2024, Selected Revisions September 26, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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