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Formerly available as Dalmane

Generic Name: Flurazepam Hydrochloride
Class: Benzodiazepines
VA Class: CN302
CAS Number: 1172-18-5

Medically reviewed on December 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 under Interactions.)

Introduction

Benzodiazepine; sedative and hypnotic.a b d

Uses for Formerly available as Dalmane

Insomnia

Short-term management of insomnia.a d Has been used effectively for periods up to 4 weeks in duration.a b d

Has been used effectively in individuals with difficulty in falling asleep, nocturnal awakenings, and/or early morning awakening.d

May exhibit carryover effect (i.e., more effective on second, third, and fourth nights of use than on first night) because of accumulation of active metabolite.b d Effect may persist on first and sometimes second night after discontinuance.b d

Because of long half-life, may be more likely to result in residual sedative effects and in impaired psychomotor and mental performance during continued therapy, although partial tolerance to these effects can occur.207 215 216 217 218 219 245 252 254 259 262 264 267 298 311 312 313 317 321 322 323 337 338 344 346 348 353 Differences among hypnotics in residual and cumulative CNS depressant effects may be particularly important in geriatric patients,215 217 221 222 224 235 252 253 259 269 276 297 312 313 317 318 319 325 356 372 377 those with potentially impaired elimination of the drugs, and those whose job or life-style requires unimpaired intellectual or psychomotor function.215 217 218 257 270 279 280 297 298

Formerly available as Dalmane Dosage and Administration

General

  • Use hypnotics only when able to get a full night’s sleep before being active again.e

  • Use the smallest effective dose (especially in geriatric or debilitated patients and in those with liver disease or low serum albumin).a b d

  • Avoid prolonged administration.a d

  • Reevaluate patient’s condition if hypnotic use exceeds 2–3 weeks.207

  • Avoid abrupt discontinuance in patients who have received prolonged therapy (e.g., several months) because of potential for precipitating withdrawal manifestations.a b d Gradually taper dosage.a d

Administration

Oral Administration

Administer at bedtime.a d

Dosage

Available as flurazepam hydrochloride; dosage expressed in terms of the salt.d

Adults

Insomnia
Oral

Usual dosage is 30 mg at bedtime.a d In some patients, 15 mg may be adequate.a d

Special Populations

Hepatic Impairment

Reduce dosage.b Use smallest effective dosage.a

Renal Impairment

No specific dosage recommendations.d

Geriatric or Debilitated Patients

Initial dose of 15 mg at bedtime.a d Use smallest effective dosage.a

Cautions for Formerly available as Dalmane

Contraindications

  • Known hypersensitivity to flurazepam.d

  • Pregnancy.b d

  • Many manufacturers state that benzodiazepines are contraindicated in patients with acute angle-closure glaucoma (but may be administered to patients with open-angle glaucoma receiving appropriate therapy); however, clinical rationale for this contraindication has been questioned.b

Warnings/Precautions

Warnings

Concomitant Use with Opiates

Concomitant use of benzodiazepines, including flurazepam, 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 flurazepam 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; avoid use of benzodiazepines as hypnotics during pregnancy.b d If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.d

Adequate Patient Evaluation

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

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.d

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 d

Adverse Psychiatric Events

Abnormal thinking and behavioral changes (e.g., aggressiveness, uncharacteristic extroversion, bizarre behavior, agitation, hallucinations, depersonalization, amnesia) may occur in patients receiving benzodiazepines.207 258 262 269 284 285 286 287 297 372 488

Immediately evaluate any new behavioral sign or symptom.207

CNS Depression

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

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

Dependence and Abuse Potential

Psychologic and physical dependence may occur following prolonged use.b d

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.d

Tolerance and Withdrawal Effects

Tolerance may occur following prolonged benzodiazepine use.b

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

Sensitivity Reactions

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

General Precautions

Suicide

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

Respiratory Effects

Use with caution in patients with compromised pulmonary function.b d

Specific Populations

Pregnancy

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

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

Lactation

Benzodiazepines generally are distributed into milk;b not known whether flurazepam is distributed into milk, but distribution into milk should be expected.c

Pediatric Use

Safety and efficacy not established in children <15 years of age.a d

Geriatric Use

Potential increased sensitivity (increased risk of oversedation, dizziness, confusion, and/or ataxia);b d use low initial dose and monitor closely.207 221 224 b d

Half-life of desalkylflurazepam is prolonged following multiple doses in geriatric men and women and after single-dose administration in geriatric men.d

Hepatic Impairment

Use with caution.b d Use reduced dosage.b

Renal Impairment

Use with caution.b d

Common Adverse Effects

Dizziness,d drowsiness,d lightheadedness,d staggering,d ataxia,d fallingd (particularly in geriatric or debilitated patients).d

Interactions for Formerly available as Dalmane

Specific Drugs

Drug

Interaction

Comments

Cimetidine

Possible decreased plasma clearance of flurazepam200 625

Use with caution; consider flurazepam dosage reduction200 372 610

Clozapine

Severe hypotension, respiratory or cardiac arrest, and loss of consciousness reported when benzodiazepines (including flurazepam) were given with or within 24 hours before clozapine529 591 592 593 595 597 598 600

Use with caution435 591 599

Some clinicians recommend discontinuance of benzodiazepine therapy ≥1 week prior to initiation of clozapine597 598

CNS depressants (alcohol, anticonvulsants, sedatives)

Additive CNS depressant effectsb d

Do not use alcohol concomitantly with hypnotics;700 e caution if other CNS depressants are used concomitantly with flurazepamb d

Disulfiram

Possible inhibition of flurazepam metabolism200

Observe closely for enhanced benzodiazepine response200

Consider possible need for flurazepam dosage reduction200

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

In patients receiving an opiate analgesic, initiate flurazepam, 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

Formerly available as Dalmane Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from the GI tract,b d with peak plasma concentration achieved within 30–60 minutes.d

Onset

Onset of hypnotic effect occurs within 15–45 minutes.b

Duration

Hypnotic effect persists for 7–8 hours.b

Distribution

Extent

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

Benzodiazepines and their metabolites generally cross the placenta and are distributed into milk.b Not known whether flurazepam is distributed into milk, but distribution into milk should be expected.c

Plasma Protein Binding

Benzodiazepines and their metabolites are highly bound to plasma proteins.b

Elimination

Metabolism

Undergoes first-pass metabolism in the liver; major metabolites are N-1-desalkylflurazepam and N-1-hydroxyethylflurazepam.b d Hydroxylated metabolite undergoes subsequent conjugation.b d

Elimination Route

Eliminated mainly in the urine; 25–55% of dose recovered as conjugates of N-1-hydroxyethylflurazepam, and <1% recovered as N-1-desalkylflurazepam.d

Half-life

Flurazepam: 2.3 hours.d

N-1-Desalkylflurazepam: 47–100 hours.b d

N-1-Hydroxyethylflurazepam: 2–4 hours.b

Special Populations

Geriatric men: Desalkylflurazepam half-life of 160 or 126 hours (after single or multiple doses, respectively) versus 74 or 111 hours in younger males.d

Geriatric women: Desalkylflurazepam half-life of 120 or 158 hours (after single or multiple doses, respectively) versus 90 or 113 hours in younger females.d

In patients with liver disease, elimination half-life may be prolonged.b

Benzodiazepines are not appreciably removed by hemodialysis.b

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).d

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.e f

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

  • Importance of informing clinicians of any behavioral or mental changes, memory impairment, sleep driving, tolerance, or dependence/withdrawal symptoms.207 470 491 d

  • Importance of taking hypnotics only when able to get a full night’s sleep before being active again.e

  • Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.b d

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

  • Importance of not consuming alcoholic beverages when taking hypnotics.e

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

  • Importance of informing patients of other important precautionary information.d (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.a d

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

Flurazepam Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

15 mg*

Flurazepam Hydrochloride Capsules (C-IV)

30 mg*

Flurazepam Hydrochloride Capsules (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.

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