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

Introduction

Benzodiazepine; sedative and hypnotic.a b d

Uses for 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

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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. Differences among hypnotics in residual and cumulative CNS depressant effects may be particularly important in geriatric patients, those with potentially impaired elimination of the drugs, and those whose job or life-style requires unimpaired intellectual or psychomotor function.

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.

  • 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 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

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. 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.

Immediately evaluate any new behavioral sign or symptom.

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 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.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.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 Dalmane

Specific Drugs

Drug

Interaction

Comments

CNS depressants (alcohol, anticonvulsants, sedatives)

Additive CNS depressant effectsb d

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

Cimetidine

Possible decreased plasma clearance of flurazepam

Use with caution; consider flurazepam dosage reduction

Clozapine

Severe hypotension, respiratory or cardiac arrest, and loss of consciousness reported when benzodiazepines (including flurazepam) were given with or within 24 hours before clozapine

Use with caution

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

Disulfiram

Possible inhibition of flurazepam metabolism

Observe closely for enhanced benzodiazepine response

Consider possible need for flurazepam dosage reduction

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.

Advice to Patients

  • Provide patient with a copy of the manufacturer’s patient information.e f

  • 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.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.

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*

Dalmane (C-IV; with parabens)

Valeant

30 mg*

Dalmane (C-IV; with parabens)

Valeant

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Flurazepam HCl 15MG Capsules (MYLAN): 30/$12.99 or 60/$18.97

Flurazepam HCl 30MG Capsules (MYLAN): 30/$13.99 or 60/$19.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

a. AHFS drug information 2008. McEvoy GK, ed. Flurazepam. Bethesda, MD: American Society of Health-System Pharmacists; 2008:2588.

b. AHFS drug information 2008. McEvoy GK, ed. Benzodiazepines general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2008: 2571-80.

c. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Baltimore, MD: Williams & Wilkins; 2005:674-5.

d. Valeant Pharmaceuticals. Dalmane (flurazepam hydrochloride) capsule prescribing information. Aliso Viejo, CA; 2007 Apr.

e. Questcor Pharmaceuticals. Doral (quazepam) tablets medication guide. Union City, CA; 2007 Jul.

f. Food and Drug Administration. FDA requests label change for all sleep disorder drug products. FDA News. March 14, 2007. From FDA website ().

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