Skip to Content

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

Warning(s)

Special Alerts:

[Posted 08/31/2016]

AUDIENCE: Pharmacy, Internal Medicine, Psychiatry, Neurology, Family Practice

ISSUE: FDA review has found that the growing combined use of opioid medicines with benzodiazepines or other drugs that depress the central nervous system (CNS) has resulted in serious side effects, including slowed or difficult breathing and deaths. Opioids are used to treat pain and cough; benzodiazepines are used to treat anxiety, insomnia, and seizures. In an effort to decrease the use of opioids and benzodiazepines, or opioids and other CNS depressants, together, FDA is adding Boxed Warnings, our strongest warnings, to the drug labeling of prescription opioid pain and prescription opioid cough medicines, and benzodiazepines. See the Drug Safety Communication, available at: , for a listing of all approved prescription opioid pain and cough medicines, and benzodiazepines and other CNS depressants.

FDA conducted and reviewed several studies showing that serious risks are associated with the combined use of opioids and benzodiazepines, other drugs that depress the CNS, or alcohol (see the FDA Drug Safety Communication, available at: , for a Data Summary). Based on these data, FDA is requiring several changes to reflect these risks in the opioid and benzodiazepine labeling, and new or revised patient Medication Guides. These changes include the new Boxed Warnings and revisions to the Warnings and Precautions, Drug Interactions, and Patient Counseling Information sections of the labeling.

FDA is continuing to evaluate the evidence regarding combined use of benzodiazepines or other CNS depressants with medication-assisted therapy (MAT) drugs used to treat opioid addiction and dependence. FDA is also evaluating whether labeling changes are needed for other CNS depressants, and will update the public when more information is available.

BACKGROUND: Opioids are powerful prescription medicines that can help manage pain when other treatments and medicines cannot be taken or are not able to provide enough pain relief. Benzodiazepines are a class of medicines that are widely used to treat conditions including anxiety, insomnia, and seizures.

RECOMMENDATION: Health care professionalsshould limit prescribing opioid pain medicines with benzodiazepines or other CNS depressants only to patients for whom alternative treatment options are inadequate. If these medicines are prescribed together, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. Warn patients and caregivers about the risks of slowed or difficult breathing and/or sedation, and the associated signs and symptoms. Avoid prescribing prescription opioid cough medicines for patients taking benzodiazepines or other CNS depressants, including alcohol.

Patients taking opioids with benzodiazepines, other CNS depressant medicines, or alcohol, and caregivers of these patients, should seek medical attention immediately if they or someone they are caring for experiences symptoms of unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

For more information visit the FDA website at: and .

Introduction

Benzodiazepine; sedative and hypnotic.a b d

Uses for Dalmane

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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. 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

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • 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

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • 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.

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*

Dalmane ( C-IV; with parabens)

Valeant

30 mg*

Dalmane ( C-IV; with parabens)

Valeant

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Date published: June 01, 2008
Last reviewed: June 01, 2008
Date modified: September 02, 2016

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 ().

Hide