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Flurazepam Hydrochloride

Class: Benzodiazepines
VA Class: CN302
CAS Number: 1172-18-5
Brands: Formerly available as Dalmane

Medically reviewed on December 11, 2017


    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.)


Benzodiazepine; sedative and hypnotic.a b d

Uses for Flurazepam Hydrochloride


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

Flurazepam Hydrochloride Dosage and Administration


  • 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


Oral Administration

Administer at bedtime.a d


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



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 Flurazepam Hydrochloride


  • 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



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


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


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


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 Flurazepam Hydrochloride

Specific Drugs





Possible decreased plasma clearance of flurazepam200 625

Use with caution; consider flurazepam dosage reduction200 372 610


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


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

Flurazepam Hydrochloride Pharmacokinetics



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


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


Hypnotic effect persists for 7–8 hours.b



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



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


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





25°C (may be exposed to 15–30°C).d


  • 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.)


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


Dosage Forms


Brand Names




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.


200. Hansten PD. Drug interactions. 5th ed. Philadelphia: Lea & Febiger; 1985:276-7, 393-4.

207. Pharmacia & Upjohn. Halcion (triazolam) tablets prescribing information (dated 1993 Jul). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2093-5.

215. Greenblatt DJ, Shader RI, Abernethy DR. Drug therapy: Current status of benzodiazepines (first of two parts). N Engl J Med. 1983; 309:354-8.

216. Greenblatt DJ, Shader RI, Abernethy DR. Drug therapy: Current status of benzodiazepines (second of two parts). N Engl J Med. 1983; 309:410-6.

217. Anon. Choice of benzodiazepines. Med Lett Drugs Ther. 1988; 30:26-8.

218. National Institutes of Health. Drugs and insomnia: the use of medications to promote sleep. Consensus Development Conference. JAMA. 1984; 251:2410-4.

219. Kales A, Soldatos CR, Kales JD. Sleep disorders: insomnia, sleepwalking, night terrors, nightmares, and enuresis. Ann Intern Med. 1987; 106:582-92.

221. Ray WA, Griffin MR, Downey W. Benzodiazepines of long and short elimination half-life and the risk of hip fracture. JAMA. 1989; 262:3303-7.

222. Ray WA, Griffin MR, Schaffner W et al. Psychotropic drug use and the risk of hip fracture. N Engl J Med. 1987; 316:363-9.

224. Sorock GS, Shimkin EE. Benzodiazepine sedatives and the risk of falling in a community-dwelling elderly cohort. Arch Intern Med. 1988; 148:2441-4.

235. Elliott WJ. You don’t have to be a neuroscientist to forget everything with triazolam—but it helps. JAMA. 1988; 259:350-1.

245. Kales A, Kales JD. Sleep laboratory studies of hypnotic drugs: efficacy and withdrawal effects. J Clin Psychopharmacol. 1983; 3:140-50.

252. Murphy P, Hindmarch I, Hyland CM. Aspects of short-term use of two benzodiazepine hypnotics in the elderly. Age Ageing. 1982; 11:222-8.

253. Carskadon MA, Seidel WF, Greenblatt DJ et al. Daytime carryover of triazolam and flurazepam in elderly insomniacs. Sleep. 1982; 5:361-71.

254. Ogura C, Nakazawa K, Majima K et al. Residual effects of hypnotics: triazolam, flurazepam, and nitrazepam. Psychopharmacology (Berl). 1980; 68:61-5.

255. Bixler EO, Kales A, Soldatos CR et al. Effectiveness of temazepam with short-, intermediate-, and long-term use: sleep laboratory evaluation. J Clin Pharmacol. 1978; 18:110-8.

256. Linnoila M, Viukari M, Lamminsivu U et al. Efficacy and side effects of lorazepam, oxazepam, and temazepam as sleep aids in psychogeriatric inpatients. Int Pharmacopsychiatry. 1980; 15:129-35.

257. Kroboth PD, Smith RB, Van Thiel DH et al. Nighttime dosing of triazolam in patients with liver disease and normal subjects: kinetics and daytime effects. J Clin Pharmacol. 1987; 27:255-60.

258. Morgan K, Oswald I. Anxiety caused by a short-life hypnotic. BMJ. 1982; 284:942.

259. Larson EB, Kukull WA, Buchner D et al. Adverse drug reactions associated with global cognitive impairment in elderly persons. Ann Inter Med. 1987; 107:169-73.

262. Bixler EO, Kales A, Brubaker BH et al. Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system. Pharmacology. 1987; 35:286-300.

264. Juhl RP, Daugherty VM, Kroboth PD. Incidence of next-day anterograde amnesia caused by flurazepam hydrochloride and triazolam. Clin Pharm. 1984; 3:622-5.

267. Kales A, Bixler EO, Vela-Bueno A et al. Comparison of short and long half-life benzodiazepine hypnotics: triazolam and quazepam. Clin Pharmacol Ther. 1986; 40:378-86.

269. Patterson JF. Triazolam syndrome in the elderly. South Med J. 1987; 80:1425-6.

270. Huff JS, Plunkett HG. Anterograde amnesia following triazolam use in two emergency physicians. J Emerg Med. 1989; 7:153-5.

276. Ewing JA. You don’t have to be a neuroscientist to forget everything with triazolam—but it helps. JAMA. 1988; 259:350.

279. Morris HH, Estes ML. You don’t have to be a neuroscientist to forget everything with triazolam—but it helps. JAMA. 1988; 259:351-2.

280. Cohen M. You don’t have to be a neuroscientist to forget everything with triazolam—but it helps. JAMA. 1988; 259:352.

284. Leary WE. F.D.A. asks stronger label on sleep pill under scrutiny. NY Times. 1989; 138(Sep 22):6.

285. Anon. Triazolam (Halcion): psychological disturbances. Drug Ther Bull. 1979; 17:76.

286. van der Kroef C. Reactions to triazolam. Lancet. 1979; 2:526.

287. Oswald I. Triazolam syndrome 10 years on. Lancet. 1989; 2:451-2.

297. Jerram T. Hypnotics and sedatives. In: Dukes MNG, ed. Meyler’s side effects of drugs. 10th ed. New York: Elsevier; 1984:81-108.

298. Jerram T. Hypnotics and sedatives. In: Dukes MNG, ed. Side effects of drugs. Annual 11. New York: Elsevier; 1987:37-43.

311. Kales A, Soldatos CR, Bixler EO et al. Diazepam: effects on sleep and withdrawal phenomena. J Clin Psychopharmacol. 1988; 8:340-6.

312. Baker Cummins Pharmaceuticals, Inc. Doral (quazepam) prescribing information. Miami, FL; 1990 May.

313. Ankier SI, Goa KL. Quazepam: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in insomnia. Drugs. 1988; 35:42-62.

317. Baker Cummins Pharmaceuticals, Inc. Doral (quazepam) drug reference. Miami, FL; 1989 Jul.

318. Baker Cummins Pharmaceuticals, Inc. Doral (quazepam) receptor-selective benzodiazepine hypnotic monograph. Miami, FL; 1990 Feb.

319. Baker Cummins Pharmaceuticals, Inc. Product information formulary data for Doral. Miami, FL; 1989 Jul.

320. Rall TW. Hypnotics and sedatives; ethanol: benzodiazepines and management of insomnia. In: Gilman AG, Rall TW, Nies AS et al. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:346-58,369-70.

321. Kales A, Bixler EO, Soldatos CR et al. Quazepam and flurazepam: long-term use and extended withdrawal. Clin Pharmacol Ther. 1982; 32:781-8.

322. Kales A, Scharf MB, Soldatos CR et al. Quazepam, a new benzodiazepine hypnotic: intermediate-term sleep laboratory evaluation. J Clin Pharmacol. 1980; 20:184-92.

323. Anon. Quazepam: a new hypnotic. Med Lett Drugs Ther. 1990; 32:39-40.

325. Hilbert JM, Chung M, Radwanski E et al. Quazepam kinetics in the elderly. Clin Pharmacol Ther. 1984; 36:566-9.

337. Kales A, Bixler EO, Soldatos CR et al. Quazepam and temazepam: effects of short- and intermediate-term use and withdrawal. Clin Pharmacol Ther. 1986; 39:345-52.

338. Lee A, Lader M. Tolerance and rebound during and after short-term administration of quazepam, triazolam and placebo to healthy human volunteers. Int Clin Psychopharmacol. 1988; 3:31-47.

344. Kales A, Scharf MB, Bixler EO et al. Dose-response studies of quazepam. Clin Pharmacol Ther. 1981; 30:194-200.

346. Aden GC, Thatcher C. Quazepam in the short-term treatment of insomnia in outpatients. J Clin Psychiatry. 1983; 44:454-6.

348. Kales JD, Kales A, Soldatos CR. Quazepam: sleep laboratory studies of effectiveness and withdrawal. Clin Neuropharmacol. 1985; 8(Suppl 1):S55-62.

353. Mendels J, Stern S. Evaluation of the short-term treatment of insomnia in out-patients with 15 milligrams of quazepam. J Int Med Res. 1983; 11:155-61.

356. Montamat SC, Cusack BJ, Vestal RE. Management of drug therapy in the elderly. N Engl J Med. 1989; 321:303-9.

358. Bloom FE. Neurohumoral transmission and the central nervous system: amino acids. In: Gilman AG, Rall TW, Nies AS et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:256-8.

359. Haefely W. The GABA-benzodiazepine interaction fifteen years later. Neurochem Res. 1990; 15:169-74.

360. De Feudis FV. Overview—GABAa receptors. Ann NY Acad Sci. 1990; 585:231-40.

361. Mohler H, Malherbe P, Draguhn A et al. GABAa-receptors: structural requirements and sites of gene expression in mammalian brain. Neurochem Res. 1990; 15:199-207.

362. Farrant M, Gibbs TT, Farb DH. Molecular and cellular mechanisms of GABA/benzodiazepine-receptor regulation: electrophysiological and biochemical studies. Neurochem Res. 1990; 15:175-91.

363. Sieghart W. Benzodiazepine receptor subtypes and their possible clinical significance. Psychopharmacol Ser. 1989; 7:131-7.

364. Knapp RJ, Malatynska E, Yamamura HI. From binding studies to the molecular biology of GABA receptors. Neurochem Res. 1990; 15:105-12.

365. Williams M. Anxioselective anxiolytics. J Med Chem. 1983; 26:619-28.

366. Rogawski MA, Porter RJ. Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol Rev. 1990; 42:223-86.

367. Haefely WE. Pharmacology of the benzodiazepine receptor. Eur Arch Psychiatry Neurol Sci. 1989; 238:294-301.

368. Haefely WE. Benzodiazepines. Int Anesthesiol Clin. 1988; 26:262-72.

369. Schoch P, Richards JG, Haring P et al. Co-localization of GABA receptors and benzodiazepine receptors in the brain shown by monoclonal antibodies. Nature. 1985; 314:168-71.

370. Haefely W. Endogenous ligands of the benzodiazepine receptor. Pharmacopsychiatry. 1988; 21:43-6.

372. Pfizer. Xanax (alprazolam) prescribing information. New York, NY; 2006 Mar.

377. Shader RI, Dreyfuss D, Gerrein JR et al. Sedative effects and impaired learning and recall after single oral doses of lorazepam. Clin Pharmacol Ther. 1986; 39:526-30.

435. Wyeth Laboratories. Ativan (lorazepam) injection prescribing information. Philadelphia, PA; 2002 Oct.

470. Bixler EO, Kales A, Manfredi RL et al. Next-day memory impairment with triazolam use. Lancet. 1991; 337:827-31.

488. Rothchild AJ. Disinhibition, amnestic reactions, and other adverse reactions secondary to triazolam: a review of the literature. J Clin Psych. 1992; 53:69-79.

491. Schneider PJ, Perry PJ. Triazolam—an “abused drug” by the lay press? DICP Ann Pharmacother. 1990; 24:389-92.

529. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004; 161(2 Suppl):1-56.

591. Novartis Pharmaceuticals. Clozaril (clozapine) prescribing information. East Hanover, NJ; 2003 Jan.

592. Grohmann R, Ruther E, Sassim N et al. Adverse effects of clozapine. Psychopharmacology. 1989; 99(Suppl):S101-4.

593. Sassim N, Grohmann R. Adverse drug reactions with clozapine and simultaneous application of benzodiazepines. Pharmacopsychiatry. 1988; 21:306-7.

595. Baldessarini RJ, Frankenburg FR. Clozapine: a novel antipsychotic agent. N Engl J Med. 1991; 324: 746-54.

597. Public Citizen Health Research Group. Citizen’s petition to Food and Drug Administration for Dear Doctor Letter and box warning on clozapine regarding risk of respiratory arrest. Washington, DC; 1991 May 29.

598. Friedman LJ, Tabb SE, Worthington JJ et al. Clozapine—a novel antipsychotic agent. N Engl J Med. 1991; 325:518.

599. Finkel MJ, Schwimmer JL. Clozapine—a novel antipsychotic agent. N Engl J Med. 1991; 325: 518-9.

600. Zenith Goldline Pharmaceuticals. Clozapine tablets prescribing information. Miami, FL; 1999 Feb.

610. Pharmacia & Upjohn Company. Halcion (triazolam) tablets prescribing information. Kalamazoo, MI; 2003 Jan.

625. Watson Laboratories. Estazolam tablets prescribing information. Corona, CA; 2006 Mar.

629. Food and Drug Administration. Sedative-hypnotic drug products. [March 14, 2007] MedWatch drug labeling changes. Rockville, MD; April 2007. From FDA website.

700. US Food and Drug Administration. Drug safety communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. Silver Spring, MD; 2016 Aug 31. From FDA website.

701. Jones CM, Mack KA, Paulozzi LJ. Pharmaceutical overdose deaths, United States, 2010. JAMA. 2013; 309:657-9.

703. Hughes A. Letter to manufacturers of benzodiazepines: safety labeling change notification. Silver Spring, MD: US Food and Drug Administration. Accessed 2017 Mar 20.

704. Seymour S. Letter to manufacturers of opioid antitussives: safety labeling change notification. Silver Spring, MD: US Food and Drug Administration. Accessed 2017 Mar 20.

705. Park TW, Saitz R, Ganoczy D et al. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015; 350:h2698.

706. Jones CM, McAninch JK. Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines. Am J Prev Med. 2015; 49:493-501.

707. Dasgupta N, Funk MJ, Proescholdbell S et al. Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality. Pain Med. 2016; 17:85-98.

708. Nuckols TK, Anderson L, Popescu I et al. Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Ann Intern Med. 2014; 160:38-47.

709. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016; 65:1-49.

710. Manchikanti L, Abdi S, Atluri S et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance. Pain Physician. 2012; 15(3 Suppl):S67-116.

711. New York City Department of Health and Mental Hygiene. New York City emergency department discharge opioid prescribing guidelines. From NYC Health website. 2013 Jan.

712. Washington State Agency Medical Directors' Group (AMDG). Interagency guideline on prescribing opioids for pain, 3rd ed. From Washington State AMDG website. 2015 Jun.

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 (