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Quazepam (Monograph)

Brand name: Doral
Drug class: Benzodiazepines
VA class: CN302
Chemical name: 7-Chloro-s-(2-fluorophenyl)-1,3-dihydro-1-(2,2,2-tr ifluoroethyl)-2H-1,4-benzodiazepine-2-thione
Molecular formula: C17H11C1F4N2S
CAS number: 36735-22-5

Medically reviewed by Drugs.com on Sep 28, 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

    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

Quazepam is a benzodiazepine.312 313 314 315 316 317 318 321 322 323

Uses for Quazepam

Insomnia

Short-term management of insomnia267 312 313 317 318 321 322 323 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 for periods up to 4 weeks in duration.312 313

Individualize choice of a specific benzodiazepine according to patient response and tolerance, taking into consideration pharmacokinetic and pharmacodynamic characteristics of the drug, patient age and other characteristics, and the underlying sleep disorder.215 216 217 218 219 348

Benzodiazepines with a relatively long elimination half-life, such as quazepam, appear to be less likely than those with a short half-life to result in transient rebound insomnia after discontinuance and tolerance and adaptation to the hypnotic effect during continued therapy; however, may be more likely to result in residual daytime sedative effects and impaired psychomotor.207 215 216 217 218 219 245 252 259 267 313 321 323 337 341 342 345 346 353

Quazepam Dosage and Administration

Administration

Administer orally at bedtime.312 313 317 318 321 322 323

Dosage

Individualize dosage and use the smallest effective dosage (especially in geriatric or debilitated patients).312 Avoid prolonged administration of quazepam.312 317 323 Because of the drug’s long elimination half-life, intermittent therapy (e.g., every second or third night) may be possible without substantial risk of rebound insomnia in some patients.218 357

Adults

Insomnia
Oral

Usual dose is 15 mg;267 312 313 317 318 321 322 323 337 338 339 340 344 348 349 351 353 a dose of 7.5 mg may be adequate for some patients.312 313 317 318 323 337 343 344 348

While a dose of 30 mg occasionally has been used,321 341 342 344 345 346 347 348 350 this dose is associated with an increased risk of daytime sedation.321 344 348

In geriatric or debilitated patients, an initial dose of 7.5 or 15 mg should be used;312 317 318 323 337 339 340 in patients receiving 15 mg initially, reduction of the dose after the first one or two nights of therapy should be attempted.312 313 317 323

In patients who have received prolonged therapy (e.g., even for periods as brief as 6 weeks), avoid abrupt discontinuance since manifestations of withdrawal can be precipitated; gradually taper dosage when the drug is being discontinued.312 317

Detailed Quazepam dosage information

Cautions for Quazepam

Warnings/Precautions

Quazepam shares the toxic potentials of the benzodiazepines, and the usual precautions of benzodiazepine administration should be observed.312 313 317 318 355

Specific Populations

Pregnancy

Benzodiazepines can cause fetal harm when administered to pregnant women,312 317 and those used solely as hypnotics, such as quazepam, are contraindicated during pregnancy.312 317 The safety of quazepam during labor or delivery has not been established.312

Fertility

Animal reproduction studies indicate that the drug produces a slight reduction in pregnancy rate.312 A similar reduction in pregnancy rates has been observed in animals with high dosages of other benzodiazepines and is believed to be related to the sedative effects of the drugs.312

Lactation

Quazepam and its metabolites are distributed into milk in humans.312 313 317 318 319 324 Therefore, use of the drug in nursing woman is not recommended.312 317

Pediatric Use

Safety and efficacy of quazepam in pediatric patients not established.312 317

Geriatric Use

Oral quazepam doses of 7.5 or 15 mg generally have been well tolerated during short-term use in geriatric patients.313 317 318 339 340 However, because elimination of the drug may be prolonged in geriatric patients312 313 317 318 319 325 and because this age group generally is at increased risk from adverse CNS effects of drugs,317 318 356 including benzodiazepines,215 217 221 222 224 252 253 256 259 297 adjust quazepam dosage carefully.312 313

Quazepam Pharmacokinetics

Absorption

Bioavailability

Rapidly312 314 315 316 317 318 319 325 334 and well absorbed from the GI tract following oral administration.312 315 317 318 319 334

Although manufacturer states that oral bioavailability is approximately 80%,319 the absolute bioavailability in humans has not been determined to date.313

Has been shown to undergo extensive first-pass metabolism following oral administration in animals.334

Peak plasma concentrations of quazepam and a principal active metabolite, 2-oxoquazepam, are achieved 1–3 hours following oral administration of single or multiple doses.313 314 316 317 318 319 323 325 GI absorption is delayed slightly and AUCs of quazepam, 2-oxoquazepam, and N-desalkyl-2-oxoquazepam (another major metabolite) are increased slightly when the drug is administered at bedtime compared with administration in the morning, but such differences are unlikely to be clinically important.314

Food Effects

Food does not appear to affect GI absorption of quazepam.319

Special Populations

AUC, peak plasma concentration, and time-to-peak plasma concentration for unchanged drug and 2-oxoquazepam following a single 15-mg oral dose are similar in geriatric adults and in younger adults.325

Distribution

Extent

Widely distributed into most body tissues and fluids.313 314 316 317 318 319 334 335

Evidence from animal studies indicates that the drug and its metabolites readily cross the blood-brain barrier,313 317 318 334 335

Quazepam and its metabolites cross the placenta in mice.312 313 317 318 333 Fetal accumulation of the drug does not appear to occur.333

Quazepam and its metabolites are distributed into milk.312 313 317 318 319 324

Plasma Protein Binding

Quazepam and its metabolites are more than 95% protein bound.312 313 317 318

Elimination

Quazepam is rapidly and extensively metabolized in the liver to 2-oxoquazepam and N-desalkyl-2-oxoquazepam (N-desalkylflurazepam),312 313 314 315 317 318 319 both of which have pharmacologic activity312 313 315 318 319 reportedly similar to that of quazepam.319 Plasma concentrations of quazepam and these metabolites decline in a biphasic manner, with half-lives in the initial distribution phase (t½α) of approximately 1.7,315 316 317 318 2.9,315 316 and 27.8315 316 hours, respectively, following single oral doses and 1.9, 2, and 57 hours, respectively, following multiple316 oral doses in healthy young adults. The elimination half-lives (t½β) of both quazepam and 2-oxoquazepam in healthy young adults average approximately 39–40 hours (range: 25–41 hours for quazepam) following single or multiple oral doses;312 313 314 315 316 317 318 319 in healthy geriatric adults, the elimination half-life appears to be somewhat prolonged for quazepam (e.g., 53 hours) but not for 2-oxoquazepam (e.g., 43 hours).313 318 325 The elimination half-life of N-desalkyl-2-oxoquazepam averages about 70–75 hours in healthy young adults following single or multiple oral doses312 313 314 315 316 317 318 319 but, in healthy geriatric adults, may be more than twice that (e.g., 190 hours).312 313 317 318 319 325 The total body clearance of quazepam reportedly is 890 mL/minute.319

Metabolism

Rapidly and extensively metabolized in the liver to 2-oxoquazepam and N-desalkyl-2-oxoquazepam (N-desalkylflurazepam);312 313 314 315 317 318 319 both metabolites have pharmacologic activity reportedly similar to that of quazepam.312 313 315 318 319

Elimination Route

Excreted slowly in both urine and feces, principally as glucuronide conjugates of inactive metabolites; only trace amounts of the drug are excreted unchanged.312 313 315 319

Following oral administration of radiolabeled drug, approximately 54% of a dose is excreted in urine (31%) and feces (23%).312 313 315 319 Approximately 50% of urinary excretion (15% of a dose) occurs as the conjugate of 3-hydroxy-2-oxoquazepam,313 315 319 with substantially lower amounts occurring as the conjugate of 3-hydroxy-N-desalkyl-2-oxoquazepam (6% of a dose), the conjugate of N-desalkyl-2-oxoquazepam (4% of a dose), polar metabolites (3% of a dose), and other metabolites and unchanged drug.313 315 319

Half-life

Plasma concentrations of quazepam and its metabolites decline in a biphasic manner, with half-lives in the initial distribution phase (t½α) of approximately 1.7,315 316 317 318 2.9,315 316 and 27.8315 316 hours, respectively, following single oral doses and 1.9, 2, and 57 hours, respectively, following multiple316 oral doses in healthy young adults. The elimination half-lives (t½β) of both quazepam and 2-oxoquazepam in healthy young adults average approximately 39–40 hours (range: 25–41 hours for quazepam) following single or multiple oral doses.312 313 314 315 316 317 318 319 The elimination half-life of N-desalkyl-2-oxoquazepam averages about 70–75 hours in healthy young adults following single or multiple oral doses.312 313 314 315 316 317 318 319

Special Populations

In healthy geriatric adults, the elimination half-life appears to be somewhat prolonged for quazepam (e.g., 53 hours) but not for 2-oxoquazepam (e.g., 43 hours).313 318 325

The elimination half-life of N-desalkyl-2-oxoquazepam in healthy geriatric adults may be more than twice as long (e.g., 190 hours) as in healthy young adults.312 313 317 318 319 325

Stability

Storage

Oral

Tablets

Store in light-resistant containers at 2–30°C.312 317 When stored as directed, quazepam tablets are stable for 3 years following the date of manufacture.317 319

Actions

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.

Quazepam is subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.312 354

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

Quazepam

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

15 mg*

Doral (C-IV; scored)

Cutis

Quazepam Tablets (C-IV; scored)

AHFS DI Essentials™. © Copyright 2024, Selected Revisions September 28, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

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