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.

Introduction

Quazepam is a benzodiazepine.

Uses for Quazepam

Insomnia

Short-term management of insomnia for periods up to 4 weeks in duration.

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.

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.

Quazepam Dosage and Administration

Administration

Administer orally at bedtime.

Dosage

Individualize dosage and use the smallest effective dosage (especially in geriatric or debilitated patients). Avoid prolonged administration of quazepam. 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.

Adults

Insomnia

Oral

Usual dose is 15 mg; a dose of 7.5 mg may be adequate for some patients.

While a dose of 30 mg occasionally has been used, this dose is associated with an increased risk of daytime sedation.

In geriatric or debilitated patients, an initial dose of 7.5 or 15 mg should be used; in patients receiving 15 mg initially, reduction of the dose after the first one or two nights of therapy should be attempted.

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.

Cautions for Quazepam

Warnings/Precautions

Quazepam shares the toxic potentials of the benzodiazepines, and the usual precautions of benzodiazepine administration should be observed.

Specific Populations

Pregnancy

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

Fertility

Animal reproduction studies indicate that the drug produces a slight reduction in pregnancy rate. 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.

Lactation

Quazepam and its metabolites are distributed into milk in humans. Therefore, use of the drug in nursing woman is not recommended.

Pediatric Use

Safety and efficacy of quazepam in pediatric patients not established.

Geriatric Use

Oral quazepam doses of 7.5 or 15 mg generally have been well tolerated during short-term use in geriatric patients. However, because elimination of the drug may be prolonged in geriatric patients and because this age group generally is at increased risk from adverse CNS effects of drugs, including benzodiazepines, adjust quazepam dosage carefully.

Quazepam Pharmacokinetics

Absorption

Bioavailability

Rapidly and well absorbed from the GI tract following oral administration.

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

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

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. 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.

Food Effects

Food does not appear to affect GI absorption of quazepam.

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.

Distribution

Extent

Widely distributed into most body tissues and fluids.

Evidence from animal studies indicates that the drug and its metabolites readily cross the blood-brain barrier,

Quazepam and its metabolites cross the placenta in mice. Fetal accumulation of the drug does not appear to occur.

Quazepam and its metabolites are distributed into milk.

Plasma Protein Binding

Quazepam and its metabolites are more than 95% protein bound.

Elimination

Quazepam is rapidly and extensively metabolized in the liver to 2-oxoquazepam and N-desalkyl-2-oxoquazepam (N-desalkylflurazepam), both of which have pharmacologic activity reportedly similar to that of quazepam. Plasma concentrations of quazepam and these metabolites decline in a biphasic manner, with half-lives in the initial distribution phase (t_½α) of approximately 1.7, 2.9, and 27.8 hours, respectively, following single oral doses and 1.9, 2, and 57 hours, respectively, following multiple oral doses in healthy young adults. The elimination half-lives (t_½β) 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; 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). The elimination half-life of N-desalkyl-2-oxoquazepam averages about 70–75 hours in healthy young adults following single or multiple oral doses but, in healthy geriatric adults, may be more than twice that (e.g., 190 hours). The total body clearance of quazepam reportedly is 890 mL/minute.

Metabolism

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

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.

Following oral administration of radiolabeled drug, approximately 54% of a dose is excreted in urine (31%) and feces (23%). Approximately 50% of urinary excretion (15% of a dose) occurs as the conjugate of 3-hydroxy-2-oxoquazepam, 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.

Half-life

Plasma concentrations of quazepam and its metabolites decline in a biphasic manner, with half-lives in the initial distribution phase (t_½α) of approximately 1.7, 2.9, and 27.8 hours, respectively, following single oral doses and 1.9, 2, and 57 hours, respectively, following multiple oral doses in healthy young adults. The elimination half-lives (t_½β) 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. The elimination half-life of N-desalkyl-2-oxoquazepam averages about 70–75 hours in healthy young adults following single or multiple oral doses.

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).

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.

Stability

Storage

Oral

Tablets

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

Actions

• Quazepam is a benzodiazepine.

• Quazepam shares the actions of other benzodiazepines. The exact sites and modes of action not fully elucidated, but appear to be mediated principally through the inhibitory neurotransmitter GABA. Sites and mechanism of action within the CNS appear to involve a macromolecular complex (GABA_A-receptor-chloride ionophore complex) that includes GABA_A receptors, high-affinity benzodiazepine receptors, and chloride channels.

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.

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

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