Medication Guide App

Quazepam

Pronunciation: KWAZ-e-pam
Class: Benzodiazepine

Trade Names

Doral
- Tablets, oral 15 mg

Pharmacology

Potentiates action of GABA, an inhibitory neurotransmitter, resulting in increased neuronal inhibition and CNS depression, especially in limbic system and reticular formation.

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Pharmacokinetics

Absorption

Well absorbed from GI tract. C max is approximately 20 ng/mL; T max is approximately 2 h.

Distribution

Protein binding is 95%. Quazepam is present in breast milk (less than 0.1% of dose).

Metabolism

It is extensively metabolized in the liver to 2 active metabolites, 2-oxoquazepam and N-desalkyl-2-oxoquazepam.

Elimination

Eliminated in the urine (31%) and feces (23%); only trace amounts of the unchanged drug are present in the urine. The half-life for the parent and 2-oxoquazepam is 39 h; the half-life for N-desalkyl-2-oxoquazepam is 73 h.

Special Populations

Renal Function Impairment

The potential for excessive sedation or impaired coordination exists.

Hepatic Function Impairment

The potential for excessive sedation or impaired coordination exists.

Elderly

Elimination half-life of N-desalkyl-2-oxoquazepam is increased 2-fold compared with younger adults.

Alcoholism

The potential for excessive sedation or impaired coordination exists.

Indications and Usage

Treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings.

Contraindications

Hypersensitivity to any component of this product or to benzodiazepines; pregnancy; sleep apnea.

Dosage and Administration

Adults

PO 15 mg at bedtime initially; may reduce to 7.5 mg once individual response is determined.

Elderly patients

PO 7.5 mg at bedtime initially; if this is not effective, may increase to 15 mg after 1 to 2 nights. Attempt to reduce the nightly dosage after 1 to 2 nights.

Debilitated patients

Attempt dosage reduction after 1 to 2 nights.

General Advice

  • Use the smallest possible effective dose.

Storage/Stability

Store between 68° and 77°F.

Drug Interactions

Alcohol, CNS depressants, psychotropic drugs

May cause additive CNS depressant effects. The incidence of complex behaviors (eg, sleep driving) may be increased. Use with caution. If complex behaviors occur, consider discontinuation of hypnotic-sedatives. Avoid concurrent use of alcohol.

Clozapine

Coadministration may result in delirium, sedation, sialorrhea, and ataxia. Severe orthostatic hypotension and respiratory depression may occur when clozapine is added to or started with quazepam. Do not start clozapine with quazepam simultaneously. The addition of quazepam to an established clozapine regimen may carry less risk than adding clozapine to quazepam. Close clinical monitoring is warranted, especially during the first 48 h of coadministration.

CYP2B6 substrates (eg, bupropion, efavirenz)

Plasma concentrations of these drugs may be elevated, increasing the risk of adverse events. Closely monitor patients for adverse reactions. If adverse events occur, consider discontinuing quazepam and giving an alternative anxiolytic agent.

Digoxin

May increase serum digoxin concentrations and the risk of toxicity. Monitor digoxin concentrations and adjust the dose as needed.

Disulfiram, nefazodone

Pharmacologic effects (eg, CNS depressant effects) of quazepam may be increased. If increased CNS depressant effects occur, the quazepam dose may need to be reduced.

Hydantoins (eg, phenytoin)

Elevated hydantoin plasma concentrations with toxicity (eg, nystagmus, ataxia and other cerebellar signs) may occur, while the pharmacologic effects of quazepam may be decreased. Close clinical and serum concentration monitoring is warranted.

Methadone

Severe potentiation of respiratory depressant effects (including death) may occur. Coadminister with caution and closely monitor the clinical response.

Omeprazole

Quazepam concentrations and half-life may be increased, increasing the pharmacologic effects and risk of adverse reactions (eg, CNS depressant effects). Quazepam dosage reduction or increased dosing interval may be needed.

Protease inhibitors (eg, ritonavir)

Quazepam concentrations may be elevated. Severe sedation and respiratory depression may occur. If coadministration cannot be avoided, close clinical monitoring is warranted.

Rifamycins (eg, rifampin)

Quazepam concentrations and pharmacologic effects may be decreased. Monitor the clinical response to quazepam when a rifamycin is started or stopped. Adjust the quazepam dose as needed.

Sodium oxybate

The pharmacologic effects of sodium oxybate and quazepam may be additive, resulting in an increase in sleep duration and CNS depression. Coadministration is contraindicated.

Adverse Reactions

CNS

Daytime drowsiness (12%); headache (5%); dizziness, fatigue (2%); agitation, dysarthria, dystonia, hallucinations, irritability, sleep disturbances, stimulation.

GI

Dry mouth (2%); dyspepsia (1%).

Genitourinary

Changes in libido, incontinence, menstrual irregularities, urinary retention.

Hepatic

Jaundice.

Lab Tests

Increased eosinophils (2%); decreased hemoglobin, decreased lymphocytes, increased AST, increased monocytes (1%).

Musculoskeletal

Increased muscle spasticity.

Miscellaneous

Slurred speech.

Precautions

Monitor

Monitor patients for worsening of insomnia and the emergence of new thinking or behavior abnormalities. Addiction-prone individuals should be under careful surveillance because of the predisposition of such patients to habituation and dependence. Monitor elderly patients, debilitated patients, and patients with impaired renal or hepatic function for excessive sedation or impaired coordination.


Pregnancy

Category X . May cause fetal harm. Contraindicated in pregnancy.

Lactation

Excreted in breast milk. Use in breast-feeding women is not recommended.

Children

Safety and efficacy have not been established.

Elderly

Use with caution and at reduced doses.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Special Risk Patients

Use drug with caution in patients with depression or suicidal tendencies, drug abuse and dependence, or chronic pulmonary insufficiency.

Dependence/Withdrawal

Prolonged use can lead to psychologic or physical dependence. Withdrawal syndrome may occur; dose must be tapered gradually.

Angioedema

Rare cases of angioedema involving the tongue, glottis, or larynx have been reported. Some patients have had additional symptoms (eg, dyspnea, throat closing, nausea and vomiting).

Complex behaviors

Sleep driving and other complex behaviors (eg, preparing and eating food, making phone calls, having sex) in patients who are not fully awake have been reported.

Depression

Signs and symptoms of depression may be intensified when depressed patients take benzodiazepines.

Hazardous tasks

Caution patients about engaging in hazardous occupations requiring complete mental alertness, such as operating machinery or driving, after ingesting benzodiazepines. Potential impairment of the performance of such activities may occur the day following ingestion.

Unrecognized psychiatric or physical disorder

Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder; such findings have emerged during treatment with sedative-hypnotics. Failure of insomnia to remit after 7 to 10 days of treatment may indicate presence of a disorder that should be evaluated.

Overdosage

Symptoms

Coma, confusion, somnolence.

Patient Information

  • Instruct patient to read the Medication Guide before starting therapy and with each refill.
  • Advise patients to report any complex behaviors (eg, sleep driving) to their health care provider immediately.
  • Advise patients to inform their health care provider about any alcohol consumption and medications that they are taking, including OTC drugs. Advise patients that alcohol should generally not be consumed during treatment with hypnotics.
  • Caution patients about the possible combined effects of alcohol and other CNS depressants. Caution patients that an additive effect may occur if alcohol is consumed during the day following the use of quazepam for nighttime sedation. The potential for this interaction continues for several days following discontinuation of quazepam until serum levels of psychoactive metabolites have declined.
  • Advise patients to inform their health care provider if planning to become pregnant, if they are pregnant, of if they become pregnant during therapy.
  • Advise patients to inform their health care provider if they are breast-feeding.
  • Advise patients not to drive a car or operate potentially dangerous machinery until they know how this medicine affects them.
  • Inform patients that this medicine may cause daytime sedation, which may persist for several days following drug discontinuation.
  • Advise patients not to increase the dose on their own and to inform their health care provider if they believe the drug does not work anymore.
  • If benzodiazepines are taken on a prolonged and regular basis (even for periods as brief as 6 wk), advise patients not to stop taking them abruptly or to decrease the dose without consulting their health care provider because withdrawal symptoms may occur.

Copyright © 2009 Wolters Kluwer Health.

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