DrugindexOnline^{2nd edition}

Pronouncation: (KWAY-zuh-pam)
Class: Benzodiazepine

Trade Names:
Doral
- Tablets 7.5 mg
- Tablets 15 mg

Mechanism of Action

Pharmacology

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

Pharmacokinetics

Absorption

Well absorbed from GI tract. The t _½ is 30 min; C _max is about 20 ng/mL; T _max is about 2 hr.

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%) as trace amounts of unchanged drug. The t _½ for parent and 2-oxoquazepam is 39 hr and 73 hr for N-desalkyl-2-oxoquazepam.

Special Populations

Hepatic Function Impairment

The potential for excessive sedation or impaired coordination exists.

Elderly

Elimination t _½ of N-desalkyl-2-oxoquazepam is increased 2-fold that of young adults.

Alcoholism

The potential for excessive sedation or impaired coordination exists.

Indications and Usage

Short-term management of insomnia.

Contraindications

Hypersensitivity 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. Administer 30 min to 1 hr before bedtime with full glass of water. If GI upset occurs, administer with snack.

Elderly or debilitated patients

Attempt dosage reduction after 1 to 2 nights.

Drug Interactions

Alcohol, CNS depressants

May cause additive CNS depressant effects.

Cimetidine, disulfiram, omeprazole

May increase quazepam effects.

Digoxin

May increase serum digoxin concentrations.

Theophylline

May antagonize sedative effects.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Palpitations, tachycardia.

CNS

Daytime drowsiness; dizziness; lethargy; confusion; memory impairment; euphoria; relaxed feeling; falling; ataxia; hallucinations; paradoxical reactions (eg, anger, hostility, mania); headache.

Dermatologic

Rash.

EENT

Blurred vision; difficulty focusing.

GI

Anorexia; diarrhea; abdominal cramping; constipation; nausea and vomiting.

Hepatic

Hepatic dysfunction.

Hematologic

Leukopenia; agranulocytopenia.

Miscellaneous

Tolerance; physical and psychological dependence; weakness; slurred speech.

Precautions

Pregnancy

Category X .

Lactation

Excreted in breast milk.

Children

Contraindicated in children less than 18 yr.

Special Risk Patients

Use drug with caution in patients with renal or hepatic impairment, depression or suicidal tendencies, drug abuse and dependence, chronic pulmonary insufficiency, seizure disorders.

Dependence/Withdrawal

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

Overdosage

Symptoms

Somnolence, confusion with reduced or absent reflexes, respiratory depression, apnea, hypotension, impaired coordination, slurred speech, seizures, coma.

Patient Information

• Caution patient that this medication must not be taken during pregnancy or when pregnancy is possible. Advise patient to use reliable form of birth control while taking this drug.
• Discuss with patient ways to facilitate sleep (eg, quiet, darkened room; avoidance of caffeine and nicotine; warm bath; warm milk; deep breathing; relaxation; self-hypnosis).
• Instruct patient not to increase dose.
• Emphasize importance of follow-up evaluation with health care provider to monitor progress of therapy. Instruct patient to inform health care provider if drug does not seem to be working.
• Instruct patient not to discontinue medication abruptly after prolonged therapy (eg, more than 2 wk).
• Advise patient that disturbed nocturnal sleep may be experienced for 1 to 2 nights after discontinuing drug.
• Instruct patient to report the following symptoms to health care provider: sudden onset of vision changes, irregular heart beat, fever, sore throat, bruising, rash, jaundice, unusual bleeding (eg, epistaxis), or if pregnancy is detected.
• Advise patient to avoid intake of alcoholic beverages or other CNS depressants.
• Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.