estazolam
ProSom

Available forms
Available by prescription only
Tablets: 1 mg, 2 mg

Indications and dosages
 Short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, or early-morning awakenings. Adults: Initially, 1 mg P.O. h.s.; may increase to 2 mg as needed and tolerated.
≡ Dosage adjustment. For small or debilitated older adults, 0.5 mg P.O. h.s. initially. May increase carefully to 1 mg if needed.

Pharmacodynamics
Hypnotic action: Estazolam depresses the CNS at the limbic and subcortical levels of the brain. It produces a sedative-hypnotic effect by potentiating the effect of the neurotransmitter gamma-aminobutyric acid on its receptor in the ascending reticular activating system, which increases inhibition and blocks both cortical and limbic arousal. Benzodiazepines decrease sleep latency, increase total sleep time, and decrease rapid-eye-movement sleep.

Pharmacokinetics
Absorption: Rapidly and completely absorbed through the GI tract.
Distribution: 93% protein-bound.
Metabolism: Extensively metabolized in the liver.
Excretion: Metabolites are excreted primarily in the urine. Less than 5% is excreted in urine as unchanged drug; 4% of a 2-mg dose is excreted in feces. Elimination half-life ranges from 10 to 24 hours; clearance is accelerated in smokers.

Contraindications and precautions
Contraindicated in pregnant women or patients hypersensitive to drug. Use cautiously in patients with depression, suicidal tendencies, and hepatic, renal, or pulmonary disease.

Interactions
Drug-drug. Antihistamines, barbiturates, general anesthetics, MAO inhibitors, narcotics, phenothiazines, tricyclic antidepressants: Increases CNS effects. Avoid use together.
Cimetidine, disulfiram, hormonal contraceptives, isoniazid: May decrease hepatic metabolism, increasing estazolam levels. Monitor patient for increased CNS depression.
Digoxin, phenytoin: Increases level of these drugs, with possible toxicity. Monitor patient closely.
Probenecid: Increases benzodiazepine effect. Monitor patient carefully.
Rifampin: Increases clearance and decreases half-life of estazolam. Monitor patient for decreased drug effect.
Theophylline: Antagonizes estazolam effects. Monitor patient for drug effectiveness.
Drug-herb. Kava: May induce lethargy, increased CNS effects, or coma. Discourage use together.
Drug-lifestyle. Alcohol use: May cause respiratory and CNS depression. Discourage alcohol use.
Caffeine: May enhance CNS effects. Discourage caffeine use.
Heavy smoking: Accelerates estazolam metabolism, resulting in diminished clinical efficacy. Discourage smoking.

Adverse reactions
CNS: fatigue, dizziness, daytime drowsiness, somnolence, asthenia, hypokinesia, abnormal thinking .
GI: dyspepsia, abdominal pain.
Musculoskeletal: back pain, stiffness.

Effects on lab test results
• May increase AST levels.

Overdose and treatment
Overdose may cause somnolence, confusion with reduced or absent reflexes, respiratory depression, apnea, hypotension, impaired coordination, slurred speech, seizures, or coma.
 If excitation occurs, don’t use barbiturates. Several agents may have been ingested. Perform gastric evacuation and lavage immediately. Monitor respiration, pulse rate, and blood pressure. Use symptomatic and supportive measures. Maintain airway and administer fluids. Flumazenil, a specific benzodiazepine antagonist, may be useful.

Special considerations
• Withdraw drug slowly after prolonged use.
• To prevent injury from dizziness and falls, tell family members or caregivers that elderly patients may need help with daily activities, especially when treatment starts or dose increases.
Pregnant patients
• Drug can cause harm to fetus when given during pregnancy. Safety during labor and delivery hasn’t been established.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. Avoid use in breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• Elderly patients may be more susceptible to CNS depressant effects of estazolam. Use cautiously. Lower dose may be required.

Patient education
• Urge patient to avoid caffeine and alcohol.
• Advise patient to immediately report suspected or intended pregnancy during therapy.
• Warn patient that drug may cause drowsiness.
• Caution patient not to stop drug abruptly after taking it daily for prolonged period and not to vary or increase dose unless prescribed. Drug should be taken until sleep pattern is established and then slowly tapered as prescribed.
• Inform patient that nocturnal sleep may be disturbed for 1 or 2 nights after drug is stopped.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use