flurazepam hydrochloride
Apo-Flurazepam ◆, Dalmane, Novoflupam ◆

Available forms
Available by prescription only
Capsules: 15 mg, 30 mg

Indications and dosages
 Insomnia. Adults: 15 to 30 mg P.O. h.s.
Elderly patients: 15 mg P.O. h.s.

Pharmacodynamics
Sedative action: Flurazepam depresses the CNS at the limbic and subcortical levels of the brain. It produces a sedative 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.

Pharmacokinetics
Absorption: Absorbed rapidly.
Distribution: Distributed widely throughout the body. About 97% of administered dose is bound to plasma protein.
Metabolism: Metabolized in the liver to the active metabolite desalkylflurazepam.
Excretion: Desalkylflurazepam is excreted in urine; half-life is 50 to 100 hours.

Contraindications and precautions
Contraindicated in pregnant women and patients hypersensitive to drug.
  Use cautiously in patients with impaired renal or hepatic function, chronic pulmonary insufficiency, mental depression, suicidal tendencies, or history of drug abuse. Use cautiously in the elderly.

Interactions
Drug-drug. Antidepressants, antihistamines, barbiturates, general anesthetics, MAO inhibitors, narcotics, phenothiazines: Increases CNS depressant effects of these drugs. Use together cautiously.
Cimetidine, disulfiram, isoniazid, hormonal contraceptives, ritonavir: May decrease benzodiazepine metabolism, leading to toxicity. Monitor patient carefully.
Digoxin: May increase serum levels, resulting in toxicity. Monitor patient closely.
Levodopa: Decreases levodopa effect. Monitor patient for drug effects.
Phenytoin: Increases phenytoin levels. Monitoring phenytoin levels.
Rifampin: Enhances benzodiazepine metabolism. Monitor patient closely.
Theophylline: May act as an antagonist with flurazepam. Monitor patient closely.
Drug-lifestyle. Alcohol use: Causes excessive CNS and respiratory depression. Discourage alcohol use.
Heavy smoking: Accelerates flurazepam metabolism. Monitor patient for drug effect. Discourage smoking.

Adverse reactions
CNS: daytime sedation, dizziness, drowsiness, disturbed coordination, lethargy, confusion, headache, light-headedness, nervousness, hallucinations, staggering, ataxia, disorientation, changes in EEG patterns, coma.
GI: nausea, vomiting, heartburn, diarrhea, abdominal pain.
Other: physical or psychological dependence.

Effects on lab test results
• May increase AST, ALT, total and direct bilirubin, and alkaline phosphatase levels.

Overdose and treatment
Signs and symptoms of overdose include somnolence, confusion, hypoactive reflexes, dyspnea, labored breathing, hypotension, bradycardia, slurred speech, unsteady gait or impaired coordination, and, eventually, coma.
 Support blood pressure and respiration until drug effects subside; monitor vital signs. Mechanical ventilatory assistance via endotracheal (ET) tube may be required to maintain a patent airway and support adequate oxygenation. Use I.V. fluids to promote diuresis and vasopressors such as dopamine and phenylephrine to treat hypotension, as needed. Flumazenil, a specific benzodiazepine antagonist, may be useful as an adjunct to supportive therapy.
 If patient is conscious, induce emesis. Use gastric lavage if ingestion was recent, but only if an ET tube is present to prevent aspiration. After emesis or lavage, administer activated charcoal with a cathartic as a single dose. Dialysis is of limited value. Don’t use barbiturates if excitation occurs to avoid exacerbation of excitatory state or potentiation of CNS depressant effects.

Special considerations
• Studies have demonstrated a carryover effect. Drug is most effective after 3 or 4 nights of use because of long half-life. Don’t increase dose more frequently than every 5 days.
• Drug is useful for patients who have trouble falling asleep and who awaken frequently at night and early in the morning.
• Although prolonged use isn’t recommended, this drug has proven effective for up to 4 weeks of continuous use.
• Rapid withdrawal after prolonged use can cause withdrawal symptoms.
• Lower doses are effective in patients with renal or hepatic dysfunction.
Pregnant patients
• Drug is contraindicated in pregnant women.
Breast-feeding patients
• Drug appears in breast milk. A breast-fed infant may become sedated, have feeding difficulties, or lose weight. Avoid use in breast-feeding women.
Pediatric patients
• Closely observe a neonate for withdrawal symptoms if the mother took flurazepam during pregnancy.
• Use of flurazepam during labor may cause neonatal flaccidity.
• Drug isn’t for use in children younger than age 15.
• Neonates are more sensitive to flurazepam because of slower metabolism. The possibility of toxicity is greatly increased.
Geriatric patients
• Elderly patients are more susceptible to CNS depressant effects of flurazepam. They may need assistance and supervision with walking and daily activities when therapy starts or dosage increases.
• Lower doses usually are effective in elderly patients because of decreased elimination.

Patient education
• Warn patient to avoid alcohol while taking drug.
• Emphasize the risk of excessive CNS depression if drug is taken with alcohol, even if taken the evening before ingestion of alcohol.
• Advise patient that rebound insomnia may occur after stopping drug.
• Tell patient not to discontinue drug abruptly after prolonged therapy and not to exceed prescribed dosage.

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