Lorazepam

A to Z Drug Facts

Actions Potentiates action of GABA, resulting in increased neuronal inhibition and CNS depression, especially in limbic system and reticular formation. Lorazepam is readily absorbed with an absolute bioavailability of 90%. Peak concentrations in plasma occur » 2 hr following administration. The mean half-life of unconjugated lorazepam in human plasma is » 12 hr and for its major metabolite, lorazepam glucoronide, » 18 hr. Lorazepam is » 85% bound to plasma proteins.

 Indications Treatment of anxiety, anxiety associated with depression; preanesthetic medication for sedation/anxiety and decreased recall (IV).

Treatment of status epilepticus; relief of chemotherapy-induced nausea and vomiting; acute alcohol withdrawal; psychogenic catatonia.

 Contraindications Psychoses; acute narrow-angle glaucoma; intra-arterial administration (injection); hypersensitivity to benzodiazepines.

 Route/Dosage

Antianxiety

ADULTS: PO Usual dose: 2 to 6 mg/day (range, 1 to 10 mg/day) in divided doses; largest dose at bedtime.

Elderly/Debilitated patients

Initial dose: 1 to 2 mg/day in divided doses; increase gradually.

Preanesthesia

ADULTS: IM 0.05 mg/kg ³ 2 hr before procedure; up to 4 mg max. IV Initial dose: 2 mg total or 0.044 mg/kg, whichever is smaller. Do not exceed in patients > 50 yr. For increased lack of recall: 0.05 mg/kg, up to 4 mg max, 15 to 20 min before procedure.

Interactions

Alcohol/CNS depressants

Additive CNS depressant effects.

Digoxin

Increased serum digoxin concentrations.

Scopolamine

May result in increased incidence of hallucinations, irrational behavior, and sedation.

Theophyllines

May antagonize sedative effects.

Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Cardiovascular collapse; hypotension; phlebitis or thrombosis at IV sites. CNS: Drowsiness; confusion; ataxia; dizziness; lethargy; fatigue; apathy; memory impairment; disorientation; anterograde amnesia, restlessness; headache; slurred speech; aphonia; stupor; coma; euphoria; irritability; vivid dreams; psychomotor retardation; paradoxical reactions (eg, anger, hostility, mania, insomnia). DERMATOLOGIC: Rash. EENT: Visual or auditory disturbances; depressed hearing. GI: Constipation; diarrhea; dry mouth; coated tongue; nausea; anorexia; vomiting; difficulty swallowing. HEMATOLOGIC: Leukopenia. HEPATIC: Elevated LDH, ALT, AST, and alkaline phosphatase; hepatic dysfunction, including hepatitis and jaundice. RESPIRATORY: Partial airway obstruction (injection); respiratory depression. OTHER: Dependence/withdrawal syndrome (eg, confusion, abnormal perception of movement, depersonalization, muscle twitching, psychosis, paranoid delusions, seizures); pain, burning, redness at IM injection site.

 Precautions

Pregnancy: Category D. Avoid use, especially during first trimester, becuase of possible increased risk of congenital malformations. Advise women of childbearing age to use effective contraceptive method. Not recommended during labor and delivery. Lactation: Undetermined. Children: Do not use in patients < 18 yr (IM/IV); safety and efficacy in patients < 12 yr (oral) not established. Dependence: Prolonged use can lead to dependence. Parenteral administration: Primarily for acute states. Keep patients under observation for up to 3 hr. Use with extreme care in elderly, very ill patients, or those with limited pulmonary reserve because of the possibility of apnea or cardiac arrest. Do not give to patients in shock, coma or those with acute alcohol intoxication. Psychiatric disorders: Not intended for use in patients with primary depressive disorder, psychosis, or disorders in which anxiety is not prominent. Renal or hepatic impairment: Injection is not recommended in these patients. Use oral form with caution. Suicide: Use with caution in patients with suicidal tendencies; do not allow access to large quantities. Benzyl alcohol: Solution for injection contains 2% benzyl alcohol; avoid use in infants because toxicity may occur.

 Administration/Storage

• Do not administer IV or IM solution if discolored or if precipitate has formed.
• IM and IV forms should be refrigerated and protected from light.

IM

• When giving by IM route, inject undiluted, deep into muscle mass.

Oral

• Oral form may be given with food to minimize GI upset. Drug may be crushed and mixed with food or juice if patient has difficulty swallowing.
• Oral form should be stored at controlled room temperature in tightly closed container.

IV

• Prepare IV solution immediately before administration. Dilute drug with equal volume of 5% Dextrose in Water, sterile water, or saline.
• When giving by IV route, inject into large veins to minimize risk of thrombophlebitis. Administer IV push at rate not to exceed 2 mg/min.
• Direct IV push injection should be made with repeated aspiration to prevent intra-arterial administration, which may produce arteriospasm leading to gangrene.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note glaucoma, renal, or hepatic impairment, suicidal tendencies, and use of nicotine (smoking may decrease drug effectiveness).
• Assess patient's anxiety level before beginning therapy and reassess daily.
• Assess for suicidal ideation as CNS depressants may aggravate symptoms of depression.
• Assess respiratory function carefully, particularly in elderly, very ill patients, or those with compromised pulmonary reserve. Apnea or cardiac arrest may occur when drug is given parenterally. Have resuscitation equipment available.
• Monitor vital signs twice daily throughout therapy and every 10 min during IV administration.
• Ensure bedrest for 3 hr after IV administration. Supervise ambulation for up to 8 hr after IV administration.
• Offer sugarless hard candy, gum, or frequent sips of water if dry mouth occurs.
• Monitor for symptoms of withdrawal syndrome, which may occur within 4 to 6 wk of treatment with therapeutic doses.

 Patient/Family Education

• Advise women of childbearing potential to use effective contraceptive method while taking lorazepam.
• Instruct patients who have used lorazepam regularly for more than a few weeks not to stop taking drug abruptly as serious withdrawal symptoms may occur. Advise that prolonged use may result in dependence.
• Advise patient to avoid sudden position changes to prevent orthostatic hypotension.
• Instruct patient to report the following symptoms to health care provider: sedation, dizziness, weakness, unsteadiness, disorientation, depression or paradoxical reactions such as anger, mania or insomnia.
• Explain that amnesia may occur, especially if drug is given via IV route.
• Advise patient that drug will cause drowsiness and to avoid driving or performing other tasks requiring mental alertness for ³ 24 to 48 hr after administration of IM form.
• Instruct patient to avoid alcohol and other CNS depressants and otc medications while taking this drug.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts