lorazepam
Apo-Lorazepam ◆, Ativan, Novo-Lorazem ◆

Available forms
Available by prescription only
Injection: 2 mg/ml, 4 mg/ml
Solution: 2 mg/ml
Tablets: 0.5 mg, 1 mg, 2 mg
Tablets (S.L.) ◆: 1 mg, 2 mg

Indications and dosages
 Anxiety, tension, agitation, irritability, especially in anxiety neuroses or organic (especially GI or CV) disorders. Adults: Initially, 2 to 3 mg P.O. daily in two to three divided doses. Usual range is 2 to 6 mg P.O. daily in divided doses; maximum dose is 10 mg daily.
 Insomnia. Adults: 2 to 4 mg P.O. h.s.
 Preoperatively. Adults: 0.05 mg/kg I.M. 2 hours before surgery (maximum, 4 mg). Or, 0.044 mg/kg (maximum total dose is 2 mg) I.V. 15 to 20 minutes before surgery; in adults younger than age 50, dosage may be increased to 0.05 mg/kg (maximum, 4 mg) I.V. when decreased recall of preoperative events is desired.
 Management of nausea and vomiting caused by emetogenic chemotherapy ◇. Adults: 2.5 mg P.O. the evening before chemotherapy and repeat just after the initiation of chemotherapy. Or, 1.5 mg/m² (maximum 3 mg) I.V. over 5 minutes 45 minutes before chemotherapy.
Elderly patients: Initially, 1 to 2 mg P.O. daily in divided doses. Then dosage is divided, p.r.n.
 Status epilepticus ◇. Adults and children: 0.05 to 0.1 mg/kg I.V. Doses may be repeated at 10- to 15-minute intervals as needed for seizure control. Or, adults may be given 4 to 8 mg I.V.

Pharmacodynamics
Anxiolytic and sedative actions: Lorazepam depresses the CNS at the limbic and subcortical levels of the brain. It produces an antianxiety effect by influencing 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 after stimulation of the reticular formation.

Pharmacokinetics
Absorption: When administered orally, drug is well absorbed through the GI tract.
Distribution: Distributed widely throughout the body. Drug is about 85% protein-bound.
Metabolism: Metabolized in the liver to inactive metabolites.
Excretion: Metabolites are excreted in urine as glucuronide conjugates.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug, other benzodiazepines, or its vehicle (used in parenteral dosage form) and in patients with acute angle-closure glaucoma.
  Use cautiously in patients with pulmonary, renal, or hepatic impairment and in elderly, acutely ill, or debilitated patients. Don’t use in pregnant women, especially during the first trimester.

Interactions
Drug-drug. Antidepressants, antihistamines, barbiturates, general anesthetics, MAO inhibitors, narcotics, phenothiazines: Potentiates CNS depressant effects of these drugs. Use together cautiously.
Cimetidine, possibly disulfiram: Diminishes hepatic metabolism of lorazepam, which increases its plasma level. Avoid use together.
Scopolamine: Combined use of parenteral lorazepam and scopalamine may cause an increased risk of hallucinations, irrational behavior, and increased sedation. Use together cautiously.
Drug-herb. Calendula, catnip, hops, kava, lady’s slipper, passionflower, valerian: May increase sedative effect of drug. Discourage use together.
Drug-lifestyle. Alcohol use: Potentiates CNS depressant effects of alcohol. Discourage alcohol use.
Heavy smoking: Accelerates lorazepam metabolism, thus lowering clinical effectiveness. Discourage smoking.

Adverse reactions
CNS: drowsiness, amnesia, insomnia, agitation, sedation, dizziness, weakness, unsteadiness, disorientation, depression, headache.
EENT: visual disturbances.
GI: abdominal discomfort, nausea, change in appetite.
Other: acute withdrawal syndrome (after sudden discontinuation in physically dependent patients).

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

Overdose and treatment
Signs and symptoms of overdose include somnolence, confusion, coma, hypoactive reflexes, dyspnea, labored breathing, hypotension, bradycardia, slurred speech, and unsteady gait or impaired coordination.
 Treatment requires support of blood pressure and respiration until drug effects subside; monitor vital signs. Mechanical ventilatory assistance via endotracheal tube may be required to maintain a patent airway and support adequate oxygenation. Flumazenil, a specific benzodiazepine antagonist, may be useful. Use I.V. fluids and vasopressors such as dopamine and phenylephrine to treat hypotension, if needed. If patient is conscious, induce emesis. Use gastric lavage if ingestion was recent, but only if an endotracheal 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.

Special considerations
• Lorazepam is one of the preferred benzodiazepines for patients with hepatic disease.
• Use lowest possible effective dose to avoid oversedation.
• Parenteral lorazepam appears to possess potent amnesic effects.
• For the oral concentrated solution, add dose to 30 ml or more of water, juice, or soda, or to semisolid foods.
• Oral drug is given in divided doses, with the largest dose given before bedtime.
 ALERT Arteriospasm may result from intra-arterial injection of lorazepam. Don’t administer by this route.
• For I.V. administration, dilute lorazepam with an equal volume of a compatible diluent, such as D₅W, sterile water for injection, or normal saline solution.
• Drug may be injected directly into a vein or into the tubing of a compatible I.V. infusion, such as normal saline solution or D₅W solution. The rate of lorazepam I.V. injection shouldn’t exceed 2 mg/minute. Have emergency resuscitative equipment available when administering I.V.
• Give diluted lorazepam solutions immediately.
• Don’t use drug solutions if they’re discolored or contain a precipitate.
• I.M. doses of lorazepam are given undiluted, deep into a large muscle mass.
• Monitor hepatic function studies to prevent cumulative effects and to ensure adequate drug metabolism.
• Monitor renal function test results.
Breast-feeding patients
• Drug may appear in breast milk. Don’t administer to breast-feeding women.
Pediatric patients
• Safety of oral lorazepam in children younger than age 12 hasn’t been established. Safety of S.L. or parenteral lorazepam in children younger than age 18 hasn’t been established. Neonates haven’t been closely observed for withdrawal symptoms when mother took lorazepam for a prolonged period during pregnancy.
Geriatric patients
• These patients are more sensitive to CNS depressant effects of lorazepam. They may need assistance with walking and daily activities when therapy starts or dosage increases.
• Lower doses usually are effective in elderly patients because of decreased elimination.
• Parenteral administration of drug is more likely to cause apnea, hypotension, bradycardia, and cardiac arrest in elderly patients.

Patient education
• Caution patient not to change drug regimen without specific instructions.
• Teach safety measures, as appropriate, to protect from injury, such as gradual position changes and supervised walking.
• Advise patient of possible retrograde amnesia after I.V. or I.M. use.
• Tell patient to avoid large amounts of caffeine-containing products, which may interfere with effectiveness of drug.
• Advise patient about risk of physical and psychological dependence with long-term use.
• Tell patient to stop drug slowly (over 8 to 12 weeks) after long-term therapy.

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