lorazepam

lorazepam

(lor a' ze pam)

Apo-Lorazepam (CAN), Ativan, Novo-Lorazem (CAN), Nu-Loraz (CAN)

Pregnancy Category D

Controlled Substance C-IV

Drug classes

Benzodiazepine

Anxiolytic

Sedative-hypnotic

Therapeutic actions

Exact mechanisms are not understood; acts mainly at subcortical levels of the CNS, leaving the cortex relatively unaffected. Main sites of action may be the limbic system and reticular formation; benzodiazepines potentiate the effects of GABA, an inhibitory neurotransmitter; anxiolytic effects occur at doses well below those necessary to cause sedation and ataxia.

Indications

·        Oral: Management of anxiety disorders or for short-term relief of symptoms of anxiety or anxiety associated with depression; insomnia due to anxiety of transient situational stress

·        Parenteral: Preanesthetic medication in adults to produce sedation, relieve anxiety, and decrease recall of events related to surgery; treatment of status epilepticus

·        Unlabeled parenteral use: Management of status epilepticus, chemotherapy-induced nausea and vomiting, acute alcohol withdrawal

Contraindications and cautions

·        Contraindicated with hypersensitivity to benzodiazepines, propylene glycol, polyethylene glycol or benzyl alcohol (parenteral lorazepam); psychoses; acute narrow-angle glaucoma; shock; coma; acute alcoholic intoxication with depression of vital signs; pregnancy (crosses placenta; risk of congenital malformations and neonatal withdrawal syndrome); labor and delivery ("floppy infant" syndrome); and lactation.

·        Use cautiously with impaired hepatic or renal function.

Available forms

Injection—2, 4 mg/mL; oral solution—2 mg/mL; tablets—0.5, 1, 2 mg

Dosages

ADULTS

Oral

Usual dose is 2–6 mg/day; range 1–10 mg/day given in divided doses with largest dose hs.

·        Insomnia due to transient stress: 2–4 mg given hs.

IM

0.05 mg/kg up to a maximum of 4 mg administered at least 2 hr before operative procedure.

IV

Initial dose is 2 mg total or 0.044 mg/kg, whichever is smaller. Do not exceed this dose in patients older than 50 yr. Doses as high as 0.05 mg/kg up to a total of 4 mg may be given 15–20 min before the procedure to those benefited by a greater lack of recall. Continuous infusion 0.5–1 mg/hr titrated, based on patient response.

PEDIATRIC PATIENTS

Drug should not be used in children < 12 yr.

GERIATRIC PATIENTS OR PATIENTS WITH HEPATIC DISEASE

Initially, 1–2 mg/day in divided doses. Adjust as needed and tolerated.

Pharmacokinetics

Route	Onset	Peak	Duration
Oral	Intermediate	1–6 hr	12–24 hr
IM	15–30 min	60–90 min	12–24 hr
IV	1–5 min	10–15 min	12–24 hr

Metabolism: Hepatic; T_1/2: 10–20 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Urine

IV facts

Preparation: Dilute lorazepam immediately before IV use. For direct IV injection or injection into IV line, dilute with an equal volume of compatible solution (sterile water for injection, sodium chloride injection, or 5% dextrose injection); do not use if solution is discolored or contains a precipitate. Protect from light.

Infusion: Direct inject slowly, or infuse at maximum rate of 2 mg/min.

Y-site incompatibilities: Do not mix with foscarnet, ondansetron.

Adverse effects

·        CNS: Transient, mild drowsiness initially; sedation, depression, lethargy, apathy, fatigue, light-headedness, disorientation, anger, hostility,episodes of mania and hypomania, restlessness, confusion, crying, delirium, headache, slurred speech, dysarthria, stupor, rigidity, tremor, dystonia, vertigo, euphoria, nervousness, difficulty concentrating, vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild paradoxical excitatory reactions during first 2 wk of treatment

·        CV: Bradycardia, tachycardia, CV collapse, hypertension and hypotension, palpitations, edema

·        Dermatologic: Urticaria, pruritus, rash, dermatitis

·        EENT: Visual and auditory disturbances, diplopia, nystagmus, depressed hearing, nasal congestion

·        GI: Constipation, diarrhea, dry mouth, salivation, nausea, anorexia, vomiting, difficulty in swallowing, gastric disorders, hepatic dysfunction

·        GU: Incontinence, urinary retention, changes in libido, menstrual irregularities

·        Hematologic: Elevations of blood enzymes: LDH, alkaline phosphatase, AST, ALT; blood dyscrasias—agranulocytosis, leukopenia

·        Other: Hiccups, fever, diaphoresis, paresthesias, muscular disturbances, gynecomastia. Drug dependence with withdrawal syndrome when drug is discontinued; more common with abrupt discontinuation of higher dosage used for > 4 mo

Interactions

Drug-drug

·        Increased CNS depression with alcohol and other sedating medications, such as barbiturates and opioids

·        Decreased effectiveness with theophyllines

·        Risk of toxicity if combined with probenecid, valproate; reduce lorazepam dose by 50%

Drug-herb

·        Kava kava increases the sedative effects of benzodiazepines; coma has been reported with concurrent use

Nursing considerations

CLINICAL ALERT!

Name confusion has occurred between lorazepam and alprazolam; use caution.

Assessment

·        History: Hypersensitivity to benzodiazepines, propylene glycol, polyethylene glycol or benzyl alcohol; psychoses; acute narrow-angle glaucoma; shock; coma; acute alcoholic intoxication with depression of vital signs; pregnancy; lactation; impaired liver or renal function, debilitation

·        Physical: Skin color, lesions; T; orientation, reflexes, affect, ophthalmologic examination; P, BP; R, adventitious sounds; liver evaluation, abdominal examination, bowel sounds, normal output; CBC, LFTs, renal function tests

Interventions

·        Sublingual administration has more rapid absorption than PO, and bioavailability compares to IM use.

·        Do not administer intra-arterially; arteriospasm or gangrene may result.

·        Give IM injections of undiluted drug deep into muscle mass, monitor injection sites.

·        Do not use solutions that are discolored or contain a precipitate. Protect drug from light, and refrigerate oral solution.

·        Intensol is a concentrated solution; it is recommended it be mixed with water, juice, soda, applesauce, or pudding.

·        WARNING: Keep equipment to maintain a patent airway readily available when drug is given IV.

·        Refrigerate injection and oral solution (36° to 46° F).

·        Reduce dose of opioid analgesics by at least half in patients who have received parenteral lorazepam.

·        Keep patients who have received parenteral doses under close observation, preferably in bed, up to 3 hr. Do not permit ambulatory patients to drive following an injection.

·        WARNING: Taper dosage gradually after long-term therapy, especially in patients with epilepsy.

Teaching points

·        Take drug exactly as prescribed; do not stop taking drug (in long-term therapy) without consulting health care provider.

·        You may experience these side effects: Drowsiness, dizziness (may be transient; avoid driving or engaging in dangerous activities); GI upset (take drug with food); nocturnal sleep disturbances for several nights after discontinuing the drug if used as a sedative and hypnotic; depression, dreams, emotional upset, crying.

·        Report severe dizziness, weakness, drowsiness that persists, rash or skin lesions, palpitations, edema of the extremities; visual changes; difficulty voiding.

Adverse effects in Italic are most common; those in Bold are life-threatening.