Yes

Benzodiazepine

Oral: Management of anxiety disorders or short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms

I.V.: Status epilepticus, preanesthesia

Unlabeled uses: Alcohol detoxification; insomnia; psychogenic catatonia; partial complex seizures; antiemetic adjunct

C-IV

D

Clinical effects on the fetus: Crosses the placenta. Respiratory depression or hypotonia if administered near time of delivery.

Breast-feeding/lactation: Crosses into breast milk and no data on clinical effects on the infant. American Academy of Pediatrics states MAY BE OF CONCERN.

Hypersensitivity to this drug or any component of its formulation (cross-sensitivity with other benzodiazepines may exist); acute narrow-angle glaucoma; sleep apnea (parenteral); intra-arterial injection of parenteral formulation; severe respiratory insufficiency (except during mechanical ventilation); pregnancy

Use with caution in elderly or debilitated patients, patients with hepatic disease (including alcoholics) or renal impairment. Use with caution in patients with respiratory disease or impaired gag reflex. Initial doses in elderly or debilitated patients should not exceed 2 mg. Prolonged lorazepam use may have a possible relationship to GI disease, including esophageal dilation.

Causes CNS depression (dose-related) resulting in sedation, dizziness, confusion, or ataxia which may impair physical and mental capabilities. Patients must be cautioned about performing tasks which require mental alertness (ie, operating machinery or driving). Use with caution in patients receiving other CNS depressants or psychoactive agents. Effects with other sedative drugs or ethanol may be potentiated. Benzodiazepines have been associated with falls and traumatic injury and should be used with extreme caution in patients who are at risk of these events (especially the elderly).

Lorazepam may cause anterograde amnesia. Paradoxical reactions, including hyperactive or aggressive behavior have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients. Does not have analgesic, antidepressant, or antipsychotic properties.

Use caution in patients with depression, particularly if suicidal risk may be present. Use with caution in patients with a history of drug dependence. Benzodiazepines have been associated with dependence and acute withdrawal symptoms on discontinuation or reduction in dose. Acute withdrawal, including seizures, may be precipitated after administration of flumazenil to patients receiving long-term benzodiazepine therapy.

As a hypnotic agent, should be used only after evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7-10 days may indicate psychiatric or medical illness. A worsening of insomnia or the emergence of new abnormalities of thought or behavior may represent unrecognized psychiatric or medical illness and requires immediate and careful evaluation.

>10%:

Central nervous system: Sedation

Respiratory: Respiratory depression

1% to 10%:

Cardiovascular: Hypotension

Central nervous system: Confusion, dizziness, akathisia, unsteadiness, headache, depression, disorientation, amnesia

Dermatologic: Dermatitis, rash

Gastrointestinal: Weight gain or loss, nausea, changes in appetite

Neuromuscular & skeletal: Weakness

Respiratory: Nasal congestion, hyperventilation, apnea

<1%: Menstrual irregularities, increased salivation, blood dyscrasias, reflex slowing, physical and psychological dependence with prolonged use

Symptoms of overdose include confusion, coma, hypoactive reflexes, dyspnea, labored breathing

Treatment for benzodiazepine overdose is supportive. Rarely is mechanical ventilation required. Flumazenil has been shown to selectively block the binding of benzodiazepines to CNS receptors, resulting in a reversal of benzodiazepine-induced CNS depression but not respiratory depression. Treatment requires support of blood pressure and respiration until drug effects subside.

Alcohol and other CNS depressants may increase the CNS effects of lorazepam

Oral contraceptives may increase the clearance of lorazepam

Lorazepam may decrease the antiparkinsonian efficacy of levodopa

Scopolamine in combination with parenteral lorazepam may increase the incidence of sedation, hallucinations, and irrational behavior

Theophylline and other CNS stimulants may antagonize the sedative effects of lorazepam

There are rare reports of significant respiratory depression, stupor, and/or hypotension with concomitant use of loxapine and lorazepam. Use caution if concomitant administration of loxapine and CNS drugs is required.

Intact vials should be refrigerated, protected from light; do not use discolored or precipitate containing solutions

May be stored at room temperature for up to 60 days

Stability of parenteral admixture at room temperature (25°C): 24 hours

Standard diluent: 1 mg/100 mL D₅W

I.V. is incompatible when administered in the same line with foscarnet, ondansetron, sargramostim

Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.

Onset of hypnosis: I.M.: 20-30 minutes

Onset of sedation, anticonvulsant: I.V.: 5 minutes; oral: 30 minutes to 1 hour

Duration: 6-8 hours

Absorption: Oral, I.M.: Prompt following administration

Distribution: Crosses the placenta; appears in breast milk

V_d:

Neonates: 0.76 L/kg

Adults: 1.3 L/kg

Protein binding: 85%, free fraction may be significantly higher in elderly

Metabolism: In the liver to inactive compounds

Half-life:

Neonates: 40.2 hours

Older Children: 10.5 hours

Adults: 12.9 hours

Elderly: 15.9 hours

End-stage renal disease: 32-70 hours

Elimination: Urinary excretion and minimal fecal clearance

Antiemetic:

Children 2-15 years: I.V.: 0.05 mg/kg (up to 2 mg/dose) prior to chemotherapy

Adults: Oral, I.V.: 0.5-2 mg every 4-6 hours as needed

Anxiety and sedation:

Infants and Children: Oral, I.V.: Usual: 0.05 mg/kg/dose (range: 0.02-0.09 mg/kg) every 4-8 hours

Adults: Oral: 1-10 mg/day in 2-3 divided doses; usual dose: 2-6 mg/day in divided doses

Elderly: 0.5-4 mg/day

Insomnia: Adults: Oral: 2-4 mg at bedtime

Preoperative: Adults:

I.M.: 0.05 mg/kg administered 2 hours before surgery; maximum: 4 mg/dose

I.V.: 0.044 mg/kg 15-20 minutes before surgery; usual maximum: 2 mg/dose

Operative amnesia: Adults: I.V.: Up to 0.05 mg/kg; maximum: 4 mg/dose

Status epilepticus: I.V.:

Infants and Children: 0.1 mg/kg slow I.V. over 2-5 minutes, do not exceed 4 mg/single dose; may repeat second dose of 0.05 mg/kg slow I.V. in 10-15 minutes if needed

Adolescents: 0.07 mg/kg slow I.V. over 2-5 minutes; maximum: 4 mg/dose; may repeat in 10-15 minutes

Adults: 4 mg/dose given slowly over 2-5 minutes; may repeat in 10-15 minutes; usual maximum dose: 8 mg

Rapid tranquilization of agitated patient (administer every 30-60 minutes):

Oral: 1-2 mg

I.M.: 0.5-1 mg

Average total dose for tranquilization: 4-8 mg

Alcohol: Additive CNS depression has been reported with benzodiazepines; avoid or limit alcohol

Respiratory and cardiovascular status, blood pressure, heart rate, symptoms of anxiety

Therapeutic: 50-240 ng/mL (SI: 156-746 nmol/L)

May increase the results of liver function tests

No information available to require special precautions

>10% of patients experience dry mouth (normal salivary flow returns with cessation of drug therapy)

Oral: Take exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. Do not use excessive alcohol or other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, lightheadedness, impaired coordination, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, or dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); altered sexual drive or ability (reversible); or photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). Report persistent CNS effects (eg, confusion, depression, increased sedation, excitation, headache, agitation, insomnia or nightmares, dizziness, fatigue, impaired coordination, changes in personality, or changes in cognition); changes in urinary pattern; chest pain, palpitations, or rapid heartbeat; muscle cramping, weakness, tremors, or rigidity; ringing in ears or visual disturbances; excessive perspiration, or excessive GI symptoms (cramping, constipation, vomiting, anorexia); or worsening of condition. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Breast-feeding is not recommended.

Keep injectable form in the refrigerator; inadvertent intra-arterial injection may produce arteriospasm resulting in gangrene which may require amputation; emergency resuscitative equipment should be available when administering by I.V.; prior to I.V. use, lorazepam injection must be diluted with an equal amount of compatible diluent; injection must be made slowly with repeated aspiration to make sure the injection is not intra-arterial and that perivascular extravasation has not occurred; provide safety measures (ie, side rails, night light, and call button); supervise ambulation

Injection: 2 mg/mL (1 mL, 10 mL); 4 mg/mL (1 mL, 10 mL)

Solution, oral concentrated, alcohol and dye free: 2 mg/mL (30 mL)

Tablet: 0.5 mg, 1 mg, 2 mg

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