lorazepam (Ativan)

Dosing and uses of Ativan, Lorazepam Intensol (lorazepam)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

tablet: Schedule IV

• 0.5mg
• 1mg
• 2mg

oral concentrate: Schedule IV

• 2mg/mL

injectable solution: Schedule IV

• 2mg/mL
• 4mg/mL

 

Anxiety Disorders

Initial: 2-3 mg PO q8-12hr PRN; not to exceed 10 mg/day

Maintenance: 2-6 mg/day PO divided q8-12hr

 

Short-Term Treatment of Insomnia

2-4 mg PO qHs

 

Preoperative Sedation, Anxiety Relief, & Anterograde Amnesia

0.05 mg/kg IM for 1 dose; 2 hours before surgery; not to exceed 4 mg (2 mg/dose in elderly), Or

0.044 mg/kg IV for 1 dose; 15-20 minutes before surgery; not to exceed 4 mg (2 mg/dose in elderly)

 

Status Epilepticus

Usual 4 mg/dose slow IV at 2 mg/min

If seizure persists after 5-10 min, administer 4 mg IV again

 

Anxiolytic/Sedation in ICU (Off-label)

Intubated and mechanically ventilated patients

• 0.02-0.04 mg/kg loading dose IV
• 0.02-0.06 mg/kg intermittent IV q2-6hr PRN, OR
• 0.01-0.1 mg/kg/hr continuous IV; not to exceed 10 mg/hr

 

Chemotherapy-Induced Nausea/Vomiting (Off-label)

0.5-2 mg PO/IV q6hr; PRN thereafter

 

Chronic Insomnia (Off-label)

2-4 mg PO qHs

 

Dosing Considerations

IV: Monitor respirations q5-15min and before each repeated IV dose

 

Dosing Modifications

Renal impairment

• PO: Dose adjustment not necessary
• IV/IM: Use with caution in mild-to-moderate impairment; not recommended in severe impairment or renal failure
• IV/IM (prolonged periods or high doses): Monitor; risk of propylene glycol toxicity

Hepatic impairment

• PO: No dose adjustment recommended in mild-to-moderate impairment; use with caution (may require lower dose) in severe impairment
• IV/IM: Use with caution in mild-to-moderate impairment; not recomended in severe impairment of hepatic failure

 

Pediatric dosage forms and strengths

tablet: Schedule IV

• 0.5mg
• 1mg
• 2mg

oral concentrate: Schedule IV

• 2mg/mL

injectable solution: Schedule IV

• 2mg/mL
• 4mg/mL

 

Status Epilepticus (Off-label)

Infants and children: 0.05-0.1 mg/kg IV over 2-5 minutes; not to exceed 4 mg/dose; may repeat q10-15min PRn

Alternatively, 0.1 mg/kg at slow IV rate not to exceed rate of 2 mg/min; not to exceed dose of 4 mg

Adolescents: 4 mg slow IV; if seizure persists after 10-15 minutes, administer 4 mg IV again

 

Anxiolytic/Sedation/Agitation (Off-label)

Children: 0.05 mg/kg/dose PO q4-8hr; not to exceed 2 mg/dose

 

Chemotherapy-Induced Nausea/Vomiting (Off-label)

Children >2 years: 0.025-0.05 mg/kg/dose IV q6hr PRN; not to exceed 2 mg/dose

 

Dosing Considerations

IV: Monitor respirations q5-15min and before each repeated IV dose

 

Geriatric dosage forms and strengths

Preferred agent in elderly because short-acting and has inactive metabolite

 

Anxiety disorders

Lower initial dose recommended; 1-2 mg PO divided q8-12hr

 

Insomnia

Lower initial dose recommended; 0.5-1 mg PO qHS, increase PRn

To avoid oversedation, initial daily dose should not exceed 2 mg

 

Dosing considerations

When higher dose indicated, increase evening dose before daytime doses

 

Ativan, Lorazepam Intensol (lorazepam) adverse (side) effects

Frequency not defined

Sedation

Dizziness

Unsteadiness

Weakness

Fatigue

Drowsiness

Amnesia

Confusion

Disorientation

Depression

Suicidal ideation/attempt

Vertigo

Ataxia

Sleep apnea

Asthenia

Extrapyramidal symptoms

Respiratory depression

Tremor

Convulsions/seizures

Visual disturbances

Dysarthria

Hypotension

Blood dyscrasias

Change in libido

Impotence

Jaundice

Increased bilirubin

Increased liver transaminases

Increase in ALp

Hypersensitivity reactions

Nausea

Constipation

Change in appetite

Paradoxical reactions (anxiety, excitation, agitation, hostility, aggression, rage)

 

Warnings

Contraindications

Documented hypersensitivity

Acute narrow angle glaucoma

Intra-arterial administration

Severe respiratory depression

Sleep apnea

 

Cautions

Not recommended for use in patients with primary depressive disorder or psychosis

Injection contains benzyl alcohol associated with potentially fatal "gasping syndrome" in neonates

Prolonged use may lead to physical and psychological dependence especially in patients with history of alcohol or drug abuse; risk of dependence is decreased with short-term treatment (eg, 2-4 weeks); evaluate need for continued treatment prior to extending therapy duration

Use caution in patients with history of suicide attempt or drug abuse

Do not withdraw abruptly after prolonged use; terminate dosage gradually

Use caution in patients with impaired gag reflex

May cause CNS depression, impairing physical and mental abilities; caution patients to not operate dangerous machinery or motor vehicles

Anterograde amnesia reported with use

Use caution in patients with respiratory disease, including COPD or sleep apnea

Hyperactive or aggressive behavior and other paradoxical reactions reported with use

Caution patients that tolerance for alcohol and other CNS depressants will be diminished

 

Pregnancy and lactation

Pregnancy category: d

Lactation: Excreted in human breast milk; not recommended

Risk of serious adverse effects, including CNS and respiratory depression, exist

Minor tranquilizers should be avoided in first trimester of pregnancy, due to increased risk of congenital malformations

Maternal use shortly before delivery is associated with floppy infant syndrome (good and consistent evidence)

Prenatal benzodiazepine exposure slightly increased oral cleft risk (limited or inconsistent evidence)

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Ativan, Lorazepam Intensol (lorazepam)

Mechanism of action

Sedative hypnotic with short onset of effects and relatively long half-life; by increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the CNS, including limbic and reticular formation

 

Absorption

Bioavailability: 90%

Onset: 1-3 min (IV in sedation); 15-30 min (IM in hypnosis)

Duration: Up to 8 hr

Peak plasma time: 2 hr (PO); <3 hr (IM)

Peak plasma concentration: 20 ng/mL

 

Distribution

Protein bound: 85-93%

Vd: 1.9 L/kg (adolescents); 1.3 L/kg (adults); 0.78 L/kg (neonates)

 

Metabolism

Metabolites: Inactive

Undergoes glucuronic acid conjugation

 

Elimination

Half-life: 18 hr (children 2-12 years); 42 hr (neonates); 28 hr (adolescents); 18 hr (end stage renal disease); 14 hr (adults)

Excretion: Urine (88% mainly as inactive metabolites); feces (7%)

 

Administration

IV Incompatibilities

Additive: Buprenorphine, dexamethasone sodium phosphate with diphenhydramine and metoclopramide

Syringe: SufentaniL

Y-site: Aldesleukin, aztreonam, floxacillin, foscarnet, idarubicin, imipenem/cilastatin, omeprazole, ondansetron, sargramostim, sufentaniL

 

IV Preparation

Parenteral admixture stable for 24 hr at room temp (25°C)

Usually given IVp

Standard IVP dilution: dilute immediately before use with equal amount of NS or SWI

Usual dilution for continuous infusion: 1 mg in 100 mL D5W

Discard if discoloration or precipitate

 

IV/IM Administration

IM administration

• Administer deep into muscle mass

IV administration

• Prior to use, dilute injection solution with an equal amount of compatible diluent (D5W, NS, SWFI)
• Administer IV injection slowly, directly into a vein or into tubing of a free-flowing, compatible IV infusion (eg, NS, D5W), at no more than 2 mg/min
• Validate patent venous catheter with repeated aspiration during infusion to visualize venous blood return
• Inadvertent intra-arterial injection may produce arteriospasm resulting in gangrene, potentially requiring amputation
• Rapid IV infusion may result in apnea, bradycardia, hypotension, cardiac arrest
• Continuous infusion solutions should have an in-line filter and should be checked frequently for possible precipitation
• Emergency resuscitative equipment should be available when administering IV

 

Storage

IV/IM injection: Refrigerate intact vials at 2-8°C (36-46°F) and protect contents from light

Tablets: Keep tightly closed; store at 25°C (77°F)

Oral concentrate: Store at cold temperature; refrigerate at 2-8°C (36-46°F); discard open bottle after 90 days