lorazepam (Ativan)
Classes: Anticonvulsants, Other; Antianxiety Agents; Anxiolytics, Benzodiazepines
Dosing and uses of Ativan, Lorazepam Intensol (lorazepam)
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