Lorazepam: Difference between revisions
| [checked revision] | [checked revision] |
MDElliottMD (talk | contribs) parser-claude: Lorazepam MedTemplate refill, Top 300 stub upgrade |
Safety wave: 2020 FDA benzo-class boxed warning (Sept 23 2020) + propylene-glycol IV toxicity monitoring (Wilson 2005) |
||
| Line 17: | Line 17: | ||
| legal = [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the benzodiazepine class '''Boxed Warning''' for risk of fatal respiratory depression, coma, and death when combined with opioids<ref name="ativan-label" /> | | legal = [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the benzodiazepine class '''Boxed Warning''' for risk of fatal respiratory depression, coma, and death when combined with opioids<ref name="ativan-label" /> | ||
| mechanism = <vote slug="lorazepam-mech-claim">Positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site (α-γ subunit interface), enhancing chloride ion conductance and consequent neuronal inhibition. The intermediate half-life sits between short-acting alprazolam and long-acting diazepam/clonazepam, making lorazepam a clinically versatile choice.</vote> Metabolized by '''glucuronidation rather than CYP''', so unlike alprazolam and diazepam, lorazepam has minimal CYP-mediated interactions, and the lack of active metabolites makes it the preferred benzodiazepine in elderly patients and in hepatic impairment. Tolerance, dependence, and significant withdrawal syndrome on abrupt discontinuation; slow taper essential after extended use<ref name="ativan-label" />. | | mechanism = <vote slug="lorazepam-mech-claim">Positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site (α-γ subunit interface), enhancing chloride ion conductance and consequent neuronal inhibition. The intermediate half-life sits between short-acting alprazolam and long-acting diazepam/clonazepam, making lorazepam a clinically versatile choice.</vote> Metabolized by '''glucuronidation rather than CYP''', so unlike alprazolam and diazepam, lorazepam has minimal CYP-mediated interactions, and the lack of active metabolites makes it the preferred benzodiazepine in elderly patients and in hepatic impairment. Tolerance, dependence, and significant withdrawal syndrome on abrupt discontinuation; slow taper essential after extended use<ref name="ativan-label" />. | ||
| monitoring = '''Boxed warning:''' in September 2020 the FDA required an updated boxed warning across the benzodiazepine class for the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions.<ref>U.S. Food and Drug Administration. Drug Safety Communication: FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. September 23, 2020.</ref> Physical dependence can develop with continued use even at prescribed doses, and abrupt discontinuation or rapid dose reduction can precipitate acute, sometimes life-threatening withdrawal (including seizures), so prolonged use requires a gradual, individualized taper. This is in addition to the earlier boxed warning for fatal respiratory depression, coma, and death when benzodiazepines are combined with opioids or other CNS depressants.<ref>U.S. Food and Drug Administration. Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines. August 31, 2016.</ref> The intravenous formulation of lorazepam is solubilized in propylene glycol; high-dose or prolonged continuous infusion (for example in refractory status epilepticus or prolonged intensive-care sedation) can cause propylene glycol to accumulate, producing a high-anion-gap metabolic (lactic) acidosis, hyperosmolarity, and acute kidney injury. The osmolar gap and serum lactate should be monitored when large cumulative intravenous doses are given.<ref>Wilson KC, Reardon C, Theodore AC, Farber HW. Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving intravenous benzodiazepines. Chest. 2005;128(3):1674-1681.</ref> | |||
}} | }} | ||
Latest revision as of 18:33, 29 June 2026
Lorazepam
Ativan (oral, injectable), Loreev XR
Experience
No personal reports yet
No clinical reports yet
Log in to add your own experience.
Problems
No problems yet. Be the first to suggest one.
+ Add a problemTitration strategies
No titration strategies yet. Be the first to suggest one.
Effects
No effects listed yet. Be the first to suggest one.
Monitoring
Relevant anecdote
No anecdotes yet. Share a relevant one.
Relevant Literature
No literature entries yet.
Log in to submit relevant literature.
Pharmacy
Starting dose
Anxiety: 0.5-1 mg PO BID-TID. Insomnia: 1-2 mg PO at bedtime. Status epilepticus: 4 mg IV (adult), repeat after 5-10 minutes if needed. Acute agitation: 1-2 mg IM
Preparations
Tablets 0.5, 1, 2 mg; oral concentrate 2 mg/mL; injection 2 mg/mL and 4 mg/mL; Loreev XR capsules 1, 2, 3 mg
US FDA Max
10 mg/day (anxiety, oral)
Common uses
Classification(s)
Pharmacology
Routes
Oral, intramuscular, intravenous
Onset
30-60 minutes (oral); 5 minutes (IV); 15-30 minutes (IM)
Duration
6-8 hours
Half-life
12-15 hours (intermediate); no active metabolites (key clinical feature)[1]
Bioavailability
~90% (oral)[1]
Pregnancy
Some signal for cleft lip/palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.[citation needed]
Legal status
Schedule IV controlled substance in US. Carries the benzodiazepine class Boxed Warning for risk of fatal respiratory depression, coma, and death when combined with opioids[1]
Purported mechanism
Positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site (α-γ subunit interface), enhancing chloride ion conductance and consequent neuronal inhibition. The intermediate half-life sits between short-acting alprazolam and long-acting diazepam/clonazepam, making lorazepam a clinically versatile choice.0 Metabolized by glucuronidation rather than CYP, so unlike alprazolam and diazepam, lorazepam has minimal CYP-mediated interactions, and the lack of active metabolites makes it the preferred benzodiazepine in elderly patients and in hepatic impairment. Tolerance, dependence, and significant withdrawal syndrome on abrupt discontinuation; slow taper essential after extended use[1].
Pharmacopedia is intended for reference. Nothing here is advice. In an emergency call 911; US Poison Control 1-800-222-1222. See the full disclaimer.
References
- ↑ 1.0 1.1 1.2 1.3 FDA Prescribing Information, Ativan (lorazepam), Bausch/Pfizer, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017794s044lbl.pdf
- ↑ U.S. Food and Drug Administration. Drug Safety Communication: FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. September 23, 2020.
- ↑ U.S. Food and Drug Administration. Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines. August 31, 2016.
- ↑ Wilson KC, Reardon C, Theodore AC, Farber HW. Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving intravenous benzodiazepines. Chest. 2005;128(3):1674-1681.