LORAZEPAM

brands

Class

• Neuroscience-based Nomenclature: GABA positive allosteric modulator (GABA-PAM)
• Benzodiazepine (anxiolytic, anticonvulsant)

LORAZEPAM commonly prescribed for

(Bold for FDA approved)

How LORAZEPAM works

• Binds to benzodiazepine receptors at the GABA-A ligand-gated chloride channel complex

• Enhances the inhibitory effects of GABA

• Boosts chloride conductance through GABA-regulated channels

• Inhibits neuronal activity presumably in amygdala-centered fear circuits to provide therapeutic benefits in anxiety disorders

• Inhibitory actions in the cerebral cortex may provide therapeutic benefits in seizure disorders

How long until LORAZEPAM works

Some immediate relief with first dosing is common; can take several weeks for maximal therapeutic benefit with daily dosing

Notable Side Effects

• Sedation

• Fatigue, depression

• Dizziness, ataxia, slurred speech, weakness

• Forgetfulness, confusion

• Hyperexcitability, nervousness

• Hypersalivation, dry mouth

• Pain at injection site

• Rare hallucinations, mania

• Rare hypotension

Life Threatening Side Effects

• Respiratory depression, especially when taken with CNS depressants in overdose

• Rare hepatic dysfunction, renal dysfunction, blood dyscrasias

weight gain

unusual

sedation

common

What to do about LORAZEPAM side effects

• Wait

• Wait

• Wait

• Lower the dose

• Take largest dose at bedtime to avoid sedative effects during the day

• Switch to another agent

• Administer flumazenil if side effects are severe or life-threatening

usual dosage range

• Oral: 2–6 mg/day in divided doses, largest dose at bedtime

• Injection: 4 mg administered slowly

• Catatonia: 1–2 mg per dose

Dosage Forms

• Tablet 0.5 mg, 1 mg, 2 mg

• Extended-release capsule 1 mg, 1.5 mg, 2 mg, 3 mg

• Liquid 2 mg/mL

• Injection 2 mg/mL, 4 mg/mL

long term use

• Evidence of efficacy up to 16 weeks

• Risk of dependence, particularly for treatment periods longer than 12 weeks and especially in patients with past or current polysubstance abuse

habit forming

• Lorazepam is a Schedule IV drug

• Patients may develop dependence and/or tolerance with long-term use

Renal Impairment

• 1–2 mg/day in 2–3 doses

Hepatic Impairment

• 1–2 mg/day in 2–3 doses

• Because of its short half-life and inactive metabolites, lorazepam may be a preferred benzodiazepine in some patients with liver disease

Cardiac Impairment

• Benzodiazepines have been used to treat anxiety associated with acute myocardial infarction

• Rare reports of QTc prolongation in patients with underlying arrhythmia

• Lorazepam may be used as an adjunct to control drug-induced cardiovascular emergencies

Elderly

• 1–2 mg/day in 2–3 doses

• May be more sensitive to sedative or respiratory effects

Children and Adolescents

• Oral: safety and efficacy not established in children under age 12

• Injection: safety and efficacy not established in children under age 18

• Long-term effects of lorazepam in children/ adolescents are unknown

• Should generally receive lower doses and be more closely monitored

Pregnancy

• Possible increased risk of birth defects when benzodiazepines taken during pregnancy

• Because of the potential risks, lorazepam is not generally recommended as a treatment for anxiety during pregnancy, especially during the first trimester

• Drug should be tapered if discontinued

• Infants whose mothers received a benzodiazepine late in pregnancy may experience withdrawal effects

• Neonatal flaccidity has been reported in infants whose mothers took a benzodiazepine during pregnancy

• Seizures, even mild seizures, may cause harm to the embryo/fetus

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or formula feed

• Effects on infants have been observed and include feeding difficulties, sedation, and weight loss