Lorazepam

Benzodiazepine Anxiolytic, Sedative, Anticonvulsant, Muscle Relaxant Rx Controlled Schedule IV (US)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 0.05-0.2 mg/kg q8-12h Duration: As needed for anxiety; for seizures, may be used as needed
Notes: For anxiety, use the lower end; for status epilepticus, IV is preferred.
Dog IV 0.1-0.2 mg/kg Once, may repeat once if needed Duration: For status epilepticus
Notes: Administer slowly; monitor for respiratory depression.
Cat PO 0.05-0.2 mg/kg q8-12h Duration: As needed for anxiety; for seizures, may be used as needed
Notes: For anxiety, use the lower end; for status epilepticus, IV is preferred.
Cat IV 0.1-0.2 mg/kg Once, may repeat once if needed Duration: For status epilepticus
Notes: Administer slowly; monitor for respiratory depression.
Horse IV 0.02-0.05 mg/kg Once Duration: For sedation
Notes: Often used in combination with other sedatives.
Rabbit PO 0.5-1 mg/kg q8-12h Duration: As needed
Notes: Off-label use; limited data.

Clinical Indications & Species Uses

General Indications
  • Anxiolytic
  • Sedative
  • Anticonvulsant
  • Muscle relaxant
  • Preanesthetic medication
Dog (Canine)
  • Anxiety and phobias (e.g., noise aversion, separation anxiety)
  • Status epilepticus and cluster seizures (as an adjunct to other anticonvulsants)
  • Preanesthetic medication
  • Appetite stimulant (in some cases, though less common)
Cat (Feline)
  • Anxiety and fear-related behaviors
  • Status epilepticus (as an adjunct)
  • Preanesthetic medication
  • Appetite stimulant (in some cases)
Horse (Equine)
  • Sedation and muscle relaxation (as an adjunct to other agents)
  • Anxiety during transport or handling
  • Anticonvulsant (rarely used)
Rabbit & Small Mammals
  • Anxiolytic and sedative (off-label use)
  • Anticonvulsant (off-label use)

Pharmacology & Mechanism of Action

Drug Class: Benzodiazepine | Pharmacological Group: Anxiolytic, Sedative, Anticonvulsant, Muscle Relaxant

Mechanism of Action: Lorazepam is a benzodiazepine that binds to the benzodiazepine site on the gamma-aminobutyric acid type A (GABA-A) receptor, a ligand-gated chloride channel. This binding enhances the affinity of the receptor for GABA, increasing the frequency of chloride channel opening, leading to hyperpolarization of the neuron and inhibition of neuronal excitability. This results in anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant effects.

Pharmacodynamics: Lorazepam produces dose-dependent central nervous system depression. It has a relatively rapid onset of action compared to other benzodiazepines due to its high lipophilicity and potency. It is more potent than diazepam and has a shorter duration of action. It also has amnesic properties and is used as a preanesthetic agent. In veterinary medicine, it is used for its anxiolytic and anticonvulsant effects, though its use is less common than diazepam or midazolam.

⚡ Pharmacokinetics Summary

Absorption: Lorazepam is well absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours in most species. Bioavailability is high (around 90% in humans). In dogs, oral absorption is rapid and complete. Intramuscular absorption is also rapid and complete.
Distribution: Lorazepam is widely distributed throughout the body. It is highly lipophilic and crosses the blood-brain barrier readily. It crosses the placenta and is distributed into milk. The volume of distribution is moderate. Protein binding is approximately 85-90% in humans, but may vary in animals.
Metabolism: Lorazepam is primarily metabolized in the liver via glucuronide conjugation to an inactive metabolite (lorazepam glucuronide). Unlike diazepam, it does not undergo oxidative metabolism to active metabolites, which may be advantageous in patients with hepatic disease. The metabolism is not significantly affected by age or hepatic dysfunction.
Excretion: The metabolites are excreted primarily in the urine (as glucuronides) and to a lesser extent in feces. The elimination half-life is relatively short compared to diazepam. In dogs, the half-life is approximately 1-2 hours; in cats, it is approximately 2-4 hours; in horses, it is approximately 1-2 hours.
Half-Life: Dog: 1-2 hours; Cat: 2-4 hours; Horse: 1-2 hours; Human: 10-20 hours
Bioavailability: Oral: ~90% in dogs; IM: ~100%
Protein Binding: Approximately 85-90% (in humans; may vary in animals)

Available Formulations & Strengths

Oral Tablet 0.5 mg, 1 mg, 2 mg (PO)
Oral Solution 2 mg/mL (PO)
Injectable Solution 2 mg/mL, 4 mg/mL (IV, IM)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to lorazepam or other benzodiazepines
  • Severe respiratory insufficiency
  • Severe hepatic insufficiency (use with caution)
  • Myasthenia gravis
  • Acute narrow-angle glaucoma
  • Concurrent use with other CNS depressants (may cause severe sedation)
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic or renal impairment
  • May cause paradoxical excitation (especially in cats and some dogs)
  • May cause physical and psychological dependence with prolonged use
  • Avoid abrupt discontinuation after prolonged therapy to prevent withdrawal symptoms
  • Use with caution in pregnant or lactating animals (teratogenic effects in some species)
  • May cause respiratory depression, especially when given IV rapidly or with other CNS depressants
  • In horses, may cause ataxia and transient excitement in some individuals

Adverse Effects & Reactions

Common:

  • Sedation
  • Ataxia
  • Increased appetite (in some animals)
  • Paradoxical excitation (especially in cats)
  • Muscle weakness

Serious / Severe:

  • Respiratory depression
  • Hypotension
  • Hepatic toxicity (rare)
  • Blood dyscrasias (rare)
  • Paradoxical aggression

Rare:

  • Hypersensitivity reactions
  • Jaundice
  • Bone marrow suppression

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other CNS depressants (e.g., opioids, barbiturates, phenothiazines) Additive CNS depression and respiratory depression High
Cimetidine May decrease metabolism of lorazepam, increasing its effects Moderate
Valproic acid May increase lorazepam levels Moderate
Probenecid May decrease clearance of lorazepam Moderate
Theophylline May antagonize the sedative effects of benzodiazepines Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe sedation
  • Ataxia
  • Respiratory depression
  • Coma
  • Hypotension
  • Hypothermia
  • Paradoxical excitation (in some animals)

Emergency Treatment Protocol: Treatment is primarily supportive. Induce vomiting if recent oral ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide respiratory support (oxygen, ventilation) if needed. Flumazenil (benzodiazepine antagonist) can be administered at 0.01-0.02 mg/kg IV, but use with caution as it may precipitate seizures in animals on chronic benzodiazepine therapy. Monitor vital signs and provide fluid therapy for hypotension.

Food Animal Withdrawal Times

Not approved for use in food animals in the US. If used off-label, withdrawal times must be established by a veterinarian, but due to lack of data, a conservative withdrawal period (e.g., 7 days for meat and 72 hours for milk) is often recommended. However, extra-label use in food animals is subject to AMDUCA regulations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25°C, excursions permitted to 15-30°C). Protect from light.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from moisture. Keep in tightly closed container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use only.

Extra-Label (Off-Label) Use: Lorazepam is not FDA-approved for veterinary use in most species. Its use in animals is extra-label and must comply with AMDUCA regulations. For food animals, a valid veterinarian-client-patient relationship is required, and withdrawal times must be established.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Lorazepam is a potent benzodiazepine with a relatively short half-life in animals compared to diazepam. It is useful for acute anxiety and as an adjunct for seizure control. However, its use in veterinary medicine is limited by cost and availability of more commonly used benzodiazepines like diazepam and midazolam. It may be preferred in patients with hepatic disease because it does not require oxidative metabolism. Caution is advised in cats due to paradoxical excitation. For status epilepticus, IV administration is preferred, but diazepam or midazolam are often first-line. Lorazepam can be used as a preanesthetic to reduce anxiety and provide muscle relaxation. Always monitor for respiratory depression, especially when combined with other CNS depressants.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)