Diazepam

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

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IV 0.5-2 mg/kg (up to 5 mg/kg for status epilepticus) Administer slowly; may repeat in 5-10 minutes if needed Duration: For acute seizure control; not for long-term maintenance
Notes: For status epilepticus, administer IV to effect. Can be followed by phenobarbital or other anticonvulsants.
Dog PO 0.5-2 mg/kg q6-8h as needed for anxiety or behavioral disorders Duration: Short-term use; tolerance may develop
Notes: Use with caution in dogs with hepatic disease.
Cat IV 0.2-0.5 mg/kg (up to 1 mg/kg for seizures) Administer slowly; may repeat in 5-10 minutes Duration: For acute seizure control
Notes: For appetite stimulation, oral dose is 1-2 mg per cat.
Cat PO 1-2 mg per cat (appetite stimulation) q12-24h Duration: Short-term use
Notes: May cause paradoxical excitement in some cats.
Horse IV 0.02-0.1 mg/kg Administer slowly; effects last 20-30 minutes Duration: For sedation or muscle relaxation
Notes: Often combined with other sedatives (e.g., alpha-2 agonists) for better sedation.
Cattle IV 0.1-0.2 mg/kg Administer slowly Duration: For sedation or muscle relaxation
Notes: Not commonly used; may cause excitement in some animals.
Small Ruminants IV 0.1-0.2 mg/kg Administer slowly Duration: For sedation or muscle relaxation
Notes: Use with caution; may cause respiratory depression.
Rabbit IV/IM/PO 0.5-2 mg/kg q6-8h as needed Duration: Short-term use
Notes: IM absorption may be erratic; IV preferred for acute effects.
Bird/Poultry IM/IV 0.5-1 mg/kg As needed Duration: Short-term use
Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications
  • Status epilepticus
  • Anxiolysis
  • Sedation
  • Muscle relaxation
  • Appetite stimulation (cats)
Dog (Canine)
  • Status epilepticus and cluster seizures (IV)
  • Anxiolytic and sedative premedication
  • Muscle relaxation
  • Appetite stimulation (less common)
  • Treatment of behavioral disorders (e.g., noise phobias, situational anxiety)
Cat (Feline)
  • Status epilepticus (IV)
  • Appetite stimulation (oral)
  • Anxiolytic and sedative premedication
  • Muscle relaxation
  • Behavioral disorders (e.g., inappropriate urination, anxiety)
Horse (Equine)
  • Sedation and muscle relaxation (often in combination with other agents)
  • Anticonvulsant for seizures
  • Tetanus management (as adjunct)
  • Chemical restraint for procedures
Cattle (Bovine)
  • Sedation and muscle relaxation
  • Anticonvulsant for seizures
  • Tetanus management (adjunct)
  • Chemical restraint
Small Ruminants (Sheep / Goat)
  • Sedation and muscle relaxation
  • Anticonvulsant
  • Anxiolytic
Rabbit & Small Mammals
  • Sedation and muscle relaxation
  • Anticonvulsant (rarely used)
  • Anxiolytic
Avian & Poultry
  • Sedation and muscle relaxation (occasionally used in pet birds)
  • Anticonvulsant (rarely)
Exotic & Other Species
  • Sedation and muscle relaxation in small mammals (e.g., ferrets, rodents)
  • Anticonvulsant in some exotic species

Pharmacology & Mechanism of Action

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

Mechanism of Action: Diazepam enhances the inhibitory effects of gamma-aminobutyric acid (GABA) at GABA-A receptors in the central nervous system. It binds to the benzodiazepine site on the receptor complex, increasing the frequency of chloride channel opening, leading to hyperpolarization and reduced neuronal excitability. This results in anxiolytic, sedative, anticonvulsant, and muscle relaxant effects.

Pharmacodynamics: Diazepam produces dose-dependent CNS depression, including sedation, anxiolysis, muscle relaxation, and anticonvulsant activity. It also has amnesic properties. In animals, it can stimulate appetite in some species (e.g., cats) and may cause paradoxical excitation in others (e.g., horses, some dogs).

⚡ Pharmacokinetics Summary

Absorption: Well absorbed after oral administration, with peak plasma concentrations occurring within 30-90 minutes in most species. Absorption after IM injection is variable and may be slower and less reliable; IV administration provides immediate effect.
Distribution: Highly lipid-soluble, rapidly distributes into tissues including the brain. Crosses the blood-brain barrier and placenta. Volume of distribution is large. Protein binding is high (85-99%) in most species.
Metabolism: Extensively metabolized in the liver via CYP450 enzymes (demethylation and hydroxylation) to active metabolites, including N-desmethyldiazepam (nordazepam), temazepam, and oxazepam. These metabolites contribute to the duration of action.
Excretion: Primarily excreted in urine as glucuronide conjugates, with some fecal excretion. Enterohepatic recirculation may occur. Elimination half-life varies widely by species.
Half-Life: Dog: 2.5-3.2 hours (parent drug); active metabolites may prolong effects. Cat: 5.5-8 hours. Horse: 7-22 hours. Cattle: 2-4 hours. Rabbit: 1-3 hours.
Bioavailability: Oral: 75-100% in dogs and cats; IM: variable and often lower; Rectal: approximately 50-80% in dogs.
Protein Binding: 85-99% depending on species

Available Formulations & Strengths

Injectable Solution 5 mg/mL (IV, IM)
Oral Tablet 2 mg, 5 mg, 10 mg (PO)
Oral Solution 1 mg/mL, 5 mg/mL (PO)
Rectal Gel 5 mg/mL (Rectal)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to diazepam or other benzodiazepines
  • Severe hepatic insufficiency
  • Severe respiratory insufficiency or respiratory depression
  • Myasthenia gravis
  • Acute narrow-angle glaucoma
  • Concurrent use with other CNS depressants (relative contraindication, use with caution)
  • Pregnancy (especially first trimester) unless benefits outweigh risks
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic or renal disease
  • May cause paradoxical excitation, especially in cats, horses, and some dogs
  • Prolonged use may lead to physical dependence and withdrawal symptoms upon abrupt discontinuation
  • May cause respiratory depression, especially when combined with other CNS depressants
  • Use with caution in debilitated or geriatric animals
  • In food animals, observe withdrawal times
  • Injectable solution contains propylene glycol and benzyl alcohol; use with caution in cats (may cause Heinz body anemia with high doses)
  • Avoid rapid IV administration to prevent hypotension and respiratory arrest
  • May cause muscle weakness and ataxia

Adverse Effects & Reactions

Common:

  • Sedation
  • Ataxia
  • Muscle weakness
  • Paradoxical excitation (especially cats, horses)
  • Increased appetite (cats)
  • Hypotension (with rapid IV)

Serious / Severe:

  • Respiratory depression
  • Cardiovascular collapse (with rapid IV)
  • Hepatic toxicity (rare, with chronic use)
  • Blood dyscrasias (rare)
  • Paradoxical aggression or agitation

Rare:

  • Anaphylaxis
  • Bone marrow suppression
  • Teratogenic effects (with high doses in pregnancy)
  • Acute hepatic necrosis (reported in cats with oral diazepam)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other CNS depressants (barbiturates, opioids, phenothiazines, alpha-2 agonists) Additive CNS depression and respiratory depression High
Cimetidine Inhibits diazepam metabolism, increasing plasma levels and toxicity Moderate
Fluoxetine, ketoconazole, omeprazole May inhibit CYP450 enzymes, increasing diazepam levels Moderate
Rifampin, phenobarbital Induce hepatic enzymes, decreasing diazepam efficacy Moderate
Theophylline May antagonize sedative effects of diazepam Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe CNS depression
  • Coma
  • Respiratory depression
  • Hypotension
  • Hypothermia
  • Muscle flaccidity
  • Paradoxical excitation (in some species)

Emergency Treatment Protocol: Treatment is primarily supportive. Induce emesis if recent oral ingestion and animal is conscious (do not induce in seizuring or comatose animals). Administer activated charcoal to reduce absorption. Provide respiratory support (oxygen, mechanical ventilation if needed). Monitor cardiovascular function and treat hypotension with IV fluids and vasopressors if necessary. Flumazenil (benzodiazepine antagonist) can be administered at 0.01-0.02 mg/kg IV (dogs, cats) to reverse effects, but use with caution as it may precipitate seizures in animals with underlying seizure disorders. Maintain body temperature and provide nursing care.

Food Animal Withdrawal Times

🥩 Meat: 3 days🥛 Milk: 3 days

Withdrawal times are not officially established for diazepam in food animals in many countries. The values provided are conservative estimates based on pharmacokinetic data. Always consult local regulations and veterinary supervision. In the US, diazepam is not approved for food animals; extra-label use requires extended withdrawal periods (e.g., 7 days meat, 7 days milk) as per FARAD recommendations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F).

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

Handling & Special Conditions: Protect from light. Store in tight, light-resistant containers. Do not freeze injectable solution. Keep out of reach of children and animals.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for human use; in veterinary medicine, diazepam is not FDA-approved for animals but is commonly used extra-label. Some formulations may be approved for specific species in certain countries (e.g., injectable for horses in some regions).

Extra-Label (Off-Label) Use: In the US, diazepam is a prescription drug and a controlled substance (C-IV). Extra-label use in food animals is permitted under AMDUCA only with a valid veterinarian-client-patient relationship, and withdrawal times must be extended. It is not approved for use in food animals in the US. In other countries, regulations may vary; always follow local laws.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Diazepam is a versatile drug in veterinary practice, primarily used for emergency seizure control (status epilepticus) and as a sedative/anxiolytic. It is important to remember that diazepam is a controlled substance and must be handled accordingly. For status epilepticus, IV administration is preferred; if IV access is not available, rectal administration can be used (dose: 0.5-2 mg/kg rectally in dogs). Diazepam is not recommended for long-term seizure management due to tolerance and dependence; other anticonvulsants (e.g., phenobarbital, levetiracetam) are preferred. In cats, oral diazepam has been associated with rare but fatal hepatic necrosis; therefore, it should be used with caution and liver function should be monitored if used chronically. For appetite stimulation in cats, low doses (1-2 mg) can be effective, but alternative drugs (e.g., mirtazapine) may be safer. In horses, diazepam is often used in combination with other sedatives for standing procedures; it provides muscle relaxation and mild sedation. Always monitor respiratory and cardiovascular status, especially when used with other CNS depressants. In food animals, extra-label use requires careful consideration of withdrawal times and regulatory compliance.

References & Literature

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