Midazolam Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	IV	0.1-0.3 mg/kg	Once for induction or premedication; may repeat once if needed	Duration: Single dose or as needed for procedure Notes: Often combined with opioids (e.g., butorphanol) for premedication. For status epilepticus, administer 0.2 mg/kg IV, may repeat.
Dog	IM	0.1-0.3 mg/kg	Once for premedication	Duration: Single dose Notes: Onset of sedation within 10-15 minutes.
Cat	IV	0.1-0.3 mg/kg	Once for induction or premedication; may repeat once if needed	Duration: Single dose or as needed for procedure Notes: Often combined with ketamine (e.g., 5 mg/kg ketamine + 0.2 mg/kg midazolam IV) for induction.
Cat	IM	0.1-0.3 mg/kg	Once for premedication	Duration: Single dose Notes: May cause excitement in cats if used alone; combine with an opioid or ketamine.
Horse	IV	0.02-0.1 mg/kg	Once for sedation or induction	Duration: Single dose Notes: For induction, often combined with ketamine (2.2 mg/kg) after premedication with alpha-2 agonist.
Cattle	IV	0.02-0.1 mg/kg	Once for sedation or induction	Duration: Single dose Notes: Use with caution in ruminants due to risk of bloat; combine with other agents for anesthesia.
Small Ruminants (sheep, goats)	IV	0.1-0.3 mg/kg	Once for sedation or induction	Duration: Single dose Notes: May be combined with ketamine for induction.
Rabbit	IV	0.1-0.5 mg/kg	Once for sedation or induction	Duration: Single dose Notes: Often combined with ketamine for anesthesia.
Birds (poultry, pet birds)	IM	0.1-0.5 mg/kg	Once for sedation	Duration: Single dose Notes: May be combined with ketamine for anesthesia.
Exotic mammals (ferrets, etc.)	IM	0.1-0.3 mg/kg	Once for sedation	Duration: Single dose Notes: Combine with ketamine for anesthesia.

Clinical Indications & Species Uses

General Indications

Sedation
Anxiolysis
Muscle relaxation
Anticonvulsant
Anesthesia induction (adjunct)

Dog (Canine)

Preanesthetic sedation
Induction of anesthesia (in combination with ketamine or other agents)
Procedural sedation
Anticonvulsant for status epilepticus
Anxiolysis

Cat (Feline)

Preanesthetic sedation
Induction of anesthesia (in combination with ketamine or other agents)
Procedural sedation
Anticonvulsant for status epilepticus
Anxiolysis

Horse (Equine)

Preanesthetic sedation
Induction of anesthesia (in combination with ketamine or other agents)
Procedural sedation
Anticonvulsant

Cattle (Bovine)

Preanesthetic sedation
Induction of anesthesia (in combination with ketamine or other agents)
Procedural sedation

Small Ruminants (Sheep / Goat)

Preanesthetic sedation
Induction of anesthesia (in combination with ketamine or other agents)
Procedural sedation

Rabbit & Small Mammals

Preanesthetic sedation
Induction of anesthesia (in combination with ketamine or other agents)
Procedural sedation

Avian & Poultry

Preanesthetic sedation
Induction of anesthesia (in combination with ketamine or other agents)
Procedural sedation

Exotic & Other Species

Preanesthetic sedation
Induction of anesthesia (in combination with ketamine or other agents)
Procedural sedation

Pharmacology & Mechanism of Action

Drug Class: Benzodiazepine | Pharmacological Group: Sedative-hypnotic, anxiolytic, muscle relaxant, anticonvulsant

Mechanism of Action: Midazolam is a short-acting benzodiazepine that binds to the benzodiazepine site on the GABA-A receptor, enhancing the inhibitory effects of gamma-aminobutyric acid (GABA). This increases the frequency of chloride channel opening, leading to hyperpolarization of neurons and central nervous system depression. It produces dose-dependent sedation, anxiolysis, muscle relaxation, and anticonvulsant effects.

Pharmacodynamics: Midazolam produces rapid onset of sedation, anxiolysis, and amnesia. It has minimal cardiovascular effects at typical doses, but can cause dose-dependent respiratory depression. It also has anticonvulsant properties and is used to control seizures. In veterinary medicine, it is often used as a premedicant, for induction of anesthesia (in combination with other agents), and for procedural sedation.

⚡ Pharmacokinetics Summary

Absorption: After oral administration, midazolam is well absorbed but undergoes extensive first-pass metabolism, resulting in low bioavailability (approximately 40% in dogs). After IM administration, absorption is rapid and complete. Onset of action after IV administration is within 1-3 minutes.

Distribution: Midazolam is highly lipophilic, leading to rapid distribution into tissues, including the brain. It crosses the blood-brain barrier and placenta. Volume of distribution is large. Protein binding is approximately 95% in dogs and cats.

Metabolism: Midazolam is extensively metabolized in the liver by cytochrome P450 enzymes (CYP3A4 in humans, analogous enzymes in animals). The primary metabolite is 1-hydroxymidazolam, which is pharmacologically active but less potent than the parent drug. In horses, metabolism may differ slightly.

Excretion: Metabolites are excreted primarily in the urine, with a small amount in feces. The elimination half-life is short, typically 1-2 hours in dogs and cats, but may be longer in some species.

Half-Life: Dogs: 1-2 hours; Cats: 1-2 hours; Horses: 0.5-1 hour; Cattle: 0.5-1 hour

Bioavailability: Oral: ~40% in dogs (due to first-pass effect); IM: ~90%

Protein Binding: Approximately 95% in dogs and cats

Available Formulations & Strengths

Injectable Solution 1 mg/mL, 5 mg/mL (IV, IM)

Oral Syrup 2 mg/mL (PO)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to benzodiazepines
Severe respiratory insufficiency
Severe hepatic insufficiency (use with caution)
Myasthenia gravis
Acute narrow-angle glaucoma
Do not use as sole induction agent in animals with cardiovascular instability (may cause hypotension)

Warnings & Clinical Precautions:

Use with caution in animals with hepatic or renal disease
May cause paradoxical excitement, especially in cats and some dogs
Respiratory depression may occur, especially with high doses or when combined with opioids
In horses, may cause ataxia and muscle weakness
In ruminants, risk of bloat and regurgitation during sedation
Use with caution in pregnant animals (may cross placenta)
Monitor vital signs during use
Have resuscitation equipment available

Adverse Effects & Reactions

Common:

Sedation
Ataxia
Muscle weakness
Respiratory depression (dose-dependent)
Paradoxical excitement (especially cats)
Hypotension (rare at low doses)

Serious / Severe:

Severe respiratory depression
Cardiovascular collapse (with rapid IV administration)
Apnea
Paradoxical aggression

Rare:

Hypersensitivity reactions
Thrombophlebitis at injection site
Hepatic enzyme elevation

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Opioids (e.g., morphine, fentanyl)	Additive respiratory depression and sedation	High
Ketamine	Synergistic anesthetic effects; often used in combination for induction	Moderate
Propofol	Additive respiratory depression and hypotension	High
Alpha-2 agonists (e.g., xylazine, dexmedetomidine)	Enhanced sedation and cardiovascular effects	Moderate
CYP3A4 inhibitors (e.g., ketoconazole, erythromycin)	May increase midazolam plasma levels and prolong effects	Moderate
CYP3A4 inducers (e.g., phenobarbital, rifampin)	May decrease midazolam efficacy	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe respiratory depression
Apnea
Hypotension
Coma
Cardiovascular collapse

Emergency Treatment Protocol: Supportive care: maintain airway, provide oxygen, assist ventilation if needed. Administer flumazenil (benzodiazepine antagonist) at 0.01-0.02 mg/kg IV, may repeat. Monitor cardiovascular function and treat hypotension with fluids and vasopressors if necessary.

Food Animal Withdrawal Times

🥩 Meat: 3 days🥛 Milk: 3 days

Withdrawal times are not established for all species; consult regulatory guidelines. In the US, extra-label use requires extended withdrawal periods. For cattle, a meat withdrawal of 3 days and milk withdrawal of 3 days is often recommended, but verify with FARAD.

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. Keep in tightly closed container. Do not freeze.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for human use; not specifically approved for veterinary use in the US, but widely used in veterinary medicine (extra-label).

Extra-Label (Off-Label) Use: Midazolam is a controlled substance (Schedule IV). Extra-label use in food animals is permitted under AMDUCA with veterinary oversight, but withdrawal times must be extended. Not approved for use in food animals in the US, but may be used extra-label.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Midazolam is a versatile benzodiazepine used in veterinary medicine for sedation, anxiolysis, muscle relaxation, and as an anticonvulsant. It is often preferred over diazepam due to its water solubility, which allows for IV administration without propylene glycol, reducing the risk of thrombophlebitis. It is commonly used in combination with opioids or ketamine for premedication and induction of anesthesia. In emergency situations, it is useful for controlling seizures. However, it can cause paradoxical excitement in some animals, particularly cats, so it is often combined with other agents. Respiratory depression is a concern, especially when used with other CNS depressants. Flumazenil is the specific antagonist and should be available when using midazolam. In food animals, withdrawal times must be observed, and extra-label use requires careful consideration.

References & Literature

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