Midazolam
Midazolam hydrochloride
Also known as: Versed · Dormicum · Dormonid · Fulsed · Hypnovel · Midaselect · Zolamid · Buccolam · Epistatus · Midazolam HCl · Ro-21-3981/003 · Midazolamum · Midazolam hydrochloride
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Reviewed non-calculator evidenceReviewed non-calculator evidence (1)
Evidence only — not for automatic calculation
Preanesthetic agent (extra-label)
Preanesthetic agent (extra-label): 0.5 – 5 mg/kg IM or IV
Governing clinical context (2)
- NOTE: There are many potential combinations that have been suggested; the following are examples and not inclusive. For additional information, refer to other anesthesia-specific references. 25
- Store midazolam injection at room temperature (15°C-30°C [59°F-86°F]) and protected from light. After being frozen for 3 days and allowed to thaw at room temperature, the injectable product is physically stable. Midazolam is stable at a pH range of 3 to 3.6.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Midazolam is a short-acting parenteral benzodiazepine widely used in veterinary medicine as a preanesthetic sedative, muscle relaxant, and anticonvulsant.
Clinical Pearls:
- Unique Solubility: Unlike diazepam, midazolam is water-soluble in the vial (at a pH < 4) but becomes highly lipid-soluble at physiologic body pH (7.4). This allows it to be mixed safely with other water-soluble drugs (like opioids and ketamine) without precipitating.
- IM Absorption: Because it does not contain propylene glycol, midazolam does not sting upon intramuscular (IM) injection and is rapidly and reliably absorbed via the IM route, making it superior to diazepam for IM use.
- Paradoxical Excitement: When given alone to healthy, non-anxious dogs and cats, midazolam often fails to provide reliable sedation and can cause paradoxical dysphoria or excitement. It is most effective when combined with other agents (e.g., opioids, ketamine, or alpha-2 agonists).
- Status Epilepticus: It is highly effective for arresting active seizures and can be administered IV, IM, or intranasally (IN).
Mechanism of action
Midazolam exerts its effects by enhancing the activity of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system.
- Target: Binds to specific allosteric benzodiazepine receptors on the GABA-A receptor complex.
- Mechanism: Binding increases the frequency of chloride channel openings → influx of chloride ions → hyperpolarization of the postsynaptic neuronal membrane → decreased neuronal excitability.
- Effects: This depression of subcortical levels (limbic, thalamic, and hypothalamic) produces anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects. Midazolam has approximately twice the affinity for benzodiazepine receptors compared to diazepam, making it more potent with a faster onset and shorter duration of action.
Safety & warnings
Contraindications
- Hypersensitivity to benzodiazepines
- Acute narrow-angle glaucoma
- Intra-carotid artery injection (must be avoided)
- Neonates (avoid use)
Adverse effects
- Respiratory depression (especially when combined with opioids or other CNS depressants)
- Paradoxical excitement, dysphoria, or agitation (especially in cats and dogs when used alone)
- Hypotension and bradycardia (when combined with other anesthetics like isoflurane or ketamine)
- Pain on injection or local irritation (rare compared to diazepam)
- Severe hypotension
- Paradoxical excitement (occasionally)
Precautions
High-Risk Patients: Use cautiously in patients with hepatic or renal disease, and in debilitated or geriatric patients.
- Cardiovascular/Respiratory: Administer with extreme caution to patients in coma, shock, or with significant respiratory depression. Patients with congestive heart failure may eliminate the drug more slowly.
- Anesthetic Combinations: While midazolam alone has minimal cardiorespiratory effects, combining it with opioids, ketamine, or inhalants can lead to significant respiratory depression, bradycardia, or hypotension.
- Pregnancy: FDA Category D in humans. May cause congenital abnormalities if used in the first trimester. Excreted in milk and may cause CNS effects in nursing neonates.
Drug interactions
Midazolam may decrease the dosages required for inhalant anesthetics.
May inhibit midazolam metabolism, increasing midazolam blood levels.
May increase midazolam levels.
May increase midazolam levels by inhibiting hepatic metabolism.
May increase the risk of profound sedation and respiratory depression.
May increase midazolam levels.
May increase the hypnotic effects of midazolam; hypotension has been reported when used with meperidine. Combination causes greater respiratory depression.
May decrease peak levels and AUC of midazolam via enzyme induction.
May decrease peak levels and AUC of midazolam.
Midazolam may decrease the dosages required for induction.
Potentiates effect, reducing the dose required for induction
Potentiates effect, reducing the dose required
May enhance the sedative effect
May enhance the sedative effect
May enhance the sedative effect
May increase the hypnotic and hypotensive effects of midazolam; enhances sedation
Inhibits the metabolism of midazolam
Monitoring
- Level of sedation and central nervous system depression
- Respiratory rate, effort, and oxygenation (especially when combined with other drugs)
- Heart rate and blood pressure
- Respiratory rate and effort
- Heart rate and rhythm
- Level of sedation and consciousness
Pharmacokinetics
Half-life
Absorption
Following IM injection, midazolam is rapidly and nearly completely (91%) absorbed. Oral absorption is good, but bioavailability is low (31-72%) due to a rapid first-pass effect. Rectal bioavailability in dogs is very low. Intranasal administration (especially via compounded gel) provides good absorption and high peak levels.
Distribution
Highly protein bound (94-97%). Due to its high lipophilicity at physiologic pH, it rapidly crosses the blood-brain barrier. Changes in plasma protein concentrations can significantly alter the response to a given dose.
Metabolism
Metabolized in the liver, principally by microsomal oxidation. Forms an active metabolite (alpha-hydroxymidazolam), which has a very short half-life and negligible clinical effects.
Elimination
Eliminated primarily via hepatic metabolism and subsequent excretion. The duration of activity is considerably shorter than that of diazepam.
Overdose
Accidental overdoses should be managed with supportive care (e.g., cardiovascular and respiratory support), similar to diazepam.
- Reversal Agent: Flumazenil is a specific benzodiazepine antagonist and can be used to reverse midazolam's effects.
- However, because midazolam has a very short duration of effect and flumazenil is costly, supportive therapy is usually sufficient for all but the most massive overdoses.
Available products
Formulations
- Injection (solution)
- Oral syrup
- Injectable solution: 1 mg/ml, 2 mg/ml, 5 mg/ml
- Oromucosal solution: 5 mg/ml (in 0.5 ml, 1 ml, 1.5 ml, 2 ml pre-filled syringes)
- Oromucosal solution: 10 mg/ml pre-filled syringe
Veterinary
- None (No veterinary-labeled products currently available)
- Buccolam
- Epistatus
- Hypnovel
Human-labeled
- Midazolam HCl Injection: 1 mg/mL in 2 mL, 5 mL, 10 mL vials
- Midazolam HCl Injection: 5 mg/mL in 1 mL, 2 mL, 5 mL, 10 mL vials & 2 mL syringes
- Midazolam HCl Syrup: 2 mg/mL in 118 mL
- Buccolam
- Epistatus
- Hypnovel
Regulatory status
POM
POM-V
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store midazolam injection at room temperature (15°-30°C) and protect from light. It is physically stable after being frozen for 3 days and thawed. Midazolam is stable at a pH from 3-3.6. Compounded oral suspensions (e.g., with Syrpalta) retain >90% potency for 56 days when stored at 7°C, 20°C, or 40°C and protected from light.
Client information
Note: Midazolam is almost exclusively administered in a veterinary hospital setting or under direct professional supervision.
- Purpose: Your pet may receive this medication to help them relax before surgery, to provide muscle relaxation, or to quickly stop an active seizure.
- Behavioral Changes: If given alone, some pets (especially healthy dogs and cats) may become temporarily restless, whiny, or uncoordinated instead of sleepy. This is a known reaction and resolves quickly.
- Safety: Because it can affect breathing and heart rate when combined with other anesthetics, your veterinary team will closely monitor your pet's vital signs while they are under its effects.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.