Tiletamine / Zolazepam — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	IM	5-10 mg/kg (combined dose)	Single dose	Duration: 30-60 minutes of anesthesia Notes: Lower doses for sedation, higher for anesthesia. May be combined with other agents for longer procedures.
Cat	IM	5-10 mg/kg (combined dose)	Single dose	Duration: 30-60 minutes of anesthesia Notes: Cats may require higher doses; recovery can be prolonged.
Horse	IV	1-2 mg/kg (combined dose)	Single dose	Duration: 15-30 minutes of anesthesia Notes: Use with caution; may cause excitement during recovery. Often used with alpha-2 agonists.
Cattle	IM	2-4 mg/kg (combined dose)	Single dose	Duration: 30-60 minutes Notes: Ruminants are prone to bloat and regurgitation; fast before anesthesia.
Small Ruminants (sheep, goats)	IM	5-10 mg/kg (combined dose)	Single dose	Duration: 30-60 minutes Notes: Similar to cattle; monitor for regurgitation.
Rabbit	IM	10-20 mg/kg (combined dose)	Single dose	Duration: 30-60 minutes Notes: Rabbits are sensitive; use lower end of dose range.
Bird (poultry)	IM	5-10 mg/kg (combined dose)	Single dose	Duration: Variable Notes: Not commonly used; other agents preferred.
Exotic mammals (e.g., ferrets, raccoons)	IM	5-15 mg/kg (combined dose)	Single dose	Duration: Variable Notes: Dose varies widely; use lowest effective dose.

Clinical Indications & Species Uses

General Indications

Chemical restraint
Short-term anesthesia
Induction of anesthesia

Dog (Canine)

Restraint and immobilization
Anesthesia for short diagnostic or surgical procedures
Induction of anesthesia (often with other agents)

Cat (Feline)

Restraint and immobilization
Anesthesia for short procedures
Induction of anesthesia

Horse (Equine)

Restraint and immobilization for minor procedures
Induction of anesthesia (in combination with other agents)

Cattle (Bovine)

Restraint and immobilization for minor procedures
Anesthesia for short procedures

Small Ruminants (Sheep / Goat)

Restraint and immobilization
Anesthesia for short procedures

Rabbit & Small Mammals

Restraint and immobilization
Anesthesia for short procedures

Avian & Poultry

Restraint and immobilization

Exotic & Other Species

Restraint and immobilization in zoo and wildlife species
Anesthesia for short procedures in various exotic mammals

Pharmacology & Mechanism of Action

Drug Class: Dissociative anesthetic / Benzodiazepine combination | Pharmacological Group: NMDA receptor antagonist / GABA-A receptor modulator

Mechanism of Action: Tiletamine is a dissociative anesthetic that acts as a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor, blocking glutamate-mediated excitatory neurotransmission in the central nervous system. This results in profound analgesia, catalepsy, and dissociation from the environment. Zolazepam is a benzodiazepine that enhances the inhibitory effects of gamma-aminobutyric acid (GABA) at GABA-A receptors, producing sedation, muscle relaxation, and anticonvulsant effects. The combination provides balanced anesthesia with muscle relaxation and reduced seizure activity.

Pharmacodynamics: Tiletamine produces a cataleptoid state with profound somatic analgesia but poor visceral analgesia. It increases heart rate, cardiac output, and blood pressure due to central sympathetic stimulation. Zolazepam provides muscle relaxation, anxiolysis, and anticonvulsant effects, counteracting the muscle rigidity and seizures that can occur with tiletamine alone. The combination has a wide margin of safety and is used for short-term anesthesia and immobilization.

⚡ Pharmacokinetics Summary

Absorption: After intramuscular (IM) injection, tiletamine and zolazepam are rapidly absorbed, with peak plasma concentrations occurring within 10-30 minutes. Oral absorption is poor and not recommended.

Distribution: Both drugs are highly lipophilic and distribute widely throughout the body, including the brain. They cross the placenta and are distributed into milk. The volume of distribution is large.

Metabolism: Tiletamine is extensively metabolized in the liver, primarily by N-dealkylation to norketamine-like metabolites. Zolazepam is also metabolized in the liver, mainly by hydroxylation and glucuronide conjugation. Some metabolites are pharmacologically active.

Excretion: Metabolites are excreted primarily in the urine, with a small amount in feces. In dogs, the elimination half-life of tiletamine is approximately 1-2 hours, and zolazepam is approximately 1 hour. In cats, the half-life is longer, with tiletamine about 2-3 hours and zolazepam about 4-5 hours.

Half-Life: Dogs: tiletamine ~1-2 h, zolazepam ~1 h; Cats: tiletamine ~2-3 h, zolazepam ~4-5 h; Horses: tiletamine ~1-2 h, zolazepam ~1-2 h.

Bioavailability: IM bioavailability is nearly complete (close to 100%). Oral bioavailability is low and erratic.

Protein Binding: Tiletamine: ~50% bound to plasma proteins; Zolazepam: ~90% bound.

Available Formulations & Strengths

Lyophilized powder for injection 500 mg tiletamine + 500 mg zolazepam per vial (reconstitute with 5 mL sterile water to yield 100 mg/mL of each) (IM, IV)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to tiletamine or zolazepam
Severe hepatic or renal disease
Pregnancy (unless benefits outweigh risks)
Animals with a history of seizures (unless controlled)
Pancreatitis or other conditions where benzodiazepines are contraindicated
Do not use in animals with glaucoma or penetrating eye injuries (may increase intraocular pressure)

Warnings & Clinical Precautions:

Use with caution in animals with cardiovascular disease, as tiletamine can increase heart rate and blood pressure.
May cause respiratory depression; monitor ventilation, especially in brachycephalic breeds.
Recovery may be prolonged and can be associated with excitement, vocalization, and hyperkinesis; provide a quiet environment.
In ruminants, fasting is recommended to reduce the risk of bloat and aspiration.
Use in horses may cause ataxia and excitement during recovery; use in a padded stall.
Not for use in animals intended for food within the withdrawal period.
Personnel handling the drug should avoid accidental self-injection; use gloves and safe injection practices.

Adverse Effects & Reactions

Common:

Salivation
Apnea (transient)
Hyperthermia or hypothermia
Muscle rigidity (if zolazepam effect is insufficient)
Prolonged recovery
Ataxia
Vocalization during recovery

Serious / Severe:

Respiratory depression or arrest
Cardiovascular collapse (rare)
Seizures (especially with tiletamine alone or in overdose)
Pulmonary edema (rare)
Anaphylaxis (rare)

Rare:

Hepatotoxicity
Nephrotoxicity
Pancreatitis
Corneal ulcers (due to decreased tear production)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Other CNS depressants (e.g., barbiturates, opioids, propofol)	Additive respiratory and cardiovascular depression	High
Alpha-2 agonists (e.g., xylazine, medetomidine)	Enhanced sedation and analgesia; may cause bradycardia and hypotension	Moderate
Anticholinergics (e.g., atropine)	May reduce bradycardia but can worsen tachycardia	Mild
Corticosteroids	May increase risk of gastrointestinal ulceration	Mild
Aminoglycoside antibiotics	May enhance neuromuscular blockade	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe respiratory depression
Apnea
Hypotension or hypertension
Cardiac arrhythmias
Seizures
Coma
Prolonged recovery

Emergency Treatment Protocol: Provide supportive care: maintain airway, administer oxygen, and provide mechanical ventilation if necessary. Monitor cardiovascular function and treat arrhythmias with appropriate agents. Administer intravenous fluids to support blood pressure. For seizures, use benzodiazepines (e.g., diazepam) or barbiturates (e.g., phenobarbital) with caution. There is no specific antidote; recovery is time-dependent.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 72 days

Withdrawal times are not established for all species; consult regulatory guidelines. In the US, tiletamine/zolazepam is not approved for food animals, so extra-label use requires extended withdrawal periods. Recommended meat withdrawal is at least 7 days, and milk withdrawal is 72 hours, but these are conservative estimates.

Storage, Handling & Regulatory Information

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

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

Handling & Special Conditions: Protect from light. Reconstituted solution should be used within 24 hours if stored at room temperature, or up to 3 days if refrigerated. Do not freeze.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats (e.g., Telazol).

Extra-Label (Off-Label) Use: In the US, tiletamine/zolazepam is approved for use in dogs and cats. Extra-label use in other species is permitted under AMDUCA, but requires a valid veterinarian-client-patient relationship and extended withdrawal times for food animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Tiletamine/zolazepam is a valuable combination for short-term anesthesia and immobilization in veterinary practice. It is particularly useful for chemical restraint in aggressive or difficult-to-handle animals. The combination provides good muscle relaxation and analgesia, but visceral analgesia is poor, so additional analgesics may be needed for painful procedures. Recovery can be prolonged and sometimes rough, especially in dogs and cats; therefore, it is often used as an induction agent followed by inhalant anesthesia. In horses, it is used cautiously due to the risk of excitement during recovery. Always have emergency drugs and equipment available when using this agent. Monitor vital signs closely, especially respiratory rate and oxygen saturation. For food animals, adhere to withdrawal times to ensure food safety.

References & Literature

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