Zolazepam/Tiletamine

Overview

Zolazepam/Tiletamine (Zoletil®) is a combination injectable anesthetic used in dogs and cats for induction of general anesthesia and short-duration anesthetic procedures. The product combines zolazepam, a benzodiazepine tranquilizer, with tiletamine, a dissociative anesthetic, to provide immobilization, sedation, and anesthesia.

Zolazepam produces sedative, anxiolytic, and muscle-relaxing effects through enhancement of gamma-aminobutyric acid (GABA) activity within the central nervous system. Tiletamine acts similarly to ketamine by antagonizing glutamate receptors, producing dissociative anesthesia through selective depression of cerebral regions such as the thalamus and cortex while some limbic activity remains preserved.

The duration of anesthesia generally ranges from 20–60 minutes depending on the administered dose and route. Recovery is progressive and may last 2–6 hours in a quiet environment with minimal light and noise stimulation. Recovery tends to be more prolonged in cats compared with dogs and may also be delayed in obese, geriatric, or debilitated patients.

The combination should not be relied upon as the sole anesthetic agent for painful surgical procedures because analgesia may be inadequate. Appropriate analgesic agents should be incorporated when deeper pain control is required. Excessive salivation and muscle rigidity during recovery may occur, and premedication is often used to improve recovery quality and anesthetic smoothness.

Regulatory — Telazol/Zoletil is a DEA Schedule III (C-III) controlled substance. Requires DEA registration, logbook entry per use, and secure storage.

IM onset averages 7.5 min, surgical anaesthesia 27 min, recovery ~4 h. Tiletamine t½ 1.25-2.5 h vs zolazepam t½ 1.5 h — tiletamine effects OUTLAST the benzo in dogs, which can produce agitated/rough recoveries (athetosis, muscle rigidity, convulsions).

IM onset 5-12 min, duration of anaesthesia 21-60 min (3× the duration of ketamine), recovery 1-5.5 h. Tiletamine t½ 2.5 h vs zolazepam t½ 4.5 h — zolazepam OUTLASTS tiletamine in cats, producing more tranquilisation than anaesthesia during recovery (smoother but longer).

Animals’ eyes remain OPEN after tiletamine/zolazepam. Ophthalmic lubricant must be applied to prevent corneal drying / ulceration. Reflexes (pinnal, palpebral, pedal, laryngeal, pharyngeal) remain preserved.

Like ketamine, tiletamine/zolazepam does NOT abolish the swallowing / laryngeal / pharyngeal reflexes, making tracheal intubation challenging especially in cats. Mitigation: topical lidocaine applied to the arytenoid cartilages OR rocuronium IV (with ventilatory support).

in CATS, IV tiletamine briefly (about 1 minute) DECREASES blood pressure, then BP rises ABOVE baseline. The respiratory pattern is APNEUSTIC (like ketamine), but normal minute ventilation and pCO2 are maintained, so transient apneustic breathing alone is not a hypoventilation alarm.

in DOGS, induction with tiletamine IV had NO clinical effects on intraocular pressure. The same outcomes were noted when administered IM and intranasal in cats. Useful for cataract, glaucoma, or other IOP-sensitive surgical patients (unlike ketamine’s historical IOP-raising reputation).

Indications

Zolazepam/tiletamine is used in dogs and cats for short-term general anesthesia, chemical restraint, and anesthetic induction when rapid immobilization and reliable dissociative anesthesia are required.

• General anesthesia: Used to induce and maintain short-duration general anesthesia in dogs and cats for diagnostic, medical, and minor surgical procedures.
• Chemical restraint and immobilization: Provides reliable restraint for handling fractious, anxious, or difficult-to-manage patients during examinations and non-painful procedures.
• Anesthetic induction: May be used as an induction agent prior to inhalant anesthesia or multimodal anesthetic protocols.
• Short procedures requiring rapid immobilization: Useful for imaging, wound management, catheter placement, and other procedures where brief anesthesia or deep sedation is needed.
• Combination anesthetic protocols: Often incorporated into balanced anesthetic protocols together with analgesics, anticholinergics, or premedication agents to improve anesthetic quality and recovery characteristics.

Dosage (Reference)

Dog

In dogs, zolazepam/tiletamine is administered either intravenously or intramuscularly depending on the required depth of anesthesia, expected degree of pain, and the need for rapid immobilization. Lower doses generally provide restraint and lighter anesthesia, while higher doses produce deeper and longer anesthetic effects with a greater risk of prolonged or excitable recovery.

Cat

In cats, zolazepam/tiletamine produces reliable dissociative anesthesia and immobilization. Recovery from anesthesia is generally more prolonged in cats than in dogs, particularly at higher doses or in debilitated patients.

Warnings & Precautions

Zolazepam/tiletamine produces dissociative anesthesia with prolonged and sometimes unpredictable recoveries, particularly at higher doses or in compromised patients. Careful patient selection, dose adjustment, and recovery monitoring are essential in dogs and cats.

• Cardiovascular and respiratory disease: Do not use in animals with severe cardiac disease, respiratory disease, or hypertension due to the risk of significant anesthetic complications.
• Hepatic and renal insufficiency: Contraindicated in patients with significant hepatic or renal dysfunction because impaired drug metabolism and elimination may prolong anesthesia and recovery.
• Pancreatic disease: Avoid use in animals with pancreatic insufficiency or significant pancreatic disease.
• Head trauma and intracranial disease: Contraindicated in patients with head trauma or intracranial tumors due to potential adverse CNS effects.
• Pregnancy: The drug crosses the placenta and may cause potentially fatal respiratory depression in puppies and kittens; avoid use during pregnancy whenever possible.
• Lactation — not recommended: Lactation contraindication — the teratogenic potential is unknown, and tiletamine/zolazepam is NOT recommended for use during any stage of pregnancy or during lactation.
• Eyes-remain-open ophthalmic lubricant: Apply ophthalmic lubricant routinely — animals’ eyes remain OPEN during anaesthesia. Without lubricant, corneal drying and ulceration follow. Mandatory before placing on the operating table.
• Hypothermia + supplemental heat: Hypothermia risk — tiletamine/zolazepam may cause hypothermia. Susceptible patients (small body surface area, low ambient temperatures) should be monitored carefully and supplemental heat provided as needed. Monitor body temperature throughout anaesthesia.
• Do NOT re-dose for athetoid movements: DO NOT give additional tiletamine/zolazepam in an attempt to diminish athetoid movements (constant succession of slow, writhing, involuntary movements of flexion, extension, pronation) during recovery. These movements are a recognised effect and do not indicate insufficient anaesthesia.
• Geriatric / debilitated / renal — dose reduction: Dosages may need to be reduced in geriatric or debilitated animals, or in animals with renal dysfunction. Anticipate longer recovery in these patients.
• Monitor body temperature + HR/rhythm: Monitor body temperature, heart rate, and rhythm during anaesthesia. Hypothermia and dog tachycardia are common.
•  Antiparasitic collar: Remove antiparasitic collar 24 hours before anaesthesia.
• Reflexes preserved — eye/throat surgery inadequate: Like ketamine, tiletamine/zolazepam does NOT abolish pinnal, palpebral, pedal, laryngeal, and pharyngeal reflexes. Use of tiletamine/zolazepam ALONE may not be adequate if surgery is to be performed on these areas.
• DEA Schedule III: Telazol is a DEA Schedule III (C-III) controlled substance — requires DEA registration, logbook entry per use, and secure storage. State controlled-substance regulations may add to federal requirements.
• Reconstituted storage 4°C / 8 days: Reconstituted product storage — store reconstituted Zoletil in fridge at 4°C and use within 8 days. People who are or may become pregnant should not handle this drug.

Drug Interactions

Clinically important interactions with zolazepam/tiletamine are primarily related to additive cardiorespiratory depression, altered anesthetic recovery, or delayed drug elimination. Careful monitoring and dose adjustment are recommended when the product is combined with other anesthetic or sedative agents.

• Phenothiazine tranquilizers (e.g., acepromazine): Premedication may increase cardiorespiratory depression and enhance hypothermia during the later stages of anesthesia.
• Chloramphenicol: Concurrent administration during the preoperative or intraoperative period may delay elimination of the anesthetic agents and prolong recovery.
• Chloramphenicol species difference (cats +30 min, dogs none): in CATS chloramphenicol prolongs anaesthesia by ~30 minutes. In DOGS, chloramphenicol apparently has NO effect on recovery times. Species-specific prolongation matters when timing protocols.
• Inhalant anaesthetics — reduce dose: Inhalant anaesthetics— isoflurane / sevoflurane dose may need to be REDUCED when used concomitantly with tiletamine/zolazepam. Standard balanced anaesthesia practice.
• Barbiturates — reduce dose: Barbiturates — phenobarbital and related barbiturate doses may need to be REDUCED when used concomitantly with tiletamine/zolazepam.
• Indirect ketamine/midazolam-class DIs: Indirect class DIs (ketamine + midazolam)which could apply to tiletamine/zolazepam — (a) neuromuscular blockers (succinylcholine, tubocurarine): enhanced / prolonged respiratory depression; (b) thyroid hormones: hypertension + tachycardia (humans; beta-blockers may help); (c) azole antifungals (fluconazole, itraconazole, ketoconazole): increased midazolam concentrations; (d) calcium-channel blockers (diltiazem, verapamil): increased midazolam concentrations; (e) cimetidine: increased midazolam concentrations; (f) macrolides (clarithromycin, erythromycin): increased midazolam concentrations; (g) opioid meperidine: hypotension reported; (h) phenobarbital + rifampin: decreased midazolam concentrations.

Side Effects & Overdose

Side Effects

Adverse effects associated with zolazepam/tiletamine are generally related to dissociative anesthesia, prolonged recovery, and dose-dependent CNS or cardiorespiratory effects. Higher doses and compromised patients are more likely to experience recovery complications.

• Injection pain in cats: Intramuscular injection may occasionally cause discomfort or pain in cats.
• Respiratory depression + transient apnea: Respiratory depression and transient apnea — respiratory depression is a possibility, especially at higher doses. Apnea may occur; observe animal carefully and have ventilation support ready.
• Dog persistent tachycardia ~30 min: Dog tachycardia ~30 min— in dogs, tachycardia may be a common effect and last for 30 minutes after induction. Cardiac output typically remains unchanged despite the tachycardia and accompanying biphasic BP changes.
• Hypersalivation + bronchial/tracheal secretions: Hypersalivation + bronchial / tracheal secretions — common; prevent with atropine 0.04 mg/kg IV/IM/SC before tiletamine/zolazepam administration.
• Athetoid + rigidity + twitching: Athetoid movements, muscle rigidity, involuntary muscular twitching, hypertonia— common during recovery. Do NOT redose tiletamine/zolazepam to suppress these.
• Emergence emesis + dysphoria + vocalization: Emergence phenomena— emesis during emergence, vocalization, erratic and/or prolonged recovery. Quiet, dark recovery environment helps.
• Rare severe AEs: cyanosis, cardiac arrest, pulmonary edema, seizure activity, and either hypertension or hypotension have been reported. Have monitoring + emergency support available.
• Preventable corneal ulcer: Corneal ulcer (preventable) — corneal drying / ulceration occurs unless ophthalmic ointment is applied. Eyes remain open; lubricate routinely.
• Insufficient anaesthesia at recommended dog doses: insufficient anaesthesia after recommended doses has been reported in dogs. Plan a deeper agent (inhalant) or higher-end of range when adequacy is critical.

Overdose

Overdose of zolazepam/tiletamine may result in severe and prolonged anesthetic depression, delayed recovery, and significant cardiorespiratory compromise. There is no specific reversal agent for the combination product.

• Severe CNS depression: Profound sedation, prolonged unconsciousness, or delayed recovery may occur.
• Respiratory depression: Excessive anesthetic depth may lead to hypoventilation or respiratory compromise.
• Cardiovascular complications: Severe cardiorespiratory depression may develop, especially in compromised or overdosed patients.
• Exaggerated recovery reactions: Marked muscle rigidity, dysphoria, or excitability may occur during prolonged recovery periods.
• Supportive care: Treatment is primarily supportive and includes airway management, oxygen supplementation, temperature support, fluid therapy, and cardiovascular monitoring.
• Recovery management: Animals should recover in a quiet, dark, low-stimulation environment to minimize dysphoria and excitement.
• Safety margins (dog 2x, cat 4.5x, lethal 5-10x): Manufacturer claims a 2× margin of safety in DOGS and a 4.5× margin in CATS. Lethal doses can occur at 5 to 10× the labeled IM doses. Cats tolerate overdose better than dogs.
• Doxapram 5.5 mg/kg respiratory stim: A preliminary dog study suggests doxapram 5.5 mg/kg will enhance respirations and arousal after tiletamine/zolazepam overdose. Useful as a non-specific respiratory stimulant when no specific reversal exists.
• Flumazenil NOT used (worsens tiletamine): Do NOT use flumazenil to reverse zolazepam. Although flumazenil reverses the benzodiazepine, it will EXACERBATE the effects of tiletamine, which cannot be reversed. There is no specific reversal agent for the combination.

Key Notes

Practical clinical considerations that help improve anesthetic planning and patient management when using zolazepam/tiletamine in dogs and cats:

• Rapid immobilization: Provides dependable restraint and anesthetic induction with relatively small injection volumes, making it useful in difficult or fractious patients.
• Balanced anesthetic protocols: Often performs best when incorporated into multimodal anesthesia rather than being used alone.
• Route selection: IV administration allows more controlled anesthetic depth and smoother titration, while IM administration is useful when venous access is difficult.
• Species differences: Cats generally maintain anesthetic effects longer than dogs at comparable doses.
• Species PK asymmetry — dog rough vs cat smoother-longer: in DOGS, tiletamine effect (t½ 1.25-2.5 h) OUTLASTS zolazepam (t½ 1.5 h) — agitated / rough recovery as the benzo wears off first. In CATS, zolazepam (t½ 4.5 h) OUTLASTS tiletamine (t½ 2.5 h) — smoother but LONGER recovery (tranquilisation persists). Different recovery management for each species.
• DEA C-III + regulatory: DEA Schedule III (C-III) controlled substance — requires DEA registration, logbook, secure storage. Check racing-commission rules before any competition use.