Tiletamine hydrochloride/Zolazepam hydrochloride

Uses and Indications

This drug is indicated for use in dogs and cats for various procedures requiring sedation and analgesia.

Indications for Dogs:

• This drug is indicated for restraint and minor procedures of short duration (average of 30 minutes) requiring mild to moderate analgesia.

• Minor surgical procedures include laceration repair, draining of abscesses, castrations, and other similar interventions.

• When administered intravenously, this drug is indicated for the induction of anesthesia, which may be followed by maintenance with an inhalant anesthetic.

Indications for Cats:

• This drug is indicated for restraint or for anesthesia combined with muscle relaxation.

Administration Notes:

• In dogs, this drug can be administered via intramuscular or intravenous injection.

• In cats, this drug is indicated for intramuscular injection only.

Limitations of Use:

• The drug is intended for short-duration procedures and should be used with caution in accordance with the specified administration routes.

Dosage and Administration

For dogs, the recommended dosage for Intramuscular (IM) administration for restraint and minor procedures is 3 to 4.5 mg/lb (6.6 to 9.9 mg/kg) for diagnostic purposes, and 4.5 to 6 mg/lb (9.9 to 13.2 mg/kg) for minor procedures. The total dose, including any supplemental doses, should not exceed 12 mg/lb (26.4 mg/kg), with a maximum safe dose of 13.6 mg/lb (29.92 mg/kg).

For Intravenous (IV) administration for induction of anesthesia, the dosage is 1-2 mg/lb (2.2-4.4 mg/kg) body weight, administered slowly over 30-45 seconds. The level of consciousness, muscle relaxation, and jaw tone should be assessed after 30-60 seconds. If anesthesia is insufficient after 60 seconds, additional doses may be given, but the total dose should not exceed 2 mg/lb (4.4 mg/kg).

For cats, the initial dosage for Intramuscular (IM) administration is 4.4 to 5.4 mg/lb (9.7 to 11.9 mg/kg) for procedures such as dentistry and abscess treatment, and 4.8 to 5.7 mg/lb (10.6 to 12.5 mg/kg) for minor procedures. For ovariohysterectomy and onychectomy, the dosage is 6.5 to 7.2 mg/lb (14.3 to 15.8 mg/kg). The total dose, including any supplemental doses, should not exceed 32.7 mg/lb (72 mg/kg).

Fasting prior to induction is not essential; however, it is recommended to withhold food for at least 12 hours for elective surgery. Individual responses to the medication may vary based on dose, physical condition, age, and preanesthetics used. Recovery time may also vary with these factors.

The onset of anesthetic effect occurs within 5 to 12 minutes following a single deep IM injection, with optimum muscle relaxation lasting approximately 20 to 25 minutes post-administration. Repeated doses may prolong the duration of effect but will not further diminish muscle tone. Continuous monitoring for conscious response to nociceptive stimuli is essential to evaluate the depth of anesthesia.

Contraindications

The use of this product is contraindicated in dogs and cats with pancreatic disease. It should not be administered to animals with severe cardiac or pulmonary dysfunction. Due to unknown teratogenic potential, the product is contraindicated in pregnant bitches or queens at any stage of pregnancy. Its use for Cesarean section is also contraindicated, as it crosses the placental barrier and may produce respiratory depression in the newborn.

Warnings and Precautions

FOR USE IN DOGS AND CATS ONLY.

When using Telazol, Zoletil, or Tzed for induction of anesthesia, patients should be continuously monitored. Facilities for the maintenance of a patent airway, artificial ventilation, and oxygen supplementation should be available.

Pulmonary Edema

Pulmonary edema has been reported to occur in cats with the use of tiletamine and zolazepam for injection. Signs and symptoms include dyspnea, lethargy, anorexia, and abnormal behavior. Deaths have been reported occasionally in severely affected individuals. Cats should be observed closely for any signs and symptoms which may suggest pulmonary edema so that appropriate therapy may be instituted.

Renal Insufficiency

Telazol, Zoletil, and Tzed are not recommended for use in cats suffering from renal insufficiency. The principal route of excretion of both components in the cat is the urine; therefore, preexistent renal pathology or impairment of renal function may be expected to result in prolonged duration of anesthesia.

Drug Interactions

Phenothiazine-derivative drugs should not be used with Telazol, Zoletil, or Tzed at dosages indicated for intramuscular (IM) injection because the combination produces respiratory and myocardial depression, hypotension, and hypothermia.

Pregnancy and Reproduction

The safe use of Telazol, Zoletil, or Tzed in pregnant animals or on reproduction has not been established. These drugs cross the placental barrier and may cause respiratory depression in the neonate.

Regulatory Information

Federal law restricts the use of Zoletil to use by or on the order of a licensed veterinarian.

Side Effects

Adverse reactions associated with the use of Telazol, Zoletil, and Tzed include a range of serious and non-serious effects, primarily observed in dogs and cats. The following adverse reactions have been reported:

Serious Adverse Reactions

• Respiratory Depression: May occur following administration of high doses. If respiration becomes excessively depressed and the animal becomes cyanotic, resuscitative measures should be instituted promptly.

• Cardiac Arrest: Reported as an adverse reaction.

• Death: Has been reported in both dogs and cats following administration, particularly in those with preexisting conditions such as pulmonary or renal disease.

• Pulmonary Edema: Observed in cats, with signs including dyspnea, lethargy, anorexia, and abnormal behavior. Deaths have been reported occasionally in severely affected individuals.

Common Adverse Reactions

• Tachycardia: Frequently occurs, particularly in dogs; usually lasts about 30 minutes.

• Emesis: Reported during emergence.

• Excessive Salivation: Reported as an adverse reaction; may be controlled with atropine sulfate.

• Transient Apnea: Observed in a significant percentage of dogs (49.3% during studies).

• Vocalization: Reported as an adverse reaction.

• Erratic Recovery: Reported as an adverse reaction.

• Prolonged Recovery: Reported as an adverse reaction.

• Excessive Tracheal and Bronchial Secretions: Reported when atropine sulfate was not administered prior to anesthesia.

• Involuntary Muscular Twitching: Reported as an adverse reaction.

• Hypertonicity: Reported as an adverse reaction.

• Cyanosis: Reported as an adverse reaction.

• Convulsions: Reported as an adverse reaction.

• Central Nervous System Stimulation: Reported as an adverse reaction.

• Muscle Rigidity: Reported during surgical procedures.

Other Adverse Reactions

• Hypertension or Hypotension: May occur.

• Insufficient Anesthesia: Reported in dogs.

• Nystagmus: Observed in clinical studies (5 occurrences).

• Diarrhea: Reported in clinical studies (2 occurrences).

• Hypersalivation: Reported in clinical studies (1 occurrence).

• Urticaria: Reported in clinical studies (1 occurrence).

• Anorexia: Reported in clinical studies (1 occurrence).

• Hyperthermia: Reported in clinical studies (1 occurrence).

• Lethargy: Reported in clinical studies (1 occurrence).

• Oxygen Saturation (SpO2) ≤90 mmHg: Experienced by 16 dogs during studies.

• Temperature Abnormalities:

  • ≥103°F: 25 dogs experienced this during studies.

  • ≤96°F: 27 dogs experienced this at one or more timepoints.

• Mean Blood Pressure (BP) ≤60 mmHg: Experienced by 59 dogs during studies.

• Ventricular Premature Depolarizations: Noted in 3 dogs in the alpha2-agonist + opioid group.

• Transient ST Depression: Observed in one dog in the phenothiazine + opioid group.

These adverse reactions highlight the importance of monitoring patients closely during and after the administration of these anesthetic agents.

Drug Interactions

There is no specific information available regarding drug interactions for Zoletil or Tzed. Both products, which are available in forms such as injection, powder, and lyophilized for solution, do not provide any documented interactions with other drugs or laboratory tests. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing these medications, as the absence of interaction data does not imply safety in combination with other therapies.

Pediatric Use

The use of Zoletil and Tzed is contraindicated in pediatric patients with pancreatic disease, severe cardiac or pulmonary dysfunction, and in pregnant animals due to their unknown teratogenic potential and the risk of respiratory depression in newborns.

Efficacy

In healthy cats, an initial dosage of 4.4 to 5.4 mg/lb (9.7 to 11.9 mg/kg) IM is recommended for procedures such as dentistry, treatment of abscesses, and foreign body removal. For minor procedures requiring mild to moderate analgesia, an initial dosage of 4.8 to 5.7 mg/lb (10.6 to 12.5 mg/kg) is suggested. For ovariohysterectomy and onychectomy, initial dosages of 6.5 to 7.2 mg/lb (14.3 to 15.8 mg/kg) are recommended. In dogs, an initial intramuscular dosage of 3 to 4.5 mg/lb (6.6 to 9.9 mg/kg) is advised for diagnostic purposes, and 4.5 to 6 mg/lb (9.9 to 13.2 mg/kg) for minor procedures of short duration.

Safety

Recovery from anesthesia varies with the age and physical condition of the animal, and is extended with high doses or multiple injections, particularly in cats. The maximum safe dose for dogs is 13.6 mg/lb (29.92 mg/kg) and for cats is 32.7 mg/lb (72 mg/kg). Death has been reported following administration in animals with preexisting pulmonary disease, renal disease, and shock.

Dosing Considerations

Dosage should be reduced in geriatric patients, those in debilitated condition, and in animals with renal impairment. It is recommended that the entire dose be administered as a single injection to improve the quality and predictability of anesthesia. Additionally, cats and smaller dogs should be protected from heat loss during anesthesia, with body temperature monitored and supplemental heat provided as necessary.

Geriatric Use

The dosage of Zoletil and Tzed should be reduced in geriatric patients, particularly those aged 65 years and older, as well as in patients who are in a debilitated condition or have renal function impairment. Recovery times may vary based on the age and physical condition of the patient, with prolonged recovery observed in cases of high doses or multiple injections, especially in cats. It is essential for healthcare providers to monitor these patients closely and consider dose modifications to ensure safety and efficacy.

Pregnancy

The use of Zoletil and Tzed is contraindicated in pregnant patients at any stage of pregnancy due to the unknown teratogenic potential associated with these medications. Both formulations contain tiletamine and zolazepam, which are known to cross the placental barrier and may lead to respiratory depression in the newborn. Consequently, their use during Cesarean sections is also contraindicated. The safety of Zoletil and Tzed in pregnant patients or their effects on reproduction have not been established, warranting caution and avoidance in this population.

Lactation

The safe use of Zoletil and Tzed in lactating mothers has not been established. Both medications have the potential for excretion in breast milk, which raises concerns regarding their effects on breastfed infants. Caution is advised when administering these drugs to nursing mothers due to the unknown risks associated with their use in this population. Healthcare professionals should carefully consider the benefits and risks before prescribing these medications to lactating patients.

Renal Impairment

Patients with renal impairment should be approached with caution when considering the use of certain anesthetic agents. Specifically, Telazol, Zoletil, and Tzed are not recommended for use in cats suffering from renal insufficiency due to their predominant renal excretion.

In patients with preexisting renal pathology or impaired renal function, there is a potential for prolonged duration of anesthesia, which may pose additional risks. Therefore, careful monitoring of these patients is essential to ensure their safety during anesthesia. Adjustments to dosing or alternative anesthetic options should be considered to mitigate the risks associated with renal impairment.

Hepatic Impairment

Patients with hepatic impairment have no specific dosage adjustments, special monitoring requirements, or precautions outlined for the use of Telazol, Zoletil, or Tzed. The available information does not provide guidance on the management of these medications in individuals with liver problems. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing these medications to patients with hepatic impairment.

Overdosage

In the event of an overdose, specific information regarding the management and symptoms associated with Telazol, Zoletil, and Tzed is not provided in the available literature. Therefore, healthcare professionals are advised to monitor patients closely for any adverse effects that may arise from excessive dosing of these medications.

Recommended actions in the case of suspected overdose include supportive care and symptomatic treatment. It is essential to maintain the patient's airway, breathing, and circulation. Continuous monitoring of vital signs and neurological status is advised to detect any potential complications early.

As no specific antidotes or treatment protocols are outlined for overdose situations with these medications, healthcare providers should exercise clinical judgment and consider consulting a poison control center or a medical toxicologist for further guidance.

Nonclinical Toxicology

Teratogenic Effects

The teratogenic potential of tiletamine and zolazepam, as found in products such as Zoletil and Tzed, is unknown. Therefore, these agents should not be used in pregnant bitches or queens at any stage of pregnancy. Studies indicate that tiletamine and zolazepam cross the placental barrier and can produce respiratory depression in newborns, making their use for Cesarean sections contraindicated.

Non-Teratogenic Effects

The safety of tiletamine and zolazepam in pregnant animals or their effects on reproduction have not been established. The agents are known to cross the placental barrier and cause respiratory depression in neonates.

Nonclinical Toxicology

Fatalities have been reported in both cats and dogs following intramuscular administration of tiletamine and zolazepam. Preexisting conditions such as pulmonary disease, renal disease, and shock were implicated at necropsy; however, at least one death was attributable to the drug in both a dog (of 1072) and a cat (of 1095).

Animal Pharmacology and Toxicology

Tiletamine and zolazepam for injection exhibit a wider margin of safety in cats compared to dogs. Dogs have tolerated repeated intramuscular dosage regimens of 13.6 mg/lb (30 mg/kg) for eight consecutive days, approximately double the maximum recommended therapeutic dose. Cats have survived intramuscular regimens of up to 32.7 mg/lb (72 mg/kg) on alternate days for seven episodes, which is 4.6 times the maximum recommended therapeutic dose for this species.

In cats, the duration of effect of zolazepam exceeds that of tiletamine, resulting in a greater degree of tranquilization than anesthetization during recovery. A slight decrease in blood pressure is observed during the first hour post-injection, while heart rate and electrocardiogram readings remain unaffected. Conversely, in dogs, the duration of effect of tiletamine surpasses that of zolazepam, leading to a lesser degree of tranquilization.

Following administration in dogs, a marked and persistent tachycardia occurs within two minutes after intramuscular injection of either 4.5 or 9 mg/lb (10 or 20 mg/kg). Stroke volume decreases in proportion to the increased heart rate at the 4.5 mg/lb (10 mg/kg) dose, with minimal change in net cardiac output. An initial increase in systolic blood pressure is noted, followed by a slight drop within five minutes, with systolic pressure remaining decreased throughout the anesthetic effect, while diastolic pressure increases.

During anesthesia with tiletamine and zolazepam, the assurance of a patent airway is enhanced by the maintenance of pharyngeal-laryngeal reflexes. Notably, within the first 15 minutes after administering 9 mg/lb (20 mg/kg), the respiratory rate doubles while tidal volume decreases to less than half of control values, leading to decreased arterial pO2 levels, which may result in hypoxemia and cyanosis. Pulmonary function typically returns to normal within 35 minutes post-administration.

Storage and Handling

The products are supplied in various forms including injection and powder for solution.

Storage Conditions:

• All products should be stored at controlled room temperature between 20° to 25°C (68° to 77°F).

• It is essential to discard any unused solution after the specified time frames:

  • For Telazol, unused solution should be discarded after 7 days at room temperature or after 56 days if refrigerated.

  • For Zoletil, the unused solution must be discarded after 4 days at room temperature or after 14 days when refrigerated.

  • For Tzed, the unused solution should be discarded after 8 days at room temperature or after 63 days if kept refrigerated.

Handling Requirements:

• Only clear solutions should be used, as the color may vary from colorless to light amber.