Tzed

Description

Tzed (tiletamine and zolazepam for injection) is a nonnarcotic, nonbarbiturate, injectable anesthetic agent indicated for use in dogs and cats. It consists of equal parts by weight of tiletamine hydrochloride and zolazepam hydrochloride. Tiletamine hydrochloride is chemically defined as 2-ethylamino-2-2-thienyl-cyclohexanone hydrochloride, while zolazepam hydrochloride is identified as 4-o-fluorophenyl-6, 8-dihydro-1,3,8-trimethylpyrazolo 3, 4-e 1,4 diazepin-7 1H-1-hydrochloride. The product is supplied sterile in vials. When 5 mL of diluent is added, the resulting solution contains the equivalent of 50 mg tiletamine base, 50 mg zolazepam base, and 57.7 mg mannitol per milliliter, with a pH range of 2 to 3.5.

Uses and Indications

This drug is indicated for intramuscular and intravenous injection in dogs. It is also indicated for intramuscular injection only in cats.

Dosage and Administration

For dogs, the recommended dosage for intramuscular (IM) administration for restraint and minor procedures is as follows: an initial dosage of 3 to 4.5 mg/lb (6.6 to 9.9 mg/kg) is advised for diagnostic purposes. For minor procedures, the dosage should be increased to 4.5 to 6 mg/lb (9.9 to 13.2 mg/kg). The total dose, including both initial and supplemental doses, must 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 aimed at the induction of anesthesia, Tzed should be administered at a dosage of 1-2 mg/lb (2.2-4.4 mg/kg) of body weight. The administration should be performed slowly over a period of 30-45 seconds. After 30-60 seconds, the level of consciousness should be assessed; if the effect is insufficient, additional Tzed may be administered, ensuring that the total does not exceed 2 mg/lb (4.4 mg/kg).

In cats, the initial dosage for IM administration for procedures such as dentistry and abscess treatment is recommended at 4.4 to 5.4 mg/lb (9.7 to 11.9 mg/kg). For minor procedures, a dosage of 4.8 to 5.7 mg/lb (10.6 to 12.5 mg/kg) is appropriate. For more invasive procedures like ovariohysterectomy and onychectomy, the dosage should be increased to 6.5 to 7.2 mg/lb (14.3 to 15.8 mg/kg). The total dose, including both initial and supplemental doses, must 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 prior to elective surgery. It is important to note that individual responses to Tzed may vary based on factors such as dose, physical condition, age, and any preanesthetics used. Recovery time will also vary according to 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 responses to nociceptive stimuli is essential to evaluate the depth of anesthesia.

Contraindications

The use of Tzed is contraindicated in dogs and cats with pancreatic disease due to the potential for exacerbating the condition. Additionally, Tzed should not be administered to animals with severe cardiac or pulmonary dysfunction, as it may worsen their clinical status.

Tzed is also contraindicated in pregnant bitches and queens at any stage of pregnancy because of its unknown teratogenic potential. Furthermore, its use during Cesarean sections is contraindicated, as the components tiletamine and zolazepam can cross the placental barrier, leading to respiratory depression in the newborn.

Warnings and Precautions

The use of Tzed is restricted to dogs and cats only. When administering Tzed for the induction of anesthesia, it is imperative that patients are continuously monitored throughout the procedure. Facilities must be equipped to maintain a patent airway, provide artificial ventilation, and offer oxygen supplementation as necessary.

In cats, the administration of tiletamine and zolazepam for injection has been associated with the occurrence of pulmonary edema. Clinicians should be vigilant for signs and symptoms such as dyspnea, lethargy, anorexia, and abnormal behavior, as these may indicate the onset of pulmonary edema. In severely affected individuals, fatalities have been reported. Therefore, close observation of cats for any indicative signs is essential to ensure timely intervention and appropriate therapy.

Tzed is primarily excreted through the kidneys, making it unsuitable for use in cats with renal insufficiency. Preexisting renal pathology or impaired renal function may lead to an extended duration of anesthesia, necessitating careful consideration of the patient's renal status prior to administration.

The concomitant use of Tzed with phenothiazine-derivative drugs at the indicated dosages for intramuscular (IM) injection is contraindicated, as this combination can result in significant respiratory and myocardial depression, hypotension, and hypothermia.

The safety of Tzed in pregnant animals or its effects on reproduction have not been established. It is important to note that Tzed crosses the placental barrier and may induce respiratory depression in neonates. Therefore, caution is advised when considering the use of Tzed in pregnant patients.

Side Effects

Respiratory depression may occur following the administration of high doses of Tzed. Serious adverse reactions reported include cardiac arrest, pulmonary edema, and death in dogs and cats following tiletamine and zolazepam administration. In addition, pulmonary edema has been specifically noted in cats, with signs and symptoms such as dyspnea, lethargy, anorexia, and abnormal behavior.

Common adverse reactions observed during the use of Tzed for restraint and minor procedures requiring mild to moderate analgesia include emesis during emergence, excessive salivation, transient apnea, vocalization, erratic and prolonged recovery, excessive tracheal and bronchial secretions (notably when atropine sulfate was not administered prior to anesthesia), involuntary muscular twitching, hypertonicity, cyanosis, central nervous system stimulation, convulsions, and tachycardia, which frequently occurs, particularly in dogs, lasting approximately 30 minutes. Additionally, either hypertension or hypotension may occur, and insufficient anesthesia has been reported in dogs.

In a study involving intravenous induction of anesthesia followed by maintenance with inhalant anesthesia in dogs, sixteen adverse reactions were documented, including nystagmus (5 cases), emesis (4), diarrhea (2), hypersalivation (1), urticarial (1), anorexia (1), hyperthermia (1), and lethargy (1). All adverse reactions resolved by the end of the study. Notably, post-induction apnea, defined as the time from induction to the first inspiration being 30 seconds or longer, was observed in 49.3% of dogs across all treatment groups, with a mean duration of one minute. Oxygen saturation (SpO2) levels of ≤90 mmHg were experienced by sixteen dogs, while twenty-five dogs had a temperature of ≥103°F, and twenty-seven dogs experienced temperatures of ≤96°F at one or more time points. Mean blood pressure (BP) values of ≤60 mmHg were noted in fifty-nine dogs, and ventricular premature depolarizations were observed in three dogs in the alpha2-agonist + opioid group, with one dog in the phenothiazine + opioid group showing transient ST depression.

During Tzed anesthesia, athetoid movement and copious salivation may occur. Ptyalism can be managed in dogs and cats by administering atropine sulfate, as exaggerated swallowing, reflex action, and accumulation of saliva may lead to vomiting and retching.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

Packaging & NDC

The table below lists each NDC Code for Tzed (tiletamine hydrochloride and zolazepam hydrochloride) veterinary formulations. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The use of Tzed is contraindicated in pediatric patients, specifically in dogs and cats with pancreatic disease, severe cardiac or pulmonary dysfunction, and in pregnant bitches or queens at any stage of pregnancy due to its unknown teratogenic potential and respiratory depression effects on newborns.

Dosage adjustments are necessary for geriatric animals, those in debilitated condition, and those with renal impairment. In healthy cats, an initial intramuscular dosage of 4.4 to 5.4 mg/lb (9.7 to 11.9 mg/kg) is recommended for procedures such as dentistry and abscess treatment, while 4.8 to 5.7 mg/lb (10.6 to 12.5 mg/kg) is suggested for minor procedures requiring mild to moderate analgesia. For more invasive surgeries like ovariohysterectomy and onychectomy, initial dosages of 6.5 to 7.2 mg/lb (14.3 to 15.8 mg/kg) are indicated. In dogs, an initial intramuscular dosage of 3 to 4.5 mg/lb (6.6 to 9.9 mg/kg) is recommended for diagnostic purposes, with 4.5 to 6 mg/lb (9.9 to 13.2 mg/kg) for minor procedures of short duration.

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). It is important to administer the entire dose as a single injection to improve the quality and predictability of anesthesia. Additionally, cats and smaller dogs should be monitored for heat loss during anesthesia, as they are at risk for hypothermia.

Adverse outcomes, including death, have been reported following intramuscular administration of Tzed, particularly in animals with preexisting pulmonary or renal disease, or those in shock. The safety of Tzed in pregnant animals and its effects on reproduction have not been established, as it crosses the placental barrier and may cause respiratory depression in neonates. Recovery from anesthesia may vary based on the age and physical condition of the animal, with prolonged recovery noted in cases of high doses or multiple injections, especially in cats.

Geriatric Use

Elderly patients may require dosage adjustments when receiving Tzed. Specifically, the dosage should be reduced in geriatric dogs and cats, as well as in animals that are in a debilitated condition or have impaired renal function.

Healthcare providers should exercise caution when prescribing Tzed to geriatric patients, ensuring that appropriate monitoring is conducted to assess the efficacy and safety of the treatment. Adjustments in dosage may be necessary to mitigate potential risks associated with the pharmacokinetics and pharmacodynamics in this population.

Pregnancy

The use of Tzed is contraindicated in pregnant bitches or queens at any stage of pregnancy due to the unknown teratogenic potential. Tiletamine and zolazepam, components of Tzed, are known to cross the placental barrier and may produce respiratory depression in the newborn. Consequently, the use of Tzed for Cesarean sections is also contraindicated. The safety of Tzed in pregnant animals or its effects on reproduction have not been established, and healthcare professionals should exercise caution when considering its use in this population.

Lactation

The safe use of Tzed in nursing mothers has not been established. There is a potential for excretion of Tzed in breast milk. Caution should be exercised when administering Tzed to lactating mothers due to the potential risk to the breastfed infant.

Renal Impairment

Patients with renal impairment may experience prolonged duration of anesthesia due to the predominant renal excretion of Tzed. As the principal route of excretion for both components is the urine, Tzed is not recommended for use in patients with renal insufficiency. It is essential for healthcare professionals to consider these factors when administering Tzed to patients with reduced kidney function, as preexisting renal pathology may significantly impact the drug's pharmacokinetics and overall safety profile.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

There is currently no specific information available regarding overdosage for this medication. Healthcare professionals are advised to monitor patients closely for any signs of adverse effects or symptoms that may arise from excessive dosing.

In the event of suspected overdosage, it is recommended that healthcare providers initiate supportive care and symptomatic treatment as necessary. Patients should be evaluated for potential complications, and appropriate interventions should be implemented based on clinical judgment.

For further guidance, healthcare professionals may refer to established protocols for managing drug overdosage or consult a poison control center.

Nonclinical Toxicology

The teratogenic potential of Tzed is currently unknown; therefore, its use in pregnant bitches or queens at any stage of pregnancy is contraindicated. Studies indicate that tiletamine and zolazepam can cross the placental barrier, leading to respiratory depression in newborns. Consequently, the use of Tzed for Cesarean sections is not recommended.

The safety of Tzed in pregnant animals or its effects on reproduction have not been established. It has been observed that Tzed crosses the placental barrier and can cause respiratory depression in neonates.

In nonclinical studies, fatalities have been reported in both cats and dogs following intramuscular administration of tiletamine and zolazepam. Necropsy findings implicated preexisting pulmonary disease, renal disease, and shock; however, at least one death was determined to be drug-related in one dog (of 1072) and one cat (of 1095).

Animal pharmacology and toxicology data suggest that tiletamine and zolazepam for injection has 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, which is approximately double the maximum recommended therapeutic dose. In contrast, cats have survived intramuscular dosages of up to 32.7 mg/lb (72 mg/kg) on alternate days for seven episodes, equating to 4.6 times the maximum recommended therapeutic dose for this species.

In cats, the duration of effect of zolazepam is longer than that of tiletamine, resulting in a greater degree of tranquilization than anesthetization during recovery. Conversely, in dogs, the duration of effect of tiletamine exceeds that of zolazepam, leading to a lesser degree of tranquilization compared to anesthetization.

Physiological effects observed following administration of tiletamine and zolazepam for injection in dogs include a marked, persistent tachycardia occurring 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 decrease within five minutes, with systolic pressure remaining at this lower level throughout the anesthetic effect, while diastolic pressure increases during the same period.

During anesthesia with tiletamine and zolazepam for injection, the maintenance of pharyngeal-laryngeal reflexes significantly enhances the assurance of a patent airway. Notably, within the first 15 minutes after intramuscular administration of 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 manifest as hypoxemia and cyanosis. Pulmonary function typically returns to normal within 35 minutes following administration.

Postmarketing Experience

Pulmonary edema has been reported in cats following the administration of tiletamine and zolazepam for injection. Clinical signs associated with this condition include dyspnea, lethargy, anorexia, and abnormal behavior, with occasional fatalities noted in severely affected individuals. It is recommended that cats be closely monitored for any signs indicative of pulmonary edema to facilitate timely therapeutic intervention.

Deaths have been documented in both cats and dogs after intramuscular administration of tiletamine and zolazepam. While preexisting pulmonary disease, renal disease, and shock were identified as potential contributing factors at necropsy, at least one case of death was determined to be drug-related in one dog (out of 1072) and one cat (out of 1095).

Adverse reactions reported include emesis during emergence, excessive salivation, transient apnea, vocalization, erratic and prolonged recovery, excessive tracheal and bronchial secretions (notably when atropine sulfate was not administered prior to anesthesia), involuntary muscular twitching, hypertonicity, cyanosis, cardiac arrest, pulmonary edema, and muscle rigidity during surgical procedures. Central nervous system stimulation and convulsions have also been observed. Tachycardia is frequently noted, particularly in dogs, typically lasting about 30 minutes. Both hypertension and hypotension may occur, and instances of insufficient anesthesia have been reported in dogs.

In a field study evaluating the safety and effectiveness of intravenous tiletamine and zolazepam at doses of 1-2 mg/lb (2.2-4.4 mg/kg) for anesthesia induction followed by inhalant maintenance in dogs, 16 adverse reactions were recorded: nystagmus (5 cases), emesis (4 cases), diarrhea (2 cases), and one case each of hypersalivation, urticaria, anorexia, hyperthermia, and lethargy. All adverse reactions resolved by the conclusion of the study.

Post-induction apnea, defined as a duration of 30 seconds or more from induction to the first inspiration, was observed in 49.3% of dogs across all treatment groups, with a mean duration of one minute. The highest frequency and duration of post-induction apnea were noted in the alpha2-agonist + opioid groups.

Sixteen dogs exhibited oxygen saturation (SpO2) levels of 90 mmHg or lower, with 7 in the alpha2-agonist + opioid groups, 6 in the phenothiazine + opioid groups, and 3 in the opioid alone groups. Additionally, 25 dogs had a temperature of 103°F or higher during the study, with 12 of these occurrences noted prior to preanesthetic administration. Among the remaining 13 dogs, 7 were in the alpha2-agonist + opioid groups, 5 in the opioid alone groups, and 1 in the phenothiazine + opioid groups. One dog in the alpha2-agonist + opioid treatment group experienced hyperthermia, which resolved with intravenous fluid treatment and cooling.

Twenty-seven dogs experienced temperatures of 96°F or lower at one or more time points, with most receiving supplemental heat during surgery. Mean blood pressure (BP) values of 60 mmHg or lower were recorded in 59 dogs across all treatment groups, with no adverse reactions attributed to hypotension or hypertension reported. Elevated or low BP values were generally transient.

Ventricular premature depolarizations were observed in 3 dogs within the alpha2-agonist + opioid group, a transient rhythm disturbance not uncommon in dogs receiving alpha2-agonists or inhalant anesthetics. One dog in the phenothiazine + opioid group exhibited transient ST depression, potentially related to cardiac hypoxia. All affected dogs recovered without complications.

Patient Counseling

Healthcare providers should inform patients that federal law restricts the use of this drug to licensed veterinarians or under their order. It is important to advise that fasting prior to the induction of general anesthesia with Tzed is not essential; however, for elective surgery, withholding food for at least 12 hours before administration is recommended.

Patients should be made aware that recovery from anesthesia can vary based on the age and physical condition of the animal, as well as the dose of Tzed administered. Recovery may be prolonged with higher doses or multiple injections, particularly in cats. It is also crucial to communicate that there may be pain associated with the injection, which is especially common in cats.

The onset of anesthetic effect typically occurs within 5 to 12 minutes following a single, deep intramuscular injection of Tzed in cats and dogs. Muscle relaxation is generally optimal for the first 20 to 25 minutes post-administration, after which it diminishes. Providers should explain that the quality of anesthesia with repeated doses may vary due to changes in the ratio of the drug's components in the animal's body, influenced by differing rates of metabolism and elimination.

Monitoring the patient for any deliberate conscious response to nociceptive stimuli is the best method for evaluating the depth of anesthesia. If the recommended dosage does not produce adequate anesthesia, supplemental anesthesia or an alternative agent should be considered.

Patients should be informed that the eyes typically remain open with dilated pupils, and the application of a bland ophthalmic ointment is advisable to protect the corneas from drying out. Additionally, copious salivation may occur during anesthesia, which can be managed in dogs and cats by administering atropine sulfate, USP, at a dosage of 0.02 mg/lb (0.04 mg/kg) body weight via IV, IM, or SC routes. It is important to note that exaggerated swallowing and saliva accumulation may lead to vomiting and retching.

Continuous monitoring of the patient during the use of Tzed for anesthesia induction is essential. Facilities for maintaining a patent airway, artificial ventilation, and oxygen supplementation should be readily available. Cats should be closely observed for any signs of pulmonary edema, allowing for timely intervention if necessary.

Healthcare providers should emphasize that stimulation during surgical procedures can help maintain adequate ventilation. The anesthetized patient must be monitored throughout the procedure, and if any cardiopulmonary issues arise, immediate measures should be taken to ensure proper alveolar ventilation and cardiovascular function. In cases of excessive respiratory depression leading to cyanosis, prompt resuscitative measures should be initiated, with adequate pulmonary ventilation using either oxygen or room air recommended as a resuscitative action.

Storage and Handling

The product is supplied in a clear solution, which may vary in color from colorless to light amber. It is essential to store the solution at a controlled room temperature of 68-77°F (20-25°C).

Unused solution should be discarded after 8 days when stored at room temperature. If the solution is kept refrigerated, it should be discarded after 63 days. Only clear solutions should be utilized, ensuring that any discolored solutions are not used.

Additional Clinical Information

No further data are available.

Drug Information (PDF)

This document includes the full labeling information for Tzed, as submitted by Dechra Veterinary Products LLC for veterinary use. It may include dosage by species, withdrawal periods, and administration instructions.

View veterinary label (PDF)