Telazol: Product Information (Page 2 of 4)

PRECAUTIONS

The dosage of TELAZOL should be reduced in
geriatric dogs and cats, in animals in debilitated
condition and in animals with impairment of
renal function. Death has occurred in both cats
and dogs following intramuscular TELAZOL
administration. Preexisting pulmonary disease,
renal disease (see Contraindications and
Warnings) and shock were causally implicated at
necropsy; however, death was drug attributable
in at least one dog (of 1072) and one cat (of 1095).
Intravenous TELAZOL has been demonstrated
to be safe in a field study in dogs when used in
conjunction with phenothiazine-derivative drugs
(acepromazine) administered at dosages from
0.04-0.06 mg/kg IM.
Cats and smaller dogs with small body masses
in relation to large body surfaces should be
protected from heat loss during TELAZOL
anesthesia. Body temperature should be
monitored, and supplemental heat may be
required to control hypothermia. As with
other anesthetics, it is prudent to provide for
hemostasis during any surgical procedure.
During TELAZOL anesthesia, athetoid movement
may occur. This athetosis should not be mistaken
for lack of anesthesia nor is it indicative of lack
of analgesia. Do not give additional anesthesia
in an attempt to abolish the athetoid movement.
Efforts to eliminate athetoid movement with
additional doses of TELAZOL can result in
anesthetic overdosage.
TELAZOL does not abolish laryngeal, pharyngeal,
pinnal, palpebral, and pedal reflexes, and may
not be adequate as the sole anesthetic for
surgical procedures in these areas. Endotracheal
tubes are not well tolerated in connection with TELAZOL anesthesia in the cat and their use may
result in impaired respiration. After removal of
the tube, normal respiration should resume.
The stimulation of surgical procedures aids in
maintaining adequate ventilation. The anesthetized
patient must be monitored throughout the
procedure, and if cardiopulmonary problems do
occur, measures must be taken to assure that
alveolar ventilation and cardiovascular functions are
maintained.
The eyes normally remain open with the pupils
dilated. The use of a bland ophthalmic ointment is
advisable to protect the corneas from desiccation.
The concurrent use of chloramphenicol will
prolong the duration of anesthesia in cats.
Copious salivation may occur during TELAZOL
anesthesia. Ptyalism may be controlled in dogs
and cats by administering atropine sulfate, USP,
0.02 mg/lb (0.04 mg/kg) body weight (IV, IM,
or SC) as concurrent medication. Exaggerated
swallowing, reflex action and accumulation of
saliva may give rise to vomiting and retching.

ADVERSE REACTIONS

For Restraint and Minor Procedures of Short
Duration Requiring Mild to Moderate
Analgesia
Respiratory depression may occur following
administration of high doses of TELAZOL. If at any
time respiration becomes excessively depressed
and the animal becomes cyanotic, resuscitative
measures should be instituted promptly. Adequate
pulmonary ventilation using either oxygen or room
air is recommended as a resuscitative measure.
Adverse reactions reported include emesis during
emergence, excessive salivation, transient apnea,
vocalization, erratic recovery and prolonged
recovery, excessive tracheal and bronchial
secretions when atropine sulfate, was not given
before 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 reported. Tachycardia
frequently occurs, particularly in the dog. This rise
in heart rate usually lasts about 30 minutes. Either
hypertension or hypotension may also occur.
Insufficient anesthesia has been reported in dogs.
Death has been reported in dogs and cats following
TELAZOL administration.

Intravenous Induction of Anesthesia followed by
Maintenance with Inhalant Anesthesia in Dogs
In a field study to assess the effectiveness and
safety of TELAZOL administered intravenously
at 1-2 mg/lb (2.2-4.4 mg/kg) for the induction of
anesthesia followed by maintenance with inhalant
anesthesia in dogs, 144 dogs were intravenously
administered TELAZOL (See Effectiveness).
Sixteen adverse reactions occurred during the
study: nystagmus (5), emesis (4), diarrhea (2), and
one occurrence each of hypersalivation, urticarial,
anorexia, hyperthermia, and lethargy. All adverse
reactions resolved by the end of the study.
Physiologic abnormalities related to general
anesthesia were transient and not severe.
Post-induction apnea (time from induction to
first inspiration ≥30 seconds) was observed in
49.3% of dogs across all treatment groups with a
mean duration of one minute. The highest overall
frequency and duration of post-induction apnea
was in the alpha2-agonist + opioid groups.
Overall, 36 dogs received assisted ventilation.
Assisted ventilation was needed most frequently
early in the procedure (at procedure start,
possibly after an apneic period) then decreased
in frequency as the procedure continued.
Sixteen dogs experienced oxygen saturation
(SpO2) ≤90 mmHg: 7 in the alpha2-agonist +
opioid groups, 6 in the phenothiazine + opioid
groups, and 3 in the opioid alone groups.
Twenty-five dogs had a temperature ≥103°F
during the study, with 12 of these occurring
prior to preanesthetic administration only. Of the
remaining 13 dogs, 7 were in the alpha2-agonist +
opioid groups, 5 were in the opioid alone groups,
and 1 in the phenothiazine + opioid groups.
One dog was reported with hyperthermia as an
adverse reaction in the alpha2-agonist + opioid
treatment groups. The dog became excitable
during recovery and its temperature elevated to
105.7°F. Hyperthermia resolved with treatment
of IV fluids and cooling.

Twenty-seven dogs experienced temperatures
≤96°F at one or more timepoints. Most dogs
received supplemental heat during surgery.
Fifty-nine dogs had mean blood pressure
(BP) values ≤60 mmHg. These values are
spread among all treatment groups. No dogs
were reported with adverse reactions due to
hypotension or hypertension in any dose groups.
Elevated or low BP values were transient.
Ventricular premature depolarizations were
noted in 3 dogs in the alpha2-agonist + opioid
group. This transient rhythm disturbance is
not uncommon in dogs receiving alpha2-
agonists or inhalant anesthetics. One dog in the
phenothiazine + opioid group showed transient
ST depression that could have been due to
cardiac hypoxia. All dogs recovered normally.
For a copy of the Safety Data Sheet (SDS) or
to report adverse reactions call Zoetis Inc. at
1-888-963-8471. Additional information can be
found at www.Zoetis.US.com.
For additional information about adverse drug
experience reporting for animal drugs, contact
FDA at 1-888-FDA-VETS or http://www.fda.gov/
reportanimalae.

CLINICAL PHARMACOLOGY

Mechanism of Action

TELAZOL is a rapid-acting anesthetic combination
of tiletamine hydrochloride and zolazepam
hydrochloride. Tiletamine hydrochloride is a
dissociative anesthetic agent whose pharmacologic
action is characterized by profound analgesia,
normal pharyngeal-laryngeal reflexes and
cataleptoid anesthesia. The anesthetic state
produced does not fit into the conventional
classification of stages of anesthesia, but instead
TELAZOL produces a state of unconsciousness
which has been termed “dissociative’’ anesthesia in
that it appears to selectively interrupt association
pathways to the brain before producing somesthetic
sensory blockade.
Cranial nerve and spinal reflexes remain active;
however, these reflexes must not be confused
with inadequate anesthesia. Analgesia results
from apparent selective interruption of sensory
inputs to the brain and usually persists after the
anesthetic effect has subsided.
Protective reflexes, such as coughing and
swallowing, are maintained under tiletamine
anesthesia. Other reflexes, e.g., corneal, pedal,
are maintained during tiletamine anesthesia,
and should not be used as criteria for judging
depth of anesthesia. The eyes normally remain
open with the pupil dilated. It is suggested that
a bland ophthalmic ointment be applied to the
cornea if anesthesia is to be prolonged.
Used alone, tiletamine hydrochloride does
not provide adequate muscle relaxation for
abdominal surgical procedures. When combined
with zolazepam hydrochloride, good muscle
relaxation is generally attained during the phase
of deep surgical anesthesia.

Pharmacokinetics
The pharmacokinetics of TELAZOL injectable
solution was evaluated in 12 healthy adult
Beagle dogs, following a single intravenous (IV)
administration of 2.2 mg/kg bodyweight, which
is equivalent to 1.1 mg/kg for both tiletamine
hydrochloride and zolazepam hydrochloride.
After administration of 2.2 mg/kg TELAZOL IV,
the initial mean concentration of tiletamine (C0)
was 1018 ng/mL, the systemic clearance (CL)
was 6223 mL/kg/h, the area under the curve to
the last measured concentration (AUC 0-last) was
178 ng*hr/mL, and steady state volume of
distribution (Vss) was 3250 mL/kg. The mean
elimination half-life of tiletamine was 0.87 hours.
For zolazepam, the mean C0 was 2594 ng/mL, CL
was 1993 mL/kg/h and Vss was 604 mL/kg. The mean
elimination half-life of zolazepam was 0.41 hours.
The mean C0 and AUC0-t(last) were approximately
2.5 and 3 times, respectively, greater for zolazepam
than for tiletamine. However, the mean half-life
(T1/2) of tiletamine was approximately 2.5 times
longer than for zolazepam, resulting in quantifiable
plasma concentrations up to 2 hours longer.
Pretreatment with an alpha-2 agonist or
phenothiazine followed by inhalant isoflurane
has been shown to increase in the initial
concentration of both tiletamine and zolazepam.