Chemistry - Xylazine HCl

Chemistry - Xylazine HCl is a alpha2-adrenergic agonist structurally related to clonidine. The pH
of the commercially prepared injections is approximately 5.5. Dosages and bottle concentrations are
expressed in terms of the base.
Storage/Stability/Compatibility - Do not store above 30¡C (86¡F). Xylazine is reportedly compatible
in the same syringe with several compounds, including: acepromazine, buprenorphine,
butorphanol, chloral hydrate, and meperidine.
Pharmacology - A potent alpha2-adrenergic agonist, xylazine is classified as a sedative/analgesic
with muscle relaxant properties. Although xylazine possesses several of the same pharmacologic
actions as morphine, it does not cause CNS excitation in cats, horses or cattle, but causes sedation
and CNS depression. In horses, the visceral analgesia produced has been demonstrated to be
superior to that produced by meperidine, butorphanol or pentazocine.
Xylazine causes skeletal muscle relaxation through central mediated pathways. Emesis is often
seen in cats, and is also seen occasionally in dogs receiving xylazine. While thought to be centrally
mediated, neither dopaminergic blockers (e.g., phenothiazines) or alpha-blockers (yohimbine,
tolazoline) block the emetic effect. Xylazine does not cause emesis in horses, cattle, sheep or goats.
Xylazine depresses thermoregulatory mechanisms and either hypothermia or hyperthermia is a
possibility depending on ambient air temperatures.
Effects on the cardiovascular system include an initial increase in total peripheral resistance with
increased blood pressure followed by a longer period of lowered blood pressures (below baseline).
A bradycardic effect can be seen with some animals developing a second degree heart block or
other arrhythmias. An overall decrease in cardiac output of up to 30% may be seen. Xylazine has
been demonstrated to enhance the arryhthmogenic effects of epinephrine in dogs with or without
concurrent halothane.
XylazineÕs effects on respiratory function are usually clinically insignificant, but at high dosages,
it can cause respiratory depression with decreased tidal volumes and respiratory rates and an overall
decreased minute volume. Brachycephalic dogs and horses with upper airway disease may develop
dyspnea.
Xylazine can induce increases in blood glucose secondary to decreased serum levels of insulin. In
non-diabetic animals, there appears to be little clinical significance associated with this effect.
In horses, sedatory signs include a lowering of the head with relaxed facial muscles and drooping
of the lower lip. The retractor muscle is relaxed in male horses, but unlike acepromazine, no reports
of permanent penile paralysis has been reported. Although, the animal may appear to be thoroughly
sedated, auditory stimuli may provoke arousal with kicking and avoidance responses.
With regard to the sensitivity of species to xylazine definite differences are seen. Ruminants are
extremely sensitive to xylazine when compared with horses, dogs, or cats. Ruminants generally
require approximately 1/10th the dosage that is required for horses to exhibit the same effect. In
cattle (and occasionally cats and horses), polyuria is seen following xylazine administration,
probably as a result of decreased production of vasopressin (anti-diuretic hormone, ADH).
Bradycardia and hypersalivation are also seen in cattle and are diminished by pretreating with atropine.
Swine, require 20-30 times the ruminant dose and therefore, xylazine is not routinely used
in this species.
Uses/Indications - Xylazine is approved for use in dogs, cats, horses, deer, and elk. It is indicated
in dogs, cats and horses to produce a state of sedation with a shorter period of analgesia, and as a
preanesthetic before local or general anesthesia. Because of the emetic action of xylazine in cats, it
is occasionally used to induce vomiting after ingesting toxins.
Pharmacokinetics - Absorption is rapid following IM injection, but bioavailabilities are incomplete
and variable. Bioavailabilities of 40-48% in the horse, 17-73% in the sheep, and 52-90% in the
dog have been reported after IM administration.
In horses, the onset of action following IV dosage occurs within 1-2 minutes with a maximum
effect 3-10 minutes after injection. The duration of effect is dose dependent but may last for approximately
1.5 hours. The serum half-life after a single dose of xylazine is approximately 50
minutes in the horse and recovery times generally take from 2-3 hours.
In dogs and cats, the onset of action following an IM or SQ dose is approximately 10-15 minutes,
and 3-5 minutes following an IV dose. The analgesic effects may persist for only 15-30 minutes,
but the sedative actions may last for 1-2 hours depending on the dose given. The serum half-live of
xylazine in dogs has been reported as averaging 30 minutes. Complete recovery after dosing may
take from 2-4 hours in dogs and cats.
Xylazine is not detected in milk of lactating dairy cattle at 5 & 21 hours post-dose, but the FDA
has not approved the use of this agent in dairy cattle and no meat or milk withdrawal times have
been specified.
Contraindications/Precautions - Xylazine is contraindicated in animals receiving epinephrine or
having active ventricular arrhythmias. It should be used with extreme
caution in animals withpreexisting cardiac dysfunction, hypotension or
shock, respiratory dysfunction, severe hepatic or
renal insufficiency, preexisting seizure disorders, or if severely debilitated. Because it may induce
premature parturition, it should generally not be used in the last trimester of pregnancy, particularly
in cattle.
Be certain of product concentration when drawing up into syringe, especially if treating ruminants.
Do not give to ruminants that are dehydrated, have urinary tract obstruction, or are debilitated. It is
not approved for any species to be consumed for food purposes.
Horses have been known to kick after a stimulatory event (usually auditory); use caution. Avoid
intra-arterial injection; may cause severe seizures and collapse. The manufacturers warn against
using in conjunction with other tranquilizers.
Adverse Effects/Warnings - Emesis is generally seen within 3-5 minutes after xylazine administration
in cats and occasionally in dogs. To prevent aspiration, do not induce further anesthesia until
this time period has lapsed. Other adverse effects listed in the package insert (Gemini¨, Butler) for
dogs and cats include: muscle tremors, bradycardia with partial A-V block, reduced respiratory rate,
movement in response to sharp auditory stimuli, and increased urination in cats.
Dogs may develop bloat from aerophagia which may require decompression. Because of gaseous
distention of the stomach, xylazineÕs use before radiography can make test interpretation difficult.
Adverse effects listed in the package insert (AnaSed¨, Lloyd) for horses include: muscle tremors,
bradycardia with partial A-V block, reduced respiratory rate, movement in response to sharp
auditory stimuli, and sweating (rarely profuse). Additionally, large animals may become ataxic
following dosing and caution should be observed.
Adverse reactions reported in cattle include salivation, ruminal atony, bloating and regurgitation,
hypothermia, diarrhea, and bradycardia. The hypersalivation and bradycardia may be alleviated by
pretreating with atropine. Xylazine may induce premature parturition in cattle.
Overdosage - In the event of an accidental overdosage, cardiac arrhythmias, hypotension, and
profound CNS and respiratory depression may occur. Seizures have also been reported after
overdoses. There has been much interest in using alpha-blocking agents as antidotes or reversal
agents to xylazine. Yohimbine or tolazoline have been suggested to be used alone and in combination
to reverse the effects of xylazine or speed recovery times. A separate monograph for
yohimbine is available which discusses suggested doses, etc.
To treat the respiratory depressant effects of xylazine toxicity, mechanical respiratory support with
respiratory stimulants (e.g., doxapram) have been recommended for use.
Drug Interactions - The use of epinephrine with & without the concurrent use of halothane
concomitantly with xylazine may induce the development of ventricular arrhythmias.
The combination use of acepromazine with xylazine is generally considered to be safe, but there
is potential for additive hypotensive effects and this combination should be used cautiously in
animals susceptible to hemodynamic complications.
Other CNS depressant agents (barbiturates, narcotics, anesthetics, phenothiazines, etc.)
may cause additive CNS depression if used with xylazine. Dosages of these agents may need to be
reduced.
A case report of a horse developing colic-like symptoms after reserpine and xylazine has been
reported. Until more is known about this potential interaction, use together of these two agents
together should be avoided.
The manufacturers warn against using xylazine in conjunction with other tranquilizers.
Doses -
Dogs:
a) 1.1 mg/kg IV, 1.1 - 2.2 mg/kg IM or SQ (Package Insert; Rompun¨ - Miles)
b) 0.6 mg/kg IV IM as a sedative (Morgan 1988)
c) To treat a hypoglycemic crises (with IV dextrose): 1.1 mg/kg IM (Schall 1985)
d) 0.5 - 1.0 mg/kg IV or 1 - 2 mg/kg IM (Davis 1985b)
e) 0.55 mg/kg IM (Mandsager 1988)
Cats:
a) 1.1 mg/kg IV, 1.1 - 2.2 mg/kg IM or SQ (Package Insert; Rompun¨ÑMiles)
b) As an emetic: 0.44 mg/kg IM (Morgan 1988), (Riviere 1985)
c) 0.5 - 1.0 mg/kg IV or 1 - 2 mg/kg IM (Davis 1985b)
d) 0.55 mg/kg IM (Mandsager 1988)
Rabbits/Rodents/Pocket Pets:
Rabbits: For minimally invasive procedures lasting less than 30-45 minutes: 5 mg/kg once
SubQ or IM in combination with ketamine (35 mg/kg)
Mice/Rats: General anesthesia 13 mg/kg once IP in combination with ketamine (87 mg/kg)
Hamsters/Guinea pigs: General anesthesia 8 - 10 mg/kg once IP in combination with ketamine
(200 mg/kg for hamsters & 60 mg/kg for Guinea pigs) (Huerkamp 199Cattle:
Caution: Cattle are extremely sensitive to xylazineÕs effects; be certain of dose and dosage
form. Pretreatment with atropine can decrease the bradycardia and hypersalivation seen.
a) 0.05 - 0.15 mg/kg IV; 0.10 - 0.33 mg/kg IM. If administering IM use an 18 or 20
gauge needle at least 1.5 inches long. Intravenous route may stress cardiovascular
function. (Thurmon and Benson 1986)
b) 0.044 - 0.11 mg/kg IV; 0.22 mg/kg IM (Mandsager 1988)
Horses:
a) 1.1 mg/kg IV; 2.2 mg/kg IM. Allow animal to rest quietly until full effect is reached.
(Package Insert; Rompun¨ - Miles)
b) Sedative/analgesic for colic: 0.3 - 0.5 mg/kg IV; repeat as necessary (Muir 1987)
c) Prior to guaifenesin/thiobarbiturate anesthesia: 0.55 mg/kg IV; Prior to ketamine induction:
1.1 mg/kg IV; In combination with opioid/tranquilizers (all IV doses):
1) xylazine 0.66 mg/kg; meperidine 1.1 mg/kg
2) xylazine 1.1 mg/kg; butorphanol 0.01 - 0.02 mg/kg
3) xylazine 0.6 mg/kg; acepromazine 0.02 mg/kg
Note: the manufacturers state that xylazine should not be used in conjunction with tranquilizers
(Thurmon and Benson 1987)
Sheep & Goats: Note: Use xyalazine with extreme caution in these species.
a) 0.05 - 0.10 mg/kg IV; 0.10 - 0. 22 IM (Thurmon and Benson 1986)
b) 0.044 - 0.11 mg/kg IV; 0.22 mg/kg IM (Mandsager 1988)
Exotics:
a) An excellent list of suggested dosages can be found on page 359 of Veterinary
Pharmacology and Therapeutics, 6th Ed., Booth, NH & McDonald, LE, Eds.; 1988;
Iowa State University Press; Ames, Iowa
Monitoring Parameters - 1) Level of anesthesia/analgesia; 2) Respiratory function; cardiovascular
status (rate, rhythm, BP if possible); 3) Hydration status if polyuria present
Client Information - Xylazine should only be used by individuals familiar with its use.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved Products:
Rompun¨ (Bayer) Gemini¨ (Butler); AnaSed¨ (Lloyd);Sedazine¨ (Fort Dodge) (Rx)
Approved for use (depending on strength) in dogs, cats, horses, deer, and elk.
While xyalzine is not approved for use in cattle in the USA, at labeled doses in Canada it reportedly
has been assigned withdrawal times of 3 days for meat and 48 hours for milk.
FARAD has reportedly suggested a withdrawal of 7 days for meat and 72 hours for milk for
extra-label use in the USA.
Human-Approved Products: None5








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