ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
DEXDOMITOR 0.5 mg/ml solution for injection
2.
Active substance:
One ml contains 0.5 mg dexmedetomidine hydrochloride
equivalent to 0.42 mg dexmedetomidine.
Excipients:
Methyl parahydroxybenzoate (E 218) 1.6 mg/ml
Propyl parahydroxybenzoate (E 216) 0.2 mg/ml
3.
Solution for injection
Clear, colourless solution
4.
Dogs and cats.
Non-invasive, mildly to moderately painful, procedures and examinations which require restraint,
sedation and analgesia in dogs and cats.
Deep sedation and analgesia in dogs in concomitant use with butorphanol for medical and minor
surgical procedures.
Premedication in dogs and cats before induction and maintenance of general anaesthesia.
Do not use in animals with cardiovascular disorders.
Do not use in animals with severe systemic disease or in animals that are moribund.
Do not use in case of known hypersensitivity to the active substance or to any of the excipients.
The administration of dexmedetomidine to puppies younger than 16 weeks and kittens younger than
12 weeks has not been studied.
The safety of dexmedetomidine has not been established in males intended for breeding.
In cats, corneal opacities may occur during sedation. The eyes should be protected by a suitable eye
lubricant.
2
Treated animals should be kept warm and at a constant temperature, both during the procedure and
recovery.
It is recommended that animals are fasted for 12 hours prior to Dexdomitor administration. Water may
be given
.
After treatment, the animal should not be given water or food before it is able to swallow.
The eyes should be protected by a suitable lubricant.
To be used with precaution in elderly animals.
Nervous, aggressive or excited animals should be given the possibility to calm down before initiation
of treatment.
Frequent and regular monitoring of respiratory and cardiac function should be performed. Pulse
oximetry may be useful but is not essential for adequate monitoring. Equipment for manual
ventilation should be available in case of respiratory depression or apnoea when dexmedetomidine
and ketamine are used sequentially to induce anaesthesia in cats. It is also advisable to have oxygen
readily available, should hypoxaemia be detected or suspected.
Sick and debilitated dogs and cats should only be premedicated with dexmedetomidine before
induction and maintenance of general anaesthesia based on a risk-benefit assessment.
Use of dexmedetomidine as a premedicant in dogs and cats significantly reduces the amount of
induction drug required for induction of anaesthesia. Attention should be given during the
administration of intravenous induction drugs to effect. Volatile anaesthetic requirements for
maintenance anaesthesia are also reduced.
Special precautions to be taken by the person administering the veterinary medicinal product to
animals
In case of accidental oral intake or self-injection, seek medical advice immediately and show the
package insert to the physician but DO NOT DRIVE as sedation and changes in blood pressure may
occur.
Avoid skin, eye or mucosal contact; the use of impermeable gloves is advisable. In case of skin or
mucosal contact, wash the exposed skin immediately after exposure with large amounts of water and
remove contaminated clothes that are in direct contact with skin. In case of eye contact, rinse
abundantly with fresh water. If symptoms occur, seek the advice of a physician.
If pregnant women handle the product, special caution should be observed not to self-inject as uterine
contractions and decreased foetal blood pressure may occur after accidental systemic exposure.
Advice to doctors: Dexdomitor is an α
2
-adrenoreceptor agonist, symptoms after absorption may
involve clinical effects including dose-dependent sedation, respiratory depression, bradycardia,
hypotension, a dry mouth, and hyperglycaemia. Ventricular arrhythmias have also been reported.
Respiratory and haemodynamic symptoms should be treated symptomatically. The specific α2
–
adrenoceptor antagonist, atipamezole, which is approved for use in animals, has been used in humans
only experimentally to antagonize dexmedetomidine-induced effects.
Persons with known hypersensitivity to the active substance or any of the excipients should administer
the product with caution.
3
By virtue of its α
2
-adrenergic activity, dexmedetomidine causes a decrease in heart rate and body
temperature.
In some dogs and cats, a decrease in respiratory rate may occur. Rare instances of pulmonary oedema
have been reported. Blood pressure will increase initially and then return to normal or below normal.
Due to peripheral vasoconstriction and venous desaturation in the presence of normal arterial
oxygenation, the mucous membranes may appear pale and/or with a blue tinge.
Vomiting may occur 5-10 minutes after injection. Some dogs and cats may also vomit at the time of
recovery.
Muscle tremors may occur during sedation.
Corneal opacities may occur during sedation (see also section 4.5).
When dexmedetomidine and ketamine are used sequentially, with a 10 minute interval, cats may
occasionally experience AV-block or extrasystole. Expected respiratory events are bradypnoea,
intermittent respiratory patterns, hypoventilation, and apnoea. In clinical trials the incidence of
hypoxaemia was common, especially within the 15 first minutes into dexmedetomidine-ketamine
anaesthesia. Vomiting, hypothermia and nervousness have been reported after such use.
When dexmedetomidine and butorphanol are used concomitantly in dogs, bradypnoea, tachypnoea, an
irregular respiratory pattern (20-30 sec apnoea followed by several rapid breaths), hypoxaemia,
muscle twitch or tremor or paddling, excitation, hypersalivation, retching, vomiting, urination, skin
erythema, a sudden arousal, or prolonged sedation may occur. Brady- and tachyarrhythmias have been
reported. These may include profound sinus bradycardia, 1
st
and 2
nd
degree AV block, sinus arrest or
pause, as well as atrial, supraventricular and ventricular premature complexes.
When dexmedetomidine is used as a premedicant in dogs bradypnoea, tachypnoea and vomiting may
occur. Brady- and tachyarrhythmias have been reported and include profound sinus bradycardia, 1
st
and 2
nd
degree AV block and sinus arrest. Supraventricular and ventricular premature complexes,
sinus pause and 3
rd
degree AV block may be observed in rare cases.
When dexmedetomidine is used as a premedicant in cats, vomiting, retching, pale mucous membranes,
and low body temperature may occur. Intramuscular dosing at 40 mcg/kg (followed by ketamine or
propofol) frequently resulted in sinus bradycardia and sinus arrhythmia, occasionally resulted in 1
st
degree atrioventricular block, and rarely resulted in supraventricular premature depolarizations, atrial
bigeminy, sinus pauses, 2
nd
degree atrioventricular block, or escape beats/rhythms.
The safety of dexmedetomidine has not been established during pregnancy and lactation in the target
species. Therefore the use of the product during pregnancy and lactation is not recommended.
The use of other central nervous system depressants is expected to potentiate the effects of
dexmedetomidine and therefore an appropriate dose adjustment should be made. Anticholinergics
should be used with caution with dexmedetomidine.
Administration of atipamezole after dexmedetomidine rapidly reverses the effects and thus shortens
the recovery period. Within 15 minutes dogs and cats are normally awake and standing.
4
Cats: After administration of 40 micrograms dexmedetomidine/kg bw intramuscularly concurrently
with 5 mg ketamine/kg bw to cats, the maximum concentration of dexmedetomidine increased twofold
but there was no effect on T
max
. The mean half-life of elimination of dexmedetomidine increased to
1.6 h and the total exposure (AUC) increased by 50%.
A dose of 10 mg ketamine/ kg used concurrently with 40 micrograms dexmedetomidine/ kg may cause
tachycardia.
For information on adverse reactions, see section 4.6.Adverse reactions.
For information on target animal safety in cases of overdosing, see section 4.10.Overdose
The product is intended for:
-
Dogs: intravenous or intramuscular use
-
Cats: intramuscular use
The product is not intended for repeat injections.
Dexdomitor, butorphanol and/or ketamine can be mixed in the same syringe as they have been shown
to be pharmaceutically compatible.
Dosage: the following doses are recommended:
DOGS:
Dexmedetomidine doses are based on body surface area:
Intravenously: up to 375 micrograms/square metre body surface area
Intramuscularly: up to 500 micrograms/square metre body surface area
When administering in conjunction with butorphanol (0.1 mg/kg) for deep sedation and analgesia, the
intramuscular dose of dexmedetomidine is 300 micrograms/square metre body surface area. The
premedication dose of dexmedetomidine is 125 – 375 micrograms/square metre body surface area,
administered 20 minutes prior to induction for procedures requiring anaesthesia. The dose should be
adjusted to the type of surgery, length of procedure and patient temperament.
Concomitant use of dexmedetomidine and butorphanol produces sedative and analgesic effects
beginning no later than 15 minutes. The peak sedative and analgesic effects are reached within 30
minutes after administration. Sedation lasts for at least 120 minutes post administration and analgesia
lasts for at least 90 minutes. Spontaneous recovery occurs within 3 hours.
Premedication with dexmedetomidine will significantly reduce the dosage of the induction agent
required and will reduce volatile anaesthetic requirements for maintenance anaesthesia. In a clinical
study, the requirement for propofol and thiopental was reduced by 30% and 60% respectively. All
anaesthetic agents used for induction or maintenance of anaesthesia should be administered to effect.
In a clinical study, dexmedetomidine contributed to postoperative analgesia for 0.5 – 4 hours.
However this duration is dependent on a number of variables and further analgesia should be
administered in accordance with clinical judgement.
The corresponding doses based on body weight are presented in the following tables. Use of an
appropriately graduated syringe is recommended to ensure accurate dosing when administering small
volumes.
5
Dog
Weight
Dexmedetomidine
125 mcg/m
2
Dexmedetomidine
375 mcg/m
2
Dexmedetomidine
500 mcg/m
2
(kg)
(mcg/kg)
(ml)
(mcg/kg)
(ml)
(mcg/kg)
(ml)
2-3
9.4
0.04
28.1
0.12
40
0.15
3-4
8.3
0.05
25
0.17
35
0.2
4-5
7.7
0.07
23
0.2
30
0.3
5-10
6.5
0.1
19.6
0.29
25
0.4
10-13
5.6
0.13
16.8
0.38
23
0.5
13-15
5.2
0.15
15.7
0.44
21
0.6
15-20
4.9
0.17
14.6
0.51
20
0.7
20-25
4.5
0.2
13.4
0.6
18
0.8
25-30
4.2
0.23
12.6
0.69
17
0.9
30-33
4
0.25
12
0.75
16
1.0
33-37
3.9
0.27
11.6
0.81
15
1.1
37-45
3.7
0.3
11
0.9
14.5
1.2
45-50
3.5
0.33
10.5
0.99
14
1.3
50-55
3.4
0.35
10.1
1.06
13.5
1.4
55-60
3.3
0.38
9.8
1.13
13
1.5
60-65
3.2
0.4
9.5
1.19
12.8
1.6
65-70
3.1
0.42
9.3
1.26
12.5
1.7
70-80
3
0.45
9
1.35
12.3
1.8
>80
2.9
0.47
8.7
1.42
12
1.9
For deep sedation and analgesia with butorphanol
Dog
Weight
Dexmedetomidine
300 mcg/m
2
intramuscularly
(kg)
(mcg/kg)
(ml)
2-3
24
0.12
3-4
23
0.16
4-5
22.2
0.2
5-10
16.7
0.25
10-13
13
0.3
13-15
12.5
0.35
15-20
11.4
0.4
20-25
11.1
0.5
25-30
10
0.55
30-33
9.5
0.6
33-37
9.3
0.65
37-45
8.5
0.7
45-50
8.4
0.8
50-55
8.1
0.85
55-60
7.8
0.9
60-65
7.6
0.95
65-70
7.4
1
70-80
7.3
1.1
>80
7
1.2
6
CATS:
The dosage for cats is 40 micrograms dexmedetomidine hydrochloride/kg bw equal to a dose volume
0.08 ml Dexdomitor/kg bw when used for non-invasive, mildly to moderately painful procedures
requiring restraint, sedation and analgesia.
When dexmedetomidine is used for premedication in cats, the same dose is used. Premedication with
dexmedetomidine will significantly reduce the dosage of the induction agent required and will reduce
volatile anaesthetic requirements for maintenance anaesthesia. In a clinical study, the requirement for
propofol was reduced by 50%. All anaesthetic agents used for induction or maintenance of
anaesthesia should be administered to effect.
Anaesthesia can be induced 10 minutes after premedication
by intramuscular administration of a
target dose of 5 mg ketamine/ kg bw or by intravenous administration of propofol to effect. Dosing for
cats is presented in the following table.
Cat
Weight
Dexmedetomidine 40 mcg/kg intramuscularly
(kg)
(mcg/kg)
(ml)
1-2
40
0.1
2-3
40
0.2
3-4
40
0.3
4-6
40
0.4
6-7
40
0.5
7-8
40
0.6
8-10
40
0.7
The expected sedative and analgesic effects are reached within 15 minutes after administration and
are maintained up to 60 minutes after administration. Sedation may be reversed with atipamezole.
Atipamezole should not be administered prior to 30 minutes following ketamine administration.
Dogs: In cases of overdosage, or if the effects of dexmedetomidine become potentially life-
threatening, the appropriate dose of atipamezole is 10 times the initial dose of dexmedetomidine
(micrograms/ kg bw or micrograms/ square meter body surface area). The dose volume of
atipamezole at the concentration of 5 mg/ml equals the dose volume of Dexdomitor that was given to
the dog, regardless of route of administration of Dexdomitor.
Cats: In cases of overdosage, or if the effects of dexmedetomidine become potentially life-threatening,
the appropriate antagonist is atipamezole, administered by intramuscular injection, at the following
dose: 5 times the initial dose dexmedetomidine in micrograms/kg bw.
After concurrent exposure to a triple (3X) overdose of dexmedetomidine and 15 mg ketamine/ kg,
atipamezole can be administered at the recommended dose level for reversal of effects induced by
dexmedetomidine. At high serum concentrations of dexmedetomidine sedation is not increased
although the level of analgesia does increase with further dose increases. The dose volume of
atipamezole at the concentration of 5 mg/ml equals one-half the volume of Dexdomitor that was given
to the cat.
Not applicable.
5.
Pharmacotherapeutic group: psycholeptic, ATCvet code: QN05CM18.
7
5.1 Pharmacodynamic properties
Dexdomitor contains dexmedetomidine as the active substance, which produces sedation and
analgesia in dogs and cats. The duration and depth of the sedation and analgesia are dose-dependent.
At maximal effect, the animal is relaxed, recumbent and does not respond to external stimulus.
Dexmedetomidine is a potent and selective α
2
-adrenoceptor agonist that inhibits the release of
noradrenaline from noradrenergic neurons. Sympathetic neurotransmission is prevented and the level
of consciousness decreases. Reduced heart rate and temporary AV-block can be seen after
administration of dexmedetomidine. Blood pressure decreases to normal or below normal levels after
an initial increase. Respiration rate can occasionally decrease. Dexmedetomidine also induces a
number of other α
2
-adrenoceptor mediated effects, which include piloerection, depression of motor
and secretory functions of the gastrointestinal tract, diuresis and hyperglycaemia.
A slight decrease in temperature may be observed.
5.2 Pharmacokinetic particulars
As a lipophilic compound, dexmedetomidine is well absorbed after intramuscular administration.
Dexmedetomidine is also rapidly distributed in the body and penetrates the blood-brain barrier
readily. According to studies in rats, the maximum concentration in the central nervous system is
several times that of the corresponding concentration in plasma. In the circulation, dexmedetomidine
is largely bound to plasma proteins (>90%).
Dogs: After an intramuscular dose of 50 micrograms/kg a maximum concentration in plasma of about
12 ng/ml is reached after 0.6 hours. The bioavailability of dexmedetomidine is 60% and the apparent
volume of distribution (Vd) is 0.9 l/kg. The elimination half-life (t½) is 40-50 minutes.
Major biotransformations in the dog include hydroxylation, glucuronic acid conjugation and N-
methylation in the liver. All known metabolites lack pharmacological activity. Metabolites are
excreted mainly in the urine and to a lesser extent in the faeces. Dexmedetomidine has a high
clearance and its elimination depends on the hepatic blood flow. A prolonged elimination half-life is
therefore expected with overdoses or when dexmedetomidine is coadministered with other substances,
which affect hepatic circulation.
Cats: The maximum plasma concentration is reached about 0.24 h after intramuscular administration.
After a 40 micrograms/kg bw intramuscular dose the Cmax is 17 ng/ml. The apparent volume of
distribution (Vd) is 2.2 l/kg and the elimination half-life (t½) is one hour.
Biotransformations in the cat occur by hydroxylation in the liver. Metabolites are excreted mainly in
the urine (51% of the dose), and to a lesser extent in the faeces. As in dogs dexmedetomidine has a
high clearance in cats and its elimination depends on the hepatic blood flow. A prolonged elimination
half-life is therefore expected with overdoses or when dexmedetomidine is coadministered with other
substances, which affect hepatic circulation.
6.
6.1 List of excipients
Methyl parahydroxybenzoate (E 218)
Propyl parahydroxybenzoate (E 216)
8
6.2 Incompatibilities
None known.
Dexdomitor is compatible with butorphanol and ketamine in the same syringe at least for two hours.
6.3 Shelf life
3 years
After withdrawal of the first dose, the product may be stored for 28 days at 25ºC.
6.4. Special precautions for storage
Do not freeze.
6.5 Nature and composition of immediate packaging
Cardboard box with 1 glass (Type I) vial of 10ml with a chlorobutyl or bromobutyl rubber stopper and
aluminium cap.
Package size: 10 ml and 10 x 10 ml
6.6
Special precautions for the disposal of unused veterinary medicinal product or waste
materials derived from the use of such products
Any unused product or waste materials derived from such veterinary medicinal products should be
disposed of in accordance with local requirements
7.
Orion Corporation
Orionintie 1
FIN-02200 Espoo
Finland
8.
EU/2/02/033/001-002
9.
30.08.2002 / 02.08.2007
18.11.2009
PROHIBITION OF SALE, SUPPLY AND/OR USE
Not applicable.
9
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR
BATCH RELEASE
B.
CONDITIONS OR RESTRICTIONS OF THE MARKETING
AUTHORISATION REGARDING SUPPLY OR USE
C.
CONDITIONS OR RESTRICTIONS OF THE MARKETING
AUTHORISATION WITH REGARD TO SAFE AND EFFECTIVE USE
D.
STATEMENT OF THE MRLs
10
A. MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer(s) responsible for batch release
Orion Corporation
Orionintie 1
FIN-02200 Espoo
Finland
B. CONDITIONS OR RESTRICTIONS OF THE MARKETING AUTHORISATION
REGARDING SUPPLY OR USE
To be supplied only on veterinary prescription.
The holder of this marketing authorisation must inform the European Commission about the
marketing plans for the medicinal product authorised by this decision.
C. CONDITIONS OR RESTRICTIONS OF THE MARKETING AUTHORISATION WITH
REGARD TO THE SAFE AND EFFECTIVE USE OF THE PRODUCT
Not applicable.
D. STATEMENT OF THE MRLs
Not applicable.
11
ANNEX III
LABELLING AND PACKAGE LEAFLET
12
A. LABELLING
13
PARTICULARS TO APPEAR ON THE OUTER PACKAGE
BOX
1.
DEXDOMITOR 0.5 mg/ml solution for injection
2.
STATEMENT OF ACTIVE AND OTHER SUBSTANCES
One ml contains 0.5 mg dexmedetomidine hydrochloride equivalent to 0.42 mg dexmedetomidine
3.
Solution for injection.
4.
PACKAGE SIZE
10 ml
5.
Dogs and cats.
6.
Non-invasive, mildly to moderately painful, procedures and examinations which require restraint,
sedation and analgesia in dogs and cats.
Deep sedation and analgesia in dogs in concomitant use with butorphanol for medical and minor
surgical procedures.
Premedication in dogs and cats before induction and maintenance of general anaesthesia.
7.
METHOD AND ROUTE(S) OF ADMINISTRATION
Dogs: intravenous or intramuscular use
Cats: intramuscular use
Read the package leaflet before use.
8.
Not applicable.
14
9.
SPECIAL WARNING(S), IF NECESSARY
10. EXPIRY DATE
EXP: month/year
Shelf life after first opening: 28 days at 25
°
C.
11. SPECIAL STORAGE CONDITIONS
Do not freeze.
12. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCTS OR
WASTE MATERIALS, IF ANY
Any unused product or waste materials derived from such veterinary medicinal products should be
disposed of in accordance with local requirements.
13. THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS OR
RESTRICTIONS REGARDING SUPPLY AND USE, if applicable
For animal treatment only – to be supplied only on veterinary prescription.
14. THE WORDS “KEEP OUT OF THE REACH AND SIGHT OF CHILDREN”
Keep out of the reach and sight of children.
Orion Corporation
Orionintie 1
FIN-02200 Espoo
Finland
EU/2/02/033/001-002
17. MANUFACTURER’S BATCH NUMBER
Batch:
15
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS/
MULTI PACKAGE
VIAL/MULTI PACKAGE
1.
DEXDOMITOR 0.5 mg/ml solution for injection
2.
QUANTITY OF THE ACTIVE SUBSTANCE(S)
0.5 mg/ml Dexmedetomidine hydrochloride
3.
CONTENTS BY WEIGHT, BY VOLUME OR BY NUMBER OF DOSES
10 ml, 10 x 10 ml
4.
ROUTE(S) OF ADMINISTRATION
Dogs: intravenous or intramuscular use
Cats: intramuscular use
5.
Not applicable.
6.
BATCH NUMBER
Batch:
7.
EXPIRY DATE
EXP:
month/year
8.
THE WORDS “FOR ANIMAL TREATMENT ONLY”
For animal treatment only.
16
B. PACKAGE LEAFLET
17
PACKAGE LEAFLET
DEXDOMITOR 0.5 mg/ml solution for injection
1.
THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE, IF DIFFERENT
Orion Corporation
Orionintie 1
FIN-02200 Espoo
Finland
2.
DEXDOMITOR 0.5 mg/ml solution for injection
3.
STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENT(S)
Active substance:
One ml contains 0.5 mg dexmedetomidine hydrochloride
equivalent to 0.42 mg dexmedetomidine.
List of excipients:
Methyl parahydroxybenzoate (E 218) 1.6 mg/ml
Propyl parahydroxybenzoate (E 216) 0.2 mg/ml
4.
Non-invasive, mildly to moderately painful, procedures and examinations which require restraint,
sedation and analgesia in dogs and cats.
Deep sedation and analgesia in dogs in concomitant use with butorphanol for medical and minor
surgical procedures.
Premedication in dogs and cats before induction and maintenance of general anaesthesia.
5.
Do not use in animals with cardiovascular disorders.
Do not use in animals with severe systemic disease or in animals that are moribund.
Do not use in case of known hypersensitivity to the active substance or to any of the excipients.
6.
By virtue of its α2-adrenergic activity, dexmedetomidine causes decreases in heart rate and body
temperature.
In some dogs and cats a decrease in respiratory rate may occur. Rare instances of pulmonary oedema
have been reported. Blood pressure will increase initially and then return to normal or below normal.
Due to peripheral vasoconstriction and venous desaturation in the presence of normal arterial
oxygenation, the mucous membranes may appear pale and/or with a blue tinge.
18
Vomiting may occur 5-10 minutes after injection.
Some dogs and cats may also vomit at the time of recovery.
Muscle tremors may occur during sedation.
When dexmedetomidine and ketamine are used sequentially, with a 10 minute interval, cats may
occasionally experience AV-block or extrasystole. Expected respiratory events are bradypnoea,
intermittent respiratory patterns, hypoventilation, and apnoea. In clinical trials the incidence of
hypoxaemia was common, especially within the 15 first minutes into dexmedetomidine-ketamine
anaesthesia. Vomiting, hypothermia and nervousness have been reported after such use.
When dexmedetomidine and butorphanol are used concomitantly in dogs bradypnoea, tachypnoea, an
irregular respiratory pattern (20-30 sec apnoea followed by several rapid breaths), hypoxaemia,
muscle twitch or tremor or paddling, excitation, hypersalivation, retching, vomiting, urination, skin
erythema, a sudden arousal, or prolonged sedation may occur. Brady- and tachyarrhythmias have been
reported. These may include profound sinus bradycardia, 1
st
and 2
nd
degree AV block, sinus arrest or
pause, as well as atrial, supraventricular and ventricular premature complexes.
When dexmedetomidine is used as a premedicant in dogs bradypnoea, tachypnoea and vomiting may
occur. Brady- and tachyarrhythmias have been reported and include profound sinus bradycardia, 1
st
and 2
nd
degree AV block and sinus arrest. Supraventricular and ventricular premature complexes,
sinus pause and 3
rd
degree AV block may be observed in rare cases.
When dexmedetomidine is used as a premedicant in cats, vomiting, retching, pale mucous membranes,
and low body temperature may occur. Intramuscular dosing at 40 mcg/kg (followed by ketamine or
propofol) frequently resulted in sinus bradycardia and sinus arrhythmia, occasionally resulted in 1
st
degree atrioventricular block, and rarely resulted in supraventricular premature depolarizations, atrial
bigeminy, sinus pauses, 2
nd
degree atrioventricular block, or escape beats/rhythms.
If you notice any serious effects or other effects not mentioned in this leaflet, please inform your
veterinary surgeon.
7.
Dogs and cats.
8.
DOSAGE FOR EACH SPECIES, ROUTE(S) AND METHOD OF ADMINISTRATION
The product is intended for:
-
Dogs: intravenous or intramuscular use
-
Cats: intramuscular use
The product is not intended for repeat injections.
Dexdomitor, butorphanol and/or ketamine can be mixed in the same syringe as they have been shown
to be pharmacologically compatible.
The following doses are recommended:
19
DOGS:
Dexdomitor doses are based on body surface area:
Intravenously: up to 375 micrograms/square metre body surface area
Intramuscularly: up to 500 micrograms/square metre body surface area
When administering in conjunction with butorphanol (0.1 mg/kg) for deep sedation and analgesia, the
intramuscular dose of dexmedetomidine is 300 micrograms/square metre body surface area. The
premedication dose of dexmedetomidine is 125 – 375 micrograms/square metre body surface area,
administered 20 minutes prior to induction for procedures requiring anaesthesia. The dose should be
adjusted to the type of surgery, length of procedure and patient temperament.
Concomitant use of dexmedetomidine and butorphanol produces sedative and analgesic effects
beginning no later than 15 minutes. The peak sedative and analgesic effects are reached within 30
minutes after administration. Sedation lasts for at least 120 minutes post administration and analgesia
lasts for at least 90 minutes. Spontaneous recovery occurs within 3 hours.
Premedication with dexmedetomidine will significantly reduce the dosage of the induction agent
required and will reduce volatile anaesthetic requirements for maintenance anaesthesia. In a clinical
study, the requirement for propofol and thiopental was reduced by 30% and 60% respectively. All
anaesthetic agents used for induction or maintenance of anaesthesia should be administered to effect.
In a clinical study, dexmedetomidine contributed to postoperative analgesia for 0.5 – 4 hours.
However this duration is dependent on a number of variables and further analgesia should be
administered in accordance with clinical judgement.
The corresponding doses based on body weight are presented in the following tables. Use of an
appropriately graduated syringe is recommended to ensure accurate dosing when administering small
volumes.
Dog
Weight
Dexmedetomidine
125 mcg/m
2
Dexmedetomidine
375 mcg/m
2
Dexmedetomidine
500 mcg/m
2
(kg)
(mcg/kg)
(ml)
(mcg/kg)
(ml)
(mcg/kg)
(ml)
2-3
9.4
0.04
28.1
0.12
40
0.15
3-4
8.3
0.05
25
0.17
35
0.2
4-5
7.7
0.07
23
0.2
30
0.3
5-10
6.5
0.1
19.6
0.29
25
0.4
10-13
5.6
0.13
16.8
0.38
23
0.5
13-15
5.2
0.15
15.7
0.44
21
0.6
15-20
4.9
0.17
14.6
0.51
20
0.7
20-25
4.5
0.2
13.4
0.6
18
0.8
25-30
4.2
0.23
12.6
0.69
17
0.9
30-33
4
0.25
12
0.75
16
1.0
33-37
3.9
0.27
11.6
0.81
15
1.1
37-45
3.7
0.3
11
0.9
14.5
1.2
45-50
3.5
0.33
10.5
0.99
14
1.3
50-55
3.4
0.35
10.1
1.06
13.5
1.4
55-60
3.3
0.38
9.8
1.13
13
1.5
60-65
3.2
0.4
9.5
1.19
12.8
1.6
65-70
3.1
0.42
9.3
1.26
12.5
1.7
70-80
3
0.45
9
1.35
12.3
1.8
>80
2.9
0.47
8.7
1.42
12
1.9
20
For deep sedation and analgesia with butorphanol
Dog
Weight
Dexmedetomidine
300 mcg/m
2
intramuscularly
(kg)
(mcg/kg)
(ml)
2-3
24
0.12
3-4
23
0.16
4-5
22.2
0.2
5-10
16.7
0.25
10-13
13
0.3
13-15
12.5
0.35
15-20
11.4
0.4
20-25
11.1
0.5
25-30
10
0.55
30-33
9.5
0.6
33-37
9.3
0.65
37-45
8.5
0.7
45-50
8.4
0.8
50-55
8.1
0.85
55-60
7.8
0.9
60-65
7.6
0.95
65-70
7.4
1
70-80
7.3
1.1
>80
7
1.2
CATS:
The dosage for cats is 40 micrograms dexmedetomidine hydrochloride/ kg bw equal to a dose volume
0.08 ml Dexdomitor/ kg bw when used for non-invasive, mildly to moderately painful procedures
requiring restraint, sedation and analgesia.
When dexmedetomidine is used for premedication in cats, the same dose is used. . Premedication with
dexmedetomidine will significantly reduce the dosage of the induction agent required and will reduce
volatile anaesthetic requirements for maintenance anaesthesia. In a clinical study, the requirement for
propofol was reduced by 50%. All anaesthetic agents used for induction or maintenance of
anaesthesia should be administered to effect.
Anaesthesia can be induced 10 minutes after premedication by intramuscular administration of a
target dose of 5 mg ketamine/kg bw or by intravenous administration of propofol to effect. Dosing for
cats is presented in the following table.
Cat
Weight
Dexmedetomidine 40 mcg/kg intramuscularly
(kg)
(mcg/kg)
(ml)
1-2
40
0.1
2-3
40
0.2
3-4
40
0.3
4-6
40
0.4
6-7
40
0.5
7-8
40
0.6
8-10
40
0.7
The expected sedative and analgesic effects are reached within 15 minutes after administration and
are maintained up to 60 minutes after administration. Sedation may be reversed with atipamezole.
Atipamezole should not be administered prior to 30 minutes following ketamine administration.
21
9.
ADVICE ON CORRECT ADMINISTRATION
It is recommended that animals are fasted for 12 hours prior to administration. Water may be given.
After treatment, the animal should not be given water or food before it is able to swallow.
10. WITHDRAWAL PERIOD
Not applicable
11. SPECIAL STORAGE PRECAUTIONS
Do not freeze.
After withdrawal of the first dose, the product may be stored for 28 days at 25ºC.
Keep out of the reach and sight of children.
12. SPECIAL WARNING(S)
Treated animals should be kept warm and at a constant temperature, both during the procedure and
recovery.
Nervous, aggressive or excited animals should be given the possibility to calm down before initiation
of treatment.
The safety of dexmedetomidine has not been established during pregnancy and lactation in the target
species. Therefore the use of the product during pregnancy and lactation is not recommended.
The safety of dexmedetomidine has not been established in males intended for breeding.
To be used with precaution in elderly animals.
The administration of dexmedetomidine to puppies younger than 16 weeks and kittens younger than
12 weeks has not been studied.
In cats corneal opacities may occur during sedation. The eyes should be protected by a suitable eye
lubricant.
The use of other central nervous system depressants is expected to potentiate the effects of
dexmedetomidine and therefore an appropriate dose adjustment should be made. Use of
dexmedetomidine as a premedicant in dogs significantly reduces the amount of induction drug
required for induction of anaesthesia. Attention should be given during the administration of
intravenous induction drugs to effect. Volatile anaesthetic requirements for maintenance anaesthesia
are also reduced.
Anticholinergics should be used with caution with dexmedetomidine.
Cats: After administration of 40 micrograms dexmedetomidine/ kg bw intramuscularly concurrently
with 5 mg ketamine /kg bw to cats, the maximum concentration of dexmedetomidine increased
twofold but there was no effect on T
max
. The mean half-life of elimination of dexmedetomidine
increased to 1.6 h and the total exposure (AUC) increased by 50%.
22
A dose of 10 mg ketamine/ kg used concurrently with 40 micrograms dexmedetomidine/ kg may cause
tachycardia.
Administration of atipamezole after dexmedetomidine rapidly reverses the effects and thus shortens
the recovery period. Within 15 minutes dogs are normally awake and standing
For information on adverse reactions, see section Adverse reactions.
Frequent and regular monitoring of respiratory and cardiac function should be performed. Pulse
oximetry may be useful but is not essential for adequate monitoring.
Equipment for manual ventilation should be available in case of respiratory depression or apnoea
when dexmedetomidine and ketamine are used sequentially to induce anaesthesia in cats. It is also
advisable to have oxygen readily available, should hypoxaemia be detected or suspected.
Sick and debilitated dogs and cats should only be premedicated with dexmedetomidine before
induction and maintenance of general anaesthesia based on a risk-benefit assessment.
In cases of overdosing the following recommendations should be followed:
DOGS: In cases of overdosage, or if the effects of dexmedetomidine become potentially life-
threatening, the appropriate dose of atipamezole is 10 times the initial dose of dexmedetomidine
(micrograms/ kg bw or micrograms/ square meter body surface area). The dose volume of
atipamezole at the concentration of 5 mg/ml equals the dose volume of Dexdomitor that was given to
the dog, regardless of route of administration of Dexdomitor.
CATS: In cases of overdosage, or if the effects of dexmedetomidine become potentially life-
threatening, the appropriate antagonist is atipamezole, administered by intramuscular injection, at the
following dose: 5 times the initial dose dexmedetomidine in micrograms/kg bw. After concurrent
exposure to a triple (3X) overdose of dexmedetomidine and 15 mg ketamine/ kg, atipamezole can be
administered at the recommended dose level for reversal of effects induced by dexmedetomidine.
At high serum concentration of dexmedetomidine sedation is not increased although the level of
analgesia does increase with further dose increases.
The dose volume of atipamezole at the concentration of 5mg/ml equals one-half the volume of
Dexdomitor that was given to the cat.
In case of accidental oral intake or self-injection, seek medical advice immediately and show the
package insert to the physician but DO NOT DRIVE as sedation and changes in blood pressure may
occur.
Avoid skin, eye or mucosal contact; the use of impermeable gloves is advisable. In case of skin or
mucosal contact, wash the exposed skin immediately after exposure with large amounts of water and
remove contaminated clothes that are in direct contact with skin. In case of eye contact, rinse
abundantly with fresh water. If symptoms occur, seek the advice of a physician.
If pregnant women handle the product, special caution should be observed not to self-inject as uterine
contractions and decreased foetal blood pressure may occur after accidental systemic exposure.
Advice to doctors: Dexdomitor is an α
2
-adrenoreceptor agonist, symptoms after absorption may
involve clinical effects including dose-dependent sedation, respiratory depression, bradycardia,
hypotension, a dry mouth, and hyperglycaemia. Ventricular arrhythmias have also been reported.
Respiratory and haemodynamic symptoms should be treated symptomatically. The specific α
2
–
adrenoceptor antagonist, atipamezole, which is approved for use in animals, has been used in humans
only experimentally to antagonize dexmedetomidine-induced effects.
Persons with known hypersensitivity to the active substance or any of the excipients should administer
the product with caution.
23
13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR
WASTE MATERIALS, IF ANY
Any unused product or waste materials derived from such veterinary medicinal products should be
disposed of in accordance with local requirements.
14. DATE ON WHICH THE PACKAGE LEAFLET WAS LAST APPROVED
18.11.2009
15. OTHER INFORMATION
Package size: 10 ml, 10 x10 ml.
For any information about this veterinary medicinal product, please contact the local representative of
the Marketing Authorisation Holder.
24
Source: European Medicines Agency
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