Introduction

Company name: Pfizer Limited

Address: Ramsgate Road

Sandwich

Kent CT13 9NJ

Telephone: 0845 300 8034 (Out of hours: 01304 616161)

Fax: 01737 332521

Email: UKVetLine@pfizer.com

Website: www.only4vets.co.uk

Presentation

Dexdomitor solution for injection contains 0.5 mg/ml dexmedetomidine hydrochloride, equivalent to 0.42 mg dexmedetomidine, as a clear, colourless solution. Also contains methyl parahydroxybenzoate and propyl parahydroxybenzoate as preservatives.

Uses

Dexdomitor is indicated for use in dogs and cats as follows:

•Non-invasive, mildly to moderately painful, procedures and examinations which require restraint, sedation and analgesia in dogs and cats.

•Premedication in cats before induction and maintenance of general anaesthesia with ketamine.

•Deep sedation and analgesia in dogs in concomitant use with butorphanol for medical and minor surgical procedures. Premedication in dogs before induction and maintenance of general anaesthesia.

Dosage and administration

Dexdomitor can be given by the intravenous or intramuscular route in dogs and by the intramuscular route in cats.

It is recommended that animals are fasted for 12 hours prior to administration. Water may be given ad libitum.

DOGS:

The doses for dogs are based on body surface area. The intravenous dose is 375 micrograms/square metre body surface area and the intramuscular dose is 500 micrograms/square metre body surface area when dexmedetomidine is used as the only agent for sedation and analgesia. When administering in conjunction with butorphanol (0.1 mg/kg) for deep sedation and analgesia, the intramuscular dose 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 up to 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.

Dogs	Single-use sedation and analgesia
Weight	Dexmedetomidine 375 mcg/m2 intravenously		Dexmedetomidine 500 mcg/m2 intravenously
(kg)	(mcg/kg)	(ml)	(mcg/kg)	(ml)
2-3	28.1	0.12	40	0.15
3-4	25	0.15	35	0.2
4-5	23	0.2	30	0.3
5-10	19.6	0.29	25	0.4
10-13	16.8	0.38	23	0.5
13-15	15.7	0.44	21	0.6
15-20	14.6	0.51	20	0.7
20-25	13.4	0.6	18	0.8
25-30	12.6	0.69	17	0.9
30-33	12	0.75	16	1.0
33-37	11.6	0.81	15	1.1
37-45	11	0.9	14.5	1.2
45-50	10.5	0.99	14	1.3
50-55	10.1	1.06	13.5	1.4
55-60	9.8	1.13	13	1.5
60-65	9.5	1.19	12.8	1.6
65-70	9.3	1.26	12.5	1.7
70-80	9	1.35	12.3	1.8
>80	8.7	1.42	12	1.9

Dogs	For deep sedation and analgesia with butorphanol		For premedication prior to general anaesthesia
Weight	Dexmedetomidine 300 mcg/m2 intramuscularly		Dexmedetomidine 125 mcg/m2 intramuscularly		Dexmedetomidine 375 mcg/m2 intramuscularly
(kg)	(mcg/kg)	(ml)	(mcg/kg)	(ml)	(mcg/kg)	(ml)
2-3	24	0.12	9.4	0.04	28.1	0.12
3-4	23	0.16	8.3	0.05	25	0.15
4-5	22.2	0.2	7.7	0.07	23	0.2
5-10	16.7	0.25	6.5	0.1	19.6	0.29
10-13	13	0.3	5.6	0.13	16.8	0.38
13-15	12.5	0.35	5.2	0.15	15.7	0.44
15-20	11.4	0.4	4.9	0.17	14.6	0.51
20-25	11.1	0.5	4.5	0.2	13.4	0.6
25-30	10	0.55	4.2	0.23	12.6	0.69
30-33	9.5	0.6	4	0.25	12	0.75
33-37	9.3	0.65	3.9	0.27	11.6	0.81
37-45	8.5	0.7	3.7	0.3	11	0.9
45-50	8.4	0.8	3.5	0.33	10.5	0.99
50-55	8.1	0.85	3.4	0.35	10.1	1.06
55-60	7.8	0.9	3.3	0.38	9.8	1.13
60-65	7.6	0.95	3.2	0.4	9.5	1.19
65-70	7.4	1	3.1	0.42	9.3	1.26
70-80	7.3	1.1	3	0.45	9	1.35
>80	7	1.2	2.9	0.47	8.7	1.42

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. Anaesthesia can be induced 10 minutes after premedication by intramuscular administration of a target dose of 5 mg ketamine/ kg bw. Dosing for cats is presented in the following table.

Cats	For single-use sedation and analgesia or for premedication
Weight	Dexmedetomidine 40 mcg/kg intramuscularly
(kg)	(mcg/kg)	(ml)
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.

Contra-indications, warnings, etc

Do not use in puppies below 6 months of age or in kittens below 5 months of age.

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 safety of dexmedetomidine has not been established in males intended for breeding.

Corneal opacities may occur during sedation. The eyes of dogs and cats should be protected by a suitable eye lubricant.

Treated animals should be kept warm and at a constant temperature, both during the procedure and recovery.

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 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.

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.

By virtue of its a2-adrenergic activity, dexmedetomidine causes a decrease in heart rate and body temperature.

Blood pressure will increase initially and then return to normal or below normal.

In some dogs and cats, a decrease in respiratory rate may occur. 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. Rare instances of pulmonary oedema have been reported.

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, 1st and 2nd 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, 1st and 2nd degree AV block and sinus arrest. Supraventricular and ventricular premature complexes, sinus pause and 3rd degree AV block may be observed in rare cases.

Operator warnings:

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 alpha2-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 a2 –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.

Pharmaceutical precautions

Do not freeze.

After withdrawal of the first dose, Dexdomitor may be stored for 28 days at 25°C.

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

Keep out of the reach and sight of children.

For animal treatment only.

Legal category

POM-V

Packaging Quantities

Dexdomitor Solution for Injection is available in 10 ml glass vials.

Further information

Dexdomitor, butorphanol and/or ketamine can be mixed in the same syringe as they have been shown to be pharmaceutically compatible.

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 are normally awake and standing.

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 two-fold but there was no effect on T max. The mean half-life of elimination of dexmedetomidine increased to 1.6 hours 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.

Overdose:

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 (half the volume of dexmedetomidine given to the cat in mls).

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.

Marketing authorisation number

EU/2/02/033/001.

Significant Changes

Dexdomitor 0.5 mg/ml Solution for Injection

Pfizer Limited

New data sheet

15/01/2008