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Properties of an ideal injectable anaesthetic Mark Senior BVSc CertVA DiplECVA MRCVS, Lecturer in Veterinary Anaesthesia at the University of Liverpool, writes: “The ideal anaesthetic agent does not exist! The list below (in no particular order) of properties of an ideal injectable anaesthetic agent, which is by no means exhaustive, shows how many criteria such an agent would need to satisfy to become the ideal agent. Hence it is unlikely such an agent will ever exist and what we strive for is an agent that possesses as many of the properties below as possible: •
Can be used predictably in a wide variety of species
•
Rapid, controllable onset of action
•
Smooth induction of anaesthesia
•
Smooth recovery from anaesthesia
•
Produces muscle relaxation
•
Produces analgesia
•
Safe - even in compromised patients i. Minimal effects on the cardiovascular system ii. Minimal effects on the respiratory system iii. No histamine release / non allergenic iv. Safe if overdosed v. No toxic metabolites
•
Short duration of action and non-cumulative >> suitable for total intravenous anaesthesia
•
Rapid metabolism independent of organ function
•
No active metabolites
•
Non-irritant to tissues
•
Can be administered by all injection routes
•
Reversible
•
Stable in solution and in storage
•
Compatible with other agents”
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What is Alfaxan®? - An injectable anaesthetic designed exclusively for veterinary use, brought to you by Vetoquinol, a veterinary-only pharmaceutical company - Facts about Alfaxan® Alfaxan® is an injectable anaesthetic agent for induction and maintenance of general anaesthesia in dogs and cats. Alfaxan® is a clear, colourless, aqueous solution of alfaxalone (3-α-hydroxy-5-α-pregnane-11,20-dione), a neuroactive steroid molecule with the properties of a general anaesthetic.
Alfaxalone molecule O
CH3
Me O
H
Me
H
H
H
H
HO H
The alfaxalone molecule is solubilised in the Alfaxan® formulation using 2α-hydroxypropyl beta cyclodextrin (HPBCD). Cyclodextrins are complex polysaccharides derived from starch that have a hydrophobic centre for lipophilic drugs like alfaxalone.
Unlike Cremaphor® EL, HPBCD does not cause histamine release in dogs and cats.
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How does Alfaxan® work? The primary mechanism for the anaesthetic action of alfaxalone is modulation of neuronal cell membrane chloride ion transport, induced by binding of alfaxalone to GABAA cell surface receptors.
GABA site Chloride ion channel Steroid site
Alfaxalone inhibits propagation of action potentials by altering chloride ion flux through the GABAA channel.
Pharmacokinetics and pharmacodynamics of alfaxalone - Alfaxalone has a very short plasma elimination half-life in dogs and cats1,2 •
Approximately 25 minutes for a 2 mg/kg dose in dogs
•
Approximately 45 minutes for a 5 mg/kg dose in cats
- Alfaxalone is completely cleared from the body within a few hours after single administration1,2 Whether Alfaxan® is administered as a repeated bolus or as total intravenous anaesthesia (TIVA) at a continuous rate infusion, alfaxalone levels do not accumulate and recovery periods do not appear to be prolonged3. This supports the claim that repeated use of the product over a short period of time does not present a risk of accumulation.
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Good quality of anaesthetic induction and reliable anaesthesia In the dog: In a multicentre clinical trial performed on 231 dogs*, Alfaxan® was assessed for the quality of induction and maintenance of anaesthesia, in a wide variety of anaesthetic protocols4 (Figure 1): •
Alfaxan® was recorded as having the highest possible scores for quality of induction in 95.2% of pre-medicated dogs induced by Alfaxan® that took part in the trial.
•
Alfaxan® was recorded as having the highest possible scores for quality of maintenance of anaesthesia in 80.6% of premedicated dogs induced by Alfaxan® that took part in the trial.
In the cat: In a multicentre clinical trial performed on 259 cats*, Alfaxan® was assessed for the quality of induction and maintenance of anaesthesia, in a wide variety of anaesthetic protocols5 (Figure 1): •
Alfaxan® was recorded as having the highest possible scores for quality of induction in 95.4% of pre-medicated cats induced by Alfaxan® that took part in the trial.
•
Alfaxan® was recorded as having the highest possible scores for quality of maintenance of anaesthesia in 93.1% of pre-medicated cats induced by Alfaxan® that took part in the trial.
Figure 1: Percentage
of pre-medicated dogs and cats with the highest possible scores for induction and maintenance.
100
95.2%
95.4%
80
93.1% 80.6%
60
% 40
20
0
Highest induction score
*
4
Highest maintenance score
Several different anaesthetic agents were used for maintenance of anaesthesia and Alfaxan® was used as the maintenance agent in one group of dogs and cats
Good quality of recovery in pre-medicated dogs and cats The quality of anaesthetic recovery was also measured in the studies mentioned opposite4,5 with the following high scores in pre-medicated dogs and cats (Figures 2): In dogs: Alfaxan® was recorded as having the highest possible scores for quality of recovery in 82.4% of pre-medicated dogs induced by Alfaxan® that took part in the trial **
•
In cats: Alfaxan® was recorded as having the highest possible scores for quality of recovery in 93.1% of pre-medicated cats induced by Alfaxan® that took part in the trial **
•
In addition, anaesthetised animals had normal mentation on recovery, which is another advantage of Alfaxan® anaesthesia. ** Several different anaesthetic agents were used for maintenance of anaesthesia and Alfaxan® was used as the maintenance agent in one group of dogs and cats.
Figure 2: Percentage
of pre-medicated dogs and cats with the highest possible score for quality of recovery Highest quality of recovery score
100
93.1% 80
82.4%
60
% 40
20
0
Dogs
Cats
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Cardiovascular stability Alfaxan® has very good cardiovascular stability, with minimal effects on the following parameters: • • • •
Systolic blood pressure Heart rate Cardiac output Central venous pressure
Figure 3: Mean
heart rate in the dog from the multicentre dog clinical study4
(2mg/kg induction)
180 Alfaxan Induction & maintenance (No premedication) ®
Heart rate / min
160 140
Alfaxan Induction & maintenance (Premedication) ®
120
Alfaxan Induction & Isoflurane maintenance (Premedication) ®
100 80
Alfaxan Induction & Halothane maintenance (Premedication) ®
60
10 mins after premedication
Immediately after induction
5-10 mins after induction & throughout maintenance
Early recovery
Figure 4: Mean
indirect blood pressure in the dog from the multicentre dog clinical study4 (2mg/kg induction)
180 Alfaxan Induction & maintenance (No premedication) ®
Indirect BP (mmHg)
160 140
Alfaxan Induction & maintenance (Premedication) ®
120
Alfaxan Induction & Isoflurane maintenance (Premedication) ®
100 80
Alfaxan Induction & Halothane maintenance (Premedication) ®
60
10 mins after premedication
5-10 mins after induction & throughout maintenance
Early recovery
Figure 5: Mean
heart rate in the dog after dosing with Alfaxan® at one, three and ten times the recommended clinical dose6 2mg/kg
200
6mg/kg
20mg/kg
Heart rate / min
180 160 140 120 100 80 60 -5
1
5
10
15
30 40 Time (min)
50
60
70
80
90
100
Alfaxan® shows minimal effect on the heart rate in dogs and does not cause bradycardia even at ten times the recommended clinical doses (20mg/kg of alfaxalone).
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Respiratory rate • Alfaxan® does not cause hypoventilation* at the recommended clinical dose (2mg/kg) during the induction phase of anaesthesia, as shown in Figures 6 and 7 below • Animals are able to breathe and thus inhale the volatile agents effectively, enabling them to have a smooth transition to the maintenance phase of anaesthesia
Respiratory rate (breaths / min)
Figure 6:
Mean respiratory rates in the dog from the multicentre dog clinical study4 (2mg/kg induction)
60
Alfaxan® Induction & maintenance (No premedication)
50
Alfaxan® Induction & maintenance (Premedication)
40 30
Alfaxan® Induction & Isoflurane maintenance (Premedication)
20 10 breaths/min
10
Alfaxan® Induction & Halothane maintenance (Premedication)
0
10 mins after premedication
Immediately after induction
5-10 mins after induction & throughout maintenance
Early recovery
Figure 7: Mean
respiratory rates in the dog after dosing with Alfaxan® at one and three times the recommended clinical dose6
Respiratory rate (breaths / min)
45
Placebo
6mg/kg
2mg/kg
40 35 30 25 20 15 10 breaths/min
10 5 0
-60
-5
1
3
5
10
15 30 Time (min)
40
50
60
70
80
90
100
* Hypoventilation is defined as less than 10 breaths /min7 Alfaxan® was administered over a period of 60 seconds.
Wide Safety Margin Alfaxan® has a very wide safety margin: •
In an acute tolerance study all dogs survived IV injection of Alfaxan® at 10 times (i.e. 20 mg/kg BW) the recommended clinical dose when given adequate ventilatory support (intermittent positive pressure ventilation)8
•
In an acute tolerance study all cats survived IV injection of Alfaxan® at 5 times (i.e. 25mg/kg BW) the recommended clinical dose when given adequate ventilatory support (intermittent positive pressure ventilation)9
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No pain at the injection site after administering Alfaxan® •
Alfaxan® is an aqueous solution of alfaxalone with a pH of 6.5 to 7.0.
•
Alfaxan® does not cause pain at the injection site and does not cause tissue damage if injected perivascularly.10
Good muscle relaxation Alfaxan® produces good muscle relaxation in both dogs and cats11,12
No histamine release Alfaxan® administration does not cause histamine release in dogs and cats. In the studies below13 (Figures 8 and 9), mean blood histamine concentrations remained below 1 µmol/L, which is the normal histamine blood concentration in dogs and cats. Figure 8: Mean
blood histamine levels in dogs dosed with 30 mg/kg* of Alfaxan® as an IV bolus injection
Blood histamine (µmol/L)
1.2
1.0
0.8
0.6
0.4 0.2 0 0
1 2 3 4 5
*
10 Time post injection (min)
15
20
30mg/kg = 15 times the recommended clinical dose
Figure 9: Mean
blood histamine levels in cats dosed with Alfaxan® at several dose rates
1.0 Mean blood histamine (µmol/L)
5mg/Kg 10mg/Kg
0.8
20mg/Kg 30mg/Kg
0.6
0.4 0.2
0.0 0
8
1
2
3
4
5 10 Time post injection (min)
15
Alfaxan® is easy to administer • Clear, colourless solution •
easy to see if you have IV access
•
easy to see contamination
Administering Alfaxan® For detailed information about dosages for the induction and maintenance of Alfaxan® anaesthesia, please refer to the enclosed Alfaxan® dosage chart.
For the best results, follow the “Best practice Alfaxan® anaesthesia” guidelines: • Pre-anaesthetic medication is desirable in most cases • Administer oxygen even if using intravenous anaesthesia • A secure IV access is recommended to facilitate injection • Administering Alfaxan®: draw up the recommended dose, then inject Alfaxan® to effect slowly, over 60 seconds • Check depth of anaesthesia at regular intervals
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Excellent support service to benefit your practice We at Vetoquinol appreciate the complexity of running a busy veterinary practice and the different requirements each practice may have. Our aim is to make your experience of Alfaxan® as easy, pleasant and the least complicated as possible. We have devised a package of various anaesthesia-related complementary services that will benefit Alfaxan®-using practices.
Vetoquinol is committed to promoting best practice anaesthesia in UK veterinary practices: Alfaxan® free dedicated technical support line access to technical advice from independent UK anaesthesia experts If you have a technical query about Alfaxan®, or anaesthesia in general, just call our technical support line free on 0800 345 7560 (lines open from 9am to 5pm Monday to Friday). Your call will be responded to by our anaesthesia expert team. This service includes access to independent UK anaesthesia experts.
Alfaxan® practice support pack - essential information which will help you integrate Alfaxan® into your practice’s anaesthetic protocols Designed to offer your practice an extensive information package about Alfaxan®, the pack contains: • Alfaxan® dosage chart • Client leaflet explaining the facts about small animal anaesthesia (additional leaflets available to order)
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Practice training meetings tailored to your exact requirements In line with our commitment to promoting best practice anaesthesia, the main purpose of these meetings is to outline the benefits of new developments in small animal anaesthesia and to help you keep your practice up-to-date with the latest advances in veterinary anaesthesia. Depending on your specific needs, our territory managers and our veterinary surgeons will tailor these meeting to your exact requirements. Places are limited so discuss these options with us as soon as possible to avoid disappointment.
Alfaxan® on the web an invaluable resource containing the most important facts about our new injectable anaesthetic, Alfaxan® • Available to you at the click of the mouse on www.alfaxan.co.uk • Video clips showing dog / cat Alfaxan® anaesthesia • Powerpoint presentations with live voice commentary, covering Alfaxan® technical information • Alfaxan® frequently asked questions • Top tips about how to best use Alfaxan® in practice • Alfaxan® research articles you can download • Alfaxan® dosage guide To find out more about Alfaxan®, please call our dedicated Alfaxan® technical support line on 0800 345 7560 and a member of our Anaesthesia expert team will be pleased to help you.
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SUMMARY OF PRODUCT CHARACTERISTICS: 1. NAME OF THE VETERINARY MEDICINAL PRODUCT: Alfaxan® 10 mg/ml solution for injection. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION: Alfaxalone 10 mg/ml. 3. PHARMACEUTICAL FORM: Solution for injection, Clear colourless solution. 4. CLINICAL PARTICULARS: 4.1 Target species: Dogs and cats. 4.2 Indications for use: As an induction agent prior to inhalation anaesthesia. As a sole anaesthetic agent for the induction and maintenance of anaesthesia for the performance of examination or surgical procedures. 4.3 Contra-indications: Do not use in combination with other intravenous anaesthetic agents. 4.4 Special warnings for each target species: The safety of Alfaxan® in animals less than 12 weeks of age has not been demonstrated. During recovery, it is preferable that animals are not handled or disturbed. This may lead to paddling, minor muscle twitching or movements that are more violent which, while better avoided, are clinically insignificant. 4.5 Special precautions for use: i) Special precautions for use in animals. Post induction apnoea may occur in some patients – see section 4.6 for details. Endotracheal intubation and oxygen supplementation should therefore be employed. In order to minimise the possibility of apnoea, administer Alfaxan® by slow intravenous injection and not as a rapid dose. Especially when using higher doses of Alfaxan®, a dose-dependent respiratory depression may occur. Oxygen and/or intermittent positive pressure ventilation should be administered to counteract the threatening hypoxaemia/hypercapnea. This should be particularly important in risky anaesthetic cases and whenever the anaesthesia is to be carried out for a longer period of time. In common with many anaesthetics, the dose for induction and maintenance may require reduction in cases of hepatic or renal (cats) compromise, and Alfaxan® should be used with care in these cases. As with all general anaesthetic agents: It is advisable to ensure that the patient has been fasted before receiving the anaesthetic. Appropriate analgesia should be provided in cases where procedures are anticipated to be painful. Special care should be taken with aged animals, where there is stress associated with conditions such as disease or shock or in caesarean section. Following induction of anaesthesia, the use of an endotracheal tube is recommended to maintain airway patency. It is advisable to administer supplemental oxygen during maintenance of anaesthesia. Respiratory embarrassment may occur - ventilation of the lungs with oxygen should be considered if haemoglobin saturation with oxygen (SpO2%) falls below 90% or if apnoea persists for longer than 60 seconds. If cardiac arrhythmias are detected, attention to respiratory ventilation with oxygen is the first priority followed by appropriate cardiac therapy or intervention. Psychomotor excitement may be encountered in a minority of dogs and cats recovering from Alfaxan® anaesthesia. Post-anaesthetic recovery should thus take place in appropriate facilities and under sufficient supervision. Use of a benzodiazepine as the sole premedicant may increase the probability of psychomotor excitement. ii) Special precautions to be taken by the person administering the medicinal product to animals. If the product comes into contact with the eyes or skin, wash off immediately with water. In case of accidental self injection seek immediate medical attention and show the product literature to the doctor. iii) Other precautions: None known. 4.6 Adverse reactions (frequency and seriousness): In clinical studies using Alfaxan®, 44% of dogs and 19% of cats experienced post induction apnoea, which was defined as the cessation of breathing for 30 seconds or more. The mean duration of apnoea in these animals was 100 seconds in dogs and 60 seconds in cats. Endotracheal intubation and oxygen supplementation should therefore be employed. 4.7 Use during pregnancy and lactation: The safety of the veterinary medicinal product has not been established during pregnancy and lactation, in breeding animals or those intended for breeding in the future. However, studies using alfaxalone in pregnant mice, rats and rabbits have demonstrated no deleterious effects on gestation of the treated animals, or on the reproductive performance of their offspring. 4.8 Interaction with other veterinary medicinal products and other forms of interaction: Alfaxan® has been demonstrated to be safe when used in combination with the following premedicant classes: Drug Class
Examples
Phenothiazines
acepromazine maleate
Anticholinergic agents
atropine sulfate
Benzodiazepines
diazepam, midazolam hydrochloride,
Alpha-2-adrenoceptor agonists
xylazine hydrochloride, medetomidine hydrochloride
Opiates
methadone, morphine sulfate, butorphanol tartrate, buprenorphine hydrochloride
NSAIDs
carprofen, meloxicam
The concomitant use of other CNS depressants should be expected to potentiate the depressant effects of either product, and appropriate dose adjustments should be made. The use of one premedicant or a combination of premedicants often reduces the dose of Alfaxan® required. Premedication with alpha-2-adrenoceptor agonists such as xylazine and medetomidine can markedly increase the duration of anaesthesia in a dose dependent fashion. In order to shorten recovery periods it may be desirable to reverse the actions of these premedicants. Benzodiazepines should not be used as sole premedicants in dogs and cats as the quality of anaesthesia in some patients may be sub-optimal. 4.9 Amounts to be administered and administration route: Induction of anaesthesia: The induction dose of Alfaxan® is based on data taken from controlled laboratory and field studies and is the amount of drug required for 9 of 10 dogs or cats (i.e. 90th percentile) to be successfully induced for anaesthesia. Dosing recommendations for induction of anaesthesia are as follows: DOGS CATS Un-premedicated Premedicated Un-premedicated Premedicated mg/kg 3 2 5 5 ml/kg 0.3 0.2 0.5 0.5
The dosing syringe should be prepared to contain the above dose. The rate of intravenous injection should be such that the total dose, if required, would be administered over the first 60 seconds. If, 60 seconds after complete delivery of this first induction dose, intubation is still not possible, one further similar dose may be administered to effect. The necessary injection rate can be achieved by administration of one quarter (1/4) of the calculated dose every 15 seconds. Administration should continue until the clinician is satisfied that the depth of anaesthesia is sufficient for endotracheal intubation, or until the entire dose has been administered. Maintenance of anaesthesia: Following induction of anaesthesia with Alfaxan®, the animal may be intubated and maintained on Alfaxan® or an inhalation anaesthetic agent. Maintenance doses of Alfaxan® may be given as supplemental boluses or as constant rate infusion. Alfaxan® has been used safely and effectively in both dogs and cats for procedures lasting for up to one hour. The following doses suggested for maintenance of anaesthesia are based on data taken from controlled laboratory and field studies and represent the average amount of drug required to provide maintenance anaesthesia for a dog or cat. However the actual dose will be based on the response of the individual patient. Alfaxan® doses suggested for maintenance of anaesthesia are as follows: DOGS Unpremedicated
Premedicated
CATS Unpremedicated
mg/kg/hour 8mg/kg/minute 0.13 ml/kg/minute 0.013 Bolus mg/kg 1.3 ml/kg 0.13 -
9 6-7 10 - 11 7-8 0.15 0.10 - 0.12 0.16 - 0.18 0.11 - 0.13 0.015 0.010 - 0.012 0.016 - 0.018 0.011 - 0.013 dose for each 10 minutes maintenance 1.5 1.0 - 1.2 1.6 - 1.8 1.1 - 1.3 0.15 0.10 - 0.12 0.16 - 0.18 0.11 - 0.13
Where maintenance of anaesthesia is with Alfaxan® for procedures lasting more than 5 to 10 minutes, a butterfly needle or catheter can be left in the vein, and small amounts of Alfaxan® injected subsequently to maintain the required level and duration of anaesthesia. In most cases the average duration of recovery when using Alfaxan® for maintenance will be longer than if using an inhalant gas as a maintenance agent. 4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary: Acute tolerance to overdose has been demonstrated up to 10 times the recommended dose in the dog and up to 5 times the recommended dose in the cat. For both dogs and cats, these excessive doses delivered over 60 seconds cause apnoea and a temporary decrease in mean arterial blood pressure. The decrease in blood pressure is not life threatening and is compensated for by changes in heart rate. These animals can be treated solely by intermittent positive pressure ventilation (if required) with either room air or, preferably, oxygen. Recovery is rapid with no residual effects. 4.11 Withdrawal periods: Not applicable. 5. PHARMACOLOGICAL PROPERTIES: 5.1 Pharmacodynamic properties: Pharmacotherapeutic group: other general anaesthetics, ATCvet code: QN01AX05. Alfaxalone (3-α-hydroxy-5-αpregnane-11,20-dione) is a neuroactive steroid molecule with properties of a general anaesthetic. The primary mechanism for the anaesthetic action of alfaxalone is modulation of neuronal cell membrane chloride ion transport, induced by binding of alfaxalone to GABAA cell surface receptors. 5.2 Pharmacokinetic particulars: The volume of distribution after a single injection of clinical doses of Alfaxan® in dogs and cats is 1.7 L/kg and 1.8 L/kg, respectively. In vitro cat and dog hepatocyte studies show that alfaxalone experiences both Phase I (cytochrome P450 dependent) and Phase II (conjugation dependent) metabolism. Both cats and dogs form the same five (5) Phase I alfaxalone metabolites. The Phase II metabolites observed in cats are alfaxalone sulphate and alfaxalone glucuronide, while alfaxalone glucuronide is observed in the dog. In cats, the mean terminal plasma elimination half-life (t1/2) for alfaxalone is approximately 45 minutes for a 5 mg/kg dose. Mean plasma clearance for a 5 mg/kg dose is 25.1 ± 7.6 ml/kg/min. In dogs, the mean terminal plasma elimination half-life (t1/2) for alfaxalone is approximately 25 minutes for a 2 mg/kg dose. Plasma clearance for a 2 mg/kg dose is 59.4 ± 12.9 ml/kg/min. Alfaxalone metabolites are likely to be eliminated from the dog and cat by the hepatic/faecal and renal routes, similar to other species. 6. PHARMACEUTICAL PARTICULARS: 6.1 List of excipients: Hydroxypropylbetadex, Sodium Chloride, Disodium Phosphate Anhydrous, Potassium Dihydrogen Phosphate, Sodium Hydroxide, Hydrochloric Acid (concentrated), Water for Injections. 6.2 Major incompatibilities: Alfaxan® should not be mixed with other veterinary medicinal products prior to its administration. 6.3 Shelf-life: 30 months. 6.4 Special precautions for storage: Do not freeze. This product does not contain an antimicrobial preservative. Any solution remaining in the vial following withdrawal of the required dose should be discarded. Keep the container in the outer carton. 6.5 Nature and composition of immediate packaging: Cardboard box with one glass vial of 10 ml with a rubber stopper and aluminium cap. 6.6 Special precautions for the disposal of unused veterinary medicinal products or waste materials derived from the use of such products, if appropriate: Any unused product or waste material should be disposed of in accordance with national requirements. 7. MARKETING AUTHORISATION HOLDER: Jurox (UK) plc, 3 Tenterden Street, Hanover Square, London W1S 1TD. 8. MARKETING AUTHORISATION NUMBER: VM25296/4000 9. DATE OF FIRST AUTHORISATION: 23rd November 2006 10. DATE OF REVISION OF THE TEXT: N/A 11. OTHER INFORMATION: Legal Category POM-V Alfaxan® is a trademark of Jurox Pty Limited, Rutherford NSW 2320, Australia.
References: 1.Data on file, Jurox study number RD9604.03-H002 2.Data on file, Jurox study number JX9604.07-H001 3.Data on file, Jurox studies number JX9604.03-E017, JX9604.03-C016, JX9604.07-H009 and JX9604.07-C006 4.Data on file, Jurox study number JX9604.03-C009 5.Data on file, Jurox study number JX9604.07-C006 6.Data on file, Jurox study number RD9604.03-H004 7.Lumb and Jones, 1996 8.Data on file, Jurox study report no. JX9604.07-H003 9.Data on file, Jurox safety studies RD9604.03-H005, JX9604.07-H004 10.Jurox Pharmacovigilance Report JX9604-SR004 11.Acute cardiovascular and tolerance study abstracts ACVIM 2004 (dog) 12.Acute cardiovascular and tolerance study abstracts VMAAC 2005 (cat) 13.Data on file, Jurox study number JX9604.03/06 (dog) , RD9604.03/01 (cat)
12
Premedicated
Dose for constant rate infusion
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VETOQUINOL UK LIMITED, VETOQUINOL HOUSE, GREAT SLADE, BUCKINGHAM INDUSTRIAL PARK, BUCKINGHAM. MK18 1PA TEL: +44 (0) 1280 814500 FAX: +44 (0) 1280 825460 EMAIL:
[email protected] WEBSITE: www.vetoquinol.co.uk
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