Use of methadone in young animals, geriatric animals, and those with concurrent disease

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1 Use of methadone in young animals, geriatric animals, and those with concurrent disease Professor Derek Flaherty BVMS, DVA, DipECVAA, MRCA, MRCVS RCVS and European Specialist in Veterinary Anaesthesia

2 Paediatric animals various definitions but usually considered as puppies and kittens less than 12 weeks old safety of methadone not demonstrated in dogs <8wks or cats <5months

3 Paediatric animals...this does not mean that methadone is unsafe in these patients, merely that appropriate testing has not been carried out

4 Are paediatric animals different? cardiovascular system respiratory system hepatic function temperature regulation

5 Cardiovascular considerations stroke volume relatively fixed in paediatrics rely on high heart rate to maintain cardiac output opioids HR combine with anticholinergic (atropine/glycopyrrolate) in animals <12 weeks

6 Methadone in paediatric animals may see: greater sedative effects longer duration with opioids in paediatrics

7 Methadone in paediatric animals initial dose should be no greater than 0.2 mg/kg** IM route preferable supplemental doses should be administered as required may require increased dose interval (pain score) ** less than SPC dose

8 Methadone in hepatic disease Do not use in animals with severe liver dysfunction protein binding of 60-90% 96-97% of the administered dose is metabolised by the liver expect potential exaggerated effect and increased duration

9 Methadone in hepatic disease start off with low doses ( mg/kg)** titrate upwards to effect anticipate increased dose interval (but high individual variability) ** less than SPC dose

10 Opioids in renal disease decreased excretion of parent drug or metabolites (active) altered drug binding increased permeability of blood-brain barrier

11 Opioids in renal disease exaggerated opioid effects (and sideeffects) potential drug accumulation overdose

12 Methadone in renal disease Do not use in animals with severe renal dysfunction A small amount (3-4% in the dog) of the administered dose is excreted unchanged in the urine

13 Methadone in renal disease methadone is probably preferable to other full agonist opioids in renal disease morphine and pethidine both have active metabolites that are renally excreted Methadone has no active metabolites

14 Methadone in renal disease Do not use in animals with severe renal dysfunction start with low doses ( mg/kg)** to assess sensitivity titrate upwards as required ** less than SPC dose

15 Opioids in geriatric animals impaired organ function increased sensitivity to opioids expect exaggerated effect and longer duration

16 Opioids in geriatric animals start with low doses ( mg/kg)** to assess sensitivity titrate upwards as required ** less than SPC dose

17 Opioids and intracranial disease if there is a significant chance the animal may require neurosurgical intervention, best to use a short-acting opioid such as pethidine IM if this is unlikely / not an option, a longer-acting opioid is more practical avoid morphine (vomiting; unlicensed) Image courtesy of Dr. Elisa Mazzaferro

18 Methadone and intracranial disease start with low doses and titrate upwards 0.1 mg/kg methadone slowly IV, repeated as required q 10 min N.B. this is less than the licensed dose and the IV route is off licence in cats

19 The generic sick animal methadone has minimal cardiovascular depressant effects (bradycardia with high doses esp. IV) and causes minimal respiratory depression reduces anaesthetic requirements anaesthetics are marked cardiopulmonary depressants

20 The recurring theme... start with low doses ( mg/kg)** to assess sensitivity titrate upwards as required ** less than SPC dose

21 In summary... many of the issues highlighted on the Comfortan SPC merely relate to the absence of controlled studies in these patient groups...in common with most other opioid drugs methadone can generally be used safely in these animals provided due consideration is given to both the dose and dosing interval