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

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”

Paediatric animals

...this does not mean that methadone is unsafe in these patients, merely

that appropriate testing has not been

carried out

Are paediatric animals different?

• cardiovascular system

• respiratory system

• hepatic function

• temperature regulation

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

Methadone in paediatric animals

• may see:

– greater sedative effects

– longer duration

with opioids in paediatrics

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

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

Methadone in hepatic disease

• start off with low doses (0.1-0.2 mg/kg)**

• titrate upwards to effect

• anticipate increased dose interval (but high individual variability)

** less than SPC dose

Opioids in renal disease

• decreased excretion of parent drug or metabolites (active)

• altered drug binding

• increased permeability of blood-brain barrier

Opioids in renal disease

• exaggerated opioid effects (and side-effects)

• potential drug accumulation over-dose

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…”

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

Methadone in renal disease

“Do not use in animals with severe renal

dysfunction”

• start with low doses (0.1-0.2 mg/kg)** to assess sensitivity

• titrate upwards as required

** less than SPC dose

Opioids in geriatric animals

• impaired organ function

• increased sensitivity to opioids

• expect exaggerated effect and longer duration

Opioids in geriatric animals

• start with low doses (0.1-0.2 mg/kg)** to assess sensitivity

• titrate upwards as required

** less than SPC dose

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

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

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

The recurring theme...

• start with low doses (0.1-0.2 mg/kg)** to assess sensitivity

• titrate upwards as required

** less than SPC dose

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