Philip Peng MBBS FRCPC

1
Management of Methadone patients in APS

• Philip Peng MBBS FRCPC
• Director, Anesthesia Chronic Pain Program,
• University Health Network
• Director of Research, Wasser Pain Management
  Center, Mount Sinai Hospital

2
Objective

• Discussion of the relevant pharmacology of
  methadone
• License requirement of methadone in Canada
• Suggested algorithm for management of methadone
  patients in APS

3
Who wants to be a millionaire

• Which of the following is a true long-acting
  opioid?

• A Fentanyl patch

• B MS Contin

• D Marijuana

• C Methadone

4
Opioids
Elimination half-life
Short-acting
Long acting E.g. methadone, buprenorphine
Sustain release
Immediate release
5
Methadone
Synthetic opioid, structure very different from
other opioid
methadone
codeine
morphine
6
Basic pharmacology

• HCl powder, formulated as liquid (PO, rectal,
  parenteral)
• Tablets form available
• Racemic mixture of 2 enantiomers
• R-Met opioid agonist
• S-Met NMDA antagonist ? reuptake of 5HT and NA

? tolerance Neuropathic pain
7
Basic pharmacology

• Excellent PO bioavailability (85)
• Onset in 30 min., peak level in 2.5 h
• Biphasic elimination

8
analgesia (? elimination 8-12 h)
maintenance (? elimination 30-60 h)
Plasma level
Time
9
Methadone License in Canada

• A controlled substance, prescription required
  exemptions (Section 56 under Controlled Drugs and
  Substances Act)
• Two types of exemptions
• MMT-provincial medial authorities
• Pain Federal Office of Controlled Substances
  except BC, Quebec, Alberta and Manitoba
• Emergency situation
• Temporary license which is MD-, patient- and
  institution-specific and expires on D/C or after
  2 months.

10

• Kim Barber B. Pharm.
• Scientific Officer
• Methadone Program
• Office of Controlled Substances
• Kim_Barber_at_hc-sc.gc.ca
• Phone [phone]
• Fax [phone]

11
Methadone license exemption for pain in Canada
12
Problem with methadone

• Drug interaction
• Single dose overdose
• Accumulated toxicity

13
Problem with methadone

• Drug interaction
• Single dose overdose
• Accumulated toxicity

14
Drug interaction

• Methadone EDDP

N-demethylation
Cytochrome system CYP 3A4, 2D6, 1A2
carvedilolS-metoprololpropafenonetimolola
mitriptyline  clomipramine  desipramineimiprami
ne  paroxetine haloperidolperphenazinerisperi
done thioridazinealprenololamphetaminebufuralo
lchlorpheniraminechlorpromazinecodeine
debrisoquine
amitriptylinecaffeineclomipramineclozapinecycl
obenzaprineestradiolfluvoxaminehaloperidolimip
ramine N-DeMemexiletinenaproxen  ondansetron
 phenacetingtacetaminophengtNAPQIpropranololri
luzoleropivacainetacrinetheophyllineverapamil
 (R)warfarinzileutonzolmitriptan
dexfenfluraminedextromethorphanencainideflecain
idefluoxetinefluvoxaminelidocaine
 metoclopramidemethoxyamphetaminemexiletinenor
triptylineminaprineondansetronperhexilinephena
cetinphenforminpropranolol  quanoxansparteine
tamoxifentramadolvenlafaxine
15
Cytochrome drug interaction
16
Other mechanisms of drug interaction

• ?1-acid glycoprotein
• Circulating level ? with stress, addiction,
  cancer and drugs such as amitriptylline
• Pharmacodynamics interaction

benzodiazepine
Excitatory NMDA
Inhibitory GABA
Respiration rhythm
methadone
17
Other mechanisms of drug interaction

• ?1-acid glycoprotein
• Circulating level ? with stress, addiction,
  cancer and drugs such as amitriptylline
• Pharmacodynamics interaction

Excitatory NMDA
Inhibitory GABA
Respiration rhythm
18
Other mechanisms of drug interaction

• ?1-acid glycoprotein
• Circulating level ? with stress, addiction,
  cancer and drugs such as amitriptylline
• Pharmacodynamics interaction

Excitatory NMDA
Inhibitory GABA
Respiration rhythm
19
Problem with methadone

• Drug interaction
• Single dose overdose
• Accumulated toxicity

20
Single dose Overdose
Problem mg vs ml
21
Problem with methadone

• Drug interaction
• Single dose overdose
• Accumulated toxicity

22
Accumulated toxicity

• Over-aggressive titration of methadone dose

23
Algorithm of managing methadone patients in APS

• Elective surgery

In-patient surgery NPO lt48h
In-patient surgery NPO gt48h
Day surgery
24
Algorithm of managing methadone patients in APS

• Elective surgery

• Pre-operative anesthesia consult
• Continue methadone until the day of surgery
• Pre-operative ECG
• Bring their own methadone

25
Continue methadone until the day of surgery
26
Algorithm of managing methadone patients in APS

• Elective surgery

In-patient surgery NPO lt48h
In-patient surgery NPO gt48h
Day surgery

• Resume regular dose of methadone after surgery
• Additional analgesic for pain control

27
Algorithm of managing methadone patients in APS

• Elective surgery

In-patient surgery NPO lt48h
In-patient surgery NPO gt48h
Day surgery

• While NPO, alternative analgesic e.g. PCA
• Resume methadone ASAP PO well

28
Algorithm of managing methadone patients in APS

• Elective surgery

In-patient surgery NPO lt48h
In-patient surgery NPO gt48h
Day surgery

• While NPO, consider PCA /- infusion
• Drug-drug interaction
• Resume methadone ASAP PO well

29
PCA with infusion

• Does not improve analgesia or sleep
• Increase opioids consumption and risk of SE

30
Case presentation

• 34 y.o. man on methadone via MMT and is coming
  for knee arthroscopic surgery.
• 65 y.o. lady , currently on methadone for her
  pain related to rheumatoid arthritis, is
  scheduled for total hip replacement
• 45 y.o. lady, on methadone for metastatic breast
  cancer, is admitted for bowel resection.

31
Case presentation

• 34 y.o. man on methadone via MMT and is coming
  for knee arthroscopic surgery.
• 65 y.o. lady , currently on methadone for her
  pain related to rheumatoid arthritis, is
  scheduled for total hip replacement
• 45 y.o. lady, on methadone for metastatic breast
  cancer, is admitted for bowel resection.

32
Case presentation

• 34 y.o. man on methadone via MMT and is coming
  for knee arthroscopic surgery.
• 65 y.o. lady , currently on methadone for her
  pain related to rheumatoid arthritis, is
  scheduled for total hip replacement
• 45 y.o. lady, on methadone for metastatic breast
  cancer, is admitted for bowel resection.

33
Case presentation

• 34 y.o. man on methadone via MMT and is coming
  for knee arthroscopic surgery.
• 65 y.o. lady , currently on methadone for her
  pain related to rheumatoid arthritis, is
  scheduled for total hip replacement
• 45 y.o. lady, on methadone for metastatic breast
  cancer, is admitted for bowel resection.