A Question of Balance

1
A Question of Balance

• Scheduling Tramadol

2
WHO Principle of Balance

• The regulation of medications, meant to decrease
  misuse should not interfere with the legitimate
  treatment of pain

3
Question

• Why is Health Canada adopting a position on
  scheduling of tramadol which is inconsistent with
  US, Germany, Australia, UK and Switzerland?

4
Health Canadas Positions on Tramadol

• Greater risk of abuse and diversion of single
  entity products vs. combination products
  containing acetaminophen.
• High dose single entity products will be chewed,
  or crushed snorted to a greater extent than
  multiple, low dose, single entity products.
• Information sources" that show increase of abuse
  in the US and other countries.
• Tramadol will be subject to more abuse in Canada
  vs. other countries where it has been marketed.

5
Health Canadas Positions on Tramadol

• Scheduling of tramadol will have no negative
  effect on patient care.  
• Stakeholder views (and materials presented to HC)
  have been considered.
• All data has been considered, leading to
  conclusion that an Expert Advisory Committee is
  not warranted.

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No one in his/her right mind would abuse a
combination compound
7
Abused Opioids of Choice in Canada

• heroin, morphine, methadone, dilaudid, T3/4,
  oxycodone
• morphine, T3/4, oxycodone, dilaudid, Percocet,
  methadone, heroin
• Percocet, T3/4, morphine, oxycodone, dilaudid,
  heroin, methadone
• heroin, dilaudid, methadone, morphine, Percocet,
  T3/4, oxycodone
• dilaudid, oxycodone, morphine, heroin, T3/4,
  methadone
• dilaudid, oxycodone, T3/4, morphine, Percocet,
  methadone
• dilaudid, T3/4, Percocet, oxycodone, morphine,
  heroin

• Vancouver
• Edmonton
• Toronto
• Montreal
• Quebec
• Fredericton
• Saint John

Fischer B et al. CMAJ 2006 175(11)1385-1387
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Tramadol might be part of the solution rather
than the problem

• Appropriate substitute for Tyl 3 and in some
  cases Percocet
• Safer than long-term NSAIDs / COXIBs

9
Higher Dose Concerns

• June 7, 2007 Ministers letter to Dr. Jovey
  high dose, single entity.it is our view that
  the risk of abuse and potential for diversion
  warrant scheduling under CDSA.
• There has always been the opportunity to consume
  several low dose tablets (eg.100mg x 4 1 x
  400mg). However, worldwide data does not
  demonstrate this.
• 400 mg single entity available in Belgium,
  Denmark, Germany, Luxembourg, Netherlands,
  Portugal, Spain, Sweden, UK, US.no extra
  controls apply.
• WHO Expert Committee considered higher dose,
  single entity tramadol in concluding tramadol
  should not be scheduled

10
Worldwide Data

• Use vs. Abuse

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Worldwide Abuse/Dependence Reporting Rates and
Tramadol Consumption 1980 to 2005
Source Grünenthal Drug Safety Database
12
Canadians are more likely to abuse tramadol than
other countries ?

• If anything, the existing data (Cicero) on other
  opioids shows that Canadian abuse rates are
  slightly less or equal to those of the U.S.
• For H.C. to suggest we are more likely to abuse
  tramadol must mean they have some evidence that
  they are not sharing!

13
Commonly abused Rx in Canada

• Gravol misused / abused as a sedative
• Dextromethorphan abused by teens
• Ventolin inhalers are being abused!
• Where do we draw the line??

14
Tramadol Metabolism

• Tramadols opioid effect comes primarily from
  the M1 metabolite which has an affinity for mu
  opioid receptors similar to that of codeine
• M1 is mostly formed by liver metabolism and has a
  delayed appearance in the blood
• ? not appealing to addicts

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Tramadol iv / snorted / smoked?

• The amount of tramadol in the blood will far
  exceed the amount of M1
• ? less euphoria for the dose taken
• ? higher risk of seizure
• ?Also not appealing to abusers

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Comparison of Abuse Liability of Tramadol,
NSAIDs, and Hydrocodone in Patients with Chronic
Pain

• Evidence of abuse at 12 month follow-up
  equivalent to that for NSAIDS
• NSAIDS 2.5 (n 4039)
• Tramadol 2.7 (n 4222)
• Hydrocodone 4.9 (n 3145)
• Adams et. al JPSM 2006

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• The scheduling of a substance may lead to
  significant barriers to its availability as a
  medicine.

WHO Expert Committee on Drug Dependence, 34th
Report. 2006
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Impact of Tramadol Scheduling International
Examples
Tramadol (INN) units in Egypt before, during
scheduling, and after de-scheduling
Tramadol (INN) units in Jordan before and after
scheduling
Scheduled in 2000
Scheduled December 2002
De-Scheduled May 2004
Source IMS
Source IMS
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The Impact of Scheduling

• Perception that the drug is more addictive and
  prescribing is being monitored, therefore
  reluctance to prescribe
• esp. family physicians, surgeons
• Triplicate status discourages use
• Special Rx pad, College monitoring
• Other more problematic drugs will be prescribed
  instead (Tyl 3)

20
Expert Position on Tramadol Based on Science and
Data

• ? availability ? ? abuse (less abuse over time)
• No evidence high dose use ? risk of abuse
• Metabolism M1 limits i.v. / i.n. abuse
  attractiveness
• No evidence long-term use ? risk of abuse
• Scheduling does impact prescribing and
  therefore patient care

21
Abuse of Rx Analgesics

• Scheduling currently does not seem to affect
  abuse of other opioid analgesics, therefore it is
  very unlikely to affect the already low risk of
  tramadol abuse
• The only predictable effect will be less
  prescribing for legitimate patients

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Rx Analgesic Abuse - Solutions

• Education not regulation
• We are teaching MDs to risk stratify patients and
  prescribe treatments accordingly
• We need a palette of treatments for the problem
  of pain
• Telling MDs that the risk of tramadol is
  equivalent to that of morphine, fentanyl,
  methadone flies in the face of this strategy
• Regulations need to stay in line with best
  practices if we are to optimize outcome and
  minimize harm.

23
Rx Analgesic Abuse - Solutions

• Monitoring
• Continue current monitoring programs and act on
  results if required
• Requires cooperation of all stakeholders
  government, law enforcement, addiction programs,
  etc
• ? National online, real-time data for physicians
  ?

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• Men stumble over the truth from time to time, but
  most pick themselves up and hurry off as if
  nothing happened
• Winston Churchill