1. Safe and Appropriate Use of Opiates
Executive Director Advisory Panel
Friday, June 22, 2018
Safe and Appropriate Use of Opiates
Good morning – again, my name is Jessica Growette and I’m the Community Pharmacist Lead for Tabula Rasa HealthCare and your primary point of contact for this Enhanced Medication Therapy Management program.
Thank you for joining me today to learn more about the region 25 EMTM program approved through the Centers for Medicare & Medicaid Innovation Center and how you can get involved.
Robert Alesiani, PharmD, BCGP
Chief Pharmacotherapy Officer, CareKinesis

2. Objectives
Understand the risks associated with opiate drug therapy in the elderly population
Learn and understand safe and effective pain management practices with opiates
Ascertain best practice for starting and ending opiate therapy using evidence-based tools
Know which medications are available for older adults, which may have pharmacogenomic implications, and how to utilize pharmacogenomic information to assure medication safety and effectiveness

3. Opioid Epidemic

4. Opioid Epidemic

5. Due, in part, to DRUG INTERACTIONS Opioid Epidemic
It is estimated that almost 80% of opioid-related overdose deaths are considered accidental or unintentional
Due, in part, to
DRUG INTERACTIONS

6. What are the states, CDC, Medical Associations doing to address
Limiting Quantities on Prescriptions
Monitor those over 90mg of Oral Morphine Milligram Equivalence (MME) / day
Monitor those that have used more than 2 or 3 prescribers for Opioids
Monitor those that have used more than 2 or 3 pharmacies to fill Opioids
Some states are requirement all control drug prescriptions to be requested electronically
Require reporting to and reviewing of all data on the PDMP database for their individual states
Recommending urine drug screening prior to initiation of opioid therapy and on-going (at least annually) to assure the patient is taking the drugs prescribed.
Develop and utilize Opioid Utilization contracts

7. Opioid Pain Management case
J.D. is an 84-year old male with post-surgical repair of spinal stenosis (L1-L2).
His PMH includes chronic, non-cancer pain with comorbid depression, HTN, COPD, and Diabetes Type II. He has NKDA.
Following surgery, he was started on tramadol by the pain management specialist:
Tramadol 50mg: Take 1 to 2 tablets every 4 to 6 hours as needed for pain

8. Opioid Pain Management case
Current Medication History
During his follow-up visit with PACE (PCP) approximately a week later, it was evident that he failed to achieve an adequate response and exhibited intolerable side effects with tramadol
J.D. stated that he tried tramadol 50mg for 2 days but has been taking tramadol 100mg every 4 hours while awake for the past 5 days with only a small reduction in his pain (7/10 at best)
He also expressed that he has been experiencing nausea, constipation, and dizziness

9. Opioid Pain Management case
Opioid Pain Management Case Current Medication History
His PCP changes tramadol to hydrocodone/APAP
His current medication profile is as follows:
Hydrocodone/acetaminophen 5/325 mg every 4 hours PRN pain – NEW
Senna-S 2 tablets daily – NEW
Sertraline 50 mg/day
Metoprolol succinate 50 mg/day
Hydrochlorothiazide 25 mg/day
Beclomethasone 80 mcg/inhalation twice daily
Albuterol MDI 2 puffs every 4 hours as needed
Unchanged
To Be Continued…

10. CareKinesis Opioid Strategy
Opioid Pain Management Case
How potent is Hydrocodone compared to other opioids?
Look for Equianalgesic table
When switching from one opioid to another, reduce dose by 25% to account for cross tolerance
Always start low and go slow

11. CareKinesis Opioid Strategy
Opioid Pain Management Case

12. CareKinesis Opioid Strategy
Opioid Pain Management Case
Need to consider how the opioid will be metabolized and excreted
Opioids are primarily metabolized by CYP2D6
Two exceptions are Fentanyl and Methadone
Both are highly lipophilic
Need to consider medications that compete for the same enzymes

13. CareKinesis Opioid Strategy
Opioid Pain Management Case
The number one side effect of all Opioids is:
CONSTIPATION not respiratory suppression
Always write a prescription for Senna when you prescribe any opioid
Must think of improving peristalsis to treat constipation

14. CareKinesis Opioid Strategy
Tramadol Metabolic Pathway

15. CareKinesis Opioid Strategy
Oxycodone Metabolic Pathway

16. Opioid Pharmacokinetic Interaction Competitive Inhibition
CYP2D6
Less ACTIVE
Metabolite
ACTIVE
Metabolite
Tramadol
Expected (normal) analgesic response
CYP2D6
Metabolite
Metoprolol
Reduced analgesic response

17. Opioid Pharmacokinetic Interaction Non-Competitive Inhibition
CYP2D6
ACTIVE
Metabolite
Less ACTIVE
Metabolite
Hydrocodone
Expected (normal) analgesic response
CYP2D6
Metabolite
Paroxetine
Reduced analgesic response

18. CareKinesis Opioid Strategy
Opioid-Related Drug Interactions
Pharmacogenomic (PGx) Mechanisms
Impact of Genetic Variations
Drug-Gene Interactions

19. CareKinesis Opioid Strategy
Opioid Related Drug Interactions

20. Oxycodone Response Normal Response
CYP2D6
Oxymorphone
CYP2D6 *1/*1
Normal Metabolizer (NM)

21. Oxycodone Response Reduced Response
CYP2D6
Oxymorphone
CYP2D6 *4/*4
Poor Metabolizer (PM)
A CYP2D6 poor metabolizer clears CYP2D6 substrates (e.g., opioids) slowly and, therefore, has greater than expected exposure to the parent drug & lower than expected exposure to active metabolites
Giving oxycodone to patients without CYP2D6 activity is like giving a placebo

22. Oxycodone Response Enhanced Response
CYP2D6
CYP2D6
Oxycodone
CYP2D6
Oxymorphone
CYP2D6
CYP2D6
CYP2D6
CYP2D6 *1/*1x2
Ultra-rapid Metabolizer (UM)

23. Oxycodone Response Altered Response – Phenoconversion
CYP2D6 *1/*1
Normal Metabolizer (NM)
Oxycodone
CYP2D6
Oxymorphone
Bupropion
This can be mitigated by giving Oxycodone 2-4 hours prior to Bupropion
CYP2D6 behaves like an Intermediate Metabolizer (IM) or
Poor Metabolizer (PM)

24. Oxycodone Response Altered Response – Phenoconversion
CYP2D6 *1/*1
Normal Metabolizer (NM)
Oxycodone
CYP2D6
Oxymorphone
Amiodarone
This can NOT be mitigated by changing time of administration
CYP2D6 behaves like
Poor Metabolizer (PM)

25. CareKinesis Opioid Strategy

26. Opioid Pain Management case
Following his PCP visit, J.D. begins taking the hydrocodone/acetaminophen as prescribed After several days, he calls his PCP to report that this pain medication does not seem to be helping much more than the tramadol His PCP writes a new prescription for hydrocodone/acetaminophen 10/325 mg every 4 to 6 hours PRN pain
What should we expect?

27. Opioid Pain Management Case Explained – Hydrocodone
Competitive inhibition
The result is expected to be the SAME
Metoprolol (moderate substrate) is blocking the metabolism of Hydrocodone (weak substrate)
As a result, Hydrocodone cannot be activated to its more potent metabolite (hydromorphone)
What happens next?

28. CareKinesis Opioid Strategy

29. CareKinesis Opioid Strategy

30. CareKinesis Opioid Strategy

31. CareKinesis Opioid Strategy

32. CareKinesis Opioid Strategy

33. CareKinesis Opioid Strategy

34. CareKinesis Opioid Strategy

35. CareKinesis Opioid Strategy

36. CareKinesis Opioid Strategy

37. CareKinesis Opioid Strategy