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 RAlesiani@carekinesis.com

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

Opioid Epidemic

Opioid Epidemic

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

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

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

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

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…

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

CareKinesis Opioid Strategy Opioid Pain Management Case

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

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

CareKinesis Opioid Strategy Tramadol Metabolic Pathway

CareKinesis Opioid Strategy Oxycodone Metabolic Pathway

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

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

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

CareKinesis Opioid Strategy Opioid Related Drug Interactions

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

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

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

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)

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)

CareKinesis Opioid Strategy

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?

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?

CareKinesis Opioid Strategy

CareKinesis Opioid Strategy

CareKinesis Opioid Strategy

CareKinesis Opioid Strategy

CareKinesis Opioid Strategy

CareKinesis Opioid Strategy

CareKinesis Opioid Strategy

CareKinesis Opioid Strategy

CareKinesis Opioid Strategy

CareKinesis Opioid Strategy