Drugs to Watch: Tramadol,Hydrocodone and Naloxone

Presenters:

• Nathan Painter, PharmD, Associate Clinical Professor, University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Science

• Roneet Lev, MD, Director of Operations, Scripps Mercy Hospital Emergency Department, and Chair, San Diego County (CA) Rx Drug Abuse Medical Task Force

• Traci Green, PhD, MSC, Deputy Director, Boston Medical Center Injury Prevention Center, and Associate Professor of Emergency Medicine, Boston University

Pharmacy Track

Moderator: Anne L. Burns, RPh, Vice President, Professional Affairs, American Pharmacists Association, & Member, Rx & Heroin Summit National Advisory Board

Disclosures

Traci Green, PhD, MSC; Roneet Lev, MD; Nathan Painter, PharmD; and Anne L. Burns, RPh, have disclosed no relevant, real, or apparent personal or professional financial relationships with proprietary entities that produce healthcare goods and services.

Disclosures

• All planners/managers hereby state that they or their spouse/life partner do not have any financial relationships or relationships to products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months.

• The following planners/managers have the following to disclose:– John J. Dreyzehner, MD, MPH, FACOEM – Ownership interest:

Starfish Health (spouse)– Robert DuPont – Employment: Bensinger, DuPont &

Associates-Prescription Drug Research Center

Learning Objectives

1. Analyze the impact of tramadol and hydrocodone schedule changes on the number of prescriptions and deaths related to these medications in California.

2. Describe reasons physicians and patients need a better education about tramadol and its potential dangers.

3. Evaluate pharmacists’ perspectives on pharmacy-based naloxone based on a nationally representative survey.

4. Provide accurate and appropriate counsel as part of the treatment team.

Tramadol and HydrocodoneThe impact of changing DEA schedules

Roneet Lev, MD FACEPNathan Painter, Pharm D, CDE

Opioids 101 Morphine

from opium poppy Semi-Synthetic Opioid - Hydrocodone Fully Synthetic Opioid - Tramadol

Morphine Hydrocodone Tramadol

Opioid ConversionOpioid ME (mg) Daily dose (mg)

Morphine 5 30

Hydrocodone 5 30 – 45

Tramadol 5-10* 150-300

Oxycodone 7.5 15 – 20

*Washington State, CMS table, cures

Advertising and Marketing

“…less potential for abuse than other opioid agonists…”“narcotic-like because it is a synthetic drug with a slightly different chemical structure than other narcotics…”

Tramadol Marketing

Tramadol Safety

Adverse Drug Reactions : seizures Higher incidence when combined with alcohol, illicit

drugs, antipsychotics, or antidepressants Withdrawal can cause seizures

Not reduced with naloxone

Caspian J Intern Med. 2012 Summer; 3(3): 484–487Int J Prev Med. 2014 Mar; 5(3): 302–307

Is Tramadol Addictive? Development of cravings when not using the drug Development of tolerance effects or requiring more and

more of the drug to achieve the same effects Use for nonmedical purposes Inability to control use Continually taking the drug regardless of the harm it

causes, physically or psychologically "Drug seeking" behavior such as constantly "losing"

prescriptions, arriving at clinics at the end of business hours, refusing examinations, or tampering with medical records or prescriptions

"Doctor shopping" Failing to perform as expected at work or school due to

drug-related impairments Neglecting friends and family in order to use or obtain

drugsPharmacoepidemiol Drug Saf. 2009 Dec;18(12):1192-8

DEA Schedule Change Hydrocodone III II

• October 6, 2014 Tramadol V IV

• August 18, 2014

Schedule Change Prediction Less hydrocodone? More tramadol? Less overall opioids?

Results

Number of PrescriptionsIMS Health National Prescription Audit

Jones CM, et.al. JAMA Intern Med. Published online January 25, 2016

Hydrocodone Combination Product

Nonhydrocodone Combination Product

Jones CM, et.al. JAMA Intern Med. Published online January 25, 2016

Hydrocodone Combination Product

Nonhydrocodone Combination Product

Number of TabletsIMS Health National Prescription Audit

Number of PrescriptionsCalifornia PDMP Aug 2013 – October 2015

August-13 March-14 September-14 April-15 October-150

500,000

1,000,000

1,500,000

2,000,000

2,500,000

Hy-drocodone

#Rx

Number of TabletsCalifornia PDMP Aug 2013 – October 2015

August-13 March-14 September-14 April-15 October-150

20,000,000

40,000,000

60,000,000

80,000,000

100,000,000

120,000,000

140,000,000

160,000,000

180,000,000

HydrocodoneTotal OpiodsTramadol

Num

ber

Tabl

ets

California PDMP Number Rx12 months Before and 12 month After DEA Schedule Change

Hydrocodone Tramadol Total Opioids0

5000000

10000000

15000000

20000000

25000000

30000000

35000000

15,667,302

0

23,562,191

15204104

4151099

29292835

25,141,736

Before ChangeAfter ChangeAfter (Less Tramadol)

Total Opioids6.7% excluding Tramadol

Hydrocodone3%

Hydrocodone DEA Schedule Change

IMS Health National Prescription Audit JAMA Internal Medicine

36 months BEFORE schedule change

12 months AFTER schedule change

Hydrocodone Rx and Tablets 8.4%, 6% 22%, 16% (refills 73.7% of decline)

Non-Hydrocodone Rx and Tablets

0.2%, 0.5% 4.9%,1.2%California Prescription Drug Monitoring System

12 months AFTER schedule change

Hydrocodone Rx and Tablets 3%, 1.7%Total Opioid Rx and Tablets (excluding Tramadol)

6.7%,5.3%

San Diego County DeathsAugust 2013 – October 2015

August-13 March-14 September-14 April-15 October-150

5

10

15

20

25

30

35

40

45

50

Hydrocodone

Total Opiods

Tramadol

Dea

ths

San Diego County Deaths12 months Before and 12 month After DEA Schedule Change

Hydrocodone Tramadol Total Opioids0

50

100

150

200

250

300

350

400

4222

338

33 18

367

Before Change

After Change

Hydrocodone 21.4

Tramadol 0.2%

Total Opioids 3.3

Deaths from Tra-madol per Total Rx Tramadol are

2xDeaths from Hy-

drocodone per To-tal Rx Hy-drocodone

Tramadol Non-Narcotic Synthetic opioid

Less-Addicting Than what?

Less Potent 50 Tramadol > 5/325 Hydrocodone

Safer 2 x deaths?Seizures: contraindication/withdrawal

False

False

False

False

Hydrocodone Schedule ChangeOctober 6, 2014

Decreased Rx 3% California, 22% US ? Less refills in California

Increase Total Opioids Rx 6.7% California, 5% US

Traci C. Green, PhD, MScDeputy Director, Boston Medical Center Injury Prevention Center

Boston Medical School, Department of Emergency Medicine, Boston, MA

Associate Professor of Emergency Medicine & EpidemiologyThe Warren Alpert School of Medicine at Brown University, Rhode Island Hospital

Perspectives onPharmacy Based Naloxone:

A Nationally Representative Survey of Pharmacists

Disclosures-Traci C. Green• No conflicts to disclose

• Funding: Research reported in this presentation was funded through the following federal grants: AHRQ R18 HS024021-01 Green (PI: Green), NIDA R01 DA034634(PIs: Friedmann/Rich)

Learning Objectives

• Evaluate pharmacists’ perspectives on pharmacy-based naloxone (PBN) based on a nationally representative survey

Effective Interventions for Opioid Overdose

• Naloxone (Narcan), an intranasal or intramuscular-administered opioid antagonist used to reverse respiratory depression caused by opioids– 26%-47% reduction in overdose

mortality

• Call or TEXT 911

• Rescue breathing

• An ANTIDOTE for OPIOID overdose• Naloxone is an opioid receptor antagonist at mu,

kappa, and delta receptors• Works at the opioid receptor to displace opioid

agonists• Shows little to no agonist activity• Shows little to no pharmacological effect in patients

who have not received opioids

Naloxone

How Naloxone Reverses Opioid Poisoning

Naloxone has a stronger affinity to the opioid receptors than the heroin, so it knocks the heroin off the receptors for a short time and lets the person breathe again

Opioid receptor

Naloxone

Heroin

Rationale for Overdose Education and Naloxone Rescue Kits

• Most opioid users do not use alone

• Known risk factors: – High dose opioids, co-prescription

benzodiazepine+opioid, mixing substances, abstinence, using alone, chronic medical illness

• Opportunity window: – Opioid overdoses take minutes to hours– Reversible with naloxone

• Bystanders are trainable to recognize and respond to overdoses

• Fear of public safety 31

Endorsement for naloxone rescue kits

32

“The AMA has been a longtime supporter of increasing the availability of Naloxone for patients, first responders and bystanders who can help save lives and has provided resources to bolster legislative efforts to increase access to this medication in several states.”www.ama-assn.org/ama/pub/news/news/2014/2014-04-07-naxolene-product-approval.page

“APhA supports the pharmacist’s role in selecting appropriate therapy and dosing and initiating and providing education about the proper use of opioid reversal agents to prevent opioid-related deaths due to overdose”

www.pharmacist.com/policy/controlled-substances-and-other-medications-potential-abuse-and-use-opioid-reversal-agents-2

ASAM Board of DirectorsApril 2010

“Naloxone has been proven to be an effective, fast-acting, inexpensive and non-addictive opioid antagonist with minimal side effects... Naloxone can be administered quickly and effectively by trained professional and lay individuals who observe the initial signs of an opioid overdose reaction.”

www.asam.org/docs/publicy-policy-statements/1naloxone-1-10.pdf

Naloxone Access Points for Active Drug Users, Family, Friends in Rhode Island

• Long-standing program • Located in one urban

setting, grassroots effort• Distributes lowest cost

formulation, for free, to highest risk individuals

Community based program

Treatment

Programs & Prison

Pharmacy

Emergency

Department & Hospita

ls

1. Certified Recovery Coaches counsel nonfatal overdose survivors at bedside, train in Nlx, connect to treatment/recovery supports post discharge

2. Hospital service (trauma services, psychiatric hospital) counsels and dispenses at discharge

Pharmacists provide naloxone upon request, initiate prescription

Programs train clients & dispense naloxone or coordinate with pharmacy to dispense

Traditional Models of Naloxone Prescribing

Prescribetoprevent.org

Prescriber co/prescribes to patientOffice-based setting

Drug treatment/MMT site

Patient fills atPharmacy

Models of Pharmacy Based Naloxone

Collaborative Pharmacy Practice

Agreement

Standing Order

Furnish upon request

Pharmacist prescribes

1 prescriber

Manypharmacists/Pharmacies

1 prescriber

1+ Pharmacies

Anyone can be patient

Rhode IslandWashington

Kentucky

Anyone obtaining Rx from the pharmacy

MassachusettsRhode Island

Anyone can be patient

California

Anyone can be patient

New Mexico

Many Pharmacists Pharmacist writes script

Prescriber notified of provision

Prescriber notified of provision

Survey Collaboration

Survey Method• Anonymous, email based survey • Randomly selected sample of American Pharmacists Association

membership– Expected response rate 5%

• Oversampled practice settings relevant for the topic (i.e., community pharmacists)

• Fielded survey over 3 week period: September 12 – October 3, 2015– weekly, motivational reminders

• Incentive: random drawing for $100 VISA giftcard for completers• BU Medical School IRB approved protocol

Survey Content & Analysis• Content

– Items reviewed by all collaborators, pre-tested items (UKY survey), harvested from prior surveys of pharmacists (Green et al., 2010), and PrescribetoPrevent evaluation

– Demographics– Attitudes and experiences with pharmacy based naloxone (PBN) and

related opioid safety measures– Assess possible PBN implementation challenges – Learn about barriers and facilitators of PBN – Self efficacy to identify, counsel, and provide naloxone

• Analysis– Descriptive, summary statistics– Psychometrics of scales, intercorrelations

Survey Respondentsn=453/6,424 7% response rate•Nationally representative•Consistent with membership in terms of gender, years of practice

DemographicsSample Percent

Age21-2526-3435-4445-64

65+

2%32%18%41%6%

Terminal degree

BSPharmPharmD

MSPharmOther

30%62%2%7%

MaleFemale

35%63%

Years in Practice

<10 years>20 years

46%39%

31%

22%9%

6%2%

12%

2%

15%

Practice SettingChain pharmacy

Independent pharmacy

Supermarket pharmacy

Clinic (outpatient) pharmacy

Mass-merchant pharmacy

Hospital/institutional

Long-term care pharmacy

other

Extant Collaborations with Patients/Settings at High Risk of Overdose

• 12% provide care for HIV infected individuals directly or through active coordination with HIV clinic

• 33% active collaborations with outside entities working with high risk populations: drug treatment provider, VA, harm reduction services, health department, HIV clinic, AIDS service organization, FQHC, homeless shelter

Opioid SafetyPercent

Frequency of checking state Prescription Monitoring ProgramDaily, at every controlled substance prescription or at every

opioid prescriptionApproximately weekly

Monthly or less frequentlyNeverOther

44%20%9%19%7%

In store opioid safety measuresHave prescription drug disposal onsite

Syringe disposal programProvide info on syringe disposal options

Sharps containers

9%14%48%57%

Ever trained to discuss overdose prevention with patients 32%

Ever trained to discuss naloxone use and administration 22%

Overdose & Naloxone Experience

0%10%20%30%40%50%

Do Pharmacies stock and are Pharmacists dispensing naloxone?

• 45% stock naloxone– 72% of pharmacies not stocking were interested in

doing so• 12% ever dispensed naloxone to an individual or

family member to take home for overdose prevention– 39% of whom had done so 1+ times in past month– Primarily to those with history of opioid overdose

(their family/friend), high dose opioid, or received buprenorphine prescription

What happens at naloxone fill?• 57% provide education on use of naloxone• 36% provide info on safe storage/disposal of Rx opioid

medications (31% not at all)• Majority (51%) do not provide education on local drug

treatment resources• 74% interested in having patient education materials for use

when speaking with patients• Willingness of PBN scale (alpha=0.91) >>Willingness of pharmacy

syringe access scale (alpha=0.75)– Means: 4.71 PBN willingness vs. 3.71 pharmacy syringe access – PBN willingness ranges at item level (how willing are you to proactively identify

individuals meeting criteria for naloxone under a protocol 4.63; willing to stock 5.32 and dispense 5.37 naloxone with a prescription)

– Willingness to provide syringes 4.63 or sharps disposal 4.65

Confidence related to PBNConfidence scale (alpha=0.86)1 (not confident) to 6 (extremely confident)

How confident are you that you can: 1-not at all

confident 2 3 4 56-

extremely confident

Mean

Identify signs and symptoms of opioid overdose 7% 14% 25% 24% 21% 9% 3.65

Proactively identify individuals who may be at

risk for opioid overdose and would benefit from a naloxone prescription

10% 14% 23% 26% 18% 9% 3.55

Educate patients to recognize opioid overdose

and safely administer naloxone when indicated 12% 19% 23% 21% 15% 9% 3.34

What are key barriers to PBN (real, perceived)?

• 49%: Time to develop, implement, sustain program• 38%: Knowledge regarding states’ laws and

regulations authorizing naloxone access• 36%: Lack of training among pharmacy technician

staff to implement program• 35%: Complications with billing and reimbursement• 25%: Concerns about clientele that might frequent

the pharmacy if a program were in place

What are Attitudes about Naloxone, other Pharmacy-Public Health Efforts?

Attitudes scale: injury prevention, prevention measures at pharmacy (immunization, syringe access), naloxone provision (alpha=0.83; mean 5.15) 1 strongly disagree to 6 strongly agree

Pharmacists have a role to play in injury prevention, including overdose prevention 4.94

Pharmacists could have a significant public health impact by providing access to syringes and needles for people who inject drugs 4.54– Correlated with injury prevention role perception (rho=0.51), access to syringes to

prevent blood borne infections (rho=0.67)

Screening patients for immunizations is a waste of time 1.46 – Low, consistent correlation with other items (rho=0.21-0.38)

Do NOT perceive that overdose prevention encourages heroin use 1.90 or opioid misuse 2.26, is a waste of $/time 1.79, or sends message that misuse/heroin use is OK 2.25

Summary• Nationally, pharmacist’s interest, willingness to stock and

provide naloxone are high• Attitudes toward overdose prevention and naloxone align with

perceptions of pharmacist as preventing injury, providers of other harm reduction supplies

• Naloxone dispensing experience is uncommon, infrequent• Least confident in ability to proactively identify those at

risk/would benefit and to educate on naloxone use– Clear policy/rubric for proactive offering of naloxone– Trainings needed: pharmacy schools, online, in stores

• Experience with naloxone and discussing overdose prevention needs practice – Community based organizations, harm reduction groups can help

AcknowledgementsThank you!

APhANickolas Zaller

Patricia FreemanThomas StopkaSuzanne NielsenJefrey Bratberg

Peter FriedmannHudson Breaud

Drugs to Watch: Tramadol,Hydrocodone and Naloxone

Presenters:

• Nathan Painter, PharmD, Associate Clinical Professor, University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Science

• Roneet Lev, MD, Director of Operations, Scripps Mercy Hospital Emergency Department, and Chair, San Diego County (CA) Rx Drug Abuse Medical Task Force

• Traci Green, PhD, MSC, Deputy Director, Boston Medical Center Injury Prevention Center, and Associate Professor of Emergency Medicine, Boston University

Pharmacy Track

Moderator: Anne L. Burns, RPh, Vice President, Professional Affairs, American Pharmacists Association, & Member, Rx & Heroin Summit National Advisory Board