Pharmacy Track:Expanding Use of Naloxone

Presenters:

• Traci Green, PhD, MSC, Brown University and Boston University/Boston Medical Center

• Ernest J. Dole, PharmD, PhC, FASHP, BCPS, Pain Consultation and Treatment Center, University of New Mexico Hospitals

• Mikiko Yamada, PharmD, University of New Mexico College of Pharmacy and Pediatric Neurology Clinic and Pain Consultation and Treatment Center

Moderator: CDR Christopher M. Jones, PharmD, MPH, U.S. Food and Drug Administration, and Member, Rx Summit National Advisory Board

Disclosures

• Traci Green, PhD, MSC, Employment: Inflexxion

• Ernest Dole, PharmD, PhC, FASHP, BCPS, Speaker Bureau: Millennium Health

• Mikiko Yamada, PharmD, has disclosed no relevant, real or apparent personal or professional financial relationships with proprietary entities that produce health care goods and services

• CDR Christopher M. Jones, PharmD, MPH, has disclosed no relevant, real or apparent personal or professional financial relationships with proprietary entities that produce health care 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:– Kelly Clark – Employment: Publicis Touchpoint Solutions;

Consultant: Grunenthal US– Robert DuPont – Employment: Bensinger, DuPont &

Associates-Prescription Drug Research Center– Carla Saunders – Speaker’s bureau: Abbott Nutrition

Learning Objectives

1. Explain the operation and benefits of Naloxone collaborative practice agreements with pharmacies.

2. Describe a model for using intranasal Naloxone in a universal precaution manner for patients with chronic non-cancer pain prescribed COT.

3. Evaluate whether co-prescribing intranasal Naloxone for patients receiving COT has a positive impact on overdose deaths involving Rx opioids.

Expanding Use of Naloxone: Novel models for the Pharmacy Setting

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

Disclosures-Traci C. Green Traci C. Green PhD, MSc, wishes to disclose her past 12-

month employment at Inflexxion, Inc. , a small business that conducts post-marketing surveillance of Scheduled medications. She will present this content in a fair and balanced manner

Her presentation will include discussion of “off-label” use of the following: Naloxone is FDA approved as an opioid antagonist Naloxone delivered as an intranasal spray with a mucosal atomizer

device has not been FDA approved and is off label use

Funding: CDC National Center for Injury Prevention and Control, 5R21CE001846-02 and 1R21CE002165-01; National Institute on Drug Abuse, 1R21DA029201-02A1

Learning Objective

• Explain the operation and benefits of Naloxone collaborative practice agreements with pharmacies

Roadmap

• Naloxone Mechanics and Evidence

• Pharmacy Based Naloxone Models

• Next steps

Are we bending the epidemic’s curve?

Sources: National Vital Statistics System mortality data. Available at http://www.cdc.gov/nchs/deaths.htm.Chen LH, Hedegaard H, Warner M. Drug-poisoning deaths involving opioid analgesics: United States, 1999–2011. NCHS data brief no. 166. Hyattsville, MD: US Department of Health and Human Services, CDC; 2014. Available at http://www.cdc.gov/nchs/data/databriefs/db166.htm.

Unintentional drug poisoning deaths Rhode Island 2009-2014

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802

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total illicit drug

illicit & med medication

Total

Source: RI Office of State Medical Examiner

Illicit, Synthetic FentanylOutbreak

Acetyl FentanylOutbreak

The View from Rhode Island

Source: MMWR, Rudd et al., http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6339a1.htm?s_cid=mm6339a1_w

Change in Heroin & prescription opioid overdose death rates from 2010 to 2012, 28 states

Overdose mortality, 2012

12

Important demographic differences to consider for public health response

,

B=Heroin only overdose deaths*Greater urban concentration*more deaths occurring in public

D=Prescription opioid overdose deaths•Greater suburban/small town distribution•*more deaths occurring at home

Source: Green et al., Epidemiologic trends and geographic patterns of fatal opioid intoxications in Connecticut, USA: 1997-2007. Drug and Alcohol Dependence, 2011.PMC3095753

Population-level Opioid Overdose Interventions

Evidence Feasibility Cost-effectiveness

Prescription monitoring programs unclear High unknown

Restrictions on prescribing/dispensing unclear Low unknown

Abuse deterrent formulations unclear High unknown

Overdose prevention education unclear High unknown

Good Samaritan Laws—partial immunity for drug-related charges

unclear High unknown

Medication assisted therapy (Methadone, Suboxone)

50-75% reduction

Challenging High

Supervised Injecting Facility 35% reduction Low High

Expanded access to naloxone 35-50% reduction

Variable Very high

Vaccinating Communities Against Overdose

• Massachusetts• 23,000 trained individuals and 2400 reversals since 2005• 50% reduction in overdose mortality in higher coverage communities

(Walley et al., BMJ 2013;346:f174 )

• Project Lazarus, NC

Risk Factors for Unintentional Opioid Poisoning

Change in TOLERANCE

using opioids ALONE, by oneself

MIXING opioids with other central nervous system depressing substances (alcohol, benzodiazepines)

ILLNESS

Extreme DOSE

Sporer 2007, Binswanger 2007, Green 2012

How to identify an opioid overdose

Respiratory depression (shallow/no breathing)

Pinpoint pupils

Blue or grayish lips/fingernails

No response to stimulus

Gurgling/ heavy wheezing or snoring sound

Typically occurs over 1-3 hours

•Opioids repress the urge to breathe and decrease the body’s/brain’s response to carbon dioxide, leading to respiratory depression (decrease rate of breathing) and death

Effective Interventions for Opioid Overdose

• Naloxone (Narcan), an intranasal or intramuscular-administered opioidantagonist used to reverserespiratory depression caused by opioids

• 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

• Not scheduled or controlled

– Fewer barriers to access

• Cannot be abused

– No euphoria from naloxone

– No effect if opioids are not present

• Effective, inexpensive, easy to administer

• Naloxone has shown success in take-home programs facilitated by community outreach programs in various states

Why use Naloxone

• Reverses clinical and toxic effects of opioid overdose

– Reverses respiratory depression, hypotension, sedation

– Restores breathing

– Reverses analgesia

– Patients can enter withdrawal after naloxone administration

Pharmacology

RI Drug Overdose Prevention & ResponseInterventions

Demand • Prescriber Toolkit• Clinician Prescription Monitoring Program Resources• Targeted Medical Education• Public Awareness Campaign• Expanded treatment (especially medication assisted treatment)• Recovery centers

Supply • Prescriber Toolkit• Clinician Prescription Monitoring Program Resources• Targeted Medical Education• Medication Dropbox es at Police Stations

Harm •Naloxone Distribution to those at risk•Naloxone Access for all•First Responder Prevention•Good Samaritan Law

Structural Drug Poisoning as part of HEALTH Injury programBHDDH Emergency regulations: drug treatment programsHEALTH Emergency regulations: pharmacy and prescriberReporting/data collection for surveillance and evaluation

Traditional Models of Naloxone Prescribing

Prescribetoprevent.org MD co/prescribes to patientOffice-based setting

Drug treatment/MMT site

Patient fills atPharmacy

Innovative Models of Naloxone Distribution

Pharmacy

RESILIENCE

Behavior RiskStigma

Emergency DepartmentCriminal Justice

Resilience & Fatal Overdose Prevention• The storytelling we do, not just to survive a

traumatic event, but to grow from it

• Individuals and communities have extraordinary resilience

• Community resilience:

– anticipation, vulnerability reduction, response, recovery

Resilience & Fatal Overdose Prevention• Individual resilience:

– Genetics – Realistic optimism– Strong moral compass– Spiritual sense– Mental/physical fitness– Psychological flexibility– Ability to face one’s fears– Meaningful community service/altruism– Skills in finding purpose & meaning– Availability of resilient role models

– Social support network

Models of Pharmacy Based Naloxone

Collaborative Pharmacy Practice

Agreement

Standing Order

Furnish upon request

Pharmacist prescribes

1 MD ManyPharmDs/Pharmacies

1 MD

1+ Pharmacies

Anyone can be patient

Rhode IslandWashington

Only MD’s patients

Massachusetts

Anyone can be patient

California

Anyone can be patient

New Mexico

Many PharmDs PharmD writes script

MD notified of provision MD notified of provision

RI Collaborative Practice Agreement for Naloxone (CPAN)

• Pharmacist-initiated prescription & distribution of naloxone

• 2011 Pharmacy Board created CPAN

– Pilot: 5 sites

– Statewide expansion following 2013 acetyl fentanyl outbreak

• All Walgreens (26 stores, 95 pharmacists)

• All CVS (63 stores, 295 pharmacists), independent, hospital pharmacies

• Naloxone on Medicaid, private insurer formularies

• Pharmacist – attends compulsory training online

– initiates therapy (naloxone prescription) based on eligibility

– obtains informed consent and release of PHI

– educates the patient on overdose response and furnishes naloxone prescription

– contacts the physician listed on the CPA if medical consultation is needed & alerts them of the medication dispensed within 7 days

• Voluntarily request

– Does not have to be someone at risk of overdose- can be a friend, family member, etc.

• Recipient of emergency medical care for acute opioid poisoning

• Suspected illicit or nonmedical opioid user

• High dose opioid prescription (>100 morphine mg equivalents daily)

• Methadone prescription to opioid naïve patient

Eligible patients to participate in CPAN

Opioid prescription and:

history of smoking

COPD

Respiratory illness or obstruction

renal dysfunction or hepatic disease

Known or suspected concurrent alcohol abuse

Concurrent benzodiazepine prescription

Concurrent SSRI or TCA anti-depressant prescription

Recently released prisoners from a correctional facility

Released from opioid detoxification or mandatory abstinence program

Patients entering a methadone maintenance treatment program

Patients that may have difficulty accessing emergency medical services

Acknowledgement of Informed consent and authorization for release of protected health information

DRAFT SAMPLE DRAFT SAMPLE

• Intramuscular injection into large muscle

– Naloxone HCl solution 0.4mg/ml 1 ml single use vial

• Dispense 2 (two) vials

• 2 (two) syringes - OR -

– Naloxone HCl solution 0.4mg/ml 10 ml multi-dose vial

• 1 (one) vial

• 9 (nine) syringes

• Intranasal

– Naloxone HCl solution 1mg/1ml prefilled 2 ml Luer-Jet syringes

• 2 (two) pre-filled syringes

• At least 1 (one) nasal drug delivery device

• No refills - Total amount dispensed not to exceed 10 mL

Protocol: Dispensing

• Before receiving naloxone patients must have overdose prevention, identification, and response training

– Purpose for naloxone

– Correct naloxone administration

– Precautions regarding interacting medications

– Identifying and avoiding high risk situations for overdose

– Risk reduction strategies

– Opioid overdose response (including calling 911, rescue breathing, Good Samaritan law)

Protocol: Patient Education

Improved Naloxone Access through CPAN

• Doubled community naloxone distribution in 2014• Increased geographic reach of community naloxone

programs• Natural partnerships between treatment centers, local

pharmacies• Adds another community resource for addiction

• Extend & build opportunities across healthcare continuum for treatment, recovery

• Reduces stigma– chance to address addiction, overdose with pharmacists– builds support for survivors, families to boost resiliency

RESILIENCE

Barriers & Next Steps

Barriers • Supply & products• Billing, co-pays• Reimbursement for patient counseling time• Time (pharmacist, patient)• Stigma: reaching high risk populations

Next steps • Study Social Marketing of Naloxone• More extensive evaluation, document efforts• Compare and contrast pharmacy based naloxone models• Integrate into curriculum for health professionals and

pharmacy students • Disseminate, Scale up

Risk-Benefit Analysis

• Concerns about increasing naloxone availability:

– Unsafe administration

– Lack of follow up care

– Additional opioids will be used to counter the withdrawal effects

– Persons administering naloxone may be intoxicated themselves

– Seizures, arrhythmias possible in patients with preexisting heart disease

– Availability may encourage riskier, more frequent or higher volume drug use

• Many concerns disproven by data from various community outreach programs

• Naloxone dispensing is relatively new. Data should be continuously collected to gauge full range of benefits, risks, impact

Thank you!Traci.c.green@gmail.com

•

www.prescribetoprevent.org

•

Free naloxone CME:

www.opioidprescribing.com

Mikiko Yamada, Pharm.D., M.S., Ph.C.1,2

Ernest Dole, Pharm.D.Ph.C.1,2

Joanna G. Katzman, M.D., MPH2,3

1 University of New Mexico College of Pharmacy2 University of New Mexico Hospital

Pain Consultation and Treatment Center3 University of New Mexico School of Medicine

Intranasal naloxone (INN) used as universal precautions for chronic, noncancer pain (CNCP) patients

on Chronic Opioid Therapy (COT)

Disclosure

• Ernest Dole, PharmD, PhC, FASHP, BCPS has disclosed that he is on the speakers bureau for Millennium Health

• Mikiko Yamada, PharmD, has disclosed no relevant, real or apparent personal or professional financial relationships with proprietary entities that produce health care goods and services

• History

• Study-team members

• Support for INN study

• Timeline of INN study

• Study design – Inclusion and exclusion criteria

– How we are different from other major naloxone studies

• Recruitment model

• Patient education

• Recruitment status

• Future plan

Outline

• July 2013– Project started at UNMH Pain Consultation and Treatment

Center (PCTC) with NM Department of Health• Protocol, informed-consent form, study-related materials

• December 2013– IRB application

• January 2014– Modifications of protocol, informed-consent form

• April 2014– IRB approval

• July 2014– Started patient recruitment

History

• Principal investigator

– Joanna Katzman, MD (neurosurgery)

• Co-investigators

– Krishna J. Chari, Psy.D (psychiatry); Ernest Dole, Pharm.D. (pharmacy); Daniel Duhigg, DO (psychiatry); Eugene Koshkin, MD (anesthesiology); Cynthia Olivas, RN (Project ECHO); Brian Starr, MD (anesthesiology); Mikiko Yamada, Pharm.D. (pharmacy)

• Significant contributors from DOH

– Melissa Heinz-Bennett, MPH; Luigi Garcia Saavedra, MPH

Study Team

• Department of Health

– INN kits for all study participants

Support for INN Study

• Timeline of INN study

– Five study visits per year

• Initial, three follow-ups, exit visit

Study Design

End of

study

• Inclusion criteria

A. All patients on COT for CNCP at UNMH PCTC age 18 or older

Study Design

• Exclusion criteria

A. Subjects who are allergic to naloxone and its inactive ingredients

• Inactive ingredients: buffering agents

B. Subjects whose pain etiology is cancer pain or acute pain

C. Subjects pregnant or breastfeeding

• If the study team identities pregnancy of a study subject, the subject will be withdrawn from the study

D. Subject younger than 18

E. Subjects unwilling to sign a consent form

Study Design

• How our study population is unique compared with other studies:

– Includes ALL patients on COT for CNCP regardless of amount of prescribed opioids

• Possible future opioid prescription model

– Universal precautions

– Analogous to the use of an EpiPen® for patients with a history of anaphylaxis, or a glucagon pen and/or sugar tablets being dispensed to patients who use insulin to treat diabetes

Study Design

• Goal of number of study population

– 500 patients per year

• COT prescribed for patients with CNCP at PCTC or outside PCTC

– Primary care physician

– Other pain specialists

» e.g., rheumatologist, neurologist

Study Design

Recruitment ModelSame-day clinic-study visit

Standard careIdentify a potential study candidate

Regular clinic visitClinician

Study visitStudy educator

Ask the patient if he/she is interested in the Naloxone study

(5 minutes)

StopNo future study

participation

No

Start informed-consent process(5 minutes)

Same-day appointment

Not same-day appointment

Assessment, education, and distribution of

naloxone(20 minutes)

Different dayor

next regular clinic visit

Yes

Recruitment ModelSame-day clinic-study visit

• How same-day clinic-study visit affects recruitment?– Increase study population

• Patients do not have to come back to clinic just for INN study education– Convenient for patients

– Save time and extra commute

– Less loss to follow up

– Effective clinic flow• Does not place an extra burden on staff members at

PCTC

• Does not impede patient flow because exam rooms are not tied up

Patient Education

• Education components

– The public health crisis in NM

• NM ranks 3rd for unintentional drug overdose deaths in the United States

• If needed patient’s are encourage to use the INN for others than it was prescribed for

– What is a drug overdose looks like

• Symptoms, what to do, what not to do

– How to use INN• Demonstrate how to assemble INN kit

Patient Education

• Educators

– Pharmacists

• Dr. Dole and Dr. Yamada

– Nurse

• Cynthia Olivas

– Medical/pharmacy students

• APPE students and third-year medical/pharmacy students

– Great opportunity to learn about public health issue

– Exposure to research

– Research assistants– Department of Neurosurgery

• Recruitment status

– Study started on July 22, 2014

– Participants at PCTC: 114 patients as of 2.26.2015

Recruitment Status

• INN study will last two years from July 2014

• The team will recruit at least 500 patients

• Study data will be shared with DOH

• Enroll patients from Alcohol and Substance Abuse Program (ASAP) at University of New Mexico

Future Plan

Pharmacist Prescribing Naloxone Under Protocol in New Mexico

• Pharmacist Education and Training– Live CE every 2 years

• Patient Consent– Patient is screened and evaluated by the Pharmacist

for the risk of overdose.

– Patient consent form must be completed and signed before the prescribing and dispensing of naloxone.

– Notify the patient’s primary care provider with the consent of the patient within 15 days of the original prescription.

Pharmacist Prescribing Naloxone Under Protocol in New Mexico

• Patient Screening Criteria– Prescribed long-acting opioid (oxycodone ER,

oxymorphone ER, morphine ER, transdermal fentanyl, methadone or buprenorphine).

– A high daily dose of opioid prescribed. Inclusion and exclusion criteria will be included in the Pharmacist’s training

– Prescribed opiates or opioid use greater than 30 days. – History of or current polyopioid use. – Concurrent prescription or OTC medication that could

potentiate the CNS and respiratory depressant properties of opioid medications, such as benzodiazepines, antipsychotics, carisoprodol, and/or antihistamine use.

Pharmacist Prescribing Naloxone Under Protocol in New Mexico

• Patient Screening Criteria (continued)– Elderly patients (> 65) receiving an opioid

prescription. – Households with people at risk of overdose, such as

children and/or someone with a substance abuse disorder.

– Patients who may have difficulty accessing emergency medical services (distance, remoteness, lack of transportation, homelessness, and/or without phone services).

– Patients as determined by the Pharmacist using their professional judgment

Pharmacist Prescribing Naloxone Under Protocol in New Mexico

• Patient RecordsOnce the patient is identified to be at high risk, the Pharmacist will

provide overdose prevention education and training, which includes proper administration of nasal naloxone and the required immediate medical follow-up after proper use of naloxone.

Face-to-face education is required on the proper use of the naloxone, including a plan for overdose prevention and adverse effects. A designated rescue person or persons must be identified by the patient.

Patients will be provided with educational materials and a handout describing caregiver medication administration.

Family member, caregiver, and/or friend are strongly encouraged to attend the appointment at the discretion of the prescribing Pharmacist, to also receive training at the time the patient receives the naloxone.

Pharmacist Prescribing Naloxone Under Protocol in New Mexico

• Patient Records (continued)Follow-up training and reinforcement is encouraged, the Pharmacist

will provide their contact information for any questions or concerns.

In the event the naloxone is used or expired, the patient will return to the Pharmacist to request a new prescription; a thorough evaluation will be completed by the Pharmacist regarding the events leading to naloxone use and to determine whether appropriate medical follow-up was completed, as required.

On site documentation of reported use to summarize approximate time/date naloxone was used, number of doses used, name of patient

Questions and comments

Pharmacy Track:Expanding Use of Naloxone

Presenters:

• Traci Green, PhD, MSC, Brown University and Boston University/Boston Medical Center

• Ernest J. Dole, PharmD, PhC, FASHP, BCPS, Pain Consultation and Treatment Center, University of New Mexico Hospitals

• Mikiko Yamada, PharmD, University of New Mexico College of Pharmacy and Pediatric Neurology Clinic and Pain Consultation and Treatment Center

Moderator: CDR Christopher M. Jones, PharmD, MPH, U.S. Food and Drug Administration, and Member, Rx Summit National Advisory Board