“Rescuing the Opiate Overdose: From Receptors to

Relatives to Regulations”Catherine A. Martin, MDDr. Laurie L. Humphries Endowed Chair in Child PsychiatryUniversity of Kentucky College of Medicine

Daniel Wermeling, Pharm.D.Professor, College of PharmacyUniversity of Kentucky

Kits for Kids and Their Families

Catherine A. Martin, MDDr. Laurie L. Humphries Endowed Chair in Child PsychiatryUniversity of Kentucky College of Medicinecmartin@uky.edu

How can we reach them?

Disclosures

Source ResearchSupport

NIDA ❋KY Cabinet for

Health and Family Services

ObjectivesParticipant will:Learn to Identify

households with opiateshouseholds at risk for opiate overdoseadolescents at risk for opiate use

Review possible interventions to prevent opiate death

safe opiate storage or disposal NARCAN for household

High

RiskYout

hHigh Risk Families

Opiates in the Household

How do we discuss opiates in the household

Screen/secure our cabinets as we do for toddles and poisons under our sinks

How do we discuss opiates in the householdWhat’s in your medicine cabinet?

(See questionnaire and information sheet)

An AdolescentBill is a 16 year old male who reported that four

months ago he had his wisdom teeth removed and was prescribed Percocet. He began taking as prescribed but over time but when the pain stopped he continued to take 2-3 tablets a week to cope with the stresses he encountered in school. These stresses included falling behind on assignments, being caught cheating on his homework, feeling pressure to succeed, and peer pressure to use drugs.

He then found his mother’s and grandfathers’ left over pain medication. This continued for approximately one month until the stresses from school became too great. He attempted suicide with the remaining opiates. He texted a friend about what he was doing and the friend informed her father who contacted Bill’s parents, who then rushed him to the local emergency room.

High Risk Families for Overdose: Is this adolescent around them ?

emergency medical care for opiate overdosehistory of opioid abuse or non-medical use IV opioidshigh-dose opioids (> 100 mg per day morphine).received their first prescription for methadone opioids with higher risk for overdose: sustained-

release/extended-release opioids, transdermal delivered opioids, methadone and buprenorphine-naloxone products

on buprenorphine or methadone for addiction treatment

Received opioids prescriptions for pain AND

smoke, COPD, emphysema, sleep apnea or other respiratory illness

hepatic disease, renal dysfunction, cardiac disease

alcohol use concurrent benzodiazepine or other

sedation prescription or illicit use concurrent antidepressant or bipolar

illness medication an attempt at suicide or suicidal ideation see checklist

Adolescents at Increased Risk for Opiate UseThe Adolescent

Use of other drugs or alcoholDelinquency or trouble with the lawPsychiatric history

The FamilyHousehold member who has been in trouble

with the lawFamily history of drug or alcohol abuseSingle parent household

Friends• Friends who are delinquent or in trouble with

the law• Hearing that drugs are not a problem from

friends or family

Opiate Safety

AHARTTAdolescent Health and Recovery Treatment &

Training

• April 30, 2016 is National Prescription Drug Take-Back Day. On April 1 the US Dept. of Justice will post location sites on its web page: http://www.deadiversion.usdoj.gov/drug_disposal/takeback/

• The National Safety Council handout includes Safe Storage and Disposal tips: http://www.nsc.org/RxDrugOverdoseDocuments/Rx%20community%20action%20kit%202015/CAK-practice-safety-at-home.pdf

• The DEA has a website that locates controlled substance Public Disposal Locations. Type in your zip code and community drop-off locations are presented. https://www.deadiversion.usdoj.gov/pubdispsearch/spring/main?execution=e1s1

• The FDA website for Disposal of Unused Medicines: What You Should Know http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/SafeDisposalofMedicines/ucm186187.htm

• http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/SafeDisposalofMedicines/ucm186188.htm

The National Safety Council handout includes Safe Storage and Disposal tips: http://www.nsc.org/RxDrugOverdoseDocuments/Rx%20community%20action%20kit%202015/CAK-practice-safety-at-home.pdf

Opioid medications need to be stored securely, preferably locked up just the way you would if you keep a firearm in your home. Safe disposal: Once an individual is finished taking an opioid painkiller, they should promptly dispose of them and not keep these medications for “later.” • Take-back programs and events allow the public to bring unused drugs to a central location for proper disposal.

• Many pharmacies offer mail-back programs where you can pick up a drug disposal envelope at their nearest store. Most pharmacies charge a small fee for a postage paid envelope.

After identification:Dispense NARCAN kitsEngage adolescent and family in

treatmentWe are exploring connecting with at

risk adolescents and their families through schools primary care mental health care

Questions, Comments

Drug Product Selection Considerations for Naloxone Products

Daniel Wermeling, Pharm.D.Professor, College of Pharmacy

University of Kentucky

Conflict StatementDaniel Wermeling is CEO and owner of

AntiOp, Inc., a company that developed and sold to a pharmaceutical company a unit-dose, ready-to use, and disposable naloxone nasal spray. The company no longer owns or controls the product.

Practice Gap & NeedNaloxone, the opioid antidote, is under-

utilized in the treatment of opioid overdose

Healthcare professionals caring for, and families of, high overdose risk patients can reduce overdose morbidity and mortality by learning new ways to prescribe, dispense and administer naloxone.

With the approval of new naloxone products, prescribers and pharmacists must understand the properties of all naloxone products consistent with providing the best medication for each patient.

Objectives:Describe the pharmacologic and human use

factors differences for the prescription naloxone products

Describe the drug administration techniques for naloxone products and the pharmacokinetic profile differences

Describe and contrast the important label (prescribing information) differences for each naloxone product

Describe patient and family counseling necessary for fulfilling naloxone prescriptions

Describe a process prescribers and pharmacists can use for drug product selection

Naloxone ( ) in the Brain

21

H OM H OM

NN

N

Pain ReliefPleasureReward

Respiratory DepressionReversal of Respiratory Depression

Opioid Withdrawal

opioids broken down and excretedopioid receptors activated

by heroin and prescription opioids

N

Naloxone Onset and Duration of ActionOnset generally quick but dependent on the

opioid taken, route of administration, and dosage

Naloxone half life about 60 minutes depending on route of administration

Duration of action follows – about and hour or so

Duration of IR analgesics are 2-6 hoursDuration of ER/LA can be 8-24 hours or

longerOral opioid overdose can also be prolongedMay need repeat dose of naloxone or infusion

since the opioid lasts longer in the body than naloxoneBuprenorphine and fentanyl as special cases

Therefore 911 must be called to continue care

https://actionindahlonega.files.wordpress.com/2015/04/narcan-with-needle3.jpg http://www.scancrit.com/wp-content/uploads/2011/11/MAD100-2-300x163.jpg https://pbs.twimg.com/media/BtPSd7JCIAASOw4.png

Naloxone Products

Naloxone – Routes of Administration

Route Dose Onset DurationIntramuscular 0.4 mg 2 – 5 min T ½ ~ 1.36 hrs

Subcutaneous 0.4 mg 2 – 5 min 0.5 – 2 hrs

Intranasal 2 mg (1 mg per

nostril)

8 – 13 min Up to 120 min

Intranasal NARCAN®Product launch anticipated end of Feb. 2016

4 mg(in single nostril)

4 – 6 min Up to 120 min

Naloxone hydrochloride Injection, USP [package insert]. Lake Forest, IL: Hospira; 2007.Evzio® Auto-Injector [package insert] Richmond, VA: kaleo;2014.Lexicomp Online®, Lexi-Drugs®

Naloxone – Pharmacokinetic Differences

Route Initial Dose Max.Conc. In

ng/mL

Time to Max. Conc. (minute)

Intramuscular 0.4 mg 1-1.1 15-20

Subcutaneous 0.4 mg 1-1.1 15-20

Intranasal 2 mg (1 mg per

nostril)

~0.5 20

Intranasal NARCAN®Product launch anticipated end of Feb. 2016

4 mg(in single nostril)

4.83 30

Naloxone hydrochloride Injection, USP [package insert]. Lake Forest, IL: Hospira; 2007.Evzio® Auto-Injector [package insert] Richmond, VA: kaleo;2014.Lexicomp Online®, Lexi-Drugs®

Administration of NaloxoneIntramuscular

http://harmreduction.org/issues/overdose-prevention/overview/overdose-basics/responding-to-opioid-overdose/administer-naloxone/

Administration of Naloxone Injection via a Nasal AtomizerIntranasal

http://harmreduction.org/issues/overdose-prevention/overview/overdose-basics/responding-to-opioid-overdose/administer-naloxone/

Administration of Naloxone

http://www.narcannasalspray.com/nns-4-mg-dose/how-to-use-nns/

Caution: do not prime the device as most or all of the medication will be dispensed

• Intranasal NARCAN® Nasal Spray

Administration of NaloxoneIntramuscular Auto-Injector Evzio®

Evzio® Auto-Injector [package insert] Richmond, VA: kaleo;2014.

Naloxone Kits

.

Verbal and Written Education Elements in Kentucky 1. Risk factors for opioid overdose and

strategies to prevent overdose2. Signs of opioid overdose3. Steps in responding to an overdose4. Information about naloxone5. Procedures of administering naloxone6. Proper storage procedures and expiration

date of naloxone to be dispensed

Naloxone – Safety and TolerabilityOpioid withdrawal syndrome

– Body aches– Diaphoresis, rhinitis– Yawning– Tremor, anxiety, irritability, agitation and

combativeness– GI effects

N/V/D Abdominal cramps Vomiting and aspiration risk

Autonomic instability – Hypertension, tachycardia, arrhythmias, cardiac arrest, pulmonary edema, seizures, death

Naloxone hydrochloride Injection, USP [package insert]. Lake Forest, IL: Hospira; 2007.Evzio® Auto-Injector [package insert] Richmond, VA: kaleo;2014.

Storage and HandlingAvoid exposure to

lightStore at room

temperatureApproximate

expiration ~ 12 – 18 months

Auto-injector should be stored in outer case as suppliedNaloxone hydrochloride Injection, USP [package insert]. Lake Forest, IL: Hospira;

2007.Evzio® Auto-Injector [package insert] Richmond, VA: kaleo;2014.http://cpnp.org/guidelines/naloxone

http://harmreduction.org/wp-content/uploads/2011/10/1naloxone-kit.jpg

Comparative CostsProduct

Average Wholesale

Price

Naloxone HCL 0.4 mg/ml injection (1ml)

$18.71 per unit

Naloxone solution Auto-injector Evzio®0.4 mg/ 0.4 ml (0.4 ml)

$3500.00 per unit

Naloxone HCL 1 mg/ ml injection (2ml)

$39.60 per unit

Intranasal atomizer (MAD®) $4.25 per unit

Naloxone HCL NARCAN® 4 mg/.01 ml (0.1 ml)*Public Interest Contract Price - $75.00 per 2-pack for Gov’t agencies, public health orgs., fire fighters, etc.

$125.00*per 2-pack

Lexicomp Online®, Lexi-Drugs®Amazon http://www.amazon.com/MAD100-Atomization-Quantity-LMA-North-America/dp/B004YTYX56

Cost- effectivenessRelatively younger population treatedClearly a life saving medicationThousands of reversals reportedWalley article cites that Massachusetts

counties with harm reduction including naloxone have decreased mortality as compared to those without service

Coffin article cites $ 15-25 per life-year saved when using the naloxone injection given nasally

Highly cost-effectiveSuggestion some patients then enter SUD

treatmentBMJ. 2013 Jan 30;346:f174Ann Intern Med. 2013 Jan 1;158

Drug Product Selection and Prescribing ConsiderationsThe dose and blood levels are different

amongst the products – effects may differ, side effects, re-dosing

Patient factors, capabilities or limitationsVision, hearing, dexterity, cognition, etc

Patient preferences for needle or needle-free delivery (no hazardous waste for nasal)

FDA approval status – indicationState lawsCost and reimbursement

Contact your pharmacist to link insurance with product options to determine if reimbursed

Models for Increasing Access to NaloxoneDevelop your protocols and standard of care

Individual Prescriber – High risk patient/household Pain/Substance abuse treatment/known addict Public health EMS Emergency rooms Hospitals Community group education Schools and family contact Mobile Pharmacy and take pharmacy with you

Factors in Healthcare System Outpatient Access to Naloxone State Medicine, Pharmacy, Nursing ActsPrescribingDispensingCounselingDrug AdministrationReimbursementLiabilityNew Laws Necessary for Prescriber,

Dispenser and Good Samaritan

ResourcesCoalition to Advance Pharmacy PracticePrescribetoprevent.orgSAHMSA websiteKentucky Board of Pharmacy web siteKaleo web pageAdapt Pharma

Questions?

Daniel Wermeling, Pharm.D.dwermel@uky.edu