Naloxone: Saving Lives Cathy Oliphant, PharmD Associate Professor of Pharmacy Practice ISU College of Pharmacy

Objectives Describe the opioid epidemic Discuss the role of naloxone for out of hospital use Identify patient populations at risk for opioid/heroin overdoses Explain how to administer intranasal and intramuscular preparations of naloxone

2014 National Survey on Drug Use and Health

Opioid Epidemic Approximately 500,000 persons in the US have died from drug overdoses between 2000 and people die everyday in the US from an opioid overdose – If heroin is added, 70 people die/day In 2014, more individuals died from drug overdoses than in any previous year on record In 2014, there were 1 ½ times more drug overdose deaths than motor vehicle accidents MMWR Jan 1, 2016/64(50); Increases in Drug and Opioid Overdose Deaths – US, ;

Opioid Epidemic During 2014, 47,055 drug overdose deaths occurred in the US – 6.5% increase from 2013 – 13.8/100,000 persons to 14.7/100,000 persons In 2014, 28,647 opioid related overdose deaths were reported (accounting for 61% of all drug overdose deaths) MMWR Jan 1, 2016/64(50); Increases in Drug and Opioid Overdose Deaths – US, ;

Opioid Epidemic Percent increases, based on type of pain reliever, between : – Natural/semisynthetic opioids 9% – Heroin 26% – Synthetic opioids (ie, fentanyl, tramadol) >50% – Methadone 0% MMWR Jan 1, 2016/64(50); Increases in Drug and Opioid Overdose Deaths – US, ;

Opioid Prescribing congress/2015/americas-addiction-to-opioids-heroin-prescription-drug-abuse

Heroin An opioid that is synthesized from morphine (extracted from the seed pod of the Asian opium poppy plant) Converted to morphine when it enters the brain which then binds to mu receptors Cheaper Easier to obtain than opioids

Heroin: A Growing Epidemic Evidence suggests a relationship between increased non-medical use of opioids and heroin abuse Opioid abuse often precedes heroin abuse ~50% of heroin users admit to opioid abuse prior to using heroin

Chemical Similarity Between Opioids and Heroin congress/2015/americas-addiction-to-opioids-heroin-prescription-drug-abuse

Heroin Overdoses

Risk Factors for Opioid Overdose Unintentional Opioid naïve Opioid dose too high Switch to different opioid Polypharmacy – Opioids, benzodiazepines, other CNS depressants Acute illness Alcohol use Illicit drug use Prescription drug abuse Taking high doses of opioids Doctor shopping Obtaining opioid prescriptions from multiple providers and pharmacies History of mental illness or substance abuse Pharmacist’s Letter Managing Opioids in the Community Setting: Balancing Risks and Benefits CE Online;

Opioid Actions Respiratory depression Reduce the brain and body’s response to increased carbon dioxide and decreased oxygen – Hypoxic brain injury – Seizures – Coma

Opioid Overdose S/S Overdose Pinpoint pupils Not arousable Not breathing or very slow breathing Choking, snorting, gurgling Bradycardia or no heartbeat Cold/clammy skin Blue lips/nailbeds S/S of Overmedication Pinpoint pupils Arousable Breathing but sleepy or intoxicated appearing Slurred speech

Naloxone: An Antidote Naloxone is an antidote for reversal of opioid induced respiratory and CNS depression Pure opioid antagonist that binds with high affinity to mu, kappa and delta receptors – Greatest affinity for mu receptors Naloxone then displaces opioid agonists Reverses clinical and toxic effects of opioids

Naloxone: Reversal Opioids Heroin May not reverse buprenorphine No effect on non-opioid overdoses – Cocaine – Methamphetamine – Bath salts – Benzodiazepines – Alcohol

Naloxone When given in an overdose: – Reverses respiratory and CNS depression – Restores breathing – Reverses pain control – May precipitate acute opioid withdrawal Pain Agitation, irritability Diaphoresis Tachycardia Seizures Onset of action is ~ 3 minutes No potential for abuse No harm to patients who have not taken opioids

Naloxone Half-life of minutes – As naloxone wears off, opioids still circulating may bind to opioid receptors causing overdose symptoms to return

Opioids: Duration of Action

Naloxone: Available Products Intranasal – Naloxone – Narcan (approved 11/15) Intramuscular – Naloxone – Evzio (auto-injector)

Intranasal Naloxone

Narcan Nasal Spray

Naloxone Intramuscular

Naloxone Dosing Naloxone nasal using syringes/atomizers – 2 mg (1 mg per nostril) using injectable solution (luer-lock prefilled syringes) with atomizer – May repeat Q2-3 minutes if no response Naloxone IM – 0.4 mg IM – May repeat Q2-3 minutes if no response Narcan nasal spray – 4 mg (1 nasal spray) in one nostril – May repeat Q2-3 minutes in alternating nostrils if no response Evzio – 0.4 mg (content of 1 auto- injector) – May repeat Q2-3 minutes until response or EMS arrives Lexi-Comp Drugs; Pharmacist’s Letter January 2016

Naloxone: Storage Store between 59 and 77⁰F – May be exposed to temperatures of ⁰F for short periods of time Typically has a shelf-life of months – Should be visually inspected occasionally to ensure that the fluid is clear/colorless – Monitor expiration date and replace as appropriate Naloxone use beyond the expiration date may not be as effective; however, in an emergency if may be used if no alternatives are available Lexi-Comp Drugs; Pharmacist’s Letter; Narcan and Evzio package inserts

Naloxone: Cost Naloxone nasal using syringes/atomizers – $50/kit Naloxone IM – $50/kit Narcan nasal spray – $125/kit Evzio IM – $750/kit Pharmacist’s Letter: January 2016;vol 32, no. 1

Naloxone: Insurance Coverage Evzio is covered by many insurance plans Medicaid – ID Medicaid will pay for naloxone prescribed by a pharmacist for the actual Medicaid patient – Can be dispensed to a family member or friend – Pharmacist needs to use their NPI number (not that of the pharmacy) Insurance usually does not cover the nasal atomizer device needed for intranasal administration ($4-5/atomizer)

Naloxone: Assistance Evzio – Patient assistance program Narcan (intranasal naloxone) – Adapt Pharma distributors may offer a reduced cost to qualified public interest groups (1 st responders, law enforcement) Referral to a community-based program or harm reduction program Pharmacist’s Letter: January 2016;vol 32, no 1

Naloxone Access Naloxone access laws Naloxone access programs The Harm Reduction Coalition reports that between 1996 and June 2014 that 152,283 naloxone kits have been dispensed to laypersons resulting in 26,463 overdose reversals MMWR Morb Mortal Wkly Rep 2015 Jun 19;64(23):631-5

samaritan-laws.aspx#Access States with Laws Providing Access to Naloxone

Naloxone Access Laws State laws vary Good Samaritan laws vary Standing order Collaborative pharmacy practice agreement Prescription Pharmacist prescribes

Idaho Pharmacist Prescriptive Authority As of July 1, 2015, Idaho pharmacists may prescribe opioid antagonists to: – A person at risk of experiencing an opioid-related overdose – A person able to help an individual at risk of experiencing an opioid-related overdose – A person who may encounter an individual experiencing an opioid-related overdose – A person known to have a valid reason to have an opioid antagonist ID State Board of Pharmacy News, Dec 2015; bop.idaho.gov

Idaho Prescriptive Authority A pharmacist acting in good faith may administer an opioid antagonist to an individual who appears to be experiencing an opioid-related overdose Per Idaho law, a pharmacist who prescribes or administers an opioid-antagonist will not be liable in a civil or administrative action or subject to criminal prosecution Idaho State Board of Pharmacy News Dec 2015; bop.idaho.gov

Idaho Law A layperson is immune from civil and criminal liability when administering naloxone

Naloxone Access Programs Community access or harm reduction programs Currently no programs exist in the Treasure Valley – Learn to Cope Harm Reduction Coalition Peer-led support network for families dealing with addiction and recovery

Who Should Receive Naloxone Anyone that has a prescription for opioids Anyone with a history of opioid or heroin abuse Family/friends of someone prescribed opioids, that has access to opioids or uses heroin Those who are recently released from incarceration or who were abstinent Programs and residential facilities that work with at-risk populations Anyone that requests it Pharmacist’s Letterwww.who

Naloxone: Kits It is recommended to dispense naloxone in kits that include 2 doses of naloxone in addition to supplies (2 of each) needed to give the naloxone by the prescribed route – Intranasal or intramuscular

Naloxone Education The individual receiving the naloxone should be educated on: – How to recognize symptoms or indications of an opiate-related overdose; – How to store, administer and dispose of an opioid antagonist; – Emergency procedures in the event of an opiate- related overdose; and Idaho Law

Naloxone: Administration Determine if an overdose Call 911 Give naloxone Give rescue breaths Once breathing on own, turn person on side Stay with person until EMS arrives May administer a 2 nd naloxone dose if no response after 2-3 minutes or symptoms return before EMS arrives Pharmacist’s Letter;

Evzio Administration

Automated device with voice instructions Pull off outer case and red safety guard Place black end of auto-injector against outer thigh – Can administer through clothing Press firmly and hold in place for 5 seconds – Needle retracts automatically Red light flashes when injection complete Pharmacist’s Letter CE Live Overdose Prevention with Naloxone May 2015; Evzio package insert;

Naloxone: Education Why naloxone? Administration Identifying and avoiding high-risk overdose scenarios Risk reduction strategies Opioid overdose response

Opioid Overdose Prevention Prescription monitoring programs Drug take-back programs Lock boxes Naloxone access programs Education