Preventing Opioid Overdose Death: Naloxone Rescue Kits
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Preventing Opioid Overdose Death:Naloxone Rescue KitsUniversity of Utah School of Medicine and College of Pharmacy; Utah State Department of Health; Utah StateDepartment of Commerce (Division of Occupational and Professional Licensing); and Utah PharmacistsAssociationJennifer Plumb, MD, MPHUniversity of Utah Department of PediatricsUtah NaloxoneShannon N. Saldaña, PharmD, MS, BCPPNicholas Weaver, PharmD.Intermountain Health CareandRoger Fitzpatrick, R.Ph.Board MemberUtah State Board of PharmacyPharmacy DirectorMidtown Community Health Center PharmacyDisclosures Jennifer Plumb has no commercial orfinancial relationships nor any conflicts ofinterest to disclose Drs. Saldaña and Weaver have nocommercial or financial relationships norany conflicts of interest to disclose Mr. Fitzpatrick has no commercial orfinancial relationships nor any conflicts ofinterest to discloseLearning Objectives Understand the background on the opiate/opioidoverdose epidemic Identify characteristics of an opioid overdose Learn how to assist in treatment of suspectedopioid overdose Understand the role for naloxone in preventingopiate overdose death1
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Death Rate Per 100,000Injury Deaths in UtahFondario, UTDOH, 09/2014Utah 2013-2014 Overdose Deaths4th Highest in the USCDC, 20162
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Drug Overdose Death Ratein the U.S. 2003-2014National Vital Statistics System7U.S. Overdose Deaths 2014CDC, 2015Utah Overdose Deaths by County2002-2014CDC, 20153
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016National Overdose DeathsNumber of Deaths from Prescription Opioid 0012,00010,0008,0006,0004,0002,0000Source: National Center for Health Statistics, CDC WonderNational Overdose DeathsNumber of Deaths from 0000Number of Unintentional/UndeterminedOpioid Deaths, Utah 2000-2014300HeroinRx Opioid Only (no illicit drugs)250Number of Deaths200We averaged one opioid-relateddeath every day in 00920102011201220132014*YearUTDOH, 20164
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Number of Prescription PainMedication Deaths per 100,000 AdultsUtah 2009-2012Fondario, UTDOH, 2014Rate of Opioid-related ED Visits per10,000 Population by Age Group,Utah 2009-2013Crude Rates per 10,000 ED Treat and Release Encounters3.5Heroin3.0Prescription Opioids2.52.01.51.00.50.0Less than 1year1‐4 years5‐14 years 15‐24 years 25‐34 years 35‐44 years 45‐54 years 55‐64 years 65‐74 years 75‐84 years85 yearsFondario, UTDOH 2015The Rx Problem 7,000 opioid prescriptions written and filled every day inthe state of Utah. 1 in 25 adults are receiving treatment for chronic painwith opiate pain relievers. Health care providers wrote 300 million prescriptions inthe U.S. for pain medications in 2015 ( 24 billion worth)– enough for every American adult to have a bottle at any time 2 million adults are addicted to opiate pain relievers. Each day 129 people die from an overdose in the U.S.(50 from prescription pain medications)5
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Prescription Painkiller Sales and DeathsCDC and DEA, 2015CDC Heroin 2015Between 2002 and 2013, the rate of heroin-related overdosedeaths nearly quadrupled, and more than 8,200 people died in2013 (more than from HIV/AIDS)CDC Heroin 20156
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Synthetic/Counterfeit Opioids DEA reports these substances are imported fromChina/Mexico– Also reports of domestic production– Efforts underway to make them illegal Little data published on human consumption ortoxicity Have been found in combination with heroin andcounterfeit prescription pain pills Some have been reported to require higher dosesof naloxoneRecognizing an Opiate OverdoseOpioid Overdose(call EMS and give naloxone)Deep snoring or gurgling (deep rattle) or wheezingBlue skin tinge‐ usually lips and fingertips show firstPinpoint pupils, very small, do not get biggerHeavy nod, will not respond to stimulationBreathing is very slow, irregular, or hasstopped/faint pulse*It is NOT appropriate to give naloxone to someone who is not overdosed.Recognizing an Opiate OverdoseImages: Peterborough Drug Strategy7
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016When to Use Naloxone (Narcan )SUSPECTED OVERDOSECALL 911UNRESPONSIVE TO STERNAL RUBBREATHING STATUSNORMAL OR FASTMONITOR PATIENTSLOW ( G/CPRREPEAT NALOXONE IN 3‐5 MINUTES IF NEEDED, STAY WITH THEMSpecial Considerations A repeat dose may be necessary in some cases (3-5 min) As they begin to awaken, can be:– nauseated, vomiting, and/or combative, due to rapid withdrawal If they do begin to vomit, help roll them to their side andmonitor their airway No pulse CPR along with naloxone No breathing Rescue breathing with naloxone There is no effect on the patient if naloxone is given andthey have not used opiates Storage recommendations: Not too hot not too coldGetting Kits into the Hands of ThoseWho NEED Them8
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Who is at Risk of Overdose Death? History/vulnerability for substance abusePrescribed high dose opioidsCurrent or history of psychiatric illnessThose with benzodiazepines and opioids in theirpossessionHistory of mis-using medications Taking more than prescribed Drinking alcohol with medsPast history of overdose, currently in ED for overdoseHave medical co-morbiditiesVeteransAfter release from prison, treatment, supervised careBottom Lines Naloxone is effective Naloxone is safe Naloxone is legal for layperson administration inthe state of Utah Lives are currently being saved These lives matter, and we are all good enough tosave a lifeOverdose Education andNaloxone Distribution (OEND)9
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Objectives Differentiate naloxone formulations for outpatientuse Teach patients and caregivers when and how touse naloxone Outline opioid overdose and naloxone educationpoints and resources for patients and caregivers Describe strategies to overcome barriers tonaloxone access for the public in UtahOpioids Opiate and opioid often used interchangeably– Opiate: substance/drug derived from opium– Opioid: newer term that includes synthetic drugs Opioids include––––Prescription pain medicationsPrescription medications used to treat opioid use disorderHeroinSynthetic, illicit substances (fentanyl analogs, �about‐heroin‐2.jpg/ALTERNATES/LANDSCAPE 1140/about‐heroin‐2.jpgOpioidsShort‐acting Opioids [t½]Long‐acting Opioids [t½] Morphine (AstroMorph ) [2‐3 hr] Methadone (Methadose ) [8‐150 hr] Fentanyl (Sublimaze) [1‐4 hr] Buprenorphine Hydromorphone (Dilaudid ) [2‐3 hr] Oxycodone (Percocet ) [2‐3 hr]– Generic buprenorphine/naloxone tabs Hydrocodone (Lortab ) [3‐4 hr]– Subutex Codeine (Tylenol 3 ) [3 hr] Meperidine (Demerol ) [3‐4 hr] Diaceytlmorphine (Heroin ) [2‐3 hr] Tramadol (Ultram ) [6‐8 hr][ 36 hr]– Generic buprenorphine tabs– Suboxone – Suboxone Film – Zubsolv – Bunavail 743.jpg10
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Opioid Pharmacology Stimulate opioid receptors:– Control nociceptive pain signals (analgesia)– Decrease breathing (can lead to death)– Produce euphoria, leading some to addiction Properties of opioid receptors– Mu1: supraspinal analgesia, decreased heart rate,sedation– Mu2: respiratory depression, euphoria, dependence– Delta: spinal analgesia, respiratory depression– Kappa: spinal analgesia, respiratory ��human‐respiratory.jpgOpioids with IncreasedOverdose/Death Risk Higher dosageMethadoneLong-acting opioidsOpioids for chronic pain managementRotating opioid regimensSAMHSA Opioid Overdose Toolkit, 2016. Community Management of Opioid Overdose, World Health Organization, ng total daily dose‐a.pdfNaloxone Safe prescription medicationNo clinical effect in the absence of opioidsNot a controlled substanceOnset as quickly as 1 minuteEffects last 30-90 minutes– Could last 30 minutes or longer– Another dose may be needed when effects wear off Effective when administered intravenously,intranasally, intramuscularly, subcutaneously Naloxone is not the same as naltrexone11
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Naloxone Pharmacology Opioids bind to opioid receptors in the centralnervous system Naloxone kicks opioids off opioid receptors– Blocks receptors so opioids cannot bind– Can reverse an opioid overdose– Has no effects if there are no opioids presentMicromedex; Image from: http://www.noperi.org/images/receptors naloxone.pngNaloxone Pharmacokinetics Absorption– Little to no oral bioavailability. Requires injection (IV, IM,subcutaneous) or intranasal absorption through mucosa Distribution– Rapidly distributed and high lipophilicity aids in naloxonecrossing blood brain barrier Metabolism– Hepatic through glucuronidation ExcretionE– Primarily through urine as metabolites– Drug effects correlate with half-life (t ½ ) 30-90 minutesAPKDMOpioid and Naloxone PharmacodynamicsOpioid side effects andoverdose signs/symptoms Opioid withdrawalsigns/symptoms Euphoria Agitation/dysphoria Constipation GI upset/diarrhea Analgesic Pain/irritability Warming/flushing Goosebumps/chilling Drowsiness/Sleepiness Restless/Insomnia Respiratory Depression Increased Respiration Pinpoint pupils Dilated pupils Decreased HR/BP Increased HR/BP Decreased temperature Increased temperature Drying effect Yawning/sweating12
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Naloxone Same dose of naloxone for everyone– Adult– Child– Infant– Pregnancy– Obesity– Kidney disease– Liver diseaseIntramuscular Naloxone Kit Two 1 mL single‐dose vials of naloxone 0.4 mg/mL Two 3 mL intramuscular (IM) syringes with needles Do not store naloxone in direct lightIntramuscular Kit Instructions Inject in large muscle (shoulder may be more accessible)– Shoulder, thigh, buttocks Be careful and pinch the thigh if administering to an nt/uploads/2012/11/one‐pager 22.pdf13
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Intranasal Naloxone Kit Absorption occurs via nasal mucosa – not from inhalation– Patient does not need to be breathing Two 2 mL pre-filled needless syringes of naloxone 1 mg/mL Two mucosal atomization devices (MAD)Intranasal Kit Instructions Do NOT insert naloxone into the prefilled syringe untilready to use– Once opened/inserted, naloxone expires within 2 v‐2012.pdfCommercial Products Nasal spray (Narcan Nasal Spray)– Approved 2015, entered market in 2016– Two 4 mg nasal spray devices Auto-injector (EvzioTM)––––Approved in 20140.4 mg/0.4 mL naloxone in a pre-filled auto-injectorTwo auto-injectors and one trainer per packageMay not be readily available in all pharmacies due tocost14
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Naloxone Nasal Spray(Narcan Nasal Spray) Each device contains only one spray dose Do NOT prime the pump Do not reuse after first ��dose/how‐to‐use‐nns/#videoNaloxone Auto-Injector (EvzioTM) Electronic voiceinstruction system May give IM /how‐to‐use‐evzio.phpCost* and Billing Some form of naloxone is covered by mostinsurances and Medicaid Intranasal and IM kit costs vary; generally 45- 100(cash price)– Pharmacies may bill separately for naloxone and other kitcontents Naloxone often covered at a generic copay Nasal atomizers, syringes, other materials not usually covered– Large price fluctuations with intranasal naloxone– Intramuscular kits are usually less expensive Nasal spray pharmacy acquisition cost 120 Auto-injector pharmacy acquisition cost 4500* Costs/estimates are as of August 1, 2016Considerable price changes have occurred in short time periods, so pharmacies are the best source for current information15
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Conversation Starters and TalkingPointsFor all medications, providers explain potential side effects and risks A risk of this medication is decreased breathing, whichcan cause sudden death– Reversing this process quickly is crucial– Naloxone can reverse this effect of the opioid medication “Sometimes, even when people are using themedications as prescribed, something changes, likethe person starts taking a new medication, and thatcould mean that this medication is not as safeanymore ” “Opioids can cause drowsiness and confusion,someone could forget if/when they took a dose ”Conversation Starters and TalkingPointsRemember there is stigma around drug use and addiction Hearing “heroin” in practice: unusual, uncomfortableThe person asking is probably uncomfortable tooNo need to ask for detailsRecovery is important – do not suggest someone mayrelapse or need naloxone themselves “You mentioned someone might use heroin” or “You said live on a street, in a house, work somewhere,etc. where people use heroin” then explain, “You could save a life. Naloxone may reverse aheroin overdose.”Legal Update16
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Legislative History H.B. 11 (2014)– Overdose Reporting Ammendments (GoodSamaritan Law) "Bystanders" Should report suspected overdose in good faith H.B. 119 (2014)– Opiate Overdose Emergency Treatment Act "Not Unlawful or Unprofessional" to prescribe ordispense to:– Person at increased risk of experiencing an opiate-relatedoverdose– Family member, etc. at increased risk of witnessing anopiate-related overdose– No physician-patient relationship requiredLegislative History (continued) Opiate Overdose Response Acts:– All passed 03/23/2016 and signed in to law 05/10/2016– H.B. 238 (2016) – Overdose Outreach Providers Authorizes Overdose Outreach Providers to furnish naloxonewithout civil/criminal liability– Law enforcement / Fire departments / EMS providers / Others– H.B. 192 (2016) – Pilot Program Created funds to be appropriated for grants, promoting publicawareness, increasing availability of educational materials, etc.– H.B. 240 (2016) – Standing Orders Authorizes the use of a Standing Order (collaborative practiceagreement) to dispense an opioid antagonist in accordance witha set protocol Pharmacist may initiate the prescription once the standing orderis in placeH.B. 240 Specifics 26-55-104 Dispensing an opiateantagonist– (3) A health care provider who dispenses anopiate antagonist to an individual underSubsection (2)(a) shall provide education to theindividual that includes instruction: (a) on the proper administration of the opiateantagonist; and (b) that the individual to whom the opiate antagonist isdispensed should ensure that the individual to whomthe opiate antagonist is administered is taken to anemergency care facility for a medical evaluationimmediately following administration of the opiateantagonist.17
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016H.B. 240 Specifics (continued) 26-55-105 Standing prescription drug ordersfor an opiate antagonist (Department of Health Law)– "(1) a person licensed under [the]Pharmacy Practice Act, to dispense an opiateantagonist may dispense the opiate antagonist: (a) pursuant to a standing prescription drug order (b) without any other prescription drug order from aperson licensed to prescribe an opiate antagonist.”– "(2) A physician including a physician as anemployee of the department may issue astanding prescription drug order inaccordance with a protocol"H.B. 240 Specifics (continued) Standing prescription drug order protocol:– Limits dispensing of the opiate antagonist to: An individual who is at increased risk to experience anopiate-related drug overdose event; or A family member of, friend of, or other individual who is in aposition to assist an individual who is at increased risk ofexperiencing an opiate-related drug overdose event.– Requires the physician to specify the persons, byprofessional license number, authorized to dispense theopiate antagonist;– Requires the physician to review at least annually thedispensing practices of the person authorized by thephysician to dispense the opiate antagonist.– Requires those authorized by the physician to makeand retain a record of each individual to whom the opiateantagonist is dispensed .Proposed Pharmacy Rules R156-17b-625 Standards – Reporting andMaintaining Records on the Dispensing of anOpiate Antagonist. Proposed Rules are posted on the DOPLwebsite (http://dopl.utah.gov/proposed rules.html) Public Hearing 11/17/2016 @ 11:00am, HearingRoom 403, 160 E 300 S (DOPL) Rule change may become effective 12/08/201618
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Proposed Pharmacy Rules (continued) R156-17b-625– (1) the pharmacist-in charge or a responsiblecorporate officer of each pharmacy licensee thatdispenses an opiate antagonist shall affirmthat the pharmacy licensee has complied withthe protocol for dispensing an opiate antagonist and shall report, on an annual basis, to thedivision and to the physician who issued the standing drug order, the following information: (a) . Total number of single doses dispensedduring the reporting period; and (b) the name of each opiate antagonist dispensed,along with the total number of single doses of thatparticular named opiate antagonist.Proposed Pharmacy Rules (continued) R156-17b-625 (continued)– (2) Corporations or organizations with multiplecomponent pharmacy licenses may submitone cumulative report – (3) Null reporting is not required – (4) The annual affirmation and reportdescribed above is due to the division ANDto the physician who issued the standingdrug order no later than 15 days followingDecember 31 of each calendar year.Proposed Pharmacy Rules (continued) R156-17b-625 (continued)– (5) a pharmacy licensee who dispenses an opiateantagonist pursuant to a valid standing prescriptionorder shall maintain, subject to audit the followinginformation: (a) the name of the individual to whom the opiateantagonist is dispensed; (b) the name of the opiate antagonist dispensed; (c) the quantity of the opiate antagonist dispensed; (d) the strength of the opiate antagonist dispensed; (f) the full name of the drug outlet which dispensed theopiate antagonist; (g) the date the opiate antagonist was dispensed; and (h) the name of physician issuing the standing order todispense the opiate antagonist.19
Naloxone Rescue Kits, Jen Plumb, MD, MPH11/2/2016Patient/Caregiver Education Emphasize calling 911 in suspected opioid overdose and stayingwith the person who overdosed until they are taken to an emergencycare facility (required education) Naloxone can prevent death from opioid overdose while waiting foremergency medical services Naloxone does not take the place of medical services Keep at room temperature (avoid temperature extremes) Routinely check expiration date, obtain a new supply when nearexpiration When there are no other alternatives, expired naloxone can beadministered but may not be as effective Same dose of naloxone for everyone Discuss signs/symptoms of opioid overdose and what to do in asuspected overdose (see earlier slides)https://cpnp.org/ rces CDC Guideline for Prescribing Opioids for Chronic Pain: JAMA Patient Page: Opioids for Chronic Pain: Substance Abuse and Mental Health Services Administration (SAMHSA)Opioid Overdose Prevention Toolkit: http://store.samhsa.gov/shin/content//SMA14- Prescribe to Prevent http://prescribetoprevent.org/Safe medication disposal Treatment– call 2-1-1 for local services or treatment centers– visit findtreatment.samhsa.govOverdose pocket leid 25035074742/Overdose Toolkit.pdf–– –– ://www.deadiversion.usdoj.gov/drug RxDrugs/rxdrug-overdose-pocketcard.pdfSpanish: dose prevention, recognition, and response video, with use ofintranasal naloxone: http://prescribetoprevent.org/video/20
Auto-injector (EvzioTM) - Approved in 2014 - 0.4 mg/0.4 mL naloxone in a pre-filled auto-injector - Two auto-injectors and one trainer per package - May not be readily available in all pharmacies due to cost. Naloxone Rescue Kits, Jen Plumb, MD, MPH 11/2/2016 15
Opioid overdose was the main cause of the estimated 99,000-253,000 deaths worldwide related to illicit drug use in 2010.1 Opioid overdose is both preventable and, if witnessed, treatable (reversible). In its resolution 55/7 on promoting measures to prevent drug overdose, in particular opioid overdose, the
Naloxone for Opioid Overdose: FAQs Background Opioid prescribing doubled from the late 1990s to 2012, when pain treatment became the subject of several quality initiatives and practice guidelines.1-3 Prescription opioid overdose deaths quadrupled between 1999 and 2010, while heroin overdoses increased by 50%.4 Now, opioid
Look for obvious indications of an opioid overdose Always request Seattle Fire and Medics Supporting an opioid overdose patient’s breathing is the most important treatment Naloxone (Narcan) administration is a secondary treatment Many other conditions appear similar to opioid overdose but will
for all opioid overdose events, including fentanyl -involved overdoses. Multiple doses of naloxone may be required when the overdose results from ingestion of large amounts of opioids or potent opioids such as fentanyl, carfentanil, or other opioid analogs. 4 (For more information regarding the various formulations of naloxone, see .
Opioid Overdose Rescue with Naloxone Nasal Spray 4mg: Patient Guide Author: U.S. Department of Veterans Affairs Subject: Patient guide on how to use the Naloxone Nasal Spray for an opioid overdose. Provides instructions on how to identify that a person might have overdosed, how to respond and notify emergency personel, how to administer the .
opioid overdose, strongly consider prescribing naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with BUNAVAIL. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or opioid
Preventing Opioid Overdose Deaths. 1. Encourage providers, persons at high risk, family members, and others to learn how to prevent and manage opioid overdose. 2. Ensure access to treatment for individuals who are misusing opioids or who have a substance use disorder. 3. Ensure ready access to naloxone. 4. Encourage the public to call 911. 5.
involve any opioid as a contributing cause of death, regardless of intent, excluding deaths related to chronic use of drugs (e.g., damage to organs from long-term use), 2016 (source: California Comprehensive Death Files). The measure for all fatal opioid overdose includes overdose related to any opioid and provided a
