Naloxone For Opioid Overdose: FAQs
PL Detail-Document #310702 This PL Detail-Document gives subscribersadditional insight related to the Recommendations published in PHARMACIST’S LETTER / PRESCRIBER’S LETTERJuly 2015Naloxone for Opioid Overdose: FAQsBackgroundOpioid prescribing doubled from the late1990s to 2012, when pain treatment became thesubject of several quality initiatives and practiceguidelines.1-3 Prescription opioid overdose deathsquadrupled between 1999 and 2010, while heroinoverdoses increased by 50%.4 Now, opioidprescribing seems to be plateauing or evendecreasing based on data from 2011 to 2013.5This may be due to prescribing restrictions andeducation, state prescription monitoring programs,and availability of abuse-deterrent formulationssuch as OxyContin.5,6 Although prescriptionopioids are still the main source of illegal opioids,these trends have been associated with an increasein heroin use and heroin overdose.5-7 Heroin isrelatively inexpensive and easier to get in someareas than prescription opioids.5,8 Based on datafrom 28 states, from 2010 to 2012, the death ratefrom heroin overdose increased from 1 to 2.1 per100,000 people.4 During this same timeframe, thedeath rate due to prescription opioid overdosedecreased slightly from 6 per 100,000 to 5.6 per100,000.4 In April 2014, the FDA approvedEvzio, a naloxone auto-injector that can beadministered by a lay person to treat a personknown or suspected to have overdosed on opioids.This article answers common questions that arisein clinical practice related to naloxone for opioidoverdose, including Evzio.How is naloxone supplied?Each Evzio carton contains two active autoinjectors, each containing naloxone 0.4 mg, andone trainer. The trainer is in a black and whiteouter case, while the active Evzio auto-injector isin a purple and yellow outer case. The trainer canbe used over 1000 times. The trainer is exactlylike Evzio, except that it does not contain a needleor naloxone, and has no expiration date. UnlikeEvzio, the red safety guard on the trainer can beremoved and replaced.9Alternatively, naloxone can be supplied invials for intramuscular injection, or in prefilledsyringes for intranasal use. For intramuscularuse, it is recommended that naloxone be providedas 0.4 mg/mL in two 1 mL single-dose vials orone 10 mL multidose vial. For each injection, a23 gauge, 3 cc syringe with a 1-inch needle willbe needed.10 Intranasal use will require twonaloxone 2 mg/2 mL luer-lock prefilled syringesmade by IMS/Amphastar (NDC# 76329-3369-1),along with two mucosal atomization devices(MAD 300), which pharmacists can order bycalling 800-788-7999. This device fits into theluer-lock of the IMS/Amphastar naloxone.11When should naloxone be administered?Respiratory and/or central nervous systemdepression in a situation where opioids may bepresent is an indication to use naloxone. Naloxoneshould be given if the patient is excessively sleepyand cannot be aroused with a loud voice or sternalrub. Other indications include slow, shallow, orno respirations, or pinpoint pupils in a patient whois difficult to arouse.9 Other signs of overdoseinclude blue or purple fingernails or lips. Thepatient may emit a death rattle, which may bemistaken for snoring. The patient may also have aslow heartbeat and/or low blood pressure.12How is naloxone administered?As mentioned previously, each Evzio cartoncontains a trainer. Patients and anyone who mayneed to help the patient in the event of anoverdose should practice with the trainer. Evzioproduct labeling recommends that the patient andcaregivers practice daily for the first week, thenweekly.9Evzio has a speaker that provides voiceinstructions. If the voice instructions don’t workfor some reason, Evzio will still work. Usersshould follow the written instructions on thelabel.9More. . .Copyright 2015 by Therapeutic Research Center3120 W. March Lane, Stockton, CA 95219 Phone: 209-472-2240 Fax: 209-472-2249www.PharmacistsLetter.com www.PrescribersLetter.com www.PharmacyTechniciansLetter.com
(PL Detail-Document #310702: Page 2 of 5)To use, Evzio must first be removed from itscase. When the user is ready to give the injection,the red safety guard is removed, and the black endof the injector is placed against the outer thigh.(Evzio can be injected through pants.)Toadminister the dose, the injector is pressed firmlyand held for five seconds. If the patient is aninfant, the injection should be given into apinched-up area of the middle of the outer thighmuscle. The injector makes a click and hiss noiseduring injection.9For naloxone supplied via vial and syringe forintramuscular injection, the caregiver shouldfirst remove the cap from the naloxone anduncover the needle. They should then insert theneedle through the rubber plug with the bottleupside down, and pull back the plunger to draw1 mL into the syringe. The naloxone can then beinjected into the muscle of the shoulder or thigh.10For intranasal use, the caregiver must attachthe atomizer device to the naloxone. They willsee three parts: the atomizer device, a plastictube, and the naloxone vial. First, they removethe two yellow caps from the plastic tube and thered cap from the naloxone. They should then holdthe atomizer device by its plastic wings and twistit onto the plastic tube. They then screw thenaloxone into the barrel of the tube. Afterinserting the atomizer into the patient’s nostril, thenaloxone is delivered by giving a short, vigorouspush on the naloxone vial, delivering half of thenaloxone into each nostril. A second dose isrepeated in three minutes if there is no response11What happens after a dose is administered?The duration of most opioids is longer thanthat of naloxone, so emergency medical help mustbe summoned immediately after use, even if thepatient wakes up.9 In fact, deaths have occurredwhen naloxone was administered in an outpatientsetting and the ambulance left.13Rescuebreathing may be required, and ideally, patientsexperiencing opioid overdose should be given100% oxygen.12 Patients who have overdosed onpartial agonists and mixed agonist-antagonists(e.g., buprenorphine) may not respond well.9Naloxone can be given every two to three minutesto achieve the desired response (i.e., adequatespontaneous breathing).9,12Naloxone use may precipitate withdrawal inopioid-dependent patients. Opioid withdrawalsymptoms include sweating, goose bumps,achiness, shivering, GI symptoms, tachycardia,irritability, and increased blood pressure.9 Fever,runny nose, sneezing, and yawning are other signsand symptoms of opioid withdrawal. The patientmay even become agitated or combative.Fortunately, most patients respond to naloxonewith a return to spontaneous breathing with onlymild withdrawal symptoms.12 Opioid withdrawalis not typically life-threatening in adults.9,12 Ifnaloxone is given to a patient who is not opioiddependent or is not opioid-intoxicated, it has noclinical effects.12Once the Evzio injector has been used, theneedle will retract into the base, the base willlock, the voice instruction will state that theinjector has been used, a red light will blink, and ared indicator will show in the viewing window.The used injector should be placed in its case anddisposed of in a sharps container, following anystate or local laws about disposal of auto-injectorsor perchlorate-containing batteries (California).9Naloxone needles used for intramuscular injectionshould also be disposed of in a sharps container.14How should naloxone be stored?Naloxone should be stored at roomtemperature and protected from light.15 Evzioshould be stored in the provided case at 59oF to77oF, although excursions to 39oF and 104oF areallowed. Product labeling advises that patientscarry Evzio with them, and tell family, friends, coworkers, and others who may need to administerEvzio where it is kept.9 While counseling patientsabout Evzio storage, consider reminding them tokeep their prescription opioid secure; divulgingopioid use to others might invite theft.Patients should periodically check theappearance of their Evzio through the window inthe auto-injector. If the solution is discolored,cloudy, or contains particulates it should bereplaced. Evzio should be replaced before theexpiration date.9 The manufacturer intends to shipEvzio with a 24-month shelf-life. If storedproperly, other naloxone products should beeffective until the manufacturer’s expiration date.Typically, the shelf-life is 12 to 18 months.16For whom should naloxone be prescribed?Consider a naloxone prescription for patientson chronic opioids and others at risk of overdose.More. . .Copyright 2015 by Therapeutic Research Center3120 W. March Lane, Stockton, CA 95219 Phone: 209-472-2240 Fax: 209-472-2249www.PharmacistsLetter.com www.PrescribersLetter.com www.PharmacyTechniciansLetter.com
(PL Detail-Document #310702: Page 3 of 5)These include patients prescribed high doses.12Twenty percent of opioid overdoses occur inpatients prescribed less than 100 mg of morphineor its equivalent per day, while 40% occur inpatients prescribed higher doses.13 Other patientsat risk are those rotating (switching) from oneopioid to another (risk of incomplete crosstolerance), patients with a history of opioidoverdose, and patients with a history of substanceabuse.12Most states currently prohibit third-partyprescribing, such as to a caregiver or familymember as opposed to a patient.Consultwww.prescribetoprevent.org or your state medicalboard to find out if third-party prescribing ofnaloxone is allowed in your state.12How much does naloxone cost?Evzio costs about 600 for two auto-injectorsand a trainer, but Evzio is covered by mostinsurance plans, including government plans.Medicaid in some states (e.g., California, NewYork, North Carolina, Washington, New Mexico),will cover naloxone.16-18 Insurance does not coverthe nasal atomizer device.15Patients with private insurance may be eligibleto have Evzio mailed directly to their homewithout a copay. A patient assistance program isalso available at www.evzio.com. Naloxone“kits” may cost 100. If cost is still an issue,consider referring patients to a community-basedprogram that offers generic naloxone kits. Seewww.prescribetoprevent.org for programs in yourarea. This site also has information on prescribingnaloxone in a vial or intranasal naloxone (offlabel) for bystander use, with patient instructions.How do Icounseling?billfornaloxone-relatedPrescribers can use the codes for Screening,Brief Intervention, and Referral to Treatment(SBIRT) to bill for counseling a patient about howto recognize overdose and how to administernaloxone.12 Complete the DAST-10 drug pa.eu/attachements.cfm/att 61480 EN DAST%202008.pdf) and refer to asubstance abuse treatment program if applicable.15Billing codes for SBIRT are CPT 99408(commercial insurance, 15 to 30 minutes), G0396(Medicare, 15 to 30 minutes), and MedicaidH0050 (Medicaid, per 15 minutes).Forcounseling and instruction on the safe use ofopioids, including the use of naloxone, outside ofthe context of SBIRT services, the prescribershould document the time spent and use the E&Mcode that accurately captures the time andcomplexity. For example, in new patients deemedappropriate for opioid pharmacotherapy when asubstantial and appropriate amount of additionaltime is used to provide a separate service such asbehavioral counseling (e.g. opioid overdose riskassessment and naloxone administration training),consider using modifier –25 in addition to theE&M code. When using an evidence-basedopioid misuse/abuse screening tool (seehttp://www.painedu.org/soapp.asp), CPT Code99420 (administration and interpretation of healthrisk assessment instrument) can be used forpatients with commercial insurance.12Does naloxone availability encourage opioidmisuse?Surveys of heroin users in the late 1990ssuggest they do not use more heroin if naloxone isavailable. This may be because they do not wantto experience withdrawal precipitated bynaloxone.19 In one naloxone program for heroinusers, the frequency of heroin injection (p 0.003)and number of overdoses (p 0.83) actuallydecreased.20 Furthermore, in communities wherenaloxone distribution programs exist, opioidoverdose deaths decrease.21,22 Monitor patients foropioid dose escalation, and discuss the risks withpatients.19Are therenaloxone?liabilityissuesrelatedtoThe medico-legal risks of prescribing naloxoneto opioid users appear low.15,19 Laws are beingdrafted and passed to protect bystanders whoadminister naloxone and prescribers whoprescribe it. This is a rapidly evolving area. Seelawatlas.org or www.prescribetoprevent.org forinformation by state.CommentaryEven though Evzio is new, use of naloxone bybystanders and first responders is not new, andhas been used across the country with reportedsuccess. This includes off-label use of intranasalnaloxone.11,21,22 Although intranasal use has someMore. . .Copyright 2015 by Therapeutic Research Center3120 W. March Lane, Stockton, CA 95219 Phone: 209-472-2240 Fax: 209-472-2249www.PharmacistsLetter.com www.PrescribersLetter.com www.PharmacyTechniciansLetter.com
(PL Detail-Document #310702: Page 4 of 5)advantages over intramuscular injection (e.g.,easier disposal, no needle stick risk, no “needleanxiety”), assembly is more difficult.15The American Medical Association has longsupported the availability of naloxone for patients,bystanders, and first responders.23 Pharmacistscan advocate for laws allowing pharmacists tofurnish or administer naloxone without aprescription, perhaps through a collaborativepractice agreement, such as in Washington, RhodeIsland, San Francisco, New Mexico, andAllegheny County, Pennsylvania.16,24The FDA views Evzio approval as another toolto combat opioid abuse, along with actions suchas labeling revisions and Risk Evaluation andMitigation Strategies (REMS) for long-actingopioids, and moving hydrocodone to ScheduleII.25Another consideration in the growing heroinproblem is dirty needles. Syringe-sharing wasrecently linked to an HIV outbreak in ruralIndiana.26 Access to clean syringes reduces thespread of HIV without increasing drug use orcrime.27 A list of needle exchange programs 5/apr/13/new-nasensep-directory-page/.In most states, it ispermissible for syringes to be dispensed without aprescription.27 On January 1, 2015, a law wentinto effect allowing California pharmacies tochoose to provide this service, which must includesafe needle disposal, and information on accessingdrug treatment and HIV and hepatitis C testing.27Many states also allow prescribers to prescribe,and pharmacists to dispense, needles for injectiondrug users to prevent the spread of infectiousdisease.28Consult with your medical andpharmacy boards to find out what is allowed inyour state, or check lawatlas.org. Prescription ofsyringes is best done within the framework of acomprehensive prescriber/patient relationship.Prescribers can discuss the dangers of continuedinjection drug use, with encouragement to stop orreduce use, and offer to refer patients toappropriate programs.28 Also consider whether thepatient may be self-medicating legitimate painwith street drugs.Naloxone is not a magic bullet for opioidoverdose. Think of it as an adjunct to othermeasures to keep patients and their families safe.These measures include limiting opioid quantities,and use of opioid treatment agreements, abuse-deterrent opioids, and your state prescription drugmonitoring programs.Users of this PL Detail-Document are cautioned to usetheir own professional judgment and consult any othernecessary or appropriate sources prior to makingclinical judgments based on the content of thisdocument.Our editors have researched theinformation with input from experts, governmentagencies, and national organizations. Information andinternet links in this article were current as of the dateof publication.Project Leader in preparation of this PL DetailDocument: Melanie Cupp, Pharm.D., BCPSReferences1.2.3.4.5.6.7.8.9.Joint Commission. Speak up. Know your now Your Rights brochure.pdf.(Accessed June 4,2015).National Pharmaceutical Council, nt, and treatments. December nagement-and-Treatments.pdf.(AccessedJune 4, 2015).CDC. Prescription drug abuse and overdose:public health perspective.October 24, e 4, 2015).Rudd RA, Paulozzi LJ, Bauer MJ, et al. Increasesin heroin overdose deaths-28 states, 2010 to 2012.MMWR Morb Mortal Wkly Rep 2014;63:849-54.Dart RC, Surratt HL, Cicero TJ, et al. Trends inopioid analgesic abuse and mortality in the UnitedStates. N Engl J Med 2015;372:241-8.Cicero TJ, Ellis MS. Abuse-deterrent formulationsand the prescription opioid abuse epidemic in theUnited States: lessons learned from OxyContin.JAMA Psychiatry 2015;72:424-30.U.S. Department of Health and Human Services.Substance Abuse and Mental Health ServicesAdministration.Center for Behavioral HealthStatistics and Quality. Results from the 2013National Survey on Drug Use and 2013/Web/NSDUHresults2013.pdf. (Accessed June 4, 2015).U.S. Department of Justice.National DrugIntelligence Center.National Drug ThreatAssessment 2010. Drug availability in the UnitedStates.Heroin availability.February 661/heroin.htm. (Accessed June 8, 2015).Product information for Evzio.Kaleo, Inc.Richmond, VA 23219. April 2014.More. . .Copyright 2015 by Therapeutic Research Center3120 W. March Lane, Stockton, CA 95219 Phone: 209-472-2240 Fax: 209-472-2249www.PharmacistsLetter.com www.PrescribersLetter.com www.PharmacyTechniciansLetter.com
(PL Detail-Document #310702: Page 5 of 5)10. Prescribe to Prevent. Naloxone for ent.org/wpcontent/uploads/2012/11/one-pager 22.pdf.(Accessed June 4, 2015).11. Prescribe to Prevent. Naloxone for one-pager-innov-2012.pdf. (Accessed June 4, 2015).12. U.S. Department of Health and Human Services.Substance Abuse and Mental Health ServicesAdministration. SAMHSA opioid overdose hsa.gov/shin/content//SMA144742/Overdose Toolkit.pdf. (Accessed June 4,2015).13. CDC. CDC grand rounds: prescription drugoverdoses-a U.S. epidemic. MMWR Morb MortalWkly Rep 2012;61:10-3.14. FDA. Best way to get rid of used needles andother sharps. Last updated January 27, oducts/Sharps/ucm263240.htm. (AccessedJune 4, 2015).15. rg/faq/. (Accessed June4, 2015).16. College of Psychiatric & Neurologic Pharmacists.Naloxone access:a practical guideline 5/wpcontent/uploads/naloxone-access.pdf. (AccessedJune 4, 2015).17. Prescribe to Prevent. Pharmacy basics. pharmacy-basics/. (Accessed June 4, 2015).18. Seiler N, Horton K, Malcarney M.Medicaidreimbursement for take-home naloxone: a toolkitfor advocates. Milken institute School of PublicHealth.The George Washington content/uploads/naloxone medicaid report gwu.pdf. (Accessed June 4, 2015).19. Burris S, Norland J, Edlin B. Legal aspects ofproviding naloxone to heroin users in the UnitedStates. Temple Law School Working toprevent.org/wpcontent/uploads/2012/11/burris legalaspectsofprescribing.pdf.
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
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
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
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
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.
take the lead in rebuilding the criminal legal system so that it is smaller, safer, less puni-tive, and more humane. The People’s Justice Guarantee has three main components: 1. To make America more free by dra-matically reducing jail and prison populations 2. To make America more equal by elim-inating wealth-based discrimination and corporate profiteering 3. To make America more secure by .
