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NARCAN NASAL SPRAY FOR OPIOID OVERDOSE. Dien Vu12/2/2015

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What was the news?1,2 • FDA approved Narcan nasal spray to treat opioid overdose on November 18th, 2015.

• The first FDA-approved naloxone that can be administered as nose spray.

• Fast-track approval and priority review for Narcan nasal spray. • Took only 4 months for FDA to approve.• Adapt Pharma Limited submitted new drug application to

FDA for Narcan nasal spray on July 29th, 2015.

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Why is Narcan nasal spray approved quickly?1

• Death due to drug overdose is now number 1 cause of injury death in the U.S.

• Death resulted from respiratory arrest from opioid overdose.

• Naloxone could reverse opioid overdose and was only available in injectable forms (syringe and auto-injector.)

• Naloxone nasal spray formulation is much easier to use. • There has been widely unapproved use of injectable naloxone with

an atomizer that delivers naloxone nasally. • High risk of contaminated needle stick is eliminated.

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Opioids3,4

• Opioids are painkillers. • Example: hydrocodone, oxycodone, morphine, codeine, heroin,

hydromorphone, methadone, fentanyl, etc. • Mechanism:

• Bind to opioid receptors in brains, spinal cords, different organs, etc.

• Opioid effects on central nervous system:• Reduce pain.• Reduce cough reflex.• Reduce respiration.• Increase euphoria/mood enhancer. • Increase sedation.• Increase nausea/vomiting. • Increase pupil constriction.

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Opioid side effects 4,5,6,7

Peripheral effects

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Opioid dependence vs opioid addiction8

• Central adaptations in brain when opioids are taken chronically. • Tolerance. • Dependence.

• Tapering opioid or detoxification cause worsening of pain.• Powerful driving force for opioid seeker.

• Addiction is the unusual and uncontrollable behaviors of opioid-seeking to achieve the euphoria effect and satisfy cravings.

• Opioid dosing is extremely important as well as monitoring for opioid-seeking behaviors.

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How do you identify drug-seeking patients?9,10

• Recognizing suspicious behaviors:• Obsessive, pushy, angry, impatient, fabricating a story, etc.• Doctor shopping/Poly-pharmacies.• Taking at a higher dose. • Excessive flattery: “You are the best pharmacist ever!”• Comes in right before closing.

• Recognizing a fake prescription:• What to do after identified a fake script?

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Treatments for opioid dependence11

• Goal: relieve withdrawal symptoms and psychological craving.

• Treatment options:• Methadone.

• Buprenorphine.

• Naltrexone.

• Maybe safe to take for even lifetime.

• Do not discontinue without consulting your doctor.

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Opioids safety12

• If taken as instructed, opioids is safe and effective to manage pain.

• Abusing opioids can lead to consequences: • Respiratory depression.• Deterioration of white matter in brain in heroin users.

• Avoid other substances that further depress the central nervous system: • Alcohol. • Drowsy antihistamines.• Barbiturates. • Benzodiazepines.• Anesthetics.

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Opioids overdose reasons13

• Accidentally or purposely takes extra doses.• Accidentally swallowed by a child or pet.• Give a prescribed opioid medications to someone else. • Mixed with other opioids, medications, alcohol, or OTC medications, etc.

• Illegal opioid overdose (heroin, opium.) • Recreational use:

• Example: Oxycontin extended releases.

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Recognizing signs of opioid overdose can help saving lives.13 • Call 911 immediately if:

• Extremely pale face, clammy to the touch.• Limp body.• Purple or blue fingernail or lips.• Vomiting or making gurgling noise.• Cant be awakened or unable to speak.• Slow or stop breathing.• Slow or stop heart beating.

• Signs and symptoms of opioid toxicity:• Pin-point pupil.• Sedation.• Respiratory depression.• Low blood pressure and/or low heart rate.

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Treatments for opioid overdose13,14

• Call 911 if suspecting an overdose.• Begin CPR rescue if breathing is very weak or has stopped while waiting for ambulance.

• Treatment: Naloxone. • Via syringe. • Via auto-injector.• Via nasal spray.

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Benefits of Narcan nasal spray15,16,17

• First line treatment for pre-hospital intervention.

• Lay person use.

• Expend availability and overcome shortage.

• Eliminate risk of contaminated needle stick injury to healthcare workers.

• People can now use an approved formulation of nasal spray.

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Narcan rescue kit18

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How does it apply to pharmacy practice?1,19,20

• Naloxone is one of the life-saving medications for medical emergency.

• Save health workers from needle stick injury.• Easier to use compared to injection formulations.• Can be used on adults and children.• Designed for lay person use. • Controversies:

• Narcan standing order.• CVS is expanding the sale of Naloxone over-the-counter in

12 more state besides Massachusetts and Rhode Island.

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Naloxone rescue kits

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Opioid overdose prevention13

• Always follow instructions. • Do not take more medications than prescribed.• Talk to your doctor if the dose is not high enough to

sustain pain.• Always consult with your doctor or pharmacist. • Use pill box or pill minder. • Never mix painkillers with alcohol and other medications without asking your doctors or pharmacist.

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Opioid overdose prevention13

• Store in a high and locked cabinet or drawer. • Dispose unused medications properly:

• Fentanyl: flush down toilet. • Grind tablets and mix with coffee grounds or cat litter, seal

and toss in trash. • Police department drop-off boxes. • Pharmacy drug-take back program.

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Abuse-deterrent opioids21,22

• Formulation:• Physical or chemical barriers. • Agonist + antagonist combination.• Aversion.• Delivery system.• Prodrug.• Combination of methods listed above.

• Example:• Suboxone SL film = agonist + antagonist.• Exalgo (hydromorphone) = crush and extraction resistant.• Oxecta (IR oxycodone) = aversion.• Oxycontin (CR oxycodone) = crush and extraction resistance, aversion.• Opana ER (oxymorphone) = crush and extraction resistance, aversion.

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Future directions23

• Monitoring for side-effects. • Expand prescription drug monitoring programs to multi-states.

• Tighten up regulations on illegal substances or prescription drug redistribution among patients.

• Provide interventions right away if patients start to experience withdrawal symptoms.

• Encourage patients to enroll in rehab programs.• More patient education.

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Reference 1. FDA Moves Quickly to Approve Easy-to-use Nasal Spray to Treat Opioid

Overdose. U.S. Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/UCM473505. Last updated 11/19/2015. Accessed 11/27/2015.

2. Narcan Approval History. http://www.drugs.com/history/narcan.html. Accessed 11/27/2015.

3. What Are Opioids? National Institute on Drug Abuse. http://www.drugabuse.gov/publications/research-reports/prescription-drugs/opioids/what-are-opioids. Accessed on 11/27/2015.

4. Al-Hasani, R, Bruchas MR. Molecular Mechanisms of Opioid Receptor-Dependent Signaling and Behavior. Anesthesiology. 2011 Dec; 115(6): 1363-1381.

5. DiPiro, JT, Talbert RL, Yee, GC, et al. Opioid. In: Pharmacotherapy: A Pathaophysiology Approach. 9e. United States: McGraw-Hill Education; 2014.

6. Swegle JM, Logemann C. Management of Common Opioid-Induced Adverse Effects. Am Fam Physician. 2006 Oct 15;74(8):1347-1354.

7. Rahman A, Choudhary MI. Frontiers in CNS Drug Discovery. Bentham Science Publishers, Jan 1,2010.

8. Ballantyne JC, Sullivan MD, Kolodny A. Opioid Dependence vs Addiction. Arch Intern Med. 2012; 172(17):1342-1343

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Reference 9. Pretorius RW, Zurick GM. A Systematic Approach to Identifying Drug-Seeking Patients. Fam

Pract Manag. 2008 Apr; 15(4):A3-A5. 10. Spera B. How to Spot and Handle Fake Rxs. http://drugtopics.modernmedicine.com/drug-

topics/news/clinical/community-pharmacy/how-spot-and-handle-fake-rxs?page=full. Last updated 8/6/2007. Accessed 11/27/2015.

11. Medication and Counseling Treatment. Substance Abuse and Mental Health Service Administration. http://www.samhsa.gov/medication-assisted-treatment/treatment#medications-used-in-mat. Last updated 9/28/2015. Accessed 11/27/2015.

12. CNS depressants. National Institute on Drug Abuse. http://www.drugabuse.gov/publications/research-reports/prescription-drugs/cns-depressants. Last updated 11/2014. Accessed 11/27/2015.

13. Opioid Overdose. Substance Abuse and Mental Health Service Administration. http://www.samhsa.gov/medication-assisted-treatment/treatment/opioid-overdose. Last updated 9/25/2015. Accessed 11/25/2015.

14. Federal Guidelines for Opioid Treatment Programs. Substance Abuse and Mental Health Service Administration. http://store.samhsa.gov/shin/content//PEP15-FEDGUIDEOTP/PEP15-FEDGUIDEOTP.pdf. Last updated 3/2015. Accessed 11/27/2015.

15. Furlano, E. Naloxone’s Basic Benefit. http://www.emsworld.com/article/11625142/naloxone-use-by-emts. EMSWorld. Last updated 10/15/2014. Accessed 11/27/2015.

16. Nasal Spray Naloxone One Step Closer to Public Availability, National Institue on Drug Abuse. https://www.drugabuse.gov/news-events/news-releases/2015/06/nasal-spray-naloxone-one-step-closer-to-public-availability. Last updated 6/12/2015. Accessed 11/27/2015.

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Reference17. Kim D, Irwin KS, Khoshnood K. Expanded Access to Naloxone: Options for Critical

Response to The Epidemic of Opioid Overdose Mortality. AM J Public Health. 2009 March;99(3): 402-407.

18. Overdose Prevention and Survival. The Drug Overdose Prevention and Education Project. http://harmreduction.org/wp-content/uploads/2012/02/dope-brochure-sept-2010.pdf. Accessed 11/27/2015.

19. CVS to Sell Over-the-counter Narcan in 12 New States. http://www.ems1.com/ems-news/9948048-CVS-to-sell-over-the-counter-Narcan-in-12-new-states/ Last updated 9/30/2015. Accessed 11/27/2015.

20. CVS Set to Expand Drug Reversing Effect of Heroin Overdoses. http://www.nbcnews.com/nightly-news/video/cvs-set-to-expand-drug-reversing-effect-of-heroin-overdoses-533323331609. Last updated 9/27/2015. Accessed 11/27/2015.

21. Abuse-Deterrent Opioids – Evaluation and Labeling- Draft. U.S. Food and Drug Administration. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm334807.htm. Accessed 11/27/2015.

22. Opioids with Abuse Deterrent Properties. http://www.empr.com/clinical-charts/opioids-with-abuse-deterrent-properties/article/333126/. Last updated 2/7/2014. Accessed 11/27/2015.

23. Opioid Overdose ToolKit. Substance Abuse and Mental Health Service Administration. https://store.samhsa.gov/shin/content/SMA13-4742/Overdose_Toolkit_2014_Jan.pdf. Accessed 11/27/2015.

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Question?• Thank you!