Fast track is a process designed to facilitate development and expedite review of drugs intended to treat serious conditions and that demonstrate the potential to address an unmet medical need.
The agency’s priority review program provides for an expedited review of drugs that offer a significant improvement in the safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition.
So how serious was opioid overdose that took only 4 months to approve nasal spray?
Death due to drug overdose MOSTLY PRESCRIPTION DRUGS is now number 1 cause of injury death in the U.S. Surpassed motor vehicle crashes
Risk of contaminated needle stick = Healthcare worker accidentally stab themselves after patient got back to life and got angry for taking away their “high” Risk of blood-borne diseases exposed to healthcare workers
Before the nasal spray formulation was approved, this is the nasal spray form of injection
Only heroin and opium are illegal drugs
Hydrocodone is the most commonly prescribed opioid. Gone from C-III to C-II last October 2014.
Hydrocodone = dental and injury pain. Morphine = severe pain after surgery, cancer pain. Codeine = mild pain and cough, severe diarrhea
Sedation, as opioid is depressing central nervous system to reduce pain Treatment may involve stimulants like Dextroamphetamine, methylphenidate
Lower blood pressure If blood pressure is too low, need to reverse with Naloxone or a steroid like dexamethasone.
Induced constipation because it can bind to opioid receptors in the GI tract and could slow down bowel movement significantly. PREVENTION dose = Senna + Docusate Or switch to Fentanyl
Opioid can activate mast cell and release of histamine causing itching, different opioid has different amount of histamine releasing. Morphine, Codeine, Meperidine causes a lot of itching. Tx= Antihistamine 2nd gen that cause less drowsy (opioid causes sedation already)
Acid reflux Due to reduce gastric motility Tx: antacid, ranitidine, omeprazole
N/V occur in about 25% patients Require antiemetic (meclizine) with an antipsychotic (Haloperiodol), prokinetic (Reglan), or serotonin antagonist (ondansetron). No antiemetic is superior to other, so it comes down to cost and pt preference.
Adaptation is a normal process of the body. There are 2 adaptation involved: Tolerance = the bar has been increased BODY ARE ADAPTED. dose needs to be increased too to achieve the same effect. Dependence = the physiologic/body responses due to: Increase in tolerance but dose is not increased to compensate. Stopping opioid. What are some withdrawal symptoms: sweating, jittery, anxiety, insomnia, restlessness, nausea vomiting, muscle and bone pain, cold flashes.
Fake prescriptions Very nice hand and neat hand writin Not a regular or LOCAL customer – patients lives 50 miles away Large quantity without insurance and paying cash. Condition and quantity dont match (dental procedure and 120 percocet) TAMPERED (written over by patients) Paper doesnt feel/look right (purposely folded, wrinkled, old) OUT OF AREA prescriber
Anybody knows other ways?
What to do if you identify a fake script? Call the police Have the patients sit and wait and then call the police. Refuse to fill (we do not have the medication), give the ID information to the police.
Methadone Tricks the brain into thinking it’s still getting the abused drug. In fact, the person is not getting high from it and feels normal, so withdrawal doesn’t occur. Pregnant or breastfeeding women must inform their treatment provider before taking methadone. Only drug approved for pregnant or breastfeeding.
Buprenorphine = Suppress and reduce craving Naltrexone = Block the euphoric and sedative effect of abused drugs
Here is the list of the reasons why overdose occurs
It could be someone that accidentally…taken extra doses. Ex: Elderly that wakes up during the night, couldn’t see well, read ½ on bottle as 12 tablets it could be someone that purposely that extra doses for the euphoria or to get high.
Children and pet = childsafety cap and in locked cabinet.
Give to someone, some medication might work well for you, but not for the others. Ex: giving percocet for headache.
Certain medication interactions can increase opioid retention in the body. Ex: Fentanyl and oxycodone = Cyp 3A4. Tramadol is also 3A4, Grape fruit juice, certain OTC herbals like ginseng.
Recreational use Release opioid slowly. People may snort or inject to get the reward sensation.
NASAL RESCUE KITS Two 2 ml luer jet luer lock syringes prefilled with naloxone (1mg/ml) Two mucosal atomization devices Intormation pamphlet with overdose prevention and step by step instructions for overdose responses and naloxone administration
MUSCLE RESCUE KITS 1 10 ml multidose fliptop vial OR 2 1 ml vials 2 intramuscular syringes, 25 G 3 cc 1in Patient information pamphlet
Instruction labeling: TYPE OUT ½ as ONE HALF can help elderly see better
Always consult with your doctor or pharmacist if you do not know how to take medications
Pillbox: take 1 to 2 tablets every 4 to 6 hours. Max 5 tabs a day.
Mix with other medication: sleeping pills, anxiety medications, allergy medications, other opioids
So why autoinjector and still risk of injection? Because autoinjector is for home-use, but not a lot of lay people know the symptoms of opioid overdose, so mostly they don’t use Evzio, hospital use syringe type of injection.
Kinetics? Same Safe? Safer
Narcan nasal spray FINAL
NARCAN NASAL SPRAY
FOR OPIOID OVERDOSE.
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
• 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.
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
• 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.
• Opioids are painkillers.
• Example: hydrocodone, oxycodone, morphine, codeine,
heroin, hydromorphone, methadone, fentanyl, etc.
• Bind to opioid receptors in brains, spinal cords, different
• 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.
Opioid side effects 4,5,6,7
Opioid dependence vs opioid addiction8
• Central adaptations in brain when opioids are taken chronically.
• 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
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?
Treatments for opioid dependence11
• Goal: relieve withdrawal symptoms and
• Treatment options:
• Maybe safe to take for even lifetime.
• Do not discontinue without consulting your doctor.
• If taken as instructed, opioids is safe and effective to
• 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:
• Drowsy antihistamines.
• 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
• Illegal opioid overdose (heroin, opium.)
• Recreational use:
• Example: Oxycontin extended releases.
Recognizing signs of opioid overdose can help
• 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.
• Respiratory depression.
• Low blood pressure and/or low heart rate.
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.
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
• People can now use an approved formulation of
How does it apply to pharmacy
• Naloxone is one of the life-saving medications for
• 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.
• Narcan standing order.
• CVS is expanding the sale of Naloxone over-the-counter in
12 more state besides Massachusetts and Rhode Island.
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
• 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
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.
• Physical or chemical barriers.
• Agonist + antagonist combination.
• Delivery system.
• Combination of methods listed above.
• 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.
• Monitoring for side-effects.
• Expand prescription drug monitoring programs to multi-
• 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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Overdose. U.S. Food and Drug Administration.
3505. Last updated 11/19/2015. Accessed 11/27/2015.
2. Narcan Approval History. http://www.drugs.com/history/narcan.html.
3. What Are Opioids? National Institute on Drug Abuse.
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Pract Manag. 2008 Apr; 15(4):A3-A5.
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updated 8/6/2007. Accessed 11/27/2015.
11. Medication and Counseling Treatment. Substance Abuse and Mental Health Service
treatment/treatment#medications-used-in-mat. Last updated 9/28/2015. Accessed
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Last updated 11/2014. Accessed 11/27/2015.
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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
naloxone-one-step-closer-to-public-availability. Last updated 6/12/2015. Accessed
17. 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
18. Overdose Prevention and Survival. The Drug Overdose Prevention and Education
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.
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334807.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
23. Opioid Overdose ToolKit. Substance Abuse and Mental Health Service Administration.