II. Physiology

  1. Pure Opioid antagonist
  2. Action in under 2 minutes
  3. Effect lasts 45 minutes

III. Indication: Opioid overdosage

  1. Respiratory depression (esp. Respiratory Rate <9 breaths/min or increased EtCO2)
  2. Sedation
  3. Hypotension
  4. Hypoperfusion

IV. Indications: Opioid examples reversed by Naloxone

  1. Heroin
  2. Methadone
  3. Pentazocine
  4. Propoxyphene

V. Indications: Opioids requiring increased Naloxone dosing

  1. Propoxyphene
  2. Pentazocine
  3. Buprenorphine

VI. Pharmacokinetics

  1. Onset: 1-2 minutes
  2. Duration: 1-2 hours

VII. Dosing: General

  1. Route:
    1. Reliable: IV, IO, and ET
    2. Erratic absorption: IM and SQ
  2. Single dose
    1. Child
      1. Under 5 years (under 20 kilograms): 0.1 mg/kg
      2. Over 5 years (over 20 kilograms): 2.0 mg
    2. Adult
      1. Dose: 0.4 to 2.0 mg IVP
      2. Start with 0.4 mg if suspecting severe withdrawal
  3. Repeat dosing
    1. May repeat at 2-3 minutes intervals
    2. Maximum total dose: 10 mg (adults)
  4. Infusion (for long acting Narcotic reversal)
    1. Dose: 0.04 to 0.16 mg/kg/h
  5. Indication-based dosing
    1. Respiratory depression: 0.4 mg IV
    2. Cardiac Arrest: 2 mg IV (if possible Overdose induced Cardiac Arrest)
    3. Concern for Opioid Withdrawal (slow titration method)
      1. See below

VIII. Dosing: Home Prescriptions

  1. Indications: Highest risk patients (but any patient on Chronic Opioids is at risk)
    1. Morphine equivalent dose >50 mg/day
    2. Long-acting Opioid use
    3. Transitioning between Opioids
    4. Concurrent use with other CNS depressants (e.g. Benzodiazepines or Alcohol)
    5. Comorbidities (e.g. Sleep Apnea)
  2. Background
    1. Caregivers or family members could administer the Naloxone in case of Overdose
    2. Risk of withdrawal symptoms
    3. Patients should be brought to medical facility after use of Naloxone, as half-life of Opioid may exceed 60-90 min
    4. Home rescue Naloxone may curb the >40 daily lethal Opioid Overdoses in the U.S.
  3. Auto-Injector
    1. Dose: 0.4 mg IM/SQ delivered by autoinjector
    2. Very expensive (2 injectors for $600)
    3. Resources: FDA
      1. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm391465.htm
    4. References
      1. Walley (2013) BMJ 346:f174 [PubMed]
  4. Nasal Spray (approved in 2015)
    1. Does not need to be inhaled to be effective
  5. Custom Naloxone Home Rescue Kit (compounded by pharmacy)
    1. Naloxone 0.4 mg/ml vials with 2 syringes, administered IM prn Overdose ($50-100) OR
    2. Naloxone 2 mg/2ml in prefilled syringes with 2 atomizers administered intranasal prn Overdose ($125)
  6. Myth busting
    1. Naloxone prescriptions do not increase risky behavior
    2. Most U.S. states allow for Naloxone prescriptions to caregivers
    3. No harm if improperly administered or given to a patient not on Opioids
  7. References
    1. (2016) Presc Lett 23(1): 2-3
    2. (2016) Presc Lett 23(8)

IX. Dosing: Very Low Dose Naloxone Protocol (slow titration method)

  1. Indications: Prevent severe Rebound Pain that would occur with complete Opioid reversal
    1. Cancer Pain
    2. Chronic Pain
  2. Prepare a 0.04 mg/ml Naloxone solution
    1. Start with one Naloxone ampule 0.04 mg/ml
    2. Add saline to make total dose of 10 ml
  3. Dosing protocol
    1. Administer 1-2 ml (0.01 to 0.04 mg) or 1.5 mcg/kg IV or IM
    2. Repeat dose every 3-5 minutes as needed
      1. Titrate dose to Respiratory Rate and mental status

X. Precautions

  1. Recurrence of narcotic Intoxication
    1. Occurs if Narcotic half life is longer than Naloxone
    2. Infusion may be useful with longer acting Opioids
  2. Infants born to addicted mothers
    1. Naloxone may precipitate acute withdrawal or Seizures
  3. Restrain patient Overdose prior to administration
    1. May precipitate withdrawal
  4. Naloxone may act as Sympathomimetic
    1. May theoretically exacerbate myocardial irritability

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Cost: Medications

naloxone (on 8/17/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
NALOXONE 0.4 MG/ML VIAL Generic $15.78 per ml
NALOXONE 2 MG/2 ML SYRINGE Generic $15.98 per ml
NALOXONE 4 MG/10 ML VIAL Generic $15.78 per ml
narcan (on 8/17/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
NARCAN 4 MG NASAL SPRAY $60.97 each
evzio (on 5/18/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
EVZIO 0.4 MG AUTO-INJECTOR $4,507.11 per ml

Ontology: Naloxone (C0027358)

Definition (NCI) A thebaine derivate with competitive opioid antagonistic properties. Naloxone reverses the effects of opioid analgesics by binding to the opioid receptors in the CNS, and inhibiting the typical actions of opioid analgesics, including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia, and physical dependence. Naloxone binds to mu-opioid receptors with a high affinity, and a lesser degree to kappa- and gamma-opioid receptors in the CNS.
Definition (NCI_NCI-GLOSS) A substance that is being studied as a treatment for constipation caused by narcotic medications. It belongs to the family of drugs called narcotic antagonists.
Definition (MSH) A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.
Definition (CSP) specific opiate antagonist with no agonist activity, a competitive antagonist at mu, delta, and kappa opioid receptors.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D009270
SnomedCT 372890007, 89018006
LNC LP28525-1, MTHU013159
English Naloxone, Morphinan-6-one, 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-, (5alpha)-, Naloxone [Chemical/Ingredient], NALOXONE, (-)-Naloxone, naloxone, Naloxone (product), Naloxone (substance), NLX
Swedish Naloxon
Czech naloxon
Finnish Naloksoni
Russian NALOKSON, НАЛОКСОН
Japanese ナルカン, ナルコン, ナロキソン塩酸塩, ナロキソン, ナロキソン臭化水素酸塩, 塩酸ナロキソン
Croatian NALOKSON
Polish Nalokson
Spanish naloxona (producto), naloxona (sustancia), naloxona, Naloxona
French Naloxone
German Naloxon
Italian Nalossone
Portuguese Naloxona

Ontology: Narcan (C0684237)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D009270
English Narcan Neonatal, narcan, Narcanti, Boots Brand of Naloxone Hydrochloride, Bristol Myers Squibb Brand of Naloxone Hydrochloride, Bristol-Myers Squibb Brand of Naloxone Hydrochloride, Endo Brand of Naloxone Hydrochloride, Lamepro Brand of Naloxone Hydrochloride, United Drug Brand of Naloxone Hydrochloride, Narcan