Canadian antidote guide

Naloxone (in-hospital administration)

• Naloxone hydrochloride
• Naloxone HCl
• Narcan®

• Coma or respiratory depression due to opioid overdose.
• Empirical treatment of comatose patient opioid ingestion is suspected based on history or clinical exam.
• Consider for the treatment of coma or respiratory depression due to overdose by clonidine or imidazolines.

• Withdrawal symptoms in people with an opioid dependence. Symptoms such as; piloerection, vomiting, diarrhea, dysphoria, agitation, delirium may develop. Although not frequent, serious adverse effects from acute opioid withdrawal may happen, including seizures, ARDS, hypertensive emergency, ventricular tachycardia and fibrillation and sudden death.
• Release of catecholamines that can manifest as nausea, particularly if the PCO₂ was high.
• Exacerbation of pain in patients using opioids for pain relief.

• State of consciousness
• Vital signs, especially respiratory rate
• Pulse oximeter.
• If administering oxygen, use capnography
• Opioid withdrawal symptoms
  • https://www.mdcalc.com/cows-score-opiate-withdrawal
• Exacerbation of signs of pain

• For asymptomatic patient who have not received naloxone:
  • If opioid injected, smoked or insufflated : 
    • Monitor for 2 hours.
  • If opioid ingested:
    • Regular release opioid (short acting): 
      • Monitor for 4 hours
    • Sustained release opioid (long acting): 
      • Monitor for 12 hours
         
• For symptomatic patient who have received naloxone:
  • Observe for a minimum of 6 hours following last IV dose of naloxone or after naloxone infusion has been stopped.
    • In case of sustained release opioid ingestion, ensure that the observation period is at least 12 hours. 
• In case of exposure to buprenorphine, transdermal fentanyl or in case of body packers and body stuffers: contact your poison centre.
• Patient must be reevaluated in a calm environment, with little sensory stimuli present.

Intravenous Route (IV)

Direct IV

• Administer the solution for injection undiluted by direct IV at a rate of 0.4 mg/15 seconds.
• To facilitate the administration of smaller doses, naloxone can be diluted:
• Suggested preparation using a concentrated solution of 0.4 mg/ml:
  • 0.4 mg (1 ml) in 9 ml of NS. Final volume: 10 ml. Final concentration: 0.04 mg/ml.
• Suggested preparation using a concentrated solution of 1 mg/ml:
  • 1 mg (1 ml) in 9 ml of NS. Final volume: 10 ml. Final concentration: 0.1 mg/ml.

Continuous IV infusion

• Suggested preparations using a concentrated solution of 0.4 mg/ml:
  • 1 mg (2.5 ml) in 47.5 ml of NS or D5W. Final volume: 50 ml. Final concentration: 0.02 mg/ml.
  • 2 mg (5 ml) in 95 ml of NS or of D5W Final volume: 100 ml. Final concentration: 0.02 mg/ml.
  • 5 mg (12.5 ml) in 237.5 ml of NS or D5W. Final volume: 250 ml. Final concentration: 0.02 mg/ml.
  • 5 mg (12.5 ml) in 37,5 ml of NS in a syringe. Final volume: 50 ml. Final concentration: 0,1 mg/ml.
• Suggested preparations using concentration solution of 1 mg/ml
  • 1 mg (1 ml) in 49 ml of NS or D5W. Final volume: 50 ml. Final concentration: 0.02 mg/ml.
  • 2 mg (2 ml) in 98 ml of NS or D5W. Final volume: 100 ml. Final concentration: 0.02 mg/ml.
  • 5 mg (5 ml) in 245 ml of NS or D5W. Final volume: 250 ml. Final concentration: 0.02 mg/ml.
  • 5mg (5ml) in 45 ml of NS in a syringe. Final volume: 50 ml. Final concentration: 0,1 mg/ml.

Subcutaneous Route (SC)

• Possible alternative to IV route.

Intramuscular Route (IM)

• Possible alternative to IV route.

Intraosseous Route (IO)

• Possible alternative to IV route.

Endotracheal Route (ET)

• Not a recommended route of administration.

Sublingual Route (SL)

• Not a recommended route of administration.

Intranasal Route (IN)

• Possible alternative to IV route.
• Use the Narcan nasal spray or use the naloxone solution for injection concentrated at 1 mg/ml.

Compatibility

Partial list only. Consult the pharmacist on duty at your health care facility.

• Compatible solutions: NS, D5W
• Y-site compatibility: atropine, benztropine, calcium (chloride, gluconate), digoxin, diltiazem, diphenhydramine, dobutamine, dopamine, epinephrine, esmolol, famotidine, fentanyl, folic acid, furosemide, heparin, regular insulin, isoproterenol, ketamine, labetalol, lorazepam, mannitol, meperidine, metoclopramide, metoprolol, midazolam, milrinone, morphine, MVI, nitroglycerin, sodium nitroprusside, norepinephrine, octreotide, ondansetron, pancuronium, phenobarbital, phenylephrine, phytonadione, potassium (acetate, chloride), propofol, propranolol, protamine, sodium (acetate, bicarbonate), succinylcholine, theophylline, vasopressin, verapamil.
• Y-site incompatibility: Dantrolene, diazepam, haloperidol (variable), hydralazyne (variable), magnesium (sulfate) (variable), pantoprazole, phenytoin.

Stability

• Preparation of naloxone for continuous IV infusion concentrated at 0.02 mg/ml will be stable for 24 h at room temperature when diluted in NS.
• Preparation of naloxone for continuous IV infusion concentrated at 0.1 mg/ml will be stable for 24 h at room temperature when diluted in NS, in a polypropylene syringe and protected from light.

• Naloxone HCl injection, 0.4 mg/ml, Inj. Sol., vials of 1 ml and 10 ml, Sandoz, DIN 02148706, 
• Naloxone HCl injection without preservatives, 0.4 mg/ml, Inj. Sol., ampoules of 1 ml, Sandoz, DIN 02382601
• Naloxone HCl injection without preservatives, 0.4 mg/ml, Inj. Sol., ampoules of 1 ml, Alveda , DIN 02382482, 
• Naloxone HCl injection, 1 mg/ml, Inj. Sol., vials of 2 ml, Sandoz , DIN 02148714, 
• Narcan Nasal Spray, 4 mg/0.1ml single-dose sprayer, adapt Pharma, DIN 02458187
  • Direct order from the manufacturer at adaptcanada@customer-/support.ca
  • 2 spray bottles per package.

• At least 30 mg.

Boyer, Edward W. 2012. “Management of Opioid Analgesic Overdose.” The New England Journal of Medicine 367 (2):146–55.

Integrated, Web-Based, and Emergency Cardiovascular Care. n.d. “Part 10: Special Circumstances of Resuscitation.”

Kim, Hong K., and Lewis S. Nelson. 2016. “Reversal of Opioid-Induced Ventilatory Depression Using Low-Dose Naloxone (0.04 Mg): A Case Series.” Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology 12 (1):107–10.

Kim, Hong K., and Lewis S. Nelson. 2015. “Reducing the Harm of Opioid Overdose with the Safe Use of Naloxone : A Pharmacologic Review.” Expert Opinion on Drug Safety 14 (7): 1137–46.

Larocque, A. 2012. “Protocole de Traitement de L’intoxication Aiguë Aux Opioïdes.” Bulletin D’information Toxicologique 28 (4):34–43.

Lucyk, Scott, and Lewis S. Nelson. 2016. “Opioid Receptor Antagonists.” In Critical Care Toxicology, edited by Jeffrey Brent, Keith Burkhart, Paul Dargan, Benjamin Hatten, Bruno Megarbane, and Robert Palmer, 1–5. Cham: Springer International Publishing.

Régie de l’assurance maladie du Québec. 2017. “Programme de Gratuité Du Médicament Naloxone et de Certaines Fournitures.” http://www.ramq.gouv.qc.ca/SiteCollectionDocuments/professionnels/infolettres/2017/info236-7.pdf.

Sivilotti, Marco L. A. 2016. “Flumazenil, Naloxone and the ‘coma Cocktail.’” British Journal of Clinical Pharmacology 81 (3):428–36.

Trissel's 2 Clinical Pharmaceutics Database, Naloxone hydrochloride 0.133mg/ml in NS (Normal Saline).