Key points
- We recommend to consult your poison centre with the use of this antidote.
- The primary survey (evaluation of the airway, the breathing and the circulation) should be prioritized over the administration of naloxone.
- This monograph do not replace the protocol in force of your institution or professional organization if applicable.
- Naloxone should initially be dosed cautiously to prevent precipitating withdrawal.
- High doses naloxone may be required for higher potency opiates such as fentanyl.
- Pain and other sensory stimuli can stimulate breathing and incorrectly suggest that the effect of the opioid has worn off. Caution is recommended in such cases.
- All patient who present with opioid overdose should be offered follow up with addictions services and provided with information regarding take home naloxone and safer drug practices.
- Community pharmacists may be authorized to provide naloxone for the treatment of overdoses in some provinces.
+ Synonyms and other terms
- Naloxone hydrochloride
- Naloxone HCl
- Narcan®
+ Indications
- Coma or respiratory depression due to opioid overdose; respiratory rate less than 10/minute or saturation less than 92% on room air.
- Empirical treatment of comatose patient, who is unable to protect is airway, if opioid ingestion is suspected based on history or clinical exam.
- Out-of-Hospital Context
- In known or suspected cases of opioid overdose in patients with a pulse, experiencing respiratory arrest or agonal breathing, it is reasonable for trained people to proceed with the empirical administration of naloxone by intramuscular or intranasal route pending the arrival of specialized care at the hospital, without delaying standard resuscitation (BLS/ACLS).
In known or suspected cases of opioid overdose without a detectable pulse, the patient must be given the standard care given to any person in cardiac arrest. Priority must be given to standard resuscitation. It is reasonable, however, for trained people to administer naloxone by intramuscular or intranasal route based on an assessment that the patient is deemed to be more in respiratory than in cardiac arrest, without delaying the delivery of standard resuscitation (BLS/ACLS).
+ Dosage
+ Pediatric Dose
Initial dose: 0.1mg/kg IV/IO/IM of body weight (max 2mg)
Subsequent dosing: If there is an insufficient response to the initial dose, subsequent doses should be administered every 2 minutes (3 minutes if IM) according to the following schedule:
- repeat initial dose according to the body weight for 1 dose and then
- 2mg,
- 4 mg
- 10mg as a final dose if there is a high clinical suspicion of opiod intoxication. If there is no response after this dosing regimen, alternate causes for symptoms should be sought.
For intranasal administration (IN):
- Initial dose:
- Narcan nasal spray: 4 mg IN in one nostril
- Injectable solution: 0.4mg ou 1mg (1mL) IN in one nostril (if available use preferably the 1mg/mL concentrated injectable solution)
- Subsequent dosing:
- Narcan nasal spray: If there is an insufficient response to the initial dose, repeat the same dose every 3 minutes in alternating nostrils. If there is no response after 5 doses of 4mg of narcan spray, alternate causes for symptoms should be sought.
- Injectable solution: If there is an insufficient response to the initial dose, subsequent doses should be administered every 3 minutes, in alternating nostrils, according to the following schedule:
- 0.4mg or 1mg IN in one nostril,
- 0.4mr or 1mg IN in each nostril (total dose: 0.8mg or 2mg) and repeat this dose (0.8mg or 2mg) every 3 minutes if needed. If there is no response after cumulative dose of 20mg, alternate causes for symptoms should be sought.
- Note: The 1 mL delivery volume per nostril is larger than that generally utilized for intranasal drug administration. Therefore, there is loss of drug from the nasal cavity, due either to drainage into the nasopharynx or externally from the nasal cavity. The IV, IO or IM routes or the Narcan nasal spray are therefore preferred.
- The narcan nasal spray has a bioavailability estimated at approximately 50% of that of IM administration.
- Several factors may interfere with the intranasal absorption of naloxone; nasal septal abnormalities, nasal trauma, excessive mucus, epistaxis and intranasal damage caused by the use of substances such as cocaine. If the patient suffers from one of these conditions, naloxone should not be administered by the intranasal route. The use of IV, IO or IM route should be preferred.
The requirement for repeat dosing following reversal should be anticipated following large overdoses of ingestion of long-acting products.
+ Adult Dose
Initial dose: 0.1 mg IV/IO or 0.4mg IM
Subsequent dosing: If there is an insufficient response to the initial dose, subsequent doses should be administered every 2 minutes (3 minutes if IM) according to the following schedule:
- 0.4mg,
- 0.4mg,
- 2mg,
- 4mg,
- 10mg as a final dose if there is a high clinical suspicion of opioid intoxication. If there is no response after this dosing regimen, look for alternate causes for symptoms should be sought.
For intranasal administration (IN):
- Initial dose:
- Narcan nasal spray: 4mg IN in one nostril
- Injectable solution: 0.4mg or 1mg (1mL) IN in one nostril (if available use preferably the 1mg/mL concentrated injectable solution)
- Subsequent dosing:
- Narcan nasal spray: If there is an insufficient response to the initial dose, repeat the same dose every 3 minutes in alternating nostrils. If there is no response after 5 doses of 4mg of narcan spray, alternate causes for symptoms should be sought.
- Injectable solution: If there is an insufficient response to the initial dose, subsequent doses should be administered every 3 minutes, in alternating nostrils, according to the following schedule:
- 0.4mg or 1mg IN in one nostril,
- 0.4mg or 1mg IN in one nostril,
- 0.4mg or 1mg IN in each nostril (total dose: 0.8mg or 2mg) and repeat this dose (0.8mg or 2mg) every 3 minutes if needed. If there is no response after cumulative dose of 20mg, alternate causes for symptoms should be sought.
- Note: The 1 mL delivery volume per nostril is larger than that generally utilized for intranasal drug administration. Therefore, there is loss of drug from the nasal cavity, due either to drainage into the nasopharynx or externally from the nasal cavity. The IV, IO or IM routes or the Narcan nasal spray are therefore preferred.
- The narcan nasal spray has a bioavailability estimated at approximately 50% of that of IM administration.
- Several factors may interfere with the intranasal absorption of naloxone; nasal septal abnormalities, nasal trauma, excessive mucus, epistaxis and intranasal damage caused by the use of substances such as cocaine. If the patient suffers from one of these conditions, naloxone should not be administered by the intranasal route. The use of IV, IO or IM route should be preferred.
The requirement for repeat dosing following reversal should be anticipated following large overdoses of ingestion of long-acting products.
+ Renal Impairment
No data suggests that the dose should be modified for short-term use.
+ Hepatic Impairment
No data suggests that the dose should be modified for short-term use.
+ Hemodialysis Patient
No data suggests that the dose should be modified for short-term use.
+ Pregnancy
- Its safety has not been demonstrated.
- Do not hesitate to use naloxone during pregnancy if the anticipated toxic effects pose a significant risk of morbidity or mortality.
- No data suggests that the dose should be modified for short-term use.
+ Obese or Overweight Patient
No data suggests that the dose should be modified for short-term use.
+ Adverse effects
- 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.
+ Monitoring
State of consciousness
- Vital signs, especially respiratory rate
- Pulse oximeter.
- If administering oxygen, use capnography
- Opioid withdrawal symptoms
- Exacerbation of signs of pain
+ End of treatment
- Refer the patient to the emergency
- See naloxone (in hospital) monograph for the suggested observation periods.
+ Special Notes on Administration
Intravenous Route (IV)
- Direct IV
- Administer the solution for injection undiluted by direct IV at a rate of 0.4 mg/15 seconds.
- Continuous IV infusion: refer to naloxone in-hospital administration monograph.
Subcutaneous Route (SC)
- Possible alternative to IV route.
Intramuscular Route (IM)
- Possible alternative to IV route.
- INSPQ video: https://www.inspq.qc.ca/sites/default/files/videos/naloxone_fiole-ampoule_en.mp4
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.
- If Narcan nasal spray is not available use the naloxone solution for injection concentrated at 0.4mg/ml or 1 mg/ml (refer to the dosage section for more information)
- INSPQ video: https://www.inspq.qc.ca/sites/default/files/videos/naloxone_spray_en.mp4
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
- Keep vials of naloxone for injection and narcan nasal spray at room temperature (15-25 °C) and protect from light.
+ Available products
- 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 , DIN02148714
- Narcan Nasal Spray, 4 mg/0.1ml single-dose sprayer, adapt Pharma, DIN02458187 ,
+ Amount required to treat a person weighting 70kg during 24 hours
- At least 30 mg of naloxone injectable solution
+ References
Lewis, Christa R., Hoa T. Vo, and Marc Fishman. 2017. “Intranasal Naloxone and Related Strategies for Opioid Overdose Intervention by Nonmedical Personnel: A Review.” Substance Abuse and Rehabilitation 8 (October): 79–95.
Robinson, Amanda, and Daniel P. Wermeling. 2014. “Intranasal Naloxone Administration for Treatment of Opioid Overdose.” American Journal of Health-System Pharmacy: AJHP: Official Journal of the American Society of Health-System Pharmacists 71 (24): 2129–35.
Wermeling, Daniel P. 2013. “A Response to the Opioid Overdose Epidemic: Naloxone Nasal Spray.” Drug Delivery and Translational Research 3 (1): 63–74.
Jesse Godwin MD, Andrew Kestler MD, Chris DeWitt MD, Roy Purssell MD, Opioid Overdose Best Practices Guideline, Nov 23, 2016, Final Revision: March 1, 2017.
Product Monograph, Narcan Nasal SprayTM, Opioid Antagonist, Adapt Pharma Operations Limited, Redaction date 3 Oct 2016, Revision Date March 24, 2017.
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.
© Centre antipoison du Québec, CIUSSS de la Capitale-Nationale, 2017. The information contained in this site may be cited, provided the source is acknowledged. Any use for commercial or advertising purposes is strictly prohibited.
ISSN : 2292-230X
Authors: Pursell R, Dubé PA, Elliott A, Friesen M, Gosselin S, Laliberté M, Larocque A, Letarte A, Mackenzie C, Murphy N, St-Onge M, Thompson M, Yarema M
