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Pronunciation
(nal OKS one)
Generic Available (U.S.)
Yes
Index Terms
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Complete or partial reversal of opioid drug effects, including respiratory depression; management of known or suspected opioid overdose; diagnosis of suspected opioid dependence or acute opioid overdose
Use: Dental
Reverse overdose effects of the two narcotic agents, fentanyl and meperidine, used in the technique of I.V. conscious sedation
Use: Unlabeled/Investigational
Opioid-induced pruritus
Pregnancy Risk Factor
C
Pregnancy Considerations
Consider benefit to the mother and the risk to the fetus before administering to a pregnant woman who is known or suspected to be opioid dependent. May precipitate withdrawal in both the mother and fetus.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
No data reported. Since naloxone is used for opiate reversal the concern should be on opiate drug levels in a breast-feeding mother and transfer to the infant rather than naloxone exposure. The safest approach would be not to breast-feed.
Contraindications
Hypersensitivity to naloxone or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Acute opioid withdrawal: May precipitate symptoms of acute withdrawal in opioid-dependent patients, including pain, hypertension, sweating, agitation, irritability; in neonates: shrill cry, failure to feed. Carefully titrate dose to reverse hypoventilation; do not fully awaken patient or reverse analgesic effect (postoperative patient).
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease or in patients receiving medications with potential adverse cardiovascular effects (eg, hypotension, pulmonary edema or arrhythmias); pulmonary edema and cardiovascular instability, including ventricular fibrillation, have been reported in association with abrupt reversal when using narcotic antagonists. Administration of naloxone causes the release of catecholamines; may precipitate acute withdrawal or unmask pain in those who regularly take opioids.
• Seizures: Use caution in patients with history of seizures; avoid use in treatment of meperidine-induced seizures.
Other warnings/precautions:
• Opioid overdose: Recurrence of respiratory depression is possible if the opioid involved is long-acting; observe patients until there is no reasonable risk of recurrent respiratory depression.
• Postoperative reversal: Appropriate use: Excessive dosages should be avoided after use of opiates in surgery. Abrupt postoperative reversal may result in nausea, vomiting, sweating, tachycardia, hypertension, seizures, and other cardiovascular events (including pulmonary edema and arrhythmias).
Adverse Reactions
Adverse reactions are related to reversing dependency and precipitating withdrawal. Withdrawal symptoms are the result of sympathetic excess. Adverse events occur secondarily to reversal (withdrawal) of narcotic analgesia and sedation.
Central nervous system: Narcotic withdrawal
Drug Interactions
There are no known significant interactions.
Storage
Store at 25°C (77°F). Protect from light.
Reconstitution
Stable in 0.9% sodium chloride and D5W at 4 mcg/mL for 24 hours.
Compatibility
Stable in D5W, NS; do not mix with alkaline solutions.
Y-site administration: Compatible: Gatifloxacin, linezolid, propofol. Incompatible: Amphotericin B cholesteryl sulfate complex.
Compatibility in syringe: Compatible: Heparin, ondansetron.
Compatibility when admixed: Compatible: Verapamil.
Mechanism of Action
Pure opioid antagonist that competes and displaces narcotics at opioid receptor sites
Pharmacodynamics/Kinetics
Onset of action: Endotracheal, I.M., SubQ: 2-5 minutes; Intranasal: ~8-13 minutes (Kelley, 2005; Robertson, 2009); I.V.: ~2 minutes
Duration: ~30-120 minutes depending on route of administration; I.V. has a shorter duration of action than I.M. administration; since naloxone's action is shorter than that of most opioids, repeated doses are usually needed
Distribution: Crosses placenta
Metabolism: Primarily hepatic via glucuronidation
Half-life elimination: Neonates: 3-4 hours; Adults: 0.5-1.5 hours
Excretion: Urine (as metabolites)
Dosage
Note: I.M., I.V. (preferred), intranasal (adults only), and SubQ routes may be used. Intratracheal administration is the least desirable and is supported by only anecdotal evidence (case report) (ACLS, 2010):
Infants and Children: Postoperative reversal: 0.01 mg/kg; may repeat every 2-3 minutes as needed based on response (adequate ventilation without significant pain)
Children:
Opioid intoxication: Respiratory depression: I.V., intraosseous (I.O), intratracheal:
Birth (including premature infants) to 5 years or ≤20 kg (unlabeled dose): Acute: Initial: 0.1 mg/kg (maximum dose: 2 mg); repeat every 2-3 minutes if needed; consider lower initial doses of 0.01 mg/kg for non-acute situations (eg, respiratory depression during pain management) (Drugs for Pediatric Emergencies, 1998)
>5 years or >20 kg: Minimum dose: 2 mg/dose; if no response, repeat every 2-3 minutes (Drugs for Pediatric Emergencies, 1998)
Note: I.O. and intratracheal routes are alternative routes recommended by PALS 2010 guidelines. Consider using lower doses to reverse respiratory depression associated with therapeutic opioid use: 1-5 mcg/kg, titrate to effect (PALS, 2010)
Continuous infusion (unlabeled dosing): I.V.: If continuous infusion is required, calculate dosage/hour based on effective intermittent dose used and duration of adequate response seen or use two-thirds (2/3) of the initial effective naloxone bolus on an hourly basis; titrate dose (typically 0.04-0.16 mg/kg/hour for 2-5 days in children); one-half (1/2) of the initial bolus dose should be readministered 15 minutes after initiation of the continuous infusion to prevent a drop in naloxone levels; increase infusion rate as needed to assure adequate ventilation and prevent withdrawal symptoms
Adults:
Opioid intoxication: Respiratory depression:
I.V.: 0.4-2 mg; may need to repeat doses every 2-3 minutes; after reversal, may need to readminister dose(s) at a later interval (ie, 20-60 minutes) depending on type/duration of opioid. If no response is observed after 10 mg, consider other causes of respiratory depression. Note: Opioid-dependent patients may require lower doses (0.1 mg) titrated incrementally to avoid precipitating acute withdrawal.
Intranasal administration (unlabeled route): 2 mg (1 mg per nostril); may repeat in 5 minutes if respiratory depression persists. Note: Onset of action is slightly delayed compared to I.M. or I.V. routes (ACLS, 2010; Kelly, 2005; Robertson, 2009).
Opioid intoxication: Respiratory depression: Opioid-dependent patient: Initial: 0.04-0.4 mg; may repeat or escalate dose up to 2 mg if initial response inadequate. Note: Atypical opioids (eg, propoxyphene) or massive opioid overdoses may require much higher doses (ACLS, 2010).
Continuous infusion (unlabeled dosing): I.V.: Calculate dosage/hour based on effective intermittent dose used and duration of adequate response seen or use two-thirds (2/3) of the initial effective naloxone bolus on an hourly basis (typically 0.25-6.25 mg/hour); one-half (1/2) of the initial bolus dose should be readministered 15 minutes after initiation of the continuous infusion to prevent a drop in naloxone levels; adjust infusion rate as needed to assure adequate ventilation and prevent withdrawal symptoms
Opioid-dependent patients being treated for cancer pain (NCCN guidelines, v.1.2010): I.V.: 0.04-0.08 mg (40-80 mcg) slow I.V. push; administer every 30-60 seconds until improvement in symptoms, if no response is observed after total naloxone dose 1 mg, consider other causes of respiratory depression. Note: May dilute 0.4 mg/mL (1 mL) ampule into 9 mL of normal saline for a total volume of 10 mL to achieve a 0.04 mg/mL (40 mcg/mL) concentration.
Postoperative reversal: I.V.: 0.1-0.2 mg every 2-3 minutes until desired response (adequate ventilation and alertness without significant pain). Note: Repeat doses may be needed within 1-2 hour intervals depending on type, dose, and timing of the last dose of opioid administered.
Opioid-induced pruritus (unlabeled use): I.V. infusion: 0.25 mcg/kg/hour; Note: Monitor pain control; verify that the naloxone is not reversing analgesia (Gan, 1997)
Dental Usual Dosing
Narcotic overdose: Adults: I.V.: 0.4-2 mg every 2-3 minutes as needed; may need to repeat doses every 20-60 minutes, if no response is observed after 10 mg, question the diagnosis. Note: Use 0.1-0.2 mg increments in patients who are opioid dependent and in postoperative patients to avoid large cardiovascular changes.
Administration: I.M.
May administer I.M. if unable to obtain I.V. access.
Administration: I.V.
I.V. push: Administer over 30 seconds as undiluted preparation or (unlabeled) administer as diluted preparation slow I.V. push by diluting 0.4 mg (1 mL) ampul with 9 mL of normal saline for a total volume of 10 mL to achieve a concentration of 0.04 mg/mL
I.V. continuous infusion: Dilute to 4 mcg/mL in D5W or normal saline
Administration: Other
Intratracheal (unlabeled route): There is only anecdotal support for this route of administration. May require a slightly higher dose than used in other routes. Dilute to 1-2 mL with normal saline; flush with 5 cc of saline and then administer 5 ventilations
Intranasal (unlabeled route): Administer total dose equally divided into each nostril using a mucosal atomizer device (MAD) (ACLS, 2010; Kelly, 2005; Robertson, 2009)
SubQ: May administer SubQ if unable to obtain I.V. access
Monitoring Parameters
Respiratory rate, heart rate, blood pressure, temperature, level of consciousness, ABGs or pulse oximetry
Patient Education
Report respiratory difficulty, palpitations, or tremors.
Geriatric Considerations
In small trials, naloxone has shown temporary improvement in Alzheimer's disease; however, is not recommended for treatment.
Additional Information
May contain methyl and propylparabens
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Naloxone may contain methyl and propylparabens. The goal of treatment in the postoperative setting is to achieve reversal of excessive opioid effects without inducing a complete reversal and acute pain.
Cardiovascular Considerations
Because of the very short duration of action of naloxone (20-60 minutes) the reversal of opiate-induced respiratory depression by naloxone may cease while the opiate action persists. Therefore, respiratory depression may recur and patients should continue to be very closely observed. Also note that naloxone reverses the effects of narcotics. Excessive doses of naloxone in the perioperative period may cause an increase in blood pressure and reversal of anesthesia. Furthermore, naloxone may precipitate symptoms of opioid withdrawal (eg, pain, hypertension, irritability) in patients addicted to opioids.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Nursing: Physical Assessment/Monitoring
Assess patient for opioid dependency. Monitor vital signs and cardiorespiratory status continuously during infusion; maintain patent airway.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride: 0.4 mg/mL (1 mL, 10 mL)
Injection, solution, as hydrochloride [preservative free]: 1 mg/mL (2 mL)
References
American Academy of Pediatrics Committee on Drugs, “Naloxone Dosage and Route of Administration for Infants and Children: Addendum to Emergency Drug Doses for Infants and Children,” Pediatrics, 1990, 86(3):484-5.
Bergasa NY, Alling DW, Talbot TL, et al, “Effects of Naloxone Infusions in Patients With the Pruritus of Cholestasis. A Double-Blind, Randomized, Controlled Trial,” Ann Intern Med, 1995, 123(3):161-7.
Boeuf B, Gauvin F, Guerguerian AM, et al, “Therapy of Shock With Naloxone: A Meta-Analysis,” Crit Care Med, 1998, 26(11):1910-6.
Chamberlain JM and Klein BL, “A Comprehensive Review of Naloxone for the Emergency Physician,” Am J Emerg Med, 1994, 12(6):650-60.
“Drugs for Pediatric Emergencies,” Pediatrics, 1998, 101(1):E13.
Field JM, Hazinski MF, Sayre MR, et al, “Part 1: Executive Summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122 (18 Suppl 3):640-56.
Gan TJ, Ginsberg B, Glass PS, et al, “Opioid-Sparing Effects of a Low-Dose Infusion of Naloxone in Patient-Administered Morphine Sulfate,” Anesthesiology, 1997, 87(5):1075-81.
Goldfrank L, Weisman RS, Errick JK, et al, “A Dosing Nomogram for Continuous Infusion Intravenous Naloxone,” Ann Emerg Med, 1986, 15(5):566-70.
Hantson P, Evenepoel E, Ziade D, et al, “Adverse Cardiac Manifestations Following Dextropropoxyphene Overdose: Can Naloxone Be Helpful?” Ann Emerg Med, 1995, 25(2):263-6.
Hoffman RS and Goldfrank LR, “The Poisoned Patient With Altered Consciousness. Controversies in the Use of a 'Coma Cocktail',” JAMA, 1995, 274(7):562-9.
Johnson C, Mayer P, and Grosz D, “Pulmonary Edema Following Naloxone Administration in a Healthy Orthopedic Patient,” J Clin Anesth, 1995, 7(4):356-7.
Kaplan JL, Marx JA, Calabro JJ, et al, “Double-Blind, Randomized Study of Nalmefene and Naloxone in Emergency Department Patients With Suspected Narcotic Overdose,” Ann Emerg Med, 1999, 34(1):42-50.
Kelly A, Kerr D, Dietze P, et al, “Randomised Trial of Intranasal Versus Intramuscular Naloxone in Prehospital Treatment for Suspected Opioid Overdose,” Med J Aust, 2005, 182(1):24-7.
Kendrick WD, Woods AM, Daly MY, et al, “Naloxone Versus Nalbuphine Infusion for Prophylaxis of Epidural Morphine-Induced Pruritus,” Anesth Analg, 1996, 82(3):641-7.
Kjellberg F and Tramer MR, “Pharmacological Control of Opioid-Induced Pruritus: A Quantitative Systematic Review of Randomized Trials,” Eur J Anaesthesiol, 2001, 18(6):346-57.
Kleinman ME, Chameides L, Schexnayder SM, et al, “Part 14: Pediatric Advanced Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122(18 Suppl 3):876-908.
Merigian KS, “Cocaine-Induced Ventricular Arrhythmias and Rapid Atrial Fibrillation Temporally Related to Naloxone Administration,” Am J Emerg Med, 1993, 11(1):96-7.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Adult Cancer Pain,” Version 1.2008. Available at http://www.nccn.org/professionals/physician_gls/PDF/pain.pdf
Neumar RW, Otto CW, Link MS, et al, “Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122(18 Suppl 3):729-67.
O'Connor PG and Kosten TR, “Rapid and Ultrarapid Opioid Detoxification Techniques,” JAMA, 1998, 279(3):229-34.
Olsen KS, “Naloxone Administration and Laryngospasm Followed by Pulmonary Edema,” Intensive Care Med, 1990, 16(5):340-1.
O'Malley-Dafner L, Davies P, “Naloxone-Induced Pulmonary Edema,” Am J Nurs, 2000, 100(11):24AA-JJ.
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Robertson TM, Hendey GW, Stroh G, et al, “Intranasal Naloxone is a Viable Alternative to Intravenous Naloxone for Prehospital Narcotic Overdose,” Prehosp Emerg Care, 2009, 13(4):512-5.
Salvucci AA Jr, Eckstein M, and Iscovich AL, “Submental Injection of Naloxone,” Ann Emerg Med, 1995, 25(5):719-20.
Storrow AB, Wians FH Jr, Mikkelsen SL, et al, “Does Naloxone Cause a Positive Urine Opiate Screen?” Ann Emerg Med, 1994, 24(6):1151-3.
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Trujillo MH, Guerrero J, Fragachan C, et al, “Pharmacologic Antidotes in Critical Care Medicine: A Practical Guide for Drug Administration,” Crit Care Med, 1998, 26(2):377-91.
Vanden Hoek TL, Morrison LJ, Shuster M, et al, “Part 12: Cardiac Arrest in Special Situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122(18 Suppl 3):829-61.
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International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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