(nal OKS one)
Opioid overdose: For the complete or partial reversal of opioid depression (including respiratory depression) induced by natural and synthetic opioids (eg, propoxyphene, methadone, nalbuphine, butorphanol, pentazocine). Naloxone is also indicated for the diagnosis of suspected or known acute opioid overdosage.
Evzio (IM, SubQ), Narcan Nasal Spray (intranasal): For the emergency treatment of known or suspected opioid overdose as manifested by respiratory and/or CNS depression. Intended for immediate administration as emergency therapy in settings where opioids may be present. Not a substitute for emergency medical care.
Septic shock: For use as an adjunctive agent to increase blood pressure in the management of septic shock. Note: Naloxone is no longer a recommended adjunctive agent for the treatment of septic shock (SCCM [Dellinger 2013]).
Hypersensitivity to naloxone or any component of the formulation
Note: Available routes of administration include IV (preferred), IM, SubQ, and intranasal; other available routes (off-label) include inhalation via nebulization (adults only), and intraosseous (IO). Endotracheal administration is the least desirable and is supported by only anecdotal evidence (case report) (AHA [Neumar 2010]):
Opioid overdose:
Note: For the initial treatment of an opioid-associated life-threatening emergency, the American Heart Association recommends, after initiation of CPR, the use of intranasal or IM naloxone with a repeat dose as needed. If there is an initial patient response (ie, purposeful movement, regular breathing, moan or other response) but the patient then stops responding, begin CPR and repeat naloxone dose. If no initial response, continue CPR and use AED as appropriate (AHA [Lavonas 2015]).
IV, IM, SubQ: Initial: 0.4 to 2 mg; may need to repeat doses every 2 to 3 minutes; after reversal, may need to readminister dose(s) at a later interval (ie, 20 to 60 minutes) depending on type/duration of opioid. If no response is observed after 10 mg total, consider other causes of respiratory depression. Note: May be given endotracheally (off-label route) as 2 to 2.5 times the initial IV dose (ie, 0.8 to 5 mg) (AHA [Neumar 2010]).
Continuous infusion (off-label dosing): IV: Note: For use with exposures to long-acting opioids (eg, methadone), sustained release product, and symptomatic body packers after initial naloxone response. Calculate dosage/hour based on effective intermittent dose used and duration of adequate response seen (Tenenbein 1984) or use two-thirds (2/3) of the initial effective naloxone bolus on an hourly basis (typically 0.25 to 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 (Goldfrank 1986).
IM, SubQ: Evzio: 0.4 mg (contents of 1 auto-injector) as a single dose; may repeat every 2 to 3 minutes until emergency medical assistance becomes available.
Inhalation via nebulization (off-label route): 2 mg; may repeat. Switch to IV or IM administration when possible (Weber 2012). Note: This administration method is not included in the AHA recommendations for initial management of opioid-associated life-threatening emergency (AHA [Lavonas 2015]).
Intranasal: Note: Onset of action is slightly delayed compared to IM or IV routes (Kelly 2005; Robertson 2009)
Narcan Nasal Spray: 4 mg (contents of 1 nasal spray) as a single dose; may repeat every 2 to 3 minutes in alternating nostrils until medical assistance becomes available.
Off label dosing: 2 mg (1 mg per nostril) using generic injectable solution (with a mucosal atomization device); may repeat in 3 to 5 minutes if respiratory depression persists (AHA [Lavonas 2015]; AHA [Vanden Hoek 2010]; Kelly 2005; Robertson 2009; Walley 2013).
Reversal of respiratory depression with therapeutic opioid doses: IV, IM, SubQ.: Initial: 0.04 to 0.4 mg; may repeat until desired response achieved. If desired response is not observed after 0.8 mg total, consider other causes of respiratory depression. Note: May be given endotracheally (off-label route) as 2 to 2.5 times the initial IV dose (ie, 0.08 to 1 mg) (AHA [Neumar 2010]).
Continuous infusion (off-label dosing): IV: Note: For use with exposures to long-acting opioids (eg, methadone) or sustained release products. Calculate dosage/hour based on effective intermittent dose used and duration of adequate response seen (Tenenbein 1984) or use two-thirds (2/3) of the initial effective naloxone bolus on an hourly basis (typically 0.2 to 0.6 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 (Goldfrank 1986).
Opioid-dependent patients being treated for cancer pain (NCCN guidelines, v.2.2011): IV: 0.04 to 0.08 mg (40 to 80 mcg) slow IV push; administer every 30 to 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) ampul 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: IV: 0.1 to 0.2 mg every 2 to 3 minutes until desired response (adequate ventilation and alertness without significant pain). Note: Repeat doses may be needed within 1 to 2 hour intervals depending on type, dose, and timing of the last dose of opioid administered.
Opioid-induced pruritus (off-label use): IV infusion: 0.25 mcg/kg/hour; Note: Monitor pain control; verify that the naloxone is not reversing analgesia (Gan 1997).
Refer to adult dosing.
Note: IV (preferred), IM, SubQ, intranasal, intraosseous (IO) (off-label), and endotracheal (off-label) routes may be used. Endotracheal administration is the least desirable and is supported by only anecdotal evidence (case report) (AHA [Neumar 2010]).
Opioid overdose:
Neonates, Infants, Children, and Adolescents: IV, IM, SubQ, IO (off-label route), endotracheal (off-label route): Note: IV administration is preferred; IO and endotracheal routes are alternative routes recommended by the PALS guidelines (AHA [Kleinman 2010]): The use of naloxone is not recommended as part of initial resuscitative efforts in the delivery room for neonates with respiratory depression; support ventilation to improve oxygenation and heart rate (AHA [Kattwinkel 2010]):
<5 years or ≤20 kg (off-label dose): 0.1 mg/kg/dose (maximum dose: 2 mg); repeat every 2 to 3 minutes if needed (AHA [Kleinman 2010]; Hegenbarth 2008)
≥5 years or >20 kg: 2 mg; if no response, repeat every 2 to 3 minutes. If no response is observed after 10 mg total, consider other causes of respiratory depression (AHA [Kleinman 2010]; Hegenbarth 2008).
Manufacturer 's labeling: IV (preferred), IM, SubQ: Initial: 0.01 mg/kg/dose; if no response, a subsequent dose of 0.1 mg/kg may be given; Note: if using IM or SubQ route, dose should be given in divided doses.
Continuous infusion (off-label dosing): IV: If continuous infusion is required, calculate dosage/hour based on effective intermittent dose used and duration of adequate response seen (Tenenbein 1984) or use two-thirds (2/3) of the initial effective naloxone bolus on an hourly basis; titrate dose (typically 0.04 to 0.16 mg/kg/hour for 2 to 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 (Goldfrank 1986).Note: The infusion should be discontinued by reducing the infusion in decrements of 25%; closely monitor the patient (eg, pulse oximetry) after each adjustment and after discontinuation of the infusion for recurrence of opioid-induced respiratory depression (Perry 1996).
IM, SubQ: Evzio: 0.4 mg (contents of 1 auto-injector) as a single dose; may repeat every 2 to 3 minutes until emergency medical assistance becomes available.
Infants, Children, and Adolescents: Intranasal: Narcan Nasal Spray: 4 mg (contents of 1 nasal spray) as a single dose; may repeat every 2 to 3 minutes in alternating nostrils until medical assistance becomes available. Note: Onset of action is slightly delayed compared to IM or IV routes (Kelly 2005; Robertson 2009). In neonates with known or suspected exposure to maternal opioid use, consider using another form of naloxone to allow dosing according to weight and titration to effect.
Reversal of respiratory depression with therapeutic opioid dosing: Infants, Children, and Adolescents: IV: 0.001 to 0.015 mg/kg/dose; dose may be repeated as needed (AHA [Kleinman 2010]; Hegenbarth 2008)
Postoperative reversal: IV: 0.005 to 0.01 mg/kg (Fischer 1974); may repeat every 2 to 3 minutes as needed based on response (adequate ventilation without significant pain)
There are no dosage adjustments provided in the manufacturer 's labeling.
There are no dosage adjustments provided in the manufacturer 's labeling.
IV push: Dilute naloxone 0.4 mg (1 mL ampul) with 9 mL of NS for a total volume of 10 mL to achieve a concentration of 0.04 mg/mL (APS 2008)
IV infusion: Dilute naloxone 2 mg in 500 mL of NS or D5W to make a final concentration of 4 mcg/mL
Inhalation via nebulization (off-label route): Dilute 2 mg of naloxone with 3 mL of normal saline (Mycyk 2003; Weber 2012)
IV push: Administer over 30 seconds as undiluted preparation or administer as diluted preparation slow IV 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 (APS 2008)
IV continuous infusion: Dilute to 4 mcg/mL in D5W or normal saline
IM, SubQ: May administer IM or SubQ if unable to obtain IV access
Auto-injector: Evzio: For IM or SubQ use only. Intended for buddy administration; the person administering the medication should follow the printed instructions on the device or the electronic voice instructions coming from the speaker on the device. If the voice instruction system does not operate properly, the device will still deliver the intended dose of naloxone when properly administered. Administer IM or SubQ into the anterolateral aspect of the thigh; may be injected through clothing. When being administered to infants <1 year of age, the thigh muscle should be pinched during administration. Following proper administration, a red indicator appears in the viewing window; the needle is not visible before, during, or after the injection. Patients who received naloxone in the out-of-hospital setting should seek immediate emergency medical assistance after the first dose due to the likelihood that respiratory and/or central nervous system depression will return. Repeat doses may be required until emergency medical assistance becomes available; a new device must be used as each device contains a single dose of naloxone.
Endotracheal (off-label 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 to 2 mL with normal saline; flush with 5 mL of saline and then administer 5 ventilations (AHA [Neumar 2010]).
Inhalation via nebulization (off-label route): Dilute 2 mg of naloxone with 3 mL of normal saline and administer via nebulizer face mask (Mycyk 2003; Weber 2012).
Intranasal:
Narcan Nasal Spray: Administer initial dose as soon as possible. Do not prime or test the device prior to administration. Administer in alternating nostrils with each dose. Place the patient in the supine position and provide support to the back of the neck to allow the head to tilt back. Following administration, turn the patient on their side. Each container contains a single intranasal spray, do not reuse; if repeat administration is necessary a new container must be used.
Alternate intranasal administration instructions using generic injectable solution: Administer total dose equally divided into each nostril using a mucosal atomization device (MAD) (AHA [Vanden Hoek 2010]; Kelly 2005; Robertson 2009). If a MAD is not available, the solution may be sprayed into the nares without a MAD; however, a significant amount of drug may be lost likely due to swallowing and subsequent first-pass metabolism (Dowling 2008; Robinson 2014).
Solution, injection: Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F). Protect from light. Use IV infusion in NS or D5W within 24 hours of preparation.
Solution, auto-injector (Evzio): Store at 15 ‚ °C to 25 ‚ °C (59 ‚ °F to 77 ‚ °F); excursions are permitted between 4 ‚ °C and 40 ‚ °C (39 ‚ °F and 104 ‚ °F). Store in the outer case provided.
Solution, nasal spray (Narcan Nasal Spray): Store at 15 ‚ °C to 25 ‚ °C (59 ‚ °F to 77 ‚ °F); excursions are permitted between 4 ‚ °C and 40 ‚ °C (39 ‚ °F and 104 ‚ °F). Do not freeze. Protect from light.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Liquid, Nasal:
Narcan: 4 mg/0.1 mL (1 ea) [contains benzalkonium chloride, edetate disodium]
Solution, Injection, as hydrochloride:
Generic: 0.4 mg/mL (1 mL, 10 mL)
Solution, Injection, as hydrochloride [preservative free]:
Generic: 1 mg/mL (2 mL)
Solution Auto-injector, Injection, as hydrochloride:
Evzio: 0.4 mg/0.4 mL (0.4 mL)
Stable in D5W, NS; do not mix with alkaline solutions or solutions containing bisulfite or metabisulfite
Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, pantoprazole.
Compatibility in syringe: Incompatible with pantoprazole.
Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Avoid combination
Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Avoid combination
Respiratory rate, heart rate, blood pressure, temperature, level of consciousness, ABGs or pulse oximetry
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 opioid analgesia and sedation.
Cardiovascular: Cardiac arrest, flushing, hypertension, hypotension, tachycardia, ventricular fibrillation, ventricular tachycardia
Central nervous system: Agitation, brain disease, coma, convulsions, hallucination, hyperreflexia (neonates), irritability, nervousness, paresthesia, restlessness, seizure (neonates), shivering, tonic-clonic seizures, withdrawal syndrome, yawning
Dermatologic: Diaphoresis, piloerection
Endocrine & metabolic: Hot flash
Gastrointestinal: Abdominal cramps, diarrhea, nausea, vomiting
Local: Injection site reaction
Neuromuscular & skeletal: Myalgia, piloerection, tremor, weakness
Respiratory: Dyspnea, hypoxia, pulmonary edema, respiratory depression, rhinorrhea, sneezing
Miscellaneous: Crying (excessive [neonates]), fever
Concerns related to adverse effects:
- Acute opioid withdrawal: Administration of naloxone causes the release of catecholamines, which may precipitate acute withdrawal or unmask pain in those who regularly take opioids. Symptoms of acute withdrawal in opioid-dependent patients may include pain, tachycardia, hypertension, fever, sweating, abdominal cramps, diarrhea, nausea, vomiting, agitation, and irritability. In neonates born to mothers with opioid dependence, opioid withdrawal may be life-threatening and symptoms may include shrill cry, failure to feed, seizures, and hyperactive reflexes. In settings other than acute opioid overdose (eg, postoperative patients), carefully titrate the dose to reverse hypoventilation; do not fully awaken patient or reverse analgesic effect.
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 opioid antagonists.
- Seizures: Use caution in patients with history of seizures; avoid use in the treatment of meperidine-induced seizures.
Dosage form specific issues:
- Auto-injector: Evzio: When administered to infants <1 year of age, monitor the injection site for residual needle parts and signs of infection.
Other warnings/precautions:
- Addiction involving opioid use: To prevent overdose deaths, there are initiatives to dispense naloxone for self- or buddy-administration to patients at risk of opioid overdose (eg, recipients of high-dose opioids, suspected or confirmed history of illicit opioid use) and individuals likely to be present in an overdose situation (eg, family members of illicit drug users) (Albert 2011; Bennett 2011). Clinical practice guidelines recommend patients being treated for opioid use disorder should be given prescriptions for naloxone. Patients and family members/significant others should be trained in the use of naloxone in overdose (Kampman [ASAM 2015]). Evzio is indicated for emergency treatment. Needleless administration via nebulization and the intranasal route using the injectable solution (with a mucosal atomization device) by first responders and bystanders has also been described (Doe-Simkins 2009; Weber 2012). Needleless administration provides an alternative route of administration in patients with venous scarring due to illicit drug use (eg, heroin). There is a low incidence of death following naloxone reversal of opioid toxicity in patients who refuse transport to a healthcare facility (Wampler 2011). Nevertheless, patients who received naloxone in the out-of-hospital setting should seek immediate emergency medical assistance after the first dose due to the likelihood that respiratory and/or central nervous system depression will return.
- Opioid overdose: Recurrence of respiratory and/or CNS depression is possible if the opioid involved is long-acting; continuously observe patients until there is no further risk of recurrent respiratory or CNS depression.
- Partial opioid agonist and mixed opioid agonist/antagonist overdose: Reversal of partial opioid agonists or mixed opioid agonist/antagonists (eg, buprenorphine, pentazocine) may be incomplete and larger or repeat doses of naloxone may be required.
- Postoperative reversal: Appropriate use: Excessive dosages should be avoided after use of opioids in surgery. Abrupt postoperative reversal may result in nausea, vomiting, sweating, tachycardia, hypertension, seizures, and other cardiovascular events (including pulmonary edema and arrhythmias).
B/C (product-specific)
Adverse events were not observed in animal reproduction studies. Naloxone crosses the placenta and may precipitate opioid withdrawal in the fetus. Naloxone is not recommended for use in pregnant women with opioid use disorder except in situations of life threatening overdose (Kampman [ASAM 2015]). Use to diagnose opioid dependence during pregnancy is contraindicated (ACOG 2012). In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003). Use caution in pregnant women with mild-to-moderate hypertension during labor; severe hypertension may occur.
Pure opioid antagonist that competes and displaces opioids at opioid receptor sites
Intranasal, IM, SubQ: Pediatric patients: May be erratic or delayed
Primarily hepatic via glucuronidation
Urine (as metabolites)
Endotracheal, IM, SubQ: 2 to 5 minutes; Inhalation via nebulization: ~5 minutes (Mycyk 2003); Intranasal: ~8 to 13 minutes (Kelley 2005; Robertson 2009); IV: ~2 minutes
IM, SubQ (Evzio): 15 minutes; Intranasal (Narcan Nasal Spray): 19.8 to 30 minutes
Depending on route of administration, ~30 to 120 minutes; IV has a shorter duration of action than IM administration; since naloxones action is shorter than that of most opioids, repeated doses are usually needed
Neonates: Mean 3.1 ‚ ± 0.5 hours; Adults: IM, IV, or SubQ: 0.5 to 1.5 hours; Intranasal: ~2 hours
Relatively weak (to albumin [major] and other plasma constituents)
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, vomiting, muscle pain, nasal dryness, stuffy nose, nasal edema. Have patient report immediately to prescriber severe dizziness, passing out, severe headache, seizures, shortness of breath, angina, tachycardia, or arrhythmia (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.