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Naloxone: Drug information

Naloxone: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Naloxone: Patient drug information" and "Naloxone: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Evzio [DSC];
  • Kloxxado;
  • LifEMS Naloxone [DSC];
  • Narcan;
  • Narcan [OTC];
  • Rextovy;
  • RiVive [OTC];
  • Zimhi
Brand Names: Canada
  • Narcan;
  • S.O.S. Naloxone Hydrochloride;
  • TEVA Naloxone
Pharmacologic Category
  • Antidote;
  • Opioid Antagonist
Dosing: Adult

Note: Available routes of administration include IV (preferred), IM, SUBQ, and intranasal; other available routes (off-label) include inhalation via nebulization (adults only), intraosseous, and oral (adults only). Endotracheal administration is the least desirable and is supported by only anecdotal evidence (Ref).

Clonidine toxicity

Clonidine toxicity (off-label use): Limited data available: Note: Consultation with a clinical toxicologist or poison control center is highly recommended.

IV: Initial: 0.4 to 2 mg; may repeat doses as needed (Ref). Larger doses (up to 14 mg) have been reported (Ref).

Opioid reversal

Opioid reversal, life-threatening overdose:

Note: Patient selection: For patients without normal breathing but with a pulse (as assessed by a health care provider), the American Heart Association (AHA) recommends naloxone administration. For patients without normal breathing and without a pulse (as assessed by a health care provider), the AHA recommends initiation of CPR, the use of an automated external defibrillator, and consideration of naloxone administration (Ref). Bystander administration: Naloxone administration by bystanders (eg, law enforcement, family members, etc) has been shown to result in successful reversal and is encouraged for patients experiencing signs of opioid toxicity in the community (Ref); bystanders should seek immediate emergency medical assistance on behalf of the patient after administration of the first dose. Larger doses: Larger doses of naloxone may or may not be required to reverse the effects of illicitly manufactured fentanyl compounds and other high potency opioids; dosing decisions should be made based on patient-specific response (Ref).

IV (preferred):

Intermittent dosing:

Initial: IV: 0.04 to 2 mg; may repeat with escalating doses every 2 to 3 minutes, as needed (Ref); the need for ≥1 dose of naloxone is common (Ref). The initial dose of naloxone is empirical and based on patient- and overdose-specific factors (Ref). An initial dose at the higher end of the dosing range may be appropriate for patients with significant toxicity (eg, respiratory or cardiorespiratory arrest) (Ref); whereas, an initial dose on the lower end of the dosing range may be appropriate in patients with opioid dependence to avoid acute withdrawal or if there are concerns regarding concurrent stimulant overdose (Ref).

After reversal, may need to readminister dose(s) at a longer interval (ie, 20 to 60 minutes) depending on the type/duration of the opioid. If no response is observed after a cumulative dose of 10 mg, consider other causes of respiratory depression, including other drugs (Ref); however, relatively large doses of naloxone may be required to reverse the effects of illicitly manufactured fentanyl compounds and other high potency opioids (Ref).

Continuous infusion (off-label dosing): Note: Consider use with exposures to long-acting opioids (eg, methadone), extended-release products, or delayed absorption (eg, symptomatic patients who have concealed opioids internally via ingestion or vaginal/rectal insertion [“body packing” or “body stuffing”]) after initial naloxone response (Ref).

IV: Administer 2/3 of the initial effective naloxone bolus per hour (usual dose: 0.25 to 6.25 mg/hour). For example, if the initial effective IV naloxone bolus is 1.5 mg, then the initial continuous IV infusion rate is 1 mg/hour. Consider administering 1/2 of the initial effective bolus dose 15 minutes after initiation of the continuous infusion; adjust infusion rate, as needed, to assure adequate ventilation and prevent withdrawal symptoms (Ref). Alternatively, may calculate dosage/hour based on effective intermittent dose used and duration of adequate response seen (Ref).

IM, SUBQ: Note: May consider when IV route is not available.

Naloxone (0.4 mg/mL): IM, SUBQ: Initial: 0.04 to 2 mg; may repeat with escalating doses every 2 to 3 minutes, as needed (Ref); the need for ≥1 dose of naloxone is common (Ref). Seek immediate medical assistance after administration of the first dose. An initial dose at the higher end of the dosing range may be appropriate for patients with significant toxicity (eg, respiratory or cardiorespiratory arrest) (Ref); whereas, an initial dose on the lower end of the dosing range may be appropriate in patients with opioid dependence to avoid acute withdrawal or if there are concerns regarding concurrent stimulant overdose (Ref).

After reversal, may need to readminister dose(s) at a longer interval (ie, 20 to 60 minutes) depending on the type/duration of the opioid. If no response is observed after a cumulative dose of 10 mg total, consider other causes of respiratory depression, including other drugs (Ref); however, relatively large doses of naloxone may be required to reverse the effects of illicitly manufactured fentanyl compounds and other high potency opioids (Ref).

Naloxone (10 mg/0.4 mL auto-injector): Note: For self- or buddy-administration by military personnel or chemical incident responders; can be administered through clothing or MOPP4 personal protective equipment.

Treatment: IM, SUBQ: 10 mg (contents of 1 auto-injector) as a single dose; may repeat as needed until emergency medical assistance becomes available. If the patient does not show some improvement after administering the dose, consider other causes of respiratory depression (eg, drugs of chemical terrorism/warfare agents). Seek immediate emergency medical assistance after administration of first dose.

Prevention: IM, SUBQ: 10 mg (contents of 1 auto-injector) as a single dose administered immediately prior to entering an area believed to be contaminated with high-potency opioids; may repeat if exposure to high-potency opioids is prolonged.

Naloxone (5 mg/0.5 mL prefilled syringe [Zimhi]): IM, SUBQ: 5 mg (contents of 1 prefilled syringe) as a single dose; may repeat every 2 to 3 minutes until emergency medical assistance becomes available. Seek immediate emergency medical assistance after administration of the first dose.

Inhalation via nebulization (off-label route): Note: May consider when IV route is not available. This administration method is not included in the AHA recommendations for initial management of an opioid-associated life-threatening emergency (Ref).

Nebulization: 2 mg; may repeat, as needed. Transition to IV or IM administration when possible (Ref).

Intranasal: Note: May consider when IV route is not available. Onset of action is slightly delayed and bioavailability reduced compared to IM or IV routes (Ref):

3, 4, or 8 mg (contents of 1 nasal spray) as a single dose in one nostril; may repeat with a new nasal spray every 2 to 3 minutes in alternating nostrils if patient does not respond or responds initially followed by recurrence of respiratory depression or 2 mg (1 mg per nostril; using injectable solution delivered with a mucosal atomization device); may repeat in 3 to 5 minutes if respiratory depression persists. Seek immediate medical assistance after administration of the first dose (Ref).

Endotracheal (off-label route): Note: May consider only when other routes are not available (Ref).

0.8 to 5 mg (ie, 2 to 2.5 times the initial recommended IV dose) (Ref).

Opioid reversal, acute therapeutic opioid use (eg, partial reversal in patients with respiratory depression): Note: Consider in patients receiving acute opioid therapy (eg, postoperative) who experience respiratory depression secondary to opioid therapy.

Intermittent dosing: IV: Initial: 0.05 to 0.2 mg every 2 to 3 minutes until desired response (eg, adequate ventilation and alertness without significant pain). Repeat doses may be needed within 1- to 2- hour intervals depending on type, dose, and timing of the last dose of opioid administered (Ref).

Continuous infusion (off-label dosing): Note: Consider use with exposures to long-acting opioids (eg, methadone), extended-release products, or delayed absorption (eg, symptomatic patients who have concealed opioids internally via ingestion or vaginal/rectal insertion [“body packing” or “body stuffing”]) after initial naloxone response (Ref).

IV: Administer 2/3 of the initial effective naloxone bolus per hour. For example, if the initial effective IV naloxone bolus is 0.15 mg, then the initial continuous IV infusion rate is 0.1 mg/hour. Consider administering 1/2 of the initial effective bolus dose 15 minutes after initiation of the continuous infusion; adjust infusion rate, as needed, to assure adequate ventilation and prevent withdrawal symptoms (Ref). Alternatively, may calculate dosage/hour based on effective intermittent dose used and duration of adequate response seen (Ref).

Opioid reversal, chronic therapeutic opioid use (eg, cancer pain) (off-label dosing): Note: Consider in patients receiving chronic opioid therapy (eg, treatment of cancer pain) who experience respiratory depression secondary to opioid therapy. Dilute 1 mL of a naloxone 0.4 mg/mL formulation with 9 mL of NS or SWFI for a total volume of 10 mL to achieve a 0.04 mg/mL concentration.

IV: 0.02 to 0.08 mg slow bolus; administer every 30 to 120 seconds until improvement in symptoms; if no response is observed after a cumulative naloxone dose of 1 mg, consider other causes of respiratory depression. If respiratory depression is due to long-acting opioids, may consider administering naloxone as a continuous infusion starting at 2/3 of the initial effective naloxone bolus per hour (or 0.2 mg per hour) (Ref).

Opioid-induced constipation

Opioid-induced constipation (alternative agent) (off-label use): Note: May be used in patients with laxative-refractory opioid-induced constipation; current guidelines recommend other peripherally acting mu-opioid receptor antagonists (eg, naldemedine, naloxegol) in this population (Ref). Optimal dose, frequency, and duration of therapy have not been established; efficacy data are limited (Ref).

Oral (administration of injectable formulation): 1 to 12 mg/day in 1 to 4 divided doses (Ref).

Opioid-induced pruritus

Opioid-induced pruritus (off-label use): Continuous IV infusion: 0.25 mcg/kg/hour (Ref). Doses up to ~3 mcg/kg/hour have been employed (Ref). However, doses >2 mcg/kg/hour are more likely to lead to reversal of analgesia and are not recommended (Ref). Note: Monitor pain control; verify that the naloxone is not reversing analgesia.

Opioid use disorder, naloxone challenge

Opioid use disorder, naloxone challenge (off-label use):

IM: 0.4 to 0.8 mg (Ref).

IV: 0.2 mg as a single dose. After 30 seconds, if withdrawal symptoms are present, stop the challenge and treat symptomatically; may repeat challenge in 24 hours. If no withdrawal symptoms and vital signs are stable, inject 0.6 mg and observe for 20 minutes. After 20 minutes, if withdrawal symptoms are present, stop the challenge and treat symptomatically; may repeat challenge in 24 hours. If no withdrawal symptoms are present may initiate naltrexone (Ref).

SUBQ: 0.8 mg as a single dose. After 20 minutes, if withdrawal symptoms are present, stop the challenge and treat symptomatically; may repeat challenge in 24 hours. If no withdrawal symptoms and vital signs are stable, may initiate naltrexone (Ref).

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

IV, IM, SUBQ, Inhalation, Intranasal, Oral, Endotracheal:

Altered kidney function:

eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary (metabolized in liver to inactive metabolites (Ref)) (Ref).

eGFR <30 mL/minute/1.73 m2: No dosage adjustment necessary (Ref). Note: Extended half-life and prolonged opioid antagonism was reported in a patient with advanced kidney impairment receiving naloxone by continuous infusion (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable (large Vd): No supplemental dose or dosage adjustment necessary (Ref). Note: Extended half-life and prolonged opioid antagonism was reported in a patient with advanced kidney impairment receiving naloxone by continuous infusion (Ref).

Peritoneal dialysis: Unlikely to be significantly dialyzable (large Vd): No dosage adjustment necessary (Ref). Note: Extended half-life and prolonged opioid antagonism was reported in a patient with advanced kidney impairment receiving naloxone by continuous infusion (Ref).

CRRT: No dosage adjustment likely to be necessary (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment likely to be necessary (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Older Adult

Refer to adult dosing. The naloxone dose is the same in patients >50 years of age as younger patients (Ref).

Dosing: Pediatric

(For additional information see "Naloxone: Pediatric drug information")

Note: Evzio auto-injector (all strengths) has been discontinued in the United States for >1 year.

Opioid intoxication/overdose

Opioid intoxication/overdose (full reversal):

IV (preferred), Intraosseous: Note: May be administered IM, SUBQ, or endotracheally, but onset of action may be delayed, especially if patient has poor perfusion; the endotracheal route is preferred if IV/Intraosseous route not available; doses may need to be repeated (Ref).

Infants and Children <5 years or ≤20 kg: IV, Intraosseous: 0.1 mg/kg/dose; repeat every 2 to 3 minutes if needed; monitor closely; may need to repeat doses (eg, every 20 to 60 minutes) if duration of action of opioid is longer than naloxone.

Children ≥5 years or >20 kg and Adolescents: IV, Intraosseous: 2 mg/dose; if no response, repeat every 2 to 3 minutes; monitor closely; may need to repeat doses (eg, every 20 to 60 minutes) if duration of action of opioid is longer than naloxone.

Endotracheal: Infants, Children, and Adolescents: Optimal endotracheal dose unknown; current expert recommendations are 2 to 3 times the IV dose (Ref).

IM, SUBQ: Note: IM or SUBQ absorption may be delayed or erratic.

Prefilled 5 mg syringe (Zimhi): Infants, Children, and Adolescents: IM, SUBQ: 5 mg (contents of 1 prefilled syringe) as a single dose; may repeat every 2 to 3 minutes if needed until emergency medical assistance becomes available.

Solutions for injection (eg, ampules, vials, prefilled 2 mg syringe): Infants, Children, and Adolescents: IM, SUBQ: 0.1 mg/kg/dose; maximum dose: 2 mg/dose; repeat every 2 to 3 minutes if needed; monitor closely; may need to repeat doses (eg, every 20 to 60 minutes) if duration of action of opioid is longer than naloxone (Ref).

Auto-injector (10 mg dose): Note: For self or buddy administration by military personnel or chemical incident responders.

Treatment: Children ≥12 years and Adolescents: IM, SUBQ: 10 mg (contents of 1 auto-injector) as a single dose; may repeat as needed until emergency medical assistance becomes available. If the patient does not show some improvement after administering the dose, consider other causes of respiratory depression. Seek immediate emergency medical assistance after administration of first dose.

Prevention: Children ≥12 years and Adolescents: IM, SUBQ: 10 mg (contents of 1 auto-injector) as a single dose administered immediately prior to entering an area believed to be contaminated with high potency opioids; may repeat if exposure to high potency opioids is prolonged.

Intranasal: Note: Onset of action is slightly delayed compared to IM or IV routes (Ref).

Intranasal formulations (eg, Kloxxado, Narcan Nasal Spray): Infants, Children, and Adolescents: Intranasal: 4 mg or 8 mg (contents of 1 nasal spray) as a single dose; may repeat every 2 to 3 minutes in alternating nostrils if needed until medical assistance becomes available (Ref).

Solution for injection (1 mg/mL injection) for intranasal administration: Adolescents ≥13 years: Intranasal: 2 mg (1 mg per nostril) (Ref). Note: Naloxone 0.4 mg/mL parenteral formulation has been evaluated and may be used for opioid overdose; however, due to the volume needed to administer the dose it is not ideal for nasal administration; should be used if intranasal administration is needed and a more concentrated naloxone is not readily available (Ref).

Continuous IV infusion: Limited data available: Infants, Children, and Adolescents: Continuous IV infusion: 24 to 40 mcg/kg/hour has been reported (Ref). Doses as low as 2.5 mcg/kg/hour have been reported in adults and a dose of 160 mcg/kg/hour was reported in one neonate (Ref). If continuous infusion is required, calculate the initial dosage/hour based on the effective intermittent dose used and duration of adequate response seen (Ref) or use two-thirds (2/3) of the initial effective naloxone bolus given as the hourly infusion (Ref); titrate dose; Note: The infusion should be discontinued by reducing the infusion rate in decrements of 25%; closely monitor the patient (eg, pulse oximetry, respiratory rate) after each adjustment and after discontinuation of the infusion for recurrence of opioid-induced respiratory depression (Ref).

Reversal of respiratory depression from therapeutic opioid dosing

Reversal of respiratory depression from therapeutic opioid dosing:

Infants, Children, and Adolescents: IV, Intraosseous, IM, SUBQ: 0.001 to 0.005 mg/kg/dose; titrate to effect (Ref); AAP recommends a wider dosage range of 0.001 to 0.02 mg/kg/dose and may increase if necessary up to 0.1 mg/kg/dose (full reversal dose); maximum dose: 2 mg/dose; may repeat dose every 2 minutes as needed based on response; monitor patient closely; symptoms may recur if duration of action of opioid is longer than naloxone; repeat doses (eg, every 20 to 60 minutes) may be required (Ref).

Opioid-induced pruritus

Opioid-induced pruritus: Limited data available:

Prevention: Children ≥6 years and Adolescents ≤17 years: Continuous IV infusion: 0.25 mcg/kg/hour was used in a double-blind, prospective, randomized, placebo-controlled study (n=20) which showed lower incidence and severity of opioid-induced side effects (ie, pruritus, nausea) without a loss of pain control (Ref).

Treatment: Children ≥3 years and Adolescents: Continuous IV infusion: Initial: 2 mcg/kg/hour; if pruritus continues, may titrate by 0.5 mcg/kg/hour every few hours; dosing based on a retrospective study (n=30, age range: 3 to 20 years) with a reported mean (±SD) dose of 2.3 ± 0.68 mcg/kg/hour; monitor closely; doses ≥3 mcg/kg/hour may increase risk for loss of pain control and patients may require an increase in opioid dose (Ref).

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified.

Frequency not defined (any route of administration):

Cardiovascular: Flushing, hypertension, hypotension, presyncope, tachycardia, ventricular fibrillation, ventricular tachycardia

Dermatologic: Diaphoresis, piloerection, xeroderma

Endocrine & metabolic: Hot flash

Gastrointestinal: Abdominal cramps, abdominal pain, constipation, diarrhea, nausea, toothache, vomiting

Hepatic: Increased serum bilirubin

Local: Erythema at injection site, injection-site reaction

Nervous system: Agitation, asthenia, body pain, coma, confusion, disorientation, dizziness, encephalopathy, excessive crying (neonates), hallucination, headache, hyperreflexia (neonates), irritability, nervousness, paresthesia, restlessness, seizure (neonates), shivering, tonic-clonic seizure, tremor, withdrawal syndrome, yawning

Neuromuscular & skeletal: Muscle spasm, musculoskeletal pain

Respiratory: Dry nose, dyspnea, hypoxia, nasal congestion, nasal discomfort (pain), nasal mucosa swelling, respiratory depression (parenteral), rhinitis, rhinorrhea, sneezing

Miscellaneous: Fever

Postmarketing (any route of administration):

Cardiovascular: Bradycardia

Nervous system: Aggressive behavior, anxiety, depression, drowsiness, loss of consciousness, malaise, outbursts of anger, pain, unresponsive to stimuli

Neuromuscular & skeletal: Back pain

Ophthalmic: Miosis

Respiratory: Pulmonary edema (Al-Azzawi 2021)

Contraindications

Hypersensitivity to naloxone or any component of the formulation

Warnings/Precautions

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 excessive crying, 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. Lower doses (eg, 2 mg nasal dose [off label]) are less likely to precipitate severe opioid withdrawal compared to higher doses (eg, 4 or 10 mg); however, the 2 mg dose may not provide an adequate and timely reversal in patients who have been exposed to an overdose of a potent or very high dose of opioids (Brenner 2021; Purssell 2021).

• Combativeness: Some patients may be agitated or combative when resuscitated with naloxone (Brenner 2021); there is greater risk of combativeness in patients using fentanyl (Gooley 2022).

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 or prefilled syringe: When administered to infants <1 year of age, monitor the injection site for residual needle parts and signs of infection.

Other warnings/precautions:

• Opioid overdose symptom recurrence: 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. Recurrence may be less likely following a heroin overdose as compared to nonheroin opioid overdoses; shorter observation times following naloxone administration after known heroin use may be warranted (Willman 2017). Time to recurrence may not be related to the naloxone initial dose (Wong 2019).

• 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).

• Substance use disorder 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 (ASAM 2020). Zimhi and intranasal products are 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 IV injection of illicit drugs. There is a low incidence of death following naloxone reversal of opioid toxicity in patients who refuse transport to a health care 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.

Product Availability

Rextovy nasal spray: FDA approved March 2023; anticipated availability in the first quarter of 2024. Information pertaining to this product within the monograph is pending revision. Consult the prescribing information for additional information.

Rezenopy nasal spray: FDA approved April 2024; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Consult the prescribing information for additional information.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Liquid, Nasal, as hydrochloride:

Kloxxado: 8 mg/0.1 mL (2 ea) [contains alcohol, usp, edetate (edta) disodium dihydrate, propylene glycol]

Narcan: 4 mg/0.1 mL (2 ea) [contains benzalkonium chloride, edetate (edta) disodium]

Rextovy: 4 mg/0.25 mL (2 ea)

RiVive: 3 mg/0.1 mL (2 ea)

Generic: 4 mg/0.1 mL (1 ea, 2 ea)

Prefilled Syringe Kit, Injection, as hydrochloride:

LifEMS Naloxone: 2 mg/2 mL (1 ea [DSC])

Solution, Injection, as hydrochloride:

Generic: 0.4 mg/mL (1 mL); 4 mg/10 mL (10 mL)

Solution, Injection, as hydrochloride [preservative free]:

Generic: 0.4 mg/mL (1 mL)

Solution Auto-injector, Injection, as hydrochloride:

Evzio: 2 mg/0.4 mL (0.4 mL [DSC])

Solution Auto-injector, Injection, as hydrochloride [preservative free]:

Generic: 2 mg/0.4 mL (0.4 mL [DSC])

Solution Cartridge, Injection, as hydrochloride:

Generic: 0.4 mg/mL (1 mL)

Solution Prefilled Syringe, Injection, as hydrochloride [preservative free]:

Zimhi: 5 mg/0.5 mL (0.5 mL) [latex free]

Generic: 2 mg/2 mL (2 mL)

Generic Equivalent Available: US

Yes

Pricing: US

Liquid (Kloxxado Nasal)

8MG/0.1ML (per each): $75.00

Liquid (Naloxone HCl Nasal)

4MG/0.1ML (per each): $48.00 - $71.25

Liquid (Narcan Nasal)

4MG/0.1ML (per each): $27.00

Liquid (Rextovy Nasal)

4 mg/0.25 mL (per each): $27.00

Liquid (RiVive Nasal)

3MG/0.1ML (per each): $18.00

Solution (Naloxone HCl Injection)

0.4 mg/mL (per mL): $5.27 - $23.72

4 mg/10 mL (per mL): $8.40 - $14.95

Solution Cartridge (Naloxone HCl Injection)

0.4 mg/mL (per mL): $18.53

Solution Prefilled Syringe (Naloxone HCl Injection)

2 mg/2 mL (per mL): $18.81 - $19.80

Solution Prefilled Syringe (Zimhi Injection)

5 mg/0.5 mL (per 0.5 mL): $75.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Liquid, Nasal, as hydrochloride:

Narcan: 4 mg/0.1 mL (0.1 mL) [contains benzalkonium chloride, edetate (edta) disodium]

Generic: 4 mg/0.1 mL (0.1 mL)

Solution, Injection, as hydrochloride:

Generic: 0.4 mg/mL (1 mL, 10 mL); 1 mg/mL (2 mL)

Administration: Adult

IV push: Administer over 30 seconds as undiluted preparation or administer lower doses (eg, 0.02 to 0.04 mg) as a slow IV push using a diluted preparation (concentration 0.04 mg/mL).

IM, SUBQ: May administer IM or SUBQ if unable to obtain IV access.

Auto-injector: For IM or SUBQ use only. Intended for self- (10 mg/0.4 mL auto-injector only) or 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 applicable). In devices equipped with a voice instruction system, if the 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 or MOPP4 personal protective equipment. Keep the 10 mg/0.4 mL auto-injector firmly in place for 5 seconds after injection (and after click and hiss sound). 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 injection 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 CNS depression will return. Repeat doses may be required until emergency medical assistance becomes available or if prolonged exposure to high-potency opioids is expected (prophylaxis using the 10 mg/0.4 mL auto-injector only); a new device must be used as each device contains a single dose of naloxone.

Prefilled syringe (Zimhi): For IM or SUBQ use only. Periodically inspect solution through the viewing window during storage; replace with new device if solution is discolored yellow to brown, cloudy, or contains particles. Intended for buddy administration (by individuals ≥12 years of age); the person administering the medication should follow the printed instructions for use and the printed instructions on the device label. Place patient in supine position; administer IM or SUBQ into the anterolateral aspect of the thigh with the needle facing downwards; may be injected through clothing. When being administered to infants <1 year of age, the thigh muscle should be pinched during administration. Ensure the needle is embedded completely before injecting. After injection, slide the safety guard over the needle using one hand and return to blue case. Place patient in the lateral recumbent position (recovery position). 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 CNS depression will return. Repeat doses may be required until emergency medical assistance becomes available. Used syringes should be given to health care provider for inspection and proper disposal.

Endotracheal (off-label route): Administer diluted preparation directly into endotracheal tube (Ref).

Inhalation via nebulization (off-label route): Administer diluted preparation (0.67 mg/mL) via nebulizer face mask (Ref).

Intranasal:

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. Patients who received naloxone in the out-of-hospital setting should receive immediate emergency medical assistance after the first dose due to the likelihood that respiratory and/or CNS depression will return. 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:

1 mg/mL formulation (preferred): Administer total dose equally divided into each nostril using a mucosal atomization device (MAD) (Ref).

0.4 mg/ml formulation: Administer total dose in repeated increments of 0.1 mL per nostril over ~2 minutes using a MAD (Ref). Note: Due to the volume needed to administer the dose, 0.4 mg/mL is not ideal for nasal administration but may be used if more concentrated naloxone is not readily available (Ref).

Note: 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 (Ref).

Oral (off-label route): For the management of opioid-induced constipation (off-label use), undiluted solution for injection may be administered orally (Ref).

Administration: Pediatric

Endotracheal: Dilute with NS prior to administration; follow with a flush ≥5 mL of NS and 5 consecutive positive-pressure ventilations (Ref).

Intranasal:

Intranasal formulation (eg, Kloxxado, Narcan Nasal Spray): Administer initial dose as soon as possible. Do not prime or test the device prior to administration. Administer additional doses (when required) in alternating nostrils. 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 (recovery position). Each container contains a single intranasal spray; do not reuse; if repeat administration is necessary, a new container must be used.

Solution for injection for intranasal use: Note: If a mucosal atomizer device (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 (Ref).

1 mg/mL formulation (preferred): Administer total dose equally divided into each nostril using a MAD (Ref).

0.4 mg/mL formulation: Administer total dose in repeated increments of 0.1 mL per nostril over ~2 minutes using a MAD (Ref). Note: Due to the volume needed to administer the dose, 0.4 mg/mL is not ideal for nasal administration but may be used if more concentrated naloxone is not readily available (Ref).

Parenteral:

IV push: Administer over 30 seconds as undiluted preparation. May also be diluted and administer slow IV push (Ref).

Continuous IV infusion: Dilute in NS or D5W prior to administering as continuous IV infusion.

IM, Intraosseous, SubQ: May administer IM, Intraosseous, or SubQ if unable to obtain IV access. Note: IM or SubQ administration in pediatric patients, hypotensive patients, or patients with peripheral vasoconstriction or hypoperfusion may result in erratic or delayed absorption.

Dosage form specific: Periodically inspect solution through the viewing window during storage; replace with new device if solution is discolored yellow to brown, cloudy, or contains particles.

Prefilled 5 mg syringe (Zimhi): For IM or SUBQ use only. Intended for buddy administration (by individuals ≥12 years of age). The person administering the medication should follow the printed instructions for use and the printed instructions on the device label. Place patient in supine position; administer IM or SUBQ into the anterolateral aspect of the thigh with the needle facing downwards; may be injected through clothing. When being administered to infants <1 year of age, the thigh muscle should be pinched during administration. Ensure the needle is embedded completely before injecting. After injection, slide the safety guard over the needle using one hand and return to case. Place patient in the lateral recumbent position (recovery position). 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 CNS depression will return. Repeat doses may be required until emergency medical assistance becomes available. Used syringes should be given to health care provider for inspection and proper disposal.

Auto-injector (10 mg dose): Children ≥12 years and Adolescents: For IM or SUBQ use only. Intended for self or buddy administration by military personnel or chemical incident responders. The person administering the medication should follow the printed instructions on the device. Administer IM or SUBQ into the anterolateral aspect of the thigh; may be injected through clothing or MOPP4 personal protective equipment. Keep the 10 mg auto-injector firmly in place for 5 seconds after injection (and after click and hiss sound). Following proper administration, a red indicator appears in the viewing window. The injection needle is not visible before, during, or after the injection. Immediately seek emergency medical assistance after the first dose due to the likelihood that respiratory and/or CNS depression will return. Repeat doses may be required until emergency medical assistance becomes available or if prolonged exposure to high-potency opioids is expected (prophylaxis using the 10 mg auto-injector only); a new device must be used for each dose as device only contains a single dose of naloxone.

Use: Labeled Indications

Opioid reversal:

Naloxone (IV): For the complete or partial reversal of opioid toxicity (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.

Naloxone intranasal (IM, SUBQ [eg, Zimhi]): 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.

Naloxone 10 mg/0.4 mL autoinjector (IM, SUBQ): For use by military personnel and chemical incident responders for the treatment of respiratory and/or CNS depression in patients ≥12 years of age where use of high-potency opioids (eg, fentanyl analogues) as a chemical weapon is suspected. May also be used to prevent respiratory and/or CNS depression in military personnel and chemical incident responders entering an area contaminated with high-potency opioids.

Use: Off-Label: Adult

Clonidine toxicity; Opioid-induced constipation (oral administration); Opioid-induced pruritus; Opioid use disorder, naloxone challenge

Medication Safety Issues
Sound-alike/look-alike issues:

Naloxone may be confused with Lanoxin, nalbuphine, naltrexone

Narcan may be confused with Marcaine, Norcuron

Pediatric patients: High-risk medication:

KIDs List: Naloxone, when used in neonates for postpartum resuscitation, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list; use should be avoided due to risk of seizure (strong recommendation; high quality of evidence) (PPA [Meyers 2020]).

International issues:

Narcan [multiple international markets] may be confused with Marcen brand name for ketazolam [Spain]

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination

Naldemedine: Opioid Antagonists may enhance the adverse/toxic effect of Naldemedine. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination

Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination

Pregnancy Considerations

Naloxone crosses the placenta.

Although naloxone may precipitate opioid withdrawal in the fetus in addition to the mother, treatment should not be withheld when needed in cases of maternal opioid overdose (ACOG 711 2017). When using the injection, starting at the low end of the dosing range is suggested to help avoid adverse fetal events but still provide treatment to the mother (Blandthorn 2018). Use of naloxone to test for opioid dependence during pregnancy is not recommended (ASAM 2020).

Naloxone is used off-label for the management of patients with opioid-induced pruritus, including women who received neuraxial opioids during labor and delivery (ACOG 209 2019; Kumar 2013; Miller 2011).

Breastfeeding Considerations

It is not known if naloxone is present in breast milk; however, systemic absorption following oral administration is minimal.

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Respiratory status (oxygenation and ventilation), level of consciousness, heart rate, blood pressure, temperature, signs or symptoms of opioid withdrawal.

Mechanism of Action

Pure opioid antagonist that competes and displaces opioids at opioid receptor sites

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Endotracheal, IM, SUBQ: 2 to 5 minutes; Inhalation via nebulization: ~5 minutes (Mycyk 2003); Intranasal: ~3 to 17 minutes (Barton 2005; Dietze 2019; Kelly 2005; Robertson 2009); IV: ~2 minutes.

Note: In clinical trials evaluating the use of naloxone in patients with an acute opioid overdose, onset of action is often defined as time to a predefined end point (eg, respiratory rate ≥10; Glasgow Coma Score ≥13 [Dietze 2019]) or is based on a predefined evaluation time point (eg, clinical response within 10 minutes of administration) (Kerr 2009).

Duration: ~30 to 120 minutes depending on route of administration; IV has a shorter duration of action than IM administration; since naloxone's action is shorter than that of most opioids, repeated doses are usually needed.

Absorption: Intranasal, IM, SUBQ: Pediatric patients: May be erratic or delayed.

Protein binding: Relatively weak (to albumin [major] and other plasma constituents).

Metabolism: Primarily hepatic via glucuronidation.

Bioavailability: 43% to 44% (0.4 mg IM compared to nasal [Narcan] dose); 37% (nasal [Kloxxado] compared to 2 mg IV dose); ≤2% (oral tablet compared to 1 mg IV infusion) (Smith 2012).

Half-life elimination: Neonates: Mean 3.1 ± 0.5 hours; Adults: IM, IV, or SUBQ: 0.5 to 1.5 hours; Intranasal: ~2 hours.

Time to peak: IM, Intranasal (Kloxxado), SUBQ: ~15 minutes; Intranasal (Narcan): 19.8 to 30 minutes.

Excretion: Urine (as metabolites).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Nyxoid;
  • (AU) Australia: Naloxone | Naloxone Minijet | Prenoxad;
  • (BE) Belgium: Narcan;
  • (BR) Brazil: Narcan;
  • (CH) Switzerland: Nyxoid;
  • (CO) Colombia: Narcan;
  • (CZ) Czech Republic: Nyxoid;
  • (EE) Estonia: Nyxoid | Prenoxad;
  • (FI) Finland: Ventizolve;
  • (FR) France: Nalone | Nalscue | Prenoxad;
  • (GB) United Kingdom: Ims naloxone | Naloxone | Nyxoid | Prenoxad;
  • (IE) Ireland: Naloxone | Prenoxad;
  • (IT) Italy: Nyxoid;
  • (JP) Japan: Naloxone hcl sankyo;
  • (KR) Korea, Republic of: Exelan | Naloxone | Narone;
  • (LT) Lithuania: Naloxonum;
  • (LU) Luxembourg: Narcan | Nyxoid;
  • (LV) Latvia: Naloxon | Narcan;
  • (NL) Netherlands: Narcan;
  • (NO) Norway: Nyxoid | Ventizolve;
  • (NZ) New Zealand: Naloxone HCL | Nyxoid;
  • (PR) Puerto Rico: Kloxxado | Lifems naloxone | Naloxone HCL | Narcan | Zimhi;
  • (PT) Portugal: Naloxona | Nyxoid;
  • (QA) Qatar: N-Xone | Naxone | Nyxoid Spray;
  • (SE) Sweden: Prenoxad | Respinal;
  • (SI) Slovenia: Nyxoid;
  • (TH) Thailand: DBL Naloxone | Naloxone | Narcan | Narcotan;
  • (TW) Taiwan: Narcan
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