Naloxone (Narcan) | Medication Reference

Bedside Snapshot

Pure opioid receptor antagonist (highest affinity for μ receptors) used to reverse opioid-induced respiratory and CNS depression. It has no agonist activity and no intrinsic analgesia.

Routes: IV, IM, subQ, intranasal (IN), intraosseous (IO). IV is preferred in monitored ED/ICU settings for rapid titration; IN/IM are common prehospital/community routes
Goal in chronic opioid users: Adequate ventilation, not full arousal—titrate slowly to avoid severe acute withdrawal, agitation, vomiting, and sympathetic surge
Onset: IV 1–2 minutes; IM/SC 3–5 minutes; IN 5–10 minutes
Duration: Shorter than many opioids (~30–90 minutes), so recurrent respiratory depression is common with long-acting opioids or large ingestions
Typical ED adult titration (known/suspected opioid dependence): Start with 0.04 mg IV, then escalate to 0.1 mg, 0.2 mg, 0.4 mg, 2 mg IV every 2–3 minutes until adequate breathing (e.g., RR >10, SpO₂ improving) rather than full wake-up
Typical ED adult dosing (no known dependence, peri-arrest, or apnea): 0.4–2 mg IV/IM/IN, repeat every 2–3 minutes as needed. Higher total doses may be required with high-potency synthetic opioids
Naloxone infusion: For long-acting opioid toxicity (e.g., methadone, extended-release formulations) or large ingestions, consider infusion after effective reversal bolus: e.g., 2/3 of the effective bolus dose per hour, titrated to maintain ventilation
Major issues: Acute withdrawal (agitation, vomiting, tachycardia, hypertension), rare noncardiogenic pulmonary edema, arrhythmias, and recurrence of respiratory depression once naloxone wears off

Brand & Generic Names

Generic Name: Naloxone hydrochloride
Brand Names: Narcan, Kloxxado, various generics

Medication Class

Opioid antagonist; antidote for opioid-induced respiratory/CNS depression

Pharmacology

Mechanism of Action:

Competitive antagonist at opioid receptors (μ > κ, δ), displacing opioids from these receptors and rapidly reversing their effects on the CNS and respiratory centers
Reverses opioid-induced respiratory depression, sedation, miosis, and hypotension; also reverses analgesia and can precipitate withdrawal in opioid-dependent patients
Has minimal intrinsic pharmacologic effects in the absence of opioids; in opioid-naïve patients, it is usually well tolerated aside from rare idiosyncratic reactions

Pharmacokinetics:

Onset: IV 1–2 minutes; IM/SC 3–5 minutes; IN 5–10 minutes
Peak effect: Generally within 5–10 minutes of IV administration
Duration: ~30–90 minutes (often cited around 45–60 minutes), shorter than most opioids; recurrent respiratory depression is common with long-acting agents (e.g., methadone, ER morphine/oxycodone, buprenorphine)
Distribution: Widely distributed; crosses the placenta; highly protein-bound to a moderate degree
Metabolism: Hepatic glucuronidation to inactive metabolites
Elimination: Primarily renal excretion of metabolites; plasma elimination half-life in adults ~30–90 minutes; prolonged in neonates and hepatic impairment

Indications

Reversal of suspected or confirmed opioid-induced respiratory and CNS depression, including from heroin, prescription opioids, and synthetic opioids
Empiric therapy in undifferentiated coma/apnea where opioid overdose is suspected, particularly when pinpoint pupils, depressed respirations, or drug paraphernalia are present
Adjunctive agent during procedural or perioperative settings to reverse opioid-associated hypoventilation or oversedation
Diagnostic tool to help confirm opioid involvement when a clear history is absent (clinical response to naloxone)
Neonatal resuscitation for maternal opioid exposure is now rarely used; current guidelines prioritize bag-valve-mask ventilation and supportive care rather than routine naloxone

Dosing & Administration

Available Forms:

IV/IM/SC solution: usually 0.4 mg/mL in 1 mL vials or prefilled syringes; higher-concentration products (e.g., 2 mg/2 mL) also exist
Intranasal (spray) devices: common community products deliver 4 mg naloxone per spray (both nostrils or alternating nostrils per instructions)
Auto-injectors (IM or subQ) are available in some systems for layperson or prehospital use (dose commonly 0.4 mg or 2 mg)

Adult Dosing (Always follow local protocol):

Scenario	Dose & Route	Frequency / Titration	Notes
Known/suspected opioid dependence – titrated reversal	0.04 mg IV initial	Escalate to 0.1 mg, 0.2 mg, 0.4 mg, then 2 mg IV q2–3 min as needed	Aim for adequate ventilation, not full arousal; avoid severe withdrawal
No known dependence, apnea, or near-arrest	0.4–2 mg IV/IM/IN	Repeat q2–3 min as needed up to 10 mg total	If no response at 10 mg, consider other causes (non-opioid) or mixed overdose
Community/prehospital intranasal (layperson)	4 mg IN (one spray)	Repeat every 2–3 min in alternating nostrils until EMS arrives	Begin CPR and rescue breathing per BLS while waiting
Continuous infusion after reversal of long-acting opioids	2/3 of effective bolus dose per hour IV (e.g., if 2 mg bolus effective → ~1.3 mg/h)	Titrate up or down to maintain adequate RR and mental status	May need up to full effective bolus per hour in some cases; consider central line for prolonged infusions
Procedural/iatrogenic opioid oversedation	Small IV increments 0.04–0.1 mg	Repeat q1–2 min until adequate ventilation and arousal	Use lower doses to preserve some analgesia when possible

Contraindications

Contraindications:

Known hypersensitivity to naloxone or formulation components (very rare)
There are no absolute contraindications when opioid-induced life-threatening respiratory depression is suspected

Major Precautions:

Opioid-dependent patients: risk of acute withdrawal (agitation, vomiting, tachycardia, hypertension, pain crisis) if reversed rapidly or completely
Cardiovascular disease: abrupt surge in sympathetic tone during withdrawal may precipitate arrhythmias, myocardial ischemia, or pulmonary edema in susceptible patients
Polysubstance overdose (e.g., opioids plus benzodiazepines/alcohol): naloxone will not reverse non-opioid CNS depressants; airway and ventilation support remain essential
Pregnancy: naloxone crosses the placenta and can precipitate withdrawal in opioid-dependent fetuses; however, it should not be withheld in maternal life-threatening overdose
Recurrent respiratory depression: due to shorter naloxone half-life than many opioids; extended observation and/or infusion may be needed

Warning: In opioid-dependent patients, rapid reversal can precipitate severe acute withdrawal. Titrate slowly to adequate ventilation, not full consciousness.

Adverse Effects

Common:

Nausea, vomiting
Sweating, tremor, tachycardia
Agitation, anxiety, irritability
Headache, dizziness

Serious:

Acute opioid withdrawal syndrome with severe agitation, vomiting, diarrhea, abdominal cramps, hypertension, and tachycardia
Noncardiogenic pulmonary edema (rare but reported), potentially related to catecholamine surge and negative pressure pulmonary edema
Arrhythmias (e.g., VT/VF, atrial fibrillation) and myocardial ischemia during abrupt withdrawal or in patients with underlying cardiac disease
Seizures (rare, usually in the setting of polysubstance overdose or severe withdrawal)

Special Populations

Opioid-Dependent Patients:

Start with very low doses (0.04 mg IV) and titrate slowly
Target adequate ventilation, not full arousal
Monitor for signs of acute withdrawal

Pregnancy:

Crosses the placenta; can precipitate withdrawal in opioid-dependent fetuses
Do not withhold in life-threatening maternal overdose
Monitor fetus after administration if pregnancy is known

Neonatal Use:

Current guidelines prioritize bag-valve-mask ventilation and supportive care
Naloxone is not routinely recommended for neonatal resuscitation
Consult NRP (Neonatal Resuscitation Program) guidelines for specific indications

Pediatric Patients:

Typical dose: 0.1 mg/kg IV/IM/IN (max 2 mg per dose)
Repeat every 2–3 minutes as needed
Confirm weight-based dosing per local protocols

Hepatic Impairment:

Prolonged elimination half-life may occur
No specific dose adjustment typically required for emergency use

Monitoring

Clinical Monitoring:

Airway patency and adequacy of ventilation (RR, depth, EtCO₂ if available) and oxygenation (SpO₂, ABG/VBG in critical cases)
Mental status and degree of arousal; aim for a cooperative, ventilating patient rather than fully awake and agitated
Vital signs (HR, BP, RR) and cardiac rhythm, especially in high-risk cardiac patients or when large doses are used
Observation for recurrent respiratory depression for at least several hours after reversal, longer with long-acting opioids or sustained-release preparations
Signs of acute withdrawal, pulmonary edema, or other complications; treat agitation and vomiting promptly to protect the airway

Clinical Pearls

Start Low, Go Slow: In chronic opioid users, start low and go slow (0.04 mg → 0.1 → 0.2 → 0.4 → 2 mg IV) and target ventilation, not complete wakefulness.

Unknown Dependence: For apneic, peri-arrest, or unknown-dependence patients, starting at 0.4–2 mg IV/IM/IN is reasonable while providing bag-valve-mask ventilation and preparing for intubation.

Consider Infusion: If you need repeated boluses to maintain respirations (especially with methadone or ER opioids), strongly consider a naloxone infusion and extended monitoring.

Airway First: Naloxone is not a substitute for basic airway management—always prioritize positioning, BVM, and advanced airway if needed; naloxone is an adjunct, not the primary resuscitation tool.

Polysubstance Awareness: In polysubstance overdoses, be prepared for only partial improvement with naloxone; persistent sedation despite normal ventilation may reflect benzos, alcohol, or other sedatives.

References

1. Lexicomp. (2025). Naloxone: Drug information. Wolters Kluwer.
2. Wermeling, D. P. (2015). Review of naloxone safety for opioid overdose: Practical considerations for new technology and expanded public access. Therapeutic Advances in Drug Safety, 6(1), 20–31. https://doi.org/10.1177/2042098614564776
3. Kim, H. K., & Nelson, L. S. (2015). Naloxone for opioid overdose. New England Journal of Medicine, 373(22), 2175–2177. https://doi.org/10.1056/NEJMc1510722
4. American Heart Association. (2020). 2020 AHA Guidelines for CPR and Emergency Cardiovascular Care.
5. EMCrit Project. (2023). Opioid intoxication (IBCC). https://emcrit.org/ibcc/opioid/