naloxone

General Information

Naloxone is an opioid receptor antagonist used for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression (label).

It is intended for immediate administration in settings where opioids may be present and is not a substitute for emergency medical care (label).

Because the duration of many opioids exceeds naloxone, relapse into respiratory depression can occur. Labeling emphasizes continued surveillance and repeat dosing when needed while emergency services are activated (label/clinical).

Rapid reversal can trigger precipitated withdrawal in physically dependent patients; safety planning often includes anticipating vomiting, agitation, and aspiration risk during reversal (label/clinical).

The compare view, naloxone evidence feed, and naloxone print page support opioid overdose prevention counseling alongside OUD treatment planning.

Increasingly incorporated into harm-reduction and OUD treatment plans as “take-home naloxone.” Effectiveness depends on access, training, and prompt emergency response (label/clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Naloxone is a competitive opioid receptor antagonist that reverses opioid-induced respiratory and CNS depression by displacing opioids from receptors (label/clinical).

Antagonism is pharmacologically “surmountable” at high opioid exposures, and repeated dosing may be required when potent opioids or partial agonists are involved (label/clinical).

• Opioid receptor antagonism (μ-opioid receptor blockade; primary clinical effect).

Metabolism and Pharmacokinetics

• Naloxone is metabolized in the liver, primarily by glucuronide conjugation with naloxone-3-glucuronide as the major metabolite (label).
• Adult serum half-life following parenteral dosing has been reported to range from ~30 to 81 minutes. Intranasal products report longer mean half-life values (~2 hours) in healthy adults (label).
• Urinary excretion is largely as metabolites; one label reports ~25–40% of an oral/IV dose excreted as metabolites within 6 hours and ~60–70% within 72 hours (label).

Dosing and Administration

• Intranasal naloxone devices are single use. Labeling for Narcan nasal spray recommends administering one spray into one nostril as quickly as possible when overdose is suspected (label).
• If the person does not respond, or responds and then relapses into respiratory depression, additional doses can be administered every 2–3 minutes using a new device each time and alternating nostrils (label).
• Labeling emphasizes activating emergency medical assistance and continuing surveillance until help arrives (label).
• Overdose involving partial agonists (e.g., buprenorphine) may be incompletely reversed and may require repeated dosing (label).

Monitoring & Labs

• After administration, continued surveillance is essential because recurrent respiratory depression can occur; labeling emphasizes repeat dosing when needed while emergency services are activated (label).
• Monitor for withdrawal-related agitation and vomiting with attention to airway/aspiration safety (label/clinical).
• When naloxone is co-prescribed, clinicians often review overdose recognition, device use, storage, and expiration tracking with patients and close contacts (clinical).

Naloxone access supports overdose response, but OUD outcomes generally improve when paired with engagement in evidence-based treatment (guideline/clinical).

Adverse Effects

Interactions

• Naloxone reverses opioid agonist effects and will reduce opioid analgesia; this is an intended effect rather than an adverse interaction (label/clinical).
• Opioid-containing medications given after reversal can re-sedate the patient as naloxone effects wane; monitoring in a medical setting is often required when significant opioid exposure has occurred (clinical).

Other Useful Information

• Systematic review evidence supports take-home naloxone programs as an effective public health intervention to reduce opioid overdose deaths (review).
• In OUD care, naloxone access is often paired with relapse-prevention planning and linkage to evidence-based OUD pharmacotherapy (guideline/clinical).

References

1. NARCAN (naloxone hydrochloride) nasal spray prescribing information — DailyMed (2025)
2. Naloxone hydrochloride injection prescribing information — DailyMed (2024)
3. ARE Take Home Naloxone Programmes Effective? Systematic Review Utilizing Application OF THE Bradford Hill Criteria — Addiction (2016)
4. TIP 63: Medications for Opioid Use Disorder — SAMHSA (2021)