Naloxone vs. Naltrexone: Understanding the Difference

Key Takeaways

• Naloxone (brand name Narcan) is an emergency overdose reversal medication that works within minutes and lasts 30-90 minutes
• Naltrexone (brand names Vivitrol, ReVia) is a long-term relapse prevention medication that blocks opioid effects for 24 hours (oral) or approximately 30 days (injectable)
• Both are opioid antagonists, but they serve completely different clinical purposes
• Naloxone cannot treat addiction; naltrexone cannot reverse an overdose
• In New Jersey, naloxone is available at pharmacies without an individual prescription under a statewide standing order

Naloxone and naltrexone are two of the most important medications in the response to the opioid crisis, but their similar names cause persistent confusion. Both are opioid antagonists — they block opioid receptors — but they do so for entirely different purposes, in different clinical contexts, with different durations of action. Confusing the two can have serious consequences. This guide clarifies the distinction.

Two Medications, Very Different Purposes

Why the Names Cause Confusion

The confusion is understandable. Both medications:

• Have names starting with “nal-”
• Are classified as opioid antagonists
• Act on the same receptor system (mu-opioid receptors)
• Are used in the context of opioid use disorder

But the similarities end there. The critical distinction is timing and purpose: naloxone is used during an emergency to reverse an overdose that is happening right now. Naltrexone is used after stabilization to prevent relapse over weeks and months.

Quick Comparison Overview

Feature	Naloxone (Narcan)	Naltrexone (Vivitrol/ReVia)
Primary purpose	Emergency overdose reversal	Long-term relapse prevention
When used	During an active opioid overdose	After detox, during sustained recovery
Duration of action	30-90 minutes	24 hours (oral) or ~30 days (injectable)
Administration	Nasal spray or injection	Daily oral pill or monthly injection
Onset	2-5 minutes	Hours (oral); days to reach full effect (injectable)
Setting	Emergency rooms, by bystanders, by first responders	Outpatient clinics, prescriber offices
Requires opioid-free period?	No — used during active opioid intoxication	Yes — 7-10 days opioid-free required before starting
Prescription required?	Available OTC and under standing orders in NJ	Requires prescription
Treats addiction?	No	Yes — FDA-approved for opioid and alcohol use disorder

Naloxone (Narcan): Emergency Overdose Reversal

How Naloxone Works

Naloxone works by rapidly displacing opioids from mu-opioid receptors in the brain. When a person is experiencing an opioid overdose, opioids are suppressing the brainstem’s respiratory drive, causing breathing to slow or stop entirely. Naloxone competes with the opioid molecules for the same receptors and, because it has a higher binding affinity, pushes them off. This restores normal respiratory function, typically within 2-5 minutes of administration.

Naloxone: An opioid antagonist that rapidly reverses opioid overdose by displacing opioid molecules from brain receptors, restoring breathing within minutes. It has no effect on non-opioid overdoses and no potential for misuse.

Naloxone is specific to opioids. It will not reverse overdoses caused by benzodiazepines, alcohol, stimulants, or other non-opioid substances. However, because many overdoses involve multiple substances and bystanders may not know what was taken, administering naloxone when opioid overdose is suspected is recommended as a safe default — it will cause no harm if opioids are not involved.

Forms and Administration

Naloxone is available in several forms:

• Narcan nasal spray (4mg): The most widely distributed form. A single-dose nasal spray that requires no assembly or medical training to administer. Spray into one nostril while the person is lying on their back.
• Kloxxado nasal spray (8mg): A higher-dose nasal spray designed for the increasing prevalence of high-potency synthetic opioids like fentanyl.
• Injectable naloxone: Used by medical professionals, available as intramuscular or intravenous injection.

A critical limitation of naloxone is its short duration of action. Naloxone wears off in 30-90 minutes, but many opioids — particularly fentanyl — remain active much longer. This means a person can be revived by naloxone and then return to overdose status as the naloxone wears off. This is why calling 911 remains essential even after successful naloxone administration.

Availability in New Jersey

New Jersey has taken significant steps to expand naloxone access:

• Standing order: The NJ Commissioner of Health has issued a standing order allowing pharmacies to dispense naloxone without an individual prescription
• Over-the-counter availability: Narcan nasal spray received FDA approval for over-the-counter sale in 2023
• Free distribution programs: NJ DMHAS funds naloxone distribution through community organizations, harm reduction programs, and local health departments
• Good Samaritan protections: NJ’s Overdose Prevention Act provides legal protections for individuals who call 911 during an overdose and for those who administer naloxone in good faith

For a more detailed guide on naloxone forms and administration, see our glossary entry on Narcan and naloxone.

Naltrexone (Vivitrol, ReVia): Relapse Prevention

How Naltrexone Works

Naltrexone blocks opioid receptors in a fundamentally different way than naloxone. Rather than a short burst of competitive binding, naltrexone provides sustained receptor blockade that prevents opioids from producing their rewarding effects. A person taking naltrexone who uses opioids will not experience the euphoria or pain relief that drives continued use — the opioids are blocked from activating the receptors.

For alcohol use disorder, naltrexone works through a different mechanism. It reduces the pleasurable effects of alcohol by blocking the endorphin release that alcohol triggers, which diminishes the reinforcement that drives compulsive drinking.

Naltrexone: An opioid antagonist used for long-term relapse prevention in opioid and alcohol use disorders. Available as a daily oral tablet (ReVia) or a monthly extended-release injection (Vivitrol). FDA-approved for both opioid and alcohol use disorder.

Oral vs. Injectable Forms

Form	Brand Name	Dosing	Key Considerations
Oral naltrexone	ReVia (generic available)	50mg daily	Requires daily adherence; effectiveness limited by compliance; lower cost
Injectable naltrexone	Vivitrol	380mg intramuscular injection monthly	Eliminates daily adherence challenge; higher cost; requires monthly clinic visit

The injectable form (Vivitrol) addresses one of the primary limitations of oral naltrexone: adherence. Individuals in early recovery may stop taking oral naltrexone when cravings are strong, negating its protective effect. A monthly injection removes the daily decision point. Research published in the Lancet found that extended-release injectable naltrexone significantly reduced opioid relapse compared to placebo.

Who Is a Good Candidate

Naltrexone is appropriate for individuals who:

• Have completed detoxification and are opioid-free for a minimum of 7-10 days (oral) or 7-14 days (injectable)
• Are motivated to maintain abstinence from opioids or alcohol
• Prefer a non-opioid medication (unlike buprenorphine or methadone, naltrexone has no opioid activity and no potential for misuse)
• Have stable enough circumstances to maintain monthly injection appointments or daily oral dosing

Naltrexone is not appropriate for individuals who are currently using opioids or have not completed detox. Administering naltrexone to someone with active opioid dependence will precipitate severe withdrawal — an intensely uncomfortable and potentially dangerous reaction as the medication rapidly displaces opioids from receptors.

For a deeper comparison of naltrexone with other medication-assisted treatments, see our glossary entry on Vivitrol and our comparison of Vivitrol vs. Suboxone vs. Sublocade.

Common Misconceptions

Can Naltrexone Reverse an Overdose?

No. While naltrexone is an opioid antagonist like naloxone, it is not formulated or indicated for emergency overdose reversal. The oral form takes hours to reach therapeutic levels, and the injectable form is designed for sustained release over 30 days, not rapid onset. During an opioid overdose, every minute matters — only naloxone provides the rapid receptor displacement needed to restore breathing.

If a person taking Vivitrol experiences an overdose (which could occur if they use extremely high doses of opioids to attempt to override the blockade), standard emergency protocols including naloxone should still be followed, and emergency medical services should be contacted immediately.

Is Naloxone a Treatment for Addiction?

No. Naloxone is a rescue medication. It reverses a single overdose event but does nothing to address the underlying substance use disorder. After naloxone revives someone from an overdose, the person still has an active opioid use disorder and remains at high risk for subsequent overdose unless connected to treatment.

This is why overdose reversal should always be followed by a referral to addiction treatment. The period immediately following a non-fatal overdose represents both a window of heightened risk (tolerance may be altered) and a window of clinical opportunity (the individual and their family may be more receptive to treatment engagement).

Can You Use Both Medications?

Not simultaneously in the way someone might take two medications for the same condition. However, they may both play roles in the same person’s recovery at different stages:

• Naloxone may be carried as emergency protection during the period before or during early treatment
• Naltrexone may be prescribed after detox as part of a long-term relapse prevention plan
• Individuals on naltrexone (or their family members) should still carry naloxone, because overdose risk exists if the person discontinues naltrexone and returns to use

Frequently Asked Questions

Does naloxone work on fentanyl overdoses? Yes, but higher or repeated doses may be needed. Fentanyl is significantly more potent than heroin, and some fentanyl overdoses may require multiple doses of naloxone. The higher-dose Kloxxado nasal spray was developed specifically to address this challenge.

How long do you need to be off opioids before starting naltrexone? A minimum of 7-10 days for oral naltrexone and 7-14 days for Vivitrol injection. Starting naltrexone while opioids are still present in the body will trigger precipitated withdrawal, which causes severe discomfort. Clinical verification of opioid-free status through urine drug screening is standard practice before initiation.

Is naltrexone addictive? No. Naltrexone has no opioid activity, produces no euphoria, and has no potential for misuse or physical dependence. It is not a controlled substance.

Can naltrexone be used for alcohol addiction? Yes. Naltrexone is FDA-approved for both opioid use disorder and alcohol use disorder. For alcohol, it reduces cravings and the reinforcing effects of drinking. Both oral and injectable forms are used for alcohol use disorder.

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This article is part of our guide to comparing addiction treatment concepts. For related reading, see our detailed glossary entries on naloxone vs. naltrexone and Vivitrol. For information about treatment options, see our review of top treatment centers in the US.

Last reviewed: March 2026.