Naltrexone vs Naloxone: What's the Difference?

Side-by-side comparison

What is naloxone?

Naloxone is an opioid antagonist. It works fast to undo the effects of opioids.

• What it treats: the label says naloxone injection is "indicated for the complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids." It is also used "for the diagnosis of suspected or known acute opioid overdosage."²
• What it does: it prevents or reverses opioid effects, including slowed breathing, sedation and low blood pressure.² SAMHSA calls it a temporary treatment whose effects do not last long, so the person still needs medical care.⁷
• Forms: the injection can be given into a vein, a muscle, or under the skin.² Narcan is a 4 mg nasal spray whose stated purpose is "Emergency treatment of opioid overdose."⁴
• Other naloxone products exist. This page uses only the labels listed in the references.

What is naltrexone?

Naltrexone is also an opioid antagonist, but it is used for ongoing treatment, not emergencies.

• Tablets: approved to treat alcohol dependence and to block the effects of opioids taken from outside the body. For alcohol, the label recommends 50 mg once daily for most patients.¹
• Vivitrol (monthly shot): used for alcohol dependence in people who can stop drinking before starting, and "for the prevention of relapse to opioid dependence, following opioid detoxification."³
• Part of a program: the Vivitrol label says treatment should be part of a broader program that includes psychosocial support.³
• Not low-dose naltrexone: LDN is an off-label use well below the 50 mg tablet dose, and neither naltrexone label covers it.^1,3 Its opioid and medicine cautions are on what to avoid on low-dose naltrexone.

See our naltrexone guide, naltrexone and alcohol, and Vivitrol pages for more.

How they are alike

• Chemical cousins. Both are "a synthetic congener of oxymorphone." In naloxone, one part of the molecule (on the nitrogen atom) is an allyl group. In naltrexone it is a cyclopropylmethyl group.^1,2
• Same main target. Both bind most strongly to the mu opioid receptor.^2,3
• Both can trigger withdrawal. In someone physically dependent on opioids, naloxone "will produce withdrawal symptoms," which "will subside in about 2 hours."² With naltrexone tablets, withdrawal symptoms "have usually appeared within five minutes of ingestion" and "have lasted for up to 48 hours."¹ Both are among the triggers of precipitated withdrawal.
• Neither is federally controlled. Federal law lists both naloxone and naltrexone as exclusions from Schedule II opiates, and neither appears on the DEA's controlled-substances list.^8,9 More in Is naltrexone a controlled substance?

Naloxone is a rescue drug; naltrexone is ongoing treatment

Naloxone is a rescue drug. It is used when someone may be overdosing on opioids. The Narcan label says it is used "to “revive” someone during an overdose" and that "this medicine can save a life."⁴

Naltrexone is a maintenance drug. It is taken on a schedule (daily tablets or a monthly shot) to help treat alcohol dependence or to block opioids during recovery.^1,3 It is not labeled for reversing an overdose, so it is not an emergency drug.

Naloxone works in minutes and can wear off; naltrexone lasts a day to a month

Naloxone is fast but short.

• Given in a vein, its effect is "generally apparent within two minutes." It is a bit slower when given into a muscle or under the skin.²
• It can wear off before the opioid does: "Since the duration of action of naloxone may be shorter than that of some opiates, the effects of the opiate may return as the effects of naloxone dissipates."² The Narcan label says to stay with the person until the ambulance arrives, "even if the person wakes up," and to give another dose if they become very sleepy again.⁴
• In one study, naloxone's half-life in adults (after injection) was 30 to 81 minutes.²

Naltrexone lasts much longer.

• A tablet reaches peak blood levels within about 1 hour.¹
• "50 mg of naltrexone hydrochloride will block the pharmacologic effects of 25 mg of intravenously administered heroin for periods as long as 24 hours."¹
• Vivitrol "blocks the effects of exogenous opioids for approximately 28 days after administration."³

See How long does naltrexone stay in your system?

Naloxone sprays are sold over the counter; naltrexone needs a prescription

• Naloxone: In March 2023, the FDA approved Narcan 4 mg nasal spray "for over-the-counter (OTC), nonprescription, use – the first naloxone product approved for use without a prescription." At that time the FDA said "Other formulations and dosages of naloxone will remain available by prescription only."⁵ In July 2023 it approved a second, RiVive 3 mg nasal spray, "for over-the-counter (OTC), nonprescription use for the emergency treatment of known or suspected opioid overdose."⁶ The naloxone injection label used here is prescription-only.² SAMHSA notes that some community programs and health departments give naloxone out free, and that availability varies by state.⁷
• Naltrexone: prescription only, in every form covered here. Tablets are "Rx only," and Vivitrol "must be prepared and administered by a healthcare provider."^1,3 See How to get naltrexone.

How naloxone and naltrexone connect in treatment

The two drugs show up together in naltrexone care in two ways.

1. A naloxone "challenge" may be used before starting naltrexone. Because naltrexone can cause sudden withdrawal, people need to be opioid-free first. The naltrexone label says it should not be given to "Any individual who has failed the naloxone challenge test or who has a positive urine screen for opioids."¹ It adds that a naloxone challenge "may be helpful," but a few people still had withdrawal after passing one.¹

2. People on naltrexone should know about naloxone. After the naltrexone blockade wears off, people who used opioids before "may respond to lower doses of opioids than previously used."¹ For Vivitrol, the label points to the end of the month after a shot, or after a missed dose, as risky times.³ So both labels tell prescribers to "inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene)."^1,3

Trying to override the naltrexone block with large doses of opioids is dangerous and "may lead to life-threatening opioid intoxication or fatal overdose."¹

What about Suboxone?

Some buprenorphine medicines also contain naloxone; the Vivitrol label, for example, gives instructions for "Switching from Buprenorphine, Buprenorphine/Naloxone, or Methadone."³ The DEA lists Suboxone as a name for buprenorphine, a Schedule III controlled substance, while naloxone itself is not on the DEA list.^8,9 Suboxone is not naltrexone: its ingredients, starting rules and trial results are compared on naltrexone vs Suboxone.