Naloxone vs. Naltrexone: Comparing Opioid Disorder Medications

Elena Hill, MD, MPH profile image
Medically Reviewed By Elena Hill, MD, MPH • Updated Mar 7, 2023 • 8 cited sources

Naloxone and naltrexone are both opioid “antagonists” or opioid-blocking medications. They also have very similar names. But don’t confuse them. These two medications are designed to do different things. 

Naloxone is the form of an opioid antagonist that can immediately reverse an opioid overdose. Naltrexone acts more slowly/long term to help you avoid misuse of opioids and/or alcohol. 

Medications to Treat Opioid Use Disorder 

An opioid use disorder (OUD) involves the compulsive use of drugs like Vicodin, OxyContin, and heroin. People with an OUD may desperately want to quit using drugs, but they may be unable to do so without help.

Naloxone and Naltrexone are both opioid antagonist medications. They have similar sounding names, but are used in different capacities:

What Is Naloxone?

Naloxone (Narcan) is a rapidly acting medication that can save someone’s life in the case of an opioid overdose. Naloxone attaches to receptors immediately, and it removes other opioids from their receptors.[5] This immediately reverses the effects of the opioid and prevents overdose. 

There are Three U.S. Food and Drug (FDA)-approved forms of naloxone: injectables, auto-injectors, and nasal sprays.[1] In September 2022, the FDA announced plans to make naloxone available without a prescription in most states. With this move, they hoped to increase access to this life saving medication so that more people could obtain it and have it ready to use in case they or a loved one experiences an overdose.[2] 

What Is Naltrexone?

Naltrexone is a medication that doctors use to treat both alcohol use disorder (AUD) and opioid use disorder (OUD).[6]

In opioid use disorder, Naltrexone works by preventing opioid intoxication.[6] If you take an opioid like heroin after using naltrexone, you won’t get as high and therefore use of this medication can help protect against overdose.  It also prevents cravings for opioids over time. 

In alcohol use disorder, the mechanism by which Naltrexone seems to work is less clear, because alcohol is not an opioid. In general, we believe Naltrexone works by acting on the brain’s reward pathways to reduce cravings for alcohol and making use of alcohol less rewarding over time. 

Naloxone comes in two forms [6]: pills (50-100 mg daily) and injections (380 mg injection once per month). The FDA approved naltrexone in 2010 to treat both alcohol use disorder and opioid use disorder.[3] Naltrexone requires a prescription.[4]

4 Main Differences Between Naloxone & Naltrexone

Designed for?Reversing opioid overdosePreventing opioid and alcohol misuse
How quickly does it work?Immediately (minutes)Throughout the day
How long does it last?Up to 90 minutes24 hours (pills) or a month (injection)
Requires a prescription?Not alwaysYes

Comparing Side Effects 

Naloxone and Naltrexone are both opioid blockers, and have similar side effects. In general both medications are extremely safe and have very few concerning side effects. Some side effects may include itching, diarrhea, or allergy in very rare circumstances.[9]

Comparing Duration of Effects

Naloxone is a fast-acting medication that gets to work quickly and fades away within 30 to 90 minutes.[5] 

Naltrexone is a pill or injection, so its effects tend to last for a day (in pill form) or a month (in injectable form).[8] 

Can I Use Both Drugs at the Same Time?

Yes, you can use both naloxone and naltrexone at the same time. For example, if you have been taking Naltrexone each day for OUD, and then use opioids and overdose, you can still safely administer Naloxone (Narcan) to help reverse that overdose. In fact, you should, as this may be life saving. 

Are There Other Options Available to treat OUD?

Yes. In fact, the two medications apart from Naltrexone that are FDA approved to treat OUD are Methadone and Suboxone. 

Suboxone is a prescription medication for OUD. It works entirely differently from naloxone and naltrexone. It contains buprenorphine, which can help to block opioid cravings and keep you from relapsing to drugs. If naltrexone isn’t helping to keep your OUD under control, Suboxone might be better. Talk to your doctor to learn more about both Naltrexone and Suboxone as treatments for OUD.

Medically Reviewed By Elena Hill, MD, MPH

Elena Hill, MD; MPH received her MD and Masters of Public Health degrees at Tufts Medical School and completed her family medicine residency at Boston Medical Center. She is currently an attending physician at Bronxcare Health Systems in the Bronx, NY where ... Read More

  1. Exemption and Exclusion From Certain Requirements of the Drug Supply Chain Security Act for the Distribution of FDA-Approved Naloxone Products During the Opioid Public Health Emergency Guidance for Industry. U.S. Department of Health and Human Services. September 2022. Accessed November 2022.
  2. FDA Announces Preliminary Assessment that Certain Naloxone Products Have the Potential to be Safe and Effective for Over-the-Counter Use. U.S. Food and Drug Administration. November 2022. Accessed November 2022.
  3. Vivitrol Prescribing Information. U.S. Food and Drug Administration. October 2010. Accessed November 2022.
  4. Naltrexone. Substance Abuse and Mental Health Services Administration. September 2022. Accessed November 2022.
  5. Naloxone Drug Facts. National Institute on Drug Abuse. January 2022. Accessed November 2022.
  6. Naltrexone. StatPearls. June 2022. Accessed November 2022.
  7. Narcan (Naloxone Nasal Spray) Approved to Reverse Opioid Overdose. U.S. Food and Drug Administration. April 2018. Accessed November 2022.
  8. What Is Naltrexone? Psychiatric Research Institute. Accessed November 2022.
  9. Naloxone in Opioid Poisoning: Walking the Tightrope. BMJ. August 2005. Accessed November 2022.

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