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What Are the Differences Between Naloxone vs. Naltrexone?

April 18, 2022

Table of Contents

Both Naltrexone and Naloxone are opioid antagonists. 

Naloxone (Brand name Narcan) is a rapidly acting opioid antagonist that reverses the effects of opioids by kicking opioids off opioid receptors in the brain and reversing an overdose. This has been a crucial component in saving lives, allowing someone suffering from an overdose to get medical attention.

Naltrexone (Brand name “Vivitrol”) is another opioid antagonist but is slower acting and blocks the euphoric effects of both opioids and alcohol, and is one of several treatments for long term abstinence from opioids in the treatment of OUD.

Tools in the Fight Against the Opioid Epidemic

Pharmaceutical researchers work hard to find new medications to help people overcome addiction to opioids. The opioid abuse and overdose epidemic continues to ravage the United States, but many beneficial treatments have been developed in the last 20 years. As a result,  more people can survive overdoses, complete rehabilitation programs, and maintain abstinence.

Naltrexone and naloxone are both medications used to combat opioids, the former over time, and the latter acutely in the setting of an acute overdose.

What Is Naloxone?

Naloxone (Narcan) is a fast-acting opioid antagonist that temporarily stops overdoses. When too many opioids are attached to receptors in the brain in an overdose, Naloxone can attach instead to the opioid receptors in the brain, kick opioids off of those receptors, and thereby reverse the overdose. This effect is temporary, though, as naloxone can quickly metabolize out of the body. If someone overdoses on opioids, you should call 911 immediately and administer naloxone if available.

There are two versions of naloxone approved by the Food and Drug Administration (FDA).[1]

  • Injectable: Originally, the proper dose of naloxone had to be drawn from a vial and injected safely, with a sterilized needle, into a vein. This required skill and attention from medical professionals. However, a single-dose, prefilled syringe of naloxone with brand name ZIMHI was approved by the FDA in 2021.[2]
  • Nasal spray: Approved under the brand names Narcan and Kloxxado, as well as a generic nasal spray, this form of naloxone is needle-free, easy to apply, and available in most pharmacies around the United States. Treatment professionals often recommend that people whose loved ones take high-dose prescription opioids or who abuse narcotics get a dose of Narcan and keep it with them.

Signs of an opioid overdose include the following:[3]

  • Pinpoint pupils
  • Labored or irregular breathing
  • Passing out and not waking up
  • Lips or fingertips turning blue from oxygen deprivation
  • Unusual gurgling or snoring sound due to breathing obstruction

What Is Naltrexone?

Naltrexone (Vivitrol) is also an opioid antagonist, but it is a long-acting form used to help people maintain abstinence after detoxing and getting behavioral therapy for addiction.[4] Like naloxone, naltrexone boots opioids off opioid receptors in the brain. This means that if a person takes an opioid like heroin or oxycodone while on Naloxone, they will not be able to “get high” off of that opioid.

Unlike naloxone, naltrexone will remain at a stable level in the bloodstream throughout the day, preventing euphoric effects of opioid use in case a person relapses and uses an opioid.

The FDA has approved two types of naltrexone:[5]

  • Injectable ("Vivitrol"): Naltrexone can be injected into the muscles once per month. This can help people who want to remain abstinent from opioids or alcohol without needing to take a pill once per day.
  • Pill (Generic Naltrexone, or Brand name “ReVia” and Depade): naltrexone can be taken as a pill at the same time every day to ease cravings and reduce the euphoric effects of both alcohol and opioids. 

Since Naltrexone is intended as a maintenance medicine, it should only be prescribed to people who have moved out of the acute phase of opioid or alcohol withdrawal and who are not taking other maintenance medications like buprenorphine. Abstinence from opioids is necessary for at least 12-24 hours prior to taking either oral or injectable Naltrexone to avoid precipitating withdrawal.

Although naltrexone is not addictive and does not cause withdrawal symptoms if you stop taking it, there are some potential side effects. They include the following:

  • Upset stomach
  • Nausea and vomiting
  • Diarrhea
  • Headache
  • Nervousness or anxiety
  • Insomnia or trouble sleeping
  • Joint or muscle pain

In summary, differences Between Naltrexone and Naloxone include:

  • Naloxone is short-acting, Naltrexone is long-acting.
  • Naloxone is for emergency use, while Naltrexone is a prescription maintenance medication.
  • Naloxone can be administered by anyone for an acute overdose, while Naltrexone can only be prescribed by a medical professional.
  • Naloxone temporarily reverses opioid overdose, while naltrexone stops the euphoric effects of opioid drugs overtime but does not stop an acute overdose.

Can I Use Naloxone & Naltrexone at the Same Time?

If you struggle with opioid use disorder, you may encounter both naloxone and naltrexone at some point. If a patient is on Naltrexone therapy and overdoses anyway, Naloxone CAN and SHOULD be used to reverse that acute overdose. If a friend or loved one encounters a patient overdosing even while on Naltrexone, they should STILL use Naloxone to reverse and acute overdose. All patients at risk of an overdose should be prescribed Naloxone (Narcan) to keep in their home or on their person in case of an accidental overdose.

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 she works as a primary care physician as well as part time in pain management and integrated health. Her clinical interests include underserved health care, chronic pain and integrated/alternative health.

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  1. Naloxone Drug Facts. National Institute on Drug Abuse (NIDA). January 2022. Accessed January 2022.
  2. FDA Approves Naloxone Injection to Counteract Opioid Overdoses. US Food and Drug Administration (FDA). October 2021. Accessed January 2022.
  3. Naloxone. Centre for Addiction and Mental Health (CAMH). Accessed January 2022.
  4. Naltrexone. Substance Abuse and Mental Health Services Administration (SAMHSA). November 2021. Accessed January 2022.
  5. What Is Naltrexone? UAMS Psychiatric Research Institute. Accessed January 2022.

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