Naloxone vs. Naltrexone: What’s the Difference Between These Opioid Blocking Medications?
Key takeaways:
Naloxone (Narcan) and naltrexone (Vivitrol) are both opioid-blocking medications.
The main difference between naloxone and naltrexone is how they’re used. Naloxone is a fast-acting medication that can reverse the effects of an opioid overdose. Naltrexone can treat alcohol use disorder and opioid use disorder, but it isn’t used in overdose situations.
Naloxone and naltrexone are usually well-tolerated. But they can cause some common side effects like nausea, constipation, and headache.
Access savings on related medications
Table of contents
Naloxone (Narcan) and naltrexone (Vivitrol) are opioid blockers. This means they reverse the effects of opioids, a group of medications that are most commonly prescribed to treat pain.
Though opioids may be effective, they can cause dependence, addiction, and overdose. Naloxone and naltrexone can play a role in preventing or treating these dangerous effects. But these medications have many important differences to know about.
Naloxone vs. naltrexone: How are they different?
The most important difference between naloxone and naltrexone is how they’re used. Naloxone is used to reverse the effects of an opioid overdose quickly.
Naltrexone is FDA approved to treat opioid use disorder and alcohol use disorder only. But it isn’t used to treat opioid overdoses. It doesn’t work fast enough to be effective in an overdose situation.
What’s naloxone?
Naloxone can reverse the effects of an opioid overdose, including slowed breathing and reduced consciousness. It works quickly, but it doesn’t last long. So someone who’s received naloxone will still need emergency treatment in a hospital.
Naloxone comes as an injection and nasal spray. These can be purchased at the pharmacy without a prescription. There are even ways to get naloxone for free.
How does naloxone work?
Naloxone is an opioid receptor antagonist (opioid blocker). To understand how it works, it helps to know how opioids work.
When you experience pain, your body releases natural opioids. The opioids attach (bind) to areas in the body called opioid receptors. This reduces the feeling of pain. When you take an opioid medication, the same thing happens. But opioid medications can also cause dangerous side effects like slowed breathing and lowered consciousness.
In severe situations, opioids can slow your breathing down so much that it stops completely. This is where naloxone comes in. It binds to opioid receptors and removes opioids off of them. This can reverse the effects of opioids and restore breathing.
What’s naltrexone?
Naltrexone is a medication that treats opioid use disorder and alcohol use disorder. It comes as a tablet and an injection that you administer into the buttocks muscle (intramuscular).
Unlike naloxone, naltrexone isn’t fast-acting. So it’s not used in emergency situations like an opioid overdose.
How does naltrexone work?
Like naloxone, naltrexone is an opioid blocker.
When you drink alcohol, your body releases a chemical called dopamine. Dopamine makes you feel good. It’s released when you do an activity that the body considers pleasurable. Drinking alcohol also releases endogenous (natural) opioids. Endogenous opioids have a lot of influence over the brain. They can create feelings of pleasure and relaxation, among other things. And when endogenous opioids are released from the body, they also promote the release of dopamine.
Taking opioid medications (exogenous opioids) also increases dopamine and opioid levels. Excessive alcohol and opioid use can make it hard for your brain to function without these substances. This may lead to dependence and addiction over time.
By blocking opioid receptors, naltrexone decreases the amount of dopamine and natural opioids that are released in the body. This makes these opioids and alcohol feel less enjoyable. It also lowers cravings for these substances.
How are naloxone and naltrexone dosed?
Naloxone and naltrexone are available in different formulations. And they’re dosed differently, as well.
Naloxone dosing
Naloxone comes as a nasal spray and an injection. Nasal spray products include generic naloxone and brand-name Narcan. Each nasal spray contains 4 mg. An 8 mg dose is also available under the brand-name Kloxxado.
Injectable naloxone products include naloxone 0.4 mg/mL and naloxone 1 mg/mL. It’s also available as brand-name Zimhi, a 5 mg auto-injector. An auto-injector is an injection device designed to easily administer a specific dose of a medication.
If you think someone has overdosed on opioids, you should administer naloxone right away if it’s available. Even if it turns out that opioids aren’t what caused the overdose, giving naloxone won’t cause the person harm. But if opioids did cause the overdose, naloxone can be life saving.
Naltrexone dosing
Naltrexone is available as 50 mg tablets. The typical dose for alcohol use disorder and opioid use disorder is 50 mg per day. But for opioid use disorder, your healthcare provider may start you at just 25 mg per day. If you tolerate it well, you’ll probably be asked to increase your dose to 50 mg per day.
Naltrexone also comes as a long-acting intramuscular (IM) injection. It’s a brand-name-only product called Vivitrol. It comes as a vial that contains 380 mg. The entire vial is given with each injection. It only needs to be administered once every 4 weeks. Vivitrol should only be injected by a healthcare provider.
Common side effects of naloxone and naltrexone
Naloxone and naltrexone are generally well-tolerated medications, but side effects are still possible. Naloxone nasal spray, oral naltrexone, and IM naltrexone can all cause some common side effects, including nausea, headache, and joint or muscle pain. Diarrhea, dizziness, and trouble sleeping have also been reported with oral naltrexone and IM naltrexone.
But the most common side effect of IM naltrexone is injection site reactions, like redness or swelling at the injection site. If you have any signs of an injection site reaction, contact your healthcare provider immediately.
Serious side effects of naloxone and naltrexone
Naloxone and naltrexone can also cause serious side effects. Still, the benefits of these medications may outweigh the risks.
Opioid withdrawal
Opioid withdrawal can occur when you’re physically dependent on opioids. If you stop taking the opioids, you can experience uncomfortable symptoms. Many of the common side effects discussed above may actually be signs of opioid withdrawal. These include muscle aches, nausea, and vomiting. You may also experience stomach cramping, diarrhea, and a runny nose.
After naloxone administration, withdrawal symptoms may occur immediately. But even though withdrawal symptoms are uncomfortable, they aren’t life-threatening. With naltrexone, you can prevent withdrawal symptoms by avoiding opioid medications for at least 7 to 10 days before starting naltrexone.
Other serious naloxone side effects
Naloxone may cause heart problems. This is because the rapid reversal of opioid effects can put stress on the heart. It’s more likely in people with existing heart conditions or those who take certain other medications. Still, naloxone can be life-saving in an opioid overdose. So you shouldn’t avoid using naloxone even in people who have existing heart problems.
Other serious naltrexone side effects
Besides opioid withdrawal, naltrexone may cause other serious side effects. These include:
Lower tolerance to opioids. Naltrexone can make you more likely to experience an overdose if you relapse to opioids. This can happen even with opioid doses that are lower than what you’ve tolerated in the past.
Liver problems. Naltrexone may cause liver problems, especially at high doses. Your healthcare provider will check labs to make sure your liver is functioning properly.
Depression and suicidal thoughts. If you notice a change in your mood while taking naltrexone, talk to your provider. If you or someone you know is having thoughts of suicide, help is available. Call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.
Severe allergic reactions (anaphylaxis). If you experience signs of a severe allergic reaction like swelling of the face or tongue, or trouble breathing, call 911 or seek emergency care.
Do naloxone and naltrexone have any drug interactions?
Naloxone doesn't have any known drug interactions. But naltrexone can interact with some medications, including cough and antidiarrheal medications that contain opioids.
How to save on naloxone and naltrexone
Naloxone and naltrexone are available as brand-name medications and lower-cost generics. There are many ways to save on these products.
Naloxone
Naloxone is covered by many insurance plans, including most Medicare plans. It’s also covered by many Medicaid plans. But if you’re uninsured or underinsured, you still have options to help you save:
Get naloxone for free. Some state and city governments, and nonprofit organizations, have programs that give out naloxone for free.
Save with GoodRx. If you can’t get naloxone for free, GoodRx can help you save close to 50% off the average retail price. The generic naloxone price at certain pharmacies is less than $50 with a free GoodRx discount.
Naltrexone
There are many ways to save on naltrexone products. These include:
Save with GoodRx. GoodRx can help you save over 65% off the average retail price of the generic version of oral naltrexone. Generic oral naltrexone at certain pharmacies can be as low as $12 with a free GoodRx discount.
Save with a copay savings card. If you have commercial insurance, you may be eligible to save up to $500 a month on out-of-pocket costs for brand-name IM Vivitrol using a savings card from the manufacturer
The bottom line
Naloxone and naltrexone are both opioid blockers. But naloxone is a fast-acting medication that reverses the effects of an opioid overdose. Naltrexone doesn’t work in overdose situations. It’s a once daily or once monthly medication that can treat alcohol use disorder or opioid use disorder.
Why trust our experts?
References
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Legislative Analysis and Public Policy Association. (2020). Naloxone access: Summary of state laws.
MedlinePlus. (2022). Opiate and opioid withdrawal.
National Alliance on Mental Illness. (2021). Naltrexone (ReVia).
Proficient Rx LP. (2022). Narcan [package insert].
Ray, L. A., et al. (2010). Naltrexone for the treatment of alcoholism: Clinical findings, mechanisms of action, and pharmacogenetics. CNS & Neurological Disorders.
Shenoy, S. S., et al. (2022). Biochemistry, endogenous opioids. StatPearls.
Substance Abuse and Mental Health Services Administration. (2022). Naltrexone.
U.S. Department of Health and Human Services. (2020). CMS should pursue strategies to increase the number of at risk beneficiaries acquiring naloxone through Medicaid.
If you or someone you know struggles with substance use, help is available. Call SAMHSA’s National Helpline at 1-800-662-4357 to learn about resources in your area.
