How are naltrexone and Suboxone different? Is naltrexone the same as Suboxone?
No, and in one important way the two are opposites. Naltrexone is an opioid antagonist, which means that it blocks opioid receptors without turning them on. Suboxone is mostly buprenorphine, a partial opioid agonist, which means that it turns those same receptors on part of the way.
Dr. Leeds is an osteopathic physician with over two decades of experience in treating medication and drug dependence and addiction. He prescribes buprenorphine for opioid dependence, and he prescribes naltrexone for alcohol use disorder using the Sinclair Method.
An analogy that might help is a lock and a key. An opioid such as heroin, fentanyl, or oxycodone is a key that fits the lock and turns it all the way. Buprenorphine is a key that fits, turns part of the way, and is very hard to pull back out.
Naltrexone is the wrong key. It fits the lock, it cannot turn, and while it sits there no other key can get in. While this is not a perfect analogy, it explains nearly everything that follows.
So, if both medications sit on the same receptor, why can one be started within a day while the other takes a week or more? Why is one of them called “non-addictive,” and is that the same thing as safe? And, which of these drugs is actually inside a Suboxone film?
Is there naltrexone in Suboxone? How much naltrexone is in a Suboxone film?
There is none. Suboxone does not contain naltrexone at all, in any amount. The second ingredient in Suboxone is naloxone, and the names are close enough that it is not hard to get them mixed up. Even doctors sometimes get it mixed up.
Suboxone is four parts buprenorphine to one part naloxone. For example, an 8 mg/2 mg Suboxone film contains 8 mg of buprenorphine and 2 mg of naloxone.
You may know naloxone as Narcan, the nasal spray that reverses an opioid overdose. It is another key that does not turn. Sprayed into the nose or injected, it pushes the opioid off of the receptor, and in most cases the person starts breathing again.
While naloxone is a powerful blocker by those routes, under the tongue it is a different story. The Suboxone prescribing information says that naloxone is absorbed only in small amounts when it is taken that way. So, when the film is taken as directed, the naloxone usually has little or no effect.
Then why is naloxone in Suboxone at all?
The naloxone was added for one purpose, which is to discourage a person from dissolving the film and injecting it. The prescribing information says that the combination is likely to cause withdrawal if it is injected by a person who is dependent on full opioids such as heroin, morphine, or methadone.
While that sounds like a strong deterrent, it is a narrower promise than most people assume. Buprenorphine holds on to the receptor tightly, and a person who takes only buprenorphine may feel far less from injected naloxone than the theory suggests.
Adding one drug to another to prevent misuse is a strange idea to begin with, and there is more on that question in the comparison of Suboxone and Subutex, which is buprenorphine without the naloxone. It is understandable when patients find it odd that their medication carries an ingredient that provides no benefit to their health.
What is the difference between naloxone and Suboxone?
Naloxone is one drug, and Suboxone is two. Naloxone by itself is a rescue medication. It acts fast, it can wear off before the opioid does, and its only job is to reverse an overdose.
Suboxone is a daily treatment for opioid dependence, and the buprenorphine does the work. The naloxone in the film is along for the ride, and little more.
And, naltrexone is a third drug altogether. The label for naltrexone tablets describes it as related to naloxone, but naltrexone works when it is swallowed, and a single tablet can block opioids for as long as 24 hours. That is why naltrexone can be a treatment and not only a rescue.
If the three names blur together, go back to the lock. Ask whether the key turns.
Suboxone can be started in withdrawal. Naltrexone cannot.
Buprenorphine is started while you are in withdrawal. The Suboxone prescribing information calls for the first dose when objective signs of moderate withdrawal appear, not less than six hours after the last opioid.
For most short-acting opioids, that means relief within about a day. While fentanyl is harder to time, and a first dose taken too early can cause precipitated withdrawal, the wait is still measured in hours or days. That timing problem is why low-dose induction exists.
Naltrexone cannot be started that way. Given to a person who still has opioids on the receptors, a pure blocker causes sudden withdrawal, and the prescribing information for Vivitrol, the monthly naltrexone injection, warns that it can be severe enough to require a hospital stay. So, the label recommends a minimum of 7 to 10 days with no opioids first, and it warns that a person coming off of buprenorphine or methadone may be vulnerable for as long as two weeks.
How does anyone know that enough time has passed? The label admits that there is no completely reliable way to tell. A doctor can check a urine test and give a test dose of naloxone, and withdrawal has still been reported afterward.
The practical dividing line between these two medications is not the chemistry. It is the week or two that has to come first. That stretch is one of the hardest things we ask of anyone, and for many people it is very hard to get through at home.
It is common for a person to make it several days into that wait and go no further. Those of us who have not gone through opioid withdrawal have no right to judge them. Suboxone can meet you there.
What forms do naltrexone and Suboxone come in?
There are three medications approved by the FDA to treat opioid dependence, and they are methadone, buprenorphine, and naltrexone. Buprenorphine comes as the Suboxone film, as generic films and tablets, and as the ZubSolv tablet, all of which dissolve under the tongue. It also comes as a long-acting injection under the skin, Sublocade or Brixadi, given once a month or, with Brixadi, once a week.
Naltrexone comes as a tablet taken once a day and as Vivitrol, an injection into the muscle that is given once a month. While the tablet and the shot are the same drug, they do not have the same track record.
For opioids, the tablet’s record is weak, and its prescribing information says so itself. It states that there are no data showing an unequivocal benefit on return to opioid use among people who take the tablets on their own.
Why would that be? The label’s own explanation is that naltrexone, unlike methadone, does nothing that draws a person back to the next dose. That is a property of the drug, and the patient is not to blame for it.
Is naltrexone an opioid or a narcotic? It is neither. Buprenorphine is an opioid and a controlled substance, with all of the prescription rules that come with that.
Naltrexone is not controlled at all, and any licensed prescriber can write for it. So, naltrexone is the simpler prescription to write. It is not the simpler treatment to start.
What about Vivitrol? Is the monthly shot better than Suboxone?
Vivitrol is naltrexone in an extended-release form. According to its prescribing information, one injection blocks the effects of opioids for approximately 28 days, so there is no daily tablet to think about.
That convenience cuts both ways. Once the shot is given, the patient has a month of naltrexone on board, and there is no taking it back. That matters if they turn out to be allergic to it, cannot tolerate the nausea that naltrexone can cause, or were not as far past their last opioid as everyone believed.
While the Vivitrol prescribing information says that pretreatment with oral naltrexone is not required, there is a good argument for a short run of the tablets before the first injection, not because the tablets work but because they wear off. A bad reaction to a tablet is over within a day or two. A bad reaction to the shot is not.
Part of the appeal of Vivitrol is that it is not an opioid, it does not cause a high, and stopping it does not cause withdrawal. Those qualities are a comfort to the people around the patient. Yet, what makes a drug comfortable for the people around the patient is not what makes it work for the patient.
Unfortunately, the monthly shot does nothing about the wait. Its approved use for opioids is to prevent a return to opioid dependence “following opioid detoxification,” which means that the hardest part must be finished before the first injection. That is where many people are lost, before treatment has even begun. Buprenorphine has no such hurdle, which is a large part of why it is easier to start and to stay with.
Is there anyone for whom Vivitrol is the better choice? Yes, and it is the person who has already been off of opioids for weeks and wants a medication that is not an opioid. That choice is theirs. There is a separate comparison of the two monthly injections in Sublocade vs Vivitrol.
Why are doctors hesitant to prescribe naltrexone?
For opioid dependence, the hesitation is reasonable, because naltrexone cannot be given to the patient who is sitting in the office in withdrawal. The Vivitrol label lists as contraindications anyone taking opioid pain medication, anyone currently dependent on opioids, anyone in acute opioid withdrawal, anyone with a positive urine test for opioids or a failed naloxone test dose, and anyone who has had an allergic reaction to the drug.
For alcohol, the hesitation is harder to defend. Naltrexone is a highly useful medication that was almost forgotten, and it is now enjoying renewed interest.
What happens when naltrexone wears off?
Naltrexone is often described as “non-addictive,” and that is true. The label for the tablets states that it does not lead to physical or psychological dependence. Yet, non-addictive is not the same as safe.
Think about what has happened to the body by the time the blocker wears off. The person went a week or more with no opioids in order to start, and then spent a month, or many months, with the receptors blocked. Most of their tolerance is gone.
The Vivitrol prescribing information says so plainly. As the blockade fades, a person may respond to lower doses of opioids than they used before, and a dose that was once routine can stop their breathing. The label warns of potentially fatal overdose at the end of a dosing interval, after a missed dose, or after stopping treatment.
The label also warns that trying to push through the block with a large amount of an opioid is especially dangerous, and it asks patients to tell the people closest to them about the risk. If someone’s breathing slows or stops, or they cannot be woken, call 911 right away and give naloxone if you have it.
There is one more warning worth knowing. The Vivitrol label reports cases of hepatitis and liver problems during treatment, so your doctor needs to know about any liver disease.
Is buprenorphine free of risk? It is not. It is an opioid, and the Suboxone prescribing information warns of life-threatening slowing of breathing, especially when it is combined with other sedating drugs or alcohol.
Still, a person who takes buprenorphine every day keeps a tolerance to opioids, and the receptors stay occupied. For a person who is physically dependent on opioids today, that is a real safety advantage.
Naltrexone’s real home is alcohol.
The tablets are approved for alcohol dependence as well as for blocking opioids. Fortunately, for a person who does not take opioids, there is no waiting period to get through first.
In Dr. Leeds’ practice, naltrexone is used with the Sinclair Method. The patient takes a tablet one hour before drinking, the alcohol appears to deliver less of its usual reward, and over time the cravings and the amount consumed come down. This gradual unlearning is known as pharmacological extinction, and it does not require abstinence to begin.
One caution carries over from the opioid side. Naltrexone blocks opioid pain medication just as it blocks heroin, and it will cause withdrawal in anyone who takes opioids every day. If you take naltrexone for drinking, every doctor and dentist who treats you needs to know.
Can you take naltrexone and Suboxone together?
No. Naltrexone would do to buprenorphine what it does to any other opioid, and the result is precipitated withdrawal. The label for naltrexone tablets lists current dependence on opioids as a contraindication, and it names buprenorphine specifically.
What about moving from Suboxone to naltrexone? While it is possible, it has to be done in order. The Suboxone prescribing information says to taper gradually when stopping, and only after the last dose does the opioid-free stretch begin.
Some people ask whether a long-acting buprenorphine injection can soften the end of a taper, and there is a separate article on the Sublocade taper. Whatever the method, if a taper is moving too fast, your doctor must slow it down.
Taking Suboxone is not trading one addiction for another.
Yet, this is the belief that the word “non-addictive” leaves behind. If naltrexone is the non-addictive choice, then Suboxone must be the addictive one, and the patient who takes it must still be addicted.
Physical dependence is not addiction. Dependence means that the body has adapted to a medication and will go into withdrawal if it is stopped suddenly, and the Suboxone prescribing information says plainly that buprenorphine causes it.
Addiction is something else. It is the loss of control, the compulsive use that continues in spite of harm.
A person who takes buprenorphine as prescribed, goes to work, and takes care of their family has a medical dependence that is being treated. They are not getting high, and they have not traded anything.
Does dependence matter, then? It does, because it means that buprenorphine should not be stopped cold turkey. If the day comes when you want to come off of it, the way down is a slow taper, as tolerated, and there is more on that in the article on whether Suboxone is addictive.
Tolerance falls after a taper as well, so the same caution about overdose applies. Whether and when to taper is your decision.
Narcotics Anonymous is one place where people hear that Suboxone is a trade. Naltrexone raises no issue in the program, because it is not an opioid and there is nothing in it that could be called a high.
Buprenorphine is treated differently. The program’s literature describes recovery as complete abstinence from all drugs, and it has long placed methadone and buprenorphine on the wrong side of that line, so a member on Suboxone may be welcome in the room and still be told that they are not yet in recovery. That position is wrong, and the program would do well to change it, because a person who takes buprenorphine as prescribed is in recovery.
So, a patient on Suboxone who wants to attend is free to go, and some of them find the meetings helpful. They owe no one in the room an explanation of their prescription. Your medical treatment is between you and your doctor. By the program’s own tradition, it is an outside issue.
So, which one should you choose?
When it comes to naltrexone vs. Suboxone, the question is not which drug is better. The question is where you are today. If you are physically dependent on opioids right now, buprenorphine is the medication that can be started this week, while you are in withdrawal.
If you have already been off of opioids for weeks, naltrexone is a legitimate choice, as long as you and the people close to you understand what happens when it wears off. And, if the problem is alcohol, naltrexone is the one to ask about.
There is no one-size-fits-all answer. While a doctor can lay out the options and what the labels say, it is ultimately your decision.
How does Dr. Leeds use these two medications?
In Dr. Leeds’ practice, buprenorphine films and tablets are prescribed by telemedicine to new patients in Florida, with in-office visits available in Fort Lauderdale. The first dose is taken at home with phone support, and when fentanyl is involved, a low-dose start is used when needed.
Naltrexone is prescribed for alcohol use disorder with the Sinclair Method. Dr. Leeds can also advise on the long-acting injections in a consultation, including Vivitrol versus oral naltrexone and how to come off of a buprenorphine injection.
To ask Dr. Leeds about buprenorphine treatment for opioid dependence, or about naltrexone and the Sinclair Method, use the contact form.
This article is educational. It is not medical advice, and reading it does not create a doctor-patient relationship. Decisions about starting, continuing, or tapering any medication should be made with your own physician.
