Subutex and Suboxone are drugs that were approved by the FDA in 2002 for the treatment of opioid dependence. Both drugs contain the active ingredient buprenorphine, a semisynthetic opioid that acts as primarily as a partial mu-opioid receptor agonist. Buprenorphine also acts as an antagonist at the kappa and delta opioid receptors.
Buprenorphine’s mechanism of action mitigates severe withdrawals associated with illicit opioid use, and serves as a “replacement” drug for illicit opioids. The goal is to help those dependent on illicit opioids transition off of them and onto a replacement therapy like Subutex or Suboxone. Once a patient has stabilized on the replacement (e.g. Subutex or Suboxone), the next step is to gradually titrate off of the replacement drug, and ultimately for the individual to remain sober.
Although Subutex and Suboxone are similar, the most notable difference between the two is the additional component of Naloxone in Suboxone. The Naloxone component makes the Buprenorphine component no longer effective past a certain dose (“ceiling effect”), and if crushed or injected, an individual will experience a withdrawal rather than a “high.” This means that Suboxone has slightly less abuse potential among those with opioid dependence compared to Subutex.
Subutex vs. Suboxone Comparison Chart
As you can see, there really aren’t many differences between Subutex and Suboxone. The primary difference is that Suboxone contains a unique formulation of 80% buprenorphine and 20% naloxone, whereas Subutex contains only buprenorphine hydrochloride.
|Drug type||Synthetic opioid (Partial agonist)||Synthetic opioid (Partial agonist)|
|Approved uses||Opioid dependence.||Opioid dependence.|
|Ingredients||Buprenorphine Hydrochloride||Buprenorphine (80%) / Naloxone (20%)|
|Formats||Sublingual tablet.||Sublingual film. Sublingual tablet.|
|Dosages||2 mg or 8 mg||Sublingual film: 2 mg/0.5 mg or 4 mg/1 mg or 8 mg/2 mg or 12 mg/3 mg + Tablet: 2 mg/0.5 mg or 8 mg/2 mg|
|Manufacturer||Reckitt Benckiser Pharmaceuticals||Reckitt Benckiser Pharmaceuticals|
|Legal Status||Schedule III (US)||Schedule III (US)|
|Mechanism of action||Functions primarily as a non-selective mixed agonist/antagonist opioid receptor modulator. Acts as a partial agonist at the mu-receptor – antagonist at the kappa-receptor – and antagonist at the delta-receptor. It has a high affinity for the sigma-receptor and a minimal effect upon the nociceptin receptor. Buprenorphine also inhibits voltage-gated sodium channels.||Functions primarily as a non-selective mixed agonist/antagonist opioid receptor modulator. Acts as a partial agonist at the mu-receptor – antagonist at the kappa-receptor – and antagonist at the delta-receptor. It has a high affinity for the sigma-receptor and a minimal effect upon the nociceptin receptor. Buprenorphine also inhibits voltage-gated sodium channels. The Naloxone component of Suboxone has a high affinity for the mu-receptor as a competitive antagonist. It also elicits antagonist effect upon the kappa and delta receptors.|
|Half life||24 to 42 hours||24 to 42 hours|
|Common side effects||Constipation. Dizziness. Drowsiness. Headaches.||Constipation. Dizziness. Drowsiness. Dry mouth. Lightheadedness. Nausea. Sweating. Vomiting.|
|Date approved||October (2002)||October (2002)|
|Effect duration||24 hours (Analgesic: 8 to 12 hours)||24 hours (Analgesic: 8 to 12 hours)|
|Investigational uses||Chronic Pain.||Chronic Pain. Neonatal abstinence syndrome. Treatment-resistant depression. (Read: Suboxone for depression).|
Subutex vs. Suboxone: What’s the difference?
These drugs both contain buprenorphine, which means they act as partial opioid agonists, most notably at the mu-receptor. However, since Subutex does not contain Naloxone, it has a greater potential for abuse and misuse. Naloxone is a drug that was developed in the 1960s to counteract the effects of opioids, especially in the event of an overdose.
It counteracts opioid effects by functioning as a competitive opioid antagonist, meaning it binds to opioid receptors with a higher affinity than agonists. After binding to the receptors it prevents activity and thus an individual will feel no opioid-based effects. Naloxone in particular has a high affinity for the mu-receptor, which offsets the buprenorphine partial agonism, especially when ingested at high doses.
Reckitt Benckiser Pharmaceuticals first developed Subutex, which contained just buprenorphine hydrochloride as the active component. In effort to further reduce abuse potential and make the drug safer, they formulated the drug Suboxone with both buprenorphine and naloxone at a 4:1 ratio. For many individuals, Subutex is administered during early stages of opioid replacement therapy, and Suboxone is given during the maintenance phase.
Since both Subutex and Suboxone are classified as “Schedule III” controlled-substance, it would be logical to conclude that both have equal potential for abuse. Schedule III substances are regarded as having less abuse potential than Schedule II drugs and are known to have medically accepted uses. Additionally, Schedule III drugs like Subutex and Suboxone may lead to some physical dependence and significant psychological dependence.
Some speculate that Subutex has a greater potential for abuse than Suboxone, especially when administered at high doses. The Naloxone component of Suboxone acts as a competitive opioid antagonist with a high affinity for the mu-receptor. At higher doses, enough Naloxone binds to the mu-receptor and is thought to inhibit additional Buprenorphine mu-receptor stimulation.
Many individuals attempting to abuse Buprenorphine inject it intravenously in attempt to get “high” during opioid replacement therapy. This intravenous injection is thought to provide individuals with a more potent opioid “high.” Should an individual attempt to take intravenous Suboxone, the Naloxone component is thought to trigger severe withdrawal symptoms rather than a Buprenorphine-induced “high.”
Evidence suggests that individuals dependent on potent opioids experience an array of unpleasant symptoms should they attempt to administer Suboxone via intravenous injection or intranasal insufflation. Individuals that are dependent on less potent opioids may not experience as many unpleasant symptoms following intravenous Suboxone administration as those who are highly dependent. That said, the Naloxone will still mitigate the opioid effect of the Buprenorphine, thus making it unlikely to achieve opioid intoxication.
Among non-dependent opioid abusers, it seems as if Subutex and Suboxone are equal in their abuse potential. A very small-scale study revealed that high doses of Subutex and Suboxone resulted in similar opioid agonist-like effects. The researchers suggested that there was not enough evidence to suggest that Naloxone mitigated Buprenorphine’s opioid agonist effects in non-dependent abusers when administered sublingually.
As a recap, Subutex has a significant abuse potential among individuals with opioid dependence and among non-dependent addicts. Suboxone has less potential for abuse, especially among those dependent upon potent opioids – this is due to the presence of Naloxone. Among non-dependent abusers, the abuse potential is regarded as being relatively similar.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10928310
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20403021
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25060839
Cost: Which is more expensive?
Those comparing Subutex and Suboxone may want to consider the cost of each medication. Due to the fact that both drugs contain mostly Buprenorphine as the active ingredient, they are similar. If you have poor insurance or have to pay out-of-pocket for your medications, you may decide to opt for the least expensive formulation.
Subutex is only manufactured in generic format as “buprenorphine” and can be obtained at a price of $45 to $70 for 30 sublingual 2 mg tablets, and between $75 and $110 for 30 sublingual 8 mg tablets. Brand name Suboxone can be purchased for a price between $128 and $470 for a 30 sublingual films. The greater the dosage of the Suboxone films, the greater the cost.
Generic Suboxone (Buprenorphine / Naloxone) can be purchased in the format of sublingual tablets for a price between $75 and $190 for a 30 day supply; the greater the dosage, the higher the cost. Clearly the cheapest option is Subutex, followed by generic Suboxone tablets, and the most expensive option is brand-name Suboxone films. Some people may prefer the sublingual films over the tablets and therefore may be willing to pay extra for them.
Dosage & Formats
Subutex is manufactured in the format of sublingual tablets with dosages of 2 mg and 8 mg. Sublingual tablets are a formulation of the drug that can be placed under the tongue and that dissolve in the mouth. The dosing options and formats of Subutex are relatively limited by comparison to Suboxone.
Suboxone is manufactured in the format of both sublingual tablets and sublingual film. The dosing options for the sublingual film are as follows: 2 mg/0.5 mg, 4 mg/1 mg, 8 mg/2 mg, and 12 mg/3 mg. The first number of each dose indicates the amount of buprenorphine, while the second indicates the amount of naloxone; each dose is engineered to have a 4:1 ratio.
Like the sublingual Subutex tablets, sublingual Suboxone tablets are only manufactured in 2 dosing options including: 2 mg/0.5 mg and 8 mg/2 mg. There really isn’t much difference in the sublingual tablet dosing options by comparison of Subutex to Suboxone, but there are 2 additional dosing options associated with the Suboxone sublingual film.
Most individuals would agree that sublingual film and sublingual tablets are similar. Some people may prefer to put a film under their tongue, while others may find the tablets easier to administer; it’s ultimately a personal preference. Suboxone may be considered advantageous over Subutex due to the fact that it offers multiple sublingual formats and extra dosing increments.
Efficacy: Which drug is more effective?
Everyone wants to know whether Subutex or Suboxone is more effective for treating opioid dependence. There is no definitive evidence suggesting that one drug is superior to the other in regards to efficacy. Both contain the active ingredient buprenorphine, which acts as a partial agonist with most of its effect elicited upon the mu-receptor.
Certain individuals may respond better to higher doses of Subutex than Suboxone in early stages of treating opioid dependence. This is due to the fact that at high doses, it is speculated that Naloxone may counteract some of the mu-receptor stimulation from the Buprenorphine. Therefore some professionals may initially treat someone with Subutex and transition them to Suboxone after several weeks.
A study published in 2010 analyzed the effects of switching individuals from Subutex to Suboxone. The study involved 94 participants that were initially treated with 8 mg per day of buprenorphine monotherapy for an average of 840 days. They were eventually switched to Suboxone (buprenorphine / naloxone) and the outcomes were monitored.
The participants rated their level of satisfaction with Suboxone in respect to management of withdrawal symptoms. Urinary toxicology data was collected throughout the study and revealed a reduction in positive toxicology tests after switching to Suboxone. This meant that they were less likely to abuse other drugs (e.g. heroin, cocaine, etc.) on Suboxone than Subutex.
Researchers also discovered that the time between clinic visits was increased with Suboxone compared to Subutex, in part due to less extracurricular drug abuse (as revealed by toxicology reports). Both drugs are considered well-tolerated, but there may be subtle advantages associated with Suboxone including: reduced abuse potential and reduced likelihood to abuse illicit drugs during treatment of opioid dependence.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20450243
Mechanisms of action
The mechanisms of action associated with Subutex and Suboxone are nearly the same. Subutex contains Buprenorphine Hydrochloride, which acts as a partial mu-opioid receptor agonist. Buprenorphine also elicits effects as a kappa receptor antagonist, delta receptor antagonist, and has a fairly high affinity for the sigma receptor. It is thought to have a minor affinity for the nociceptin receptor as well and inhibit voltage-gated sodium channels.
Since Suboxone is comprised of 80% buprenorphine, its mechanism of action is nearly identical to that of Subutex. However, Suboxone was engineered to contain the additional component of Naloxone, which functions as a pure opioid-receptor antagonist. It has a high affinity for the mu-receptor as a competitive antagonist and modest antagonist effects on kappa and delta opioid receptors.
As a pure antagonist, Naloxone is capable of binding to opioid receptors and ultimately preventing stimulation from opioid receptor agonists. Since 20% of Suboxone is formulated with Naloxone, it elicits these additional effects, compared to Subutex which solely contains Buprenorphine.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22504149
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12435410
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24903063
Subutex and Suboxone are FDA approved for the treatment of opioid dependence. Despite the fact that they are sometimes prescribed off-label to treat chronic pain, they are not technically approved for that condition. Subutex and Suboxone are different in that Suboxone is considered to have slightly less potential for abuse and therefore is prescribed more frequently as an investigational drug.
Investigational uses for Suboxone include the treatment of neonatal abstinence syndrome and treatment-resistant depression. Neonatal abstinence syndrome is a condition in which a baby is exposed to opioids via a pregnant mother and experienced withdrawal symptoms when the mother stops using and/or after birth. Specially formatted Suboxone for infants is currently being studied for this condition.
In rare cases, individuals are prescribed Suboxone as an antidepressant augmentation strategy. While Suboxone may be highly effective in treating depressive symptoms, it is seldom prescribed due to its lacking of approval and the presence of safer, more established options. A drug similar to Suboxone called “ALKS-5461” has demonstrated significant efficacy in alleviating depressive symptoms.
Subutex and Suboxone are considered relatively popular drugs in the realm of opioid replacement therapy. Suboxone is the more popular drug by comparison due to the fact that it is regarded as a safer, upgraded version of Subutex. From the perspective of a hardcore opioid addicts, Subutex may be the more sought out format of the drug.
That said, among medical professionals, Suboxone is clearly the favorable treatment for opioid dependence. In part, this popularity is due to the added presence of Naloxone, a component that has been marketed to produce a “ceiling effect.” This purported “ceiling effect” is thought to prevent any additional “high” or intoxication past a certain dose, making abuse less likely.
In addition, the Naloxone within Suboxone inhibits the intravenous and intranasal potential for a “high” compared to Subutex. Popularity of Suboxone has largely increased due to the belief that it is both newer and regarded as being a safer treatment for opioid dependence.
Theoretically, the side effect profiles of Subutex and Suboxone shouldn’t be much different. Common side effects associated with both drugs include: constipation, dizziness, drowsiness, headaches, and nausea. Some speculate that since Subutex does not contain Naloxone, that it has a favorable side effect profile.
Rationally it would make sense that among individuals sensitive to the effect of Naloxone, side effects may emerge. There is an extra substance within Suboxone, and therefore is likely an increased potential for side effects. Examples of common side effects associated with Naloxone include: constipation, dizziness, drowsiness, dry mouth, lightheadedness, and sweating.
The presence of Naloxone may amplify certain side effects derived from Buprenorphine, and may trigger additional side effects. Naloxone has potential to induce catecholamine release, cause pulmonary edema, and cardiac arrythmias. For this reason, Subutex may have a slightly favorable side effect profile.
That said, the counterpoint could be made that Naloxone may mitigate certain side effects associated with Buprenorphine. The number and severity of side effects experienced may be subject to significant individual variation. Some people may report reductions in side effects when taking Subutex, while others may find that they have less side effects on Suboxone.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17367258
The withdrawal symptoms associated with Subutex and Suboxone tend to be most severe within the first couple weeks of discontinuation. Most individuals find that withdrawal gets easier as time continues to pass. This is in part due to the fact that a person’s neurophysiology is being restored back to homeostatic functioning.
Those that took Subutex or Suboxone for a long-term and/or a high dose are likely to have the most severe withdrawal periods. Many long-term, high-dose users will experience protracted discontinuation effects in the form of “post-acute withdrawal syndrome” (PAWS) which can last for months (or longer) following the date of discontinuation. Some individuals may have a tougher time discontinuing Subutex, while others may have a more difficult time coping with Suboxone withdrawal.
Both should produce similar symptoms due to the fact that individuals are primarily withdrawing from Buprenorphine. While users may not experience any withdrawal symptoms from the Naloxone component, to suggest that there’s no discontinuation effect (even if undetectable) from Naloxone is relatively short-sighted. Certain individuals may have a slightly easier time discontinuing Subutex for this reason.
Similarities (Recap): Subutex vs. Suboxone
Listed below are the similarities shared between Subutex and Suboxone.
- Drug type: Subutex and Suboxone are regarded as semisynthetic opioids and are first-line treatments for opioid dependence.
- Duration of effect: The duration of effect associated with these drugs is 24 hours, with a 8 to 12 hour analgesic window.
- Efficacy: Subutex and Suboxone are regarded as having nearly identical efficacy due to the same dosage content of buprenorphine.
- Generic availability: Generic formats are available for both drugs. Subutex is manufactured as “buprenorphine hydrochloride” and Suboxone is sold as “buprenorphine/naloxone.”
- Half-life: The elimination half-life for both drugs is thought to range between 24 and 42 hours.
- Legal status: Both drugs are classified as “Schedule III” controlled-substances.
- Medical uses: Both medications have been FDA approved for the treatment of opioid dependence.
- Manufacturers: Reckitt Benckiser Pharmaceuticals is responsible for manufacturing both Subutex and Suboxone.
- Withdrawal: Discontinuation from Subutex and Suboxone is thought to be relatively difficult. There is no evidence that discontinuation from one is more or less severe than the other.
Differences (Recap): Subutex vs. Suboxone
Listed below are some differences between Subutex and Suboxone.
- Abuse potential: Despite classification of both substances as “Schedule III” – Suboxone may have slightly less abuse potential among individuals with opioid dependence. This reduced abuse potential stems from the ingredient naloxone, which triggers unfavorable symptoms when intravenously injected or insufflated.
- Cost: Purchasing generic Subutex is regarded as cheaper than generic Suboxone. Purchasing brand name Suboxone is more expensive than the respective generic formulations.
- Formats: Subutex is manufactured in the format of sublingual tablets, whereas Suboxone can be taken in the formats of sublingual films or sublingual tablets.
- Ingredients: Subutex is comprised of buprenorphine hydrochloride, while Suboxone contains buprenorphine and naloxone.
- Investigational uses: Subutex isn’t known to have any investigational uses, whereas Suboxone has been investigated for treating neonatal abstinence syndrome and refractory depression.
- Mechanisms of action: While both drugs primarily act as partial mu-receptor agonists as a result of the buprenorphine content, a slight mu-receptor antagonist effect is triggered as a result of naloxone in Suboxone. This effect is not present in Subutex.
- Side effects: The side effects associated with both drugs are thought to be relatively similar due to the fact that buprenorphine is the primary active ingredient. There may be increased propensity for side effects with Suboxone due to its naloxone content.
- Popularity: Among medical professionals, Suboxone remains the more popular drug than Subutex. This increase popularity results from the fact that Suboxone is thought to have less abuse potential.
Which drug is a better opioid replacement therapy? Subutex vs. Suboxone.
Anecdotal reports across the internet may claim that Subutex is better than Suboxone, while others may claim the opposite. There is some evidence that the presence of naloxone within Suboxone may result in more favorable opioid withdrawal symptoms during the transition from an illicit drug (e.g. heroin) to the replacement. This favorable mitigation of withdrawal symptoms during the transition may be due to the presence of naloxone.
One study involving patients transitioning from Subutex to Suboxone noted that after 2 weeks of Suboxone usage, participants were less likely to abuse illicit opioids. They were able to detect a reduction in illicit opioid abuse as a result of toxicology data collected. Some people like the fact that Suboxone is manufactured in multiple formats (sublingual film and sublingual tablet) compared to Subutex which is only sold in the format of sublingual tablets.
In terms of side effects, some individuals may respond slightly better to Subutex due to the fact that it contains zero naloxone, while others may respond better to the Suboxone as a result of the naloxone content. In some cases, a doctor may prescribe Subutex in early stages of opioid replacement therapy and transition a patient to Suboxone after a couple weeks. This is due to the fact that Suboxone is less likely to be abused, particularly intravenous or intranasal due to the naloxone content.
Some have argued that the naloxone content within Suboxone was mostly added for marketing purposes and that it doesn’t really provide a “ceiling effect” or reduce abuse potential. This speculation has to do with the fact that the patent expired for Subutex, whereas the patent had not expired for Suboxone. This may have lead the developers to create a campaign suggesting that their revised formulation of Suboxone is favorable to the generic Subutex.
Ultimately there is some evidence to suggest that Suboxone may be the safer option with reduced abuse potential when compared to Subutex. For this reason, Suboxone is generally regarded as the superior option for the treatment of opioid dependence. However, cost differences and unfavorable side effects associated with naloxone may prompt some patients to request Subutex over Suboxone.
Which drug do you prefer: Subutex or Suboxone?
If you have experience using both Subutex and Suboxone, feel free to share a comment regarding any differences you noticed between the two drugs. Specifically, you may want to mention whether you experienced an increased number of unfavorable side effects while taking one drug compared to the other. If you’ve had the experience of withdrawing from both, mention whether one was easier than the other.
Keep in mind that some perceived differences between the two drugs may be due to: naloxone content, dosage differences, a nocebo effect, and/or subjectivity.