There are many new medications that have been engineered specifically for the treatment of opioid dependence. Those dependent on opioids tend to experience debilitating physical and psychological withdrawal symptoms upon discontinuation. To help individuals discontinue illicit opioids like heroin, an “opioid replacement therapy” drug is often prescribed.
Two of the most common opioid replacement therapy drug options include Zubsolv and Suboxone. Suboxone is a drug that hit the market in 2002 as a treatment for opioid dependence. It differed from previous opioid replacement therapy drugs in that it was formulated with a 4:1 ratio of buprenorphine to naloxone.
The buprenorphine was thought to elicit partial agonist effects on the mu-receptor, while the naloxone was included in the formulation to limit abuse potential. Zubsolv is similar to Suboxone in that it contains both buprenorphine and naloxone at approximately 4:1 ratios. However, Zubsolv is considered an improvement over Suboxone in that it has a higher bioavailability, faster dissolve time, and smaller tablet size by comparison.
Zubsolv vs. Suboxone Comparison Chart
The chart below highlights the general characteristics of both Zubsolv and Suboxone. Both drugs contain the same active ingredients and are administered sublingually. They are manufactured by different companies and are known to differ in dosing options.
|Drug type||Synthetic opioid (Partial agonist)||Synthetic opioid (Partial agonist)|
|Approved uses||Opioid dependence.||Opioid dependence.|
|Ingredients||Buprenorphine (~80%) / Naloxone (~20%)||Buprenorphine (80%) / Naloxone (20%)|
|Formats||Sublingual tablet.||Sublingual film. Sublingual tablet.|
|Dosages||0.7 mg/0.18 mg or 1.4 mg/0.36 mg or 5.7 mg/1.4 mg or 8.6 mg/2.1 mg or 11.4 mg/2.9 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||Orexo 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. The Naloxone component of Zubsolv has a high affinity for the mu-receptor as a competitive antagonist. It also elicits antagonist effect upon the kappa and delta receptors.||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. Dry mouth. Lightheadedness. Nausea. Sweating. Vomiting.||Constipation. Dizziness. Drowsiness. Dry mouth. Lightheadedness. Nausea. Sweating. Vomiting.|
|Date approved||July (2013)||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).|
Zubsolv vs. Suboxone: What’s the difference?
The primary difference between Zubsolv and Suboxone is the bioavailability of each drug. Zubsolv is regarded as having a significantly greater bioavailability than Suboxone. This means that when you take Zubsolv, the percentage of the drug that has an active effect is greater than that of Suboxone.
The active ingredients of both drugs include buprenorphine and naloxone. These ingredients are present at exact 4:1 ratios in Suboxone and approximate 4:1 ratios in Zubsolv. Since your body uses Zubsolv more efficiently than it uses Suboxone, it takes a greater dose of Suboxone to elicit the same effect as a lower dose of Zubsolv.
In addition, the Zubsolv sublingual formulation dissolves quicker under the tongue than Suboxone and includes a menthol (mint) flavor. Many individuals and doctors regard Zubsolv as an “upgraded” version of Suboxone. Although Suboxone remains a popular opioid replacement therapy option, many believe that the competitor drug Zubsolv is a superior formula.
Zubsolv and Suboxone are regarded as “Schedule III” controlled-substances, meaning they have equal potential for abuse. Schedule III drugs tend to have reduced potential for abuse compared to those considered “Schedule II” and are known to have medically accepted uses. It is known that Schedule III substances like Zubsolv and Suboxone may cause dependence physical and psychological dependence.
Both of these formulations contain buprenorphine and naloxone. By itself, buprenorphine is regarded as one of the most addictive drugs; its addiction rating is “1.64” on a scale from 0 to 3. However, since naloxone is included in each of the formulations, it limits potential for abuse, especially by those that attempt to intravenously inject or snort (insufflate) either drug.
Should an individual intravenously inject or intranasally insufflate either Zubsolv or Suboxone, the naloxone component is thought to mitigate any “high” that a person would’ve received from the buprenorphine component. While buprenorphine stimulates the mu-receptor as a partial agonist, naloxone acts as a competitive mu-receptor antagonist and serves as a built-in safety mechanism.
As an antagonist, the naloxone binds to the mu-receptor and inhibits any agonist stimulation from the buprenorphine, thus sending the individual into full-blown withdrawal. Individuals that were dependent on highly-potent opioids that attempt to abuse Zubsolv or Suboxone may experience unpleasant symptoms. Those that were dependent on less potent opioids may not experience unpleasant symptoms, but are unlikely to derive any “high” from either drug.
The potential for abuse of Zubsolv and Suboxone is considered high among those who aren’t physically dependent on opioids. Since both drugs contain “naloxone” their potential for abuse is lower than formulations without it (e.g. Subutex). Neither Zubsolv nor Suboxone should be considered to have any greater potential for abuse compared to the other; their ingredient composition is nearly identical.
- 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 considering Zubsolv and Suboxone as potential opioid replacement therapy options may also want to consider the price of each drug. Individuals without good insurance coverage may end up having to pay for a prescription out-of-pocket and therefore probably will want to chose the most affordable option. The cost for a 30 day supply of Zubsolv ranges between $221 and $240.
Due to the fact that Zubsolv wasn’t approved until 2013, a generic will not be available for awhile. Therefore if you’re getting Zubsolv without insurance, the associated costs can get quite expensive. The cost for a 30 day supply of “brand name” Suboxone sublingual films will cost between $130 and $470; the higher the dosage, the greater the cost.
Fortunately, Suboxone is sold under the generic “buprenorphine / naloxone” ranging between $75 and $190 for a 30 day supply. This means that if you’re looking to save yourself money, the generic Suboxone is probably your best option. Zubsolv tends to be more expensive than certain doses of brand name Suboxone, but at the highest doses, Suboxone may be more expensive.
Dosage & Formats
Zubsolv is manufactured in a sublingual tablet format with a variety of dosages including: 1.4 mg/0.36 mg, 5.7 mg/1.4 mg, 8.6 mg/2.1 mg and 11.4 mg/2.9 mg. The first number associated with each pill is the dosage of buprenorphine, while the second number reflects the dosage of naloxone. As you can see, each pill contains an approximate (but not exact) 4:1 ratio of buprenorphine to naloxone.
Suboxone is manufactured in multiple formats including sublingual films and sublingual tablets. The sublingual Suboxone films have dosages of: 2 mg/0.5 mg, 4 mg/1 mg, 8 mg/2 mg, and 12 mg/3 mg. The generic sublingual Suboxone tablets are manufactured with only 2 dosing options of 2 mg/0.5 mg and 8 mg/2 mg. The first number in each formulation reflects the buprenorphine dose, while the second reflects the naloxone.
As you can see, the ratio of buprenorphine to naloxone in Suboxone is exactly 4:1. The dosage ratios differ in Zubsolv such as: 3.8 to 1, 4.07 to 1, 4.09 to 1, and 3.93 to 1 (from lowest dose to highest). That said, Zubsolv’s is manufactured in 4 doses to match the 4 dosing options of Suboxone. The only difference between the two is that Suboxone is manufactured in sublingual “films” and “tablets” whereas Zubsolv is only manufactured in sublingual “tablets.”
Each dose of Zubsolv is thought to be calibrated to elicit similar potency as higher doses of Suboxone. For example, the Zubsolv 8.6 mg/2.1 mg is thought to correspond with the 12 mg/3 mg of Suboxone. Some individuals may like the idea of taking a lower dosage that has a higher bioavailability (Zubsolv) compared to a higher dosage with a lower bioavailability (Suboxone).
Efficacy: Which drug is more effective?
Due to the fact that Zubsolv has a greater bioavailability than Suboxone, a lower dose can be taken to achieve the same effect as a higher dose of Suboxone. The percentage of Zubsolv that has an effect is greater than the percentage of Suboxone that has an effect. Every dosing option of Zubsolv is equivalent to a higher corresponding dosage of Suboxone.
For example, the Zubsolv 1.4 mg/0.36 mg is equivalent to the Suboxone 2 mg/0.5 mg. Similarly the Zubsolv 5.7 mg is equivalent to the Suboxone 8 mg and the Zubsolv 8.6 mg is equivalent to the Suboxone 12 mg. There is even a higher dose of Zubsolv 11.4 mg/2.9 mg that would be equivalent to a Suboxone 16 mg if it was manufactured.
The onset of action is quicker for Zubsolv due to the fact that it dissolves sublingually in seconds rather than minutes like Suboxone. It also may have a slightly longer duration of effect by comparison. Clearly Zubsolv is the more potent drug due to its enhanced bioavailability and as a result, it may be slightly more effective than Suboxone.
That said, the difference in efficacy is unlikely to be significant in a head-to-head comparison. If dosage equivalencies were taken into account, the efficacy in treating opioid dependence should be nearly identical. Subtle differences may result from the ratios of buprenorphine to naloxone, which differ slightly in Zubsolv based on dose compared to Suboxone.
If the naloxone component offsets some of the buprenorphine, the lowest dose (1.4 mg/0.36 mg) and the highest dose of Zubsolv (11.4 mg/2.9 mg) have ratios of less than 4:1 buprenorphine to naloxone, which may make them slightly less effective than Suboxone; this is assuming the naloxone elicits a slight antagonist effect. However, the middle doses of Zubsolv including the 5.7 mg/1.4 mg and 8.6 mg/2.1 mg may be slightly more effective than Suboxone due to greater than 4:1 ratios of buprenorphine to naloxone.
Mechanisms of action
The respective mechanisms of action associated with Zubsolv and Suboxone are the same. The buprenorphine component of each drug functions primarily as a mu-opioid receptor partial agonist. This produces less of an opoioid effect than a full agonist, but still may result in sedation, reduced blood pressure, analgesia, euphoria, nausea, and relaxation.
The primary benefit derived from these drugs is a result of the buprenorphine, hence it accounts for nearly 80% of each formulation. The buprenorphine also acts as a kappa receptor and delta receptor antagonist, meaning it inhibits stimulation at these sites. In addition, it is known to have a subtle affinity for the nocioceptin receptor and is capable of blocking various voltage-gated sodium channels.
The remaining 20% of Zubsolv and Suboxone formulations is comprised of naloxone. Naloxone is a drug that acts as a pure opioid-receptor antagonist. It acts primarily as a competitive antagonist at the mu-opioid receptor and acts as a moderate antagonist at kappa and delta opioid receptors. The effect of naloxone is thought to mitigate abuse and prevent excess intoxication as a result of the 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
Zubsolv and Suboxone are drugs solely approved by the FDA for the treatment of opioid dependence. They are not formally approved to treat chronic pain, despite the fact that they may be approved off-label for this purpose. Both drugs are regarded as being significantly more effective than a placebo in double-blind, randomized, clinical trials for the treatment of opioid dependence.
Due to the fact that Suboxone has been on the market for a longer period of time, it has been investigated for the treatment of neonatal abstinence syndrome. This is a condition in which a baby was exposed to opioids during pregnancy and experiences withdrawal symptoms while in the womb or following birth. Specially engineered neonatal Suboxone is being investigated by the FDA for the treatment of this condition.
Furthermore, some doctors may prescribe Suboxone as an antidepressant augmentation strategy for individuals suffering from refractory depression with a history of opioid dependence. Many anecdotal reports suggest that it is significantly more effective than standard antidepressant options. A drug similar to Suboxone called “ALKS-5461” which contains buprenorphine and samidorphan has shown promise as an adjunct treatment in cases of refractory depression.
Suboxone is more commonly prescribed off-label compared to Zubsolv and has been investigated for the treatment of neonatal abstinence syndrome and depression. Zubsolv is a relatively new drug and therefore hasn’t gained as much widespread off-label use nor investigational use by comparison. That said, the outcomes associated with using either drug should be nearly identical.
In the mainstream, Suboxone remains the more popular opioid replacement therapy option. Some would argue that there’s a battle between Methadone and Suboxone for the top opioid replacement therapy drug. That said, doctors have recognized that Suboxone is likely safer than Methadone due to its decreased potential for addiction and reduced potency as a partial mu-receptor agonist.
Since Suboxone also contains naloxone, it is thought to have a reduce potential for abuse. The reduced abuse potential is appealing to professionals. Although Zubsolv isn’t yet as popular as Suboxone or Methadone, it is gaining momentum. Professionals are starting to recognize that its higher bioavailability and quicker absorption make it superior to Suboxone; this should bolster Zubsolv’s popularity in forthcoming years.
Among patients that have tried both Suboxone and Zubsolv, most prefer Zubsolv for a number of reasons. Most individuals like the fact that Zubsolv dissolves quickly – in seconds rather than minutes associated with Suboxone. The Zubsolv tablets also are very small and provide a menthol, minty flavor which many individuals prefer over Suboxone.
The side effect profiles of Zubsolv and Suboxone aren’t much different. This is due to the fact that both contain approximately 80% buprenorphine and 20% naloxone. Common side effects associated with these medications include: constipation, dizziness, drowsiness, headaches, and nausea.
Due to the fact that both drugs contain the same active ingredients, there shouldn’t be many differences in side effects from Zubsolv compared to Suboxone. Some claim that since Zubsolv is more efficiently absorbed that side effects are less likely; whether this is true is unknown. Those experiencing side effect differences on one drug compared to the other are likely placebo-related.
If you experience more side effects on one drug compared to the other, it may have to do with the dosing. As was already mentioned, lower doses of Zubsolv correspond with higher doses of Suboxone. The higher the dose of either drug that you’re taking, the more likely you’ll be to experience side effects. Subtle differences in perceived side effects may be due to slight increases or decreases in the ratio of buprenorphine to naloxone as occur in Zubsolv.
The discontinuation process associated with Zubsolv and Suboxone can be difficult. In fact, many claim that discontinuing these medications is nearly as difficult as discontinuing more potent opioids. This is due to the fact that many individuals stay on Zubsolv or Suboxone for an extended duration of time without making any effort to reduce their dosage.
The longer the time span over which a person takes either of these drugs, the more difficult the discontinuation process will be. There are many anecdotal reports highlighting the difficulty of Suboxone withdrawal, but not as many discussing Zubsolv withdrawal due to the fact that it is a newer drug. Both drugs should theoretically have the same degree of difficulty in regards to withdrawal.
Since both drugs are manufactured in 4 dosing options, the tapering process shouldn’t be considered more or less difficult with one drug compared to the other. Many individuals discontinuing from high doses may experience post-acute withdrawal syndrome (PAWS). This means that withdrawal symptoms may linger for months following the date of discontinuation from either drug.
Similarities (Recap): Zubsolv vs. Suboxone
Below is a recap of the similarities shared between Zubsolv and Suboxone.
- Abuse potential: Both drugs are considered to have a minimized potential for abuse when used in accordance to medical recommendations.
- Dosages: Each drug is manufactured with four dosing options. While the dosages differ in milligrams of buprenorphine and naloxone, most are equivalent in potency.
- Drug type: Zubsolv and Suboxone are considered semisynthetic opioids and are regarded as first-line treatments for opioid dependence.
- Duration of effect: With both drugs, the duration of effect is thought to be 24 hours, with an 8 to 12 hour analgesic effect.
- Efficacy: The efficacy associated with Zubsolv is no different than that of Suboxone when dosages are properly calibrated.
- Half-life: The associated half-life of elimination for both drugs is between 24 and 42 hours.
- Ingredients: The ingredient composition associated with these drugs is identical with approximately 80% buprenorphine and 20% naloxone.
- Legal status: Both drugs are classified as “Schedule III” controlled-substances.
- Mechanisms of action: These drugs have the same mechanisms of action as a result of identical ingredients and nearly identical contents of buprenorphine and naloxone.
- Medical uses: Each drug has been granted FDA approval to treat opioid dependence.
- Side effects: The side effect profile of Zubsolv and Suboxone should be identical. Common side effects include dizziness, dry mouth, nausea, and sweating.
- Withdrawal: Discontinuation of either drug will result in withdrawal symptoms. There is no evidence to suggest that the difficulty of withdrawal is greater with one drug than the other.
Differences (Recap): Zubsolv vs. Suboxone
Below is a synopsis of some differences between Zubsolv and Suboxone.
- Aftertaste: Zubsolv has a built-in “menthol” flavoring which leaves a minty aftertaste following sublingual administration. Many individuals dislike the taste of Suboxone or find that it lacks any flavor.
- Bioavailability: Zubsolv has a significantly greater bioavailability than Suboxone (approximately 1.4 times). This means that a lower dose of Zubsolv delivers the same effect as a higher dose of Suboxone.
- Cost: Buying a 30 day supply of generic Suboxone is cheaper than Zubsolv. Purchasing brand name Zubsolv is more expensive than lower-dose Suboxone, but cheaper than higher-dose Suboxone.
- Dissolving speed: Zubsolv proved in clinical trials that it dissolved significantly faster sublingually than Suboxone. Zubsolv dissolves in seconds, whereas Suboxone dissolves in minutes.
- Formats: Both drugs are available in sublingual tablet format, but Suboxone is also manufactured in the form of sublingual “films.”
- Generic availability: Suboxone is manufactured in the generic form of “buprenorphine / naloxone” whereas Zubsolv remains patent-protected.
- Investigational uses: Suboxone has been subject to significantly greater investigational use including: neonatal abstinence syndrome and depression, whereas Zubsolv has not.
- Manufacturers: Reckitt Benckiser Pharmaceuticals manufactures Suboxone, and Orexo Pharmaceuticals manufactures Zubsolv.
- Onset of action: Zubsolv has the quicker onset of action as a result of its faster dissolve time.
- Popularity: Suboxone remains more popular than Zubsolv due to the fact that it has been on the market since 2002, whereas Zubsolv didn’t enter the market until 2013.
Which drug is a better at treating opioid dependence? Zubsolv vs. Suboxone.
Neither Zubsolv nor Suboxone should be regarded as a superior in efficacy when compared to the other. Both are effective options for the treatment of opioid dependence and the respective formulations are nearly identical. Zubsolv is regarded as a newer drug, and therefore may be preferred by doctors and patients alike for the treatment of opioid dependence.
Scientific evidence suggest that Zubsolv has nearly 1.4 times the bioavailability as Suboxone, it dissolves significantly quicker (seconds rather than minutes), and it leaves a preferable (menthol) aftertaste in the mouth following sublingual administration. While nothing really changed in terms of ingredients or efficacy, there are some “upgrades” associated with Zubsolv compared to Suboxone.
For these upgrades such as the: increased bioavailability, quicker onset of action (faster dissolve time), and superior aftertaste – you will pay extra. The cost of Zubsolv is significantly greater than generic Suboxone. It will also cost more than low doses of brand name Suboxone. If you are taking high doses of brand name Suboxone, Zubsolv is actually a bit cheaper.
Which drug do you prefer: Zubsolv or Suboxone?
If you have taken both Zubsolv and Suboxone, be sure to share a comment regarding your preference for one drug over the other. If you prefer Zubsolv, is it due to the fact that it dissolves quicker or tastes better? If you subjectively experienced less side effects or a longer duration of effect associated with one drug or the other – mention that too.
If you believe that Zubsolv is more effective than Suboxone or vice-versa, were you on an equivalent dose? Experiencing greater efficacy with one drug over the other may be a result of the specific dose you were taking. Understand that any perceived differences between the two drugs may be a result of: subjectivity, nocebo effects, and/or subtle variations in buprenorphine to naloxone ratios.