Suboxone is a semisynthetic drug manufactured by Reckitt Benckiser pharmaceuticals for the treatment of opioid dependence. It was introduced to the market in October 2002 and gained popularity as a result of its efficacy and reduced potential for abuse compared to other opioid replacement agents such as methadone. The drug is comprised of the ingredients buprenorphine and naloxone in a strategically formatted 4:1 ratio.
The buprenorphine component within Suboxone functions primarily as a mu-opioid receptor (MOR) partial agonist. It also elicits effects as a kappa-opioid receptor (KOR) and delta-opioid receptor (DOR) antagonist. The combination of these opioidergic effects can produce a neurophysiological “high” characterized by: elevated mood, physical relaxation, pleasure, reduced anxiety, and CNS depression.
As a result, many people become addicted to the buprenorphine within Suboxone; evidence confirms it is an addictive drug. Though Suboxone may mitigate discontinuation effects of a more potent opioid, it could also provoke adverse reactions such as: nausea, vomiting, dizziness, decreased motivation, etc. – as well as deleterious long-term effects (e.g. downregulation of endogenous endorphins). For these reasons, many users stop taking the drug and hope to fully clear it from their system.
How long does Suboxone stay in your system? (Half-Life)
If you’ve ceased usage of this drug and are struggling with Suboxone withdrawal symptoms, you’re probably wondering whether any of the drug is still in your system. To determine how long the drug is likely to stay in your system after your last dose, it is necessary to consider Suboxone’s half-life, or more specifically, the half-lives of its active ingredients buprenorphine and naloxone. The half-life of buprenorphine is an estimated 37 hours, which is considered extremely long.
It takes your body nearly 2 full days to excrete just 50% of the buprenorphine within a Suboxone dose. Considering the 37 hour half-life of buprenorphine, it could be estimated to be fully cleared from your system in under 9 days (8.48). The half-life of naloxone is reportedly between 30 minutes and 1 hour 21 minutes.
This means that the naloxone component of Suboxone is cleared from the body well before buprenorphine. Most people will excrete naloxone within 8 hours post-ingestion as a result of its extremely short half-life. It is important to note that although the elimination half-life of buprenorphine is around 37 hours, it is metabolized into “norbuprenorphine” which has a half-life that exceeds 37 hours.
Though the specific half-life of the metabolite “norbuprenorphine” hasn’t been scientifically elucidated, it is likely to remain in the body for longer than 9 days. This means that Suboxone metabolites may remain in your system for potentially up to 2 weeks after your last dose.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/buprenorphine
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/naloxone
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17517480
- Source: http://jat.oxfordjournals.org/content/20/4/229.abstract
Variables that influence how long Suboxone stays in your system
Though the average person should fully clear buprenorphine from their system in about 9 days, not everyone fits the “average.” Some people may take longer-than-average to excrete the drug, while others may be quicker-than-average in their excretion times. Variables to that account for clearance speed differences include: individual factors, dosage, frequency of ingestion, and co-administration of other drugs.
A variety of individual factors may result in faster clearance of buprenorphine (and naloxone) from your system compared to another person. Even if you started taking Suboxone on the same day (and at the same dosage) as someone else, and ceased usage at the exact same time, you may excrete the drug (and its metabolites) faster. This faster excretion may be due to factors such as: your age, body mass, genetics, food intake, hydration, and urinary pH.
Age: Although there isn’t any specific research analyzing differences in absorption, distribution, and metabolism of Suboxone in the elderly (age 65+), it doesn’t mean differences don’t exist. Many speculate that elderly patients are likely to metabolize and excrete Suboxone at a substantially slower rate than younger adults. The extended half-life of buprenorphine (within the elderly) could be due to reduced hepatic blood flow, health problems, other medications, and/or decreased overall physiologic efficiency.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21124750
Body height/weight/fat: Your body mass (height/weight) relative to the dosage of Suboxone you take can influence drug clearance. Usually the greater the dosage of Suboxone you take relative to your body mass, the longer it will remain in your system prior to clearance. The lesser the dosage of Suboxone you take relative to your body mass, the shorter it should remain in your body post-ingestion.
Since Suboxone is lipophilic, it is known to get stored within lipids, tissues, and fats throughout the body. The greater a person’s percentage of body fat, the longer they are likely to retain Suboxone (specifically the buprenorphine component). If you have a low percentage of body fat, you may clear the drug quicker than someone with high body fat.
- Source: http://www.ncbi.nlm.nih.gov/books/NBK64152/
Genetics: A person’s genetics may influence the pace at which buprenorphine within Suboxone is metabolized. Genes regulating activation of the CYP3A4 enzyme within the liver could dictate whether buprenorphine is efficiently metabolized or poorly metabolized. Someone who quickly metabolizes buprenorphine may excrete it quicker than a poor CYP3A4 metabolizer. Although CYP3A4 may not have a substantial impact on half-life of Suboxone, it may have a subtle one.
Hydration: The degree to which you stay hydrated could influence the clearance rate of buprenorphine within Suboxone. Individuals who stay hydrated often exhibit superior urinary flow rates compared to those who are dehydrated, resulting in quicker systemic clearance. The clearance time of Suboxone in a well-hydrated individual may be substantially less than that of a dehydrated person.
Liver function: Should you suffer from hepatic impairment or cirrhosis, the half-life of buprenorphine within Suboxone will be prolonged. The liver is responsible for metabolizing buprenorphine, and if its functionality is compromised, less of Suboxone is metabolized. Reduction in metabolism leads to a greater amount of the drug accumulating within the body.
Since individuals with liver disease tend to have decreased CYP3A4 enzymatic expression, clearance of Suboxone will take longer. The specifics regarding how much longer it’ll take to clear Suboxone from your system if you have liver disease are unknown. Generally, the more severe the impairment (and higher the dosage taken), the longer the elimination period.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12799931/
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15966752
Metabolic rate: Your basal metabolic rate (BMR) is thought to influence the speed at which drugs are cleared from your body. Since the buprenorphine component of Suboxone is lipophilic, it accumulates within bodily tissues and fat stores. Individuals with faster metabolic rates tend to have less body fat (due to the fact that they’re burning more energy at rest), and as a result, they excrete buprenorphine in less time.
A person with a slow basal metabolic rate (BMR) is burning less energy at rest, and tends to have a greater amount of buprenorphine stored in fat. For this reason, it can take an individual with a slower BMR longer to excrete the buprenorphine than average.
Urinary pH: It is understood that a person’s urinary pH can influence how long Suboxone stays in their system. A person with acidic urine (characterized by a low pH) will typically excrete Suboxone faster than a person with an alkaline urine (characterized by a high pH). Highly alkalinized urine could extend the half-life by several hours, whereas acidified urine may do the opposite (decreasing the half-life by hours).
Dosage (Low vs. High)
The dosage of Suboxone you take may affect how long it stays in your body prior to 100% excretion. In general, the greater the dosage of Suboxone you consistently administered (especially relative to your bodyweight), the longer it should stay in your system upon discontinuation. On the other hand, the lower the dose of Suboxone you took, the shorter the duration it should stay in your system after stopping.
Suboxone dosages (Sublingual Tablets or Sublingual Films)
Suboxone is manufactured to contain a 4:1 ratio of buprenorphine to naloxone. Individuals taking the 2 mg (buprenorphine) / 0.5 mg (naloxone) are considered to be taking a “low dose” and thus should clear the drug from their system with efficiency. Those taking the 12 mg (buprenorphine) / 3 mg (naloxone) formulation are considered to be taking a “high dose” and may clear the drug with reduced efficiency, thus extending the clearance time.
- Lowest dose: 2 mg/0.5 mg
- Normal dose: 4 mg/1 mg
- Moderate dose: 8 mg/2 mg
- High dose: 12 mg/3 mg
- Highest dose: 24 mg/6 mg
There are several reasons why higher doses of Suboxone are likely to stay in your system for a longer duration than lower doses. Firstly, high doses of Suboxone deliver a greater amount of buprenorphine and naloxone, meaning more of these exogenous substances will be distributed throughout your body. Since the buprenorphine component of Suboxone is highly lipophilic, it attaches to fat stores, resulting in greater accumulation in bodily tissues of high dose users.
Low dose users, on the other hand, will end up with less buprenorphine circulating throughout their system, and less will accumulate in fat stores. Greater levels of accumulation in bodily tissues (e.g. fat stores) are known to prolong the elimination half-life of Suboxone. In addition to prolonged elimination from greater accumulation of buprenorphine in high dose users, those taking high doses will also need to metabolize a greater amount of the drug.
The higher dosages place a greater burden on hepatic enzymes, resulting in less efficient metabolism, which prolongs excretion. In other words, your liver cannot metabolize high doses of buprenorphine as efficiently as lower doses because there is a greater amount of buprenorphine to process. A lower dose doesn’t tax the liver to the same extent as a high dose, and thus is metabolized more efficiently, resulting in faster excretion.
It is also necessary to consider the increased concentrations of metabolites resulting from ingestion of a high dose. Since there’s more total metabolites in high dose users, these metabolites circulate throughout the body and the drug isn’t cleared from a person’s system as quickly. For these reasons, a higher dose Suboxone user should expect an extended detoxification period compared to a lower dose user.
Frequency of use / Duration
When considering how long Suboxone stays in your body after stopping, it is necessary to consider how frequently you used it, as well as the total time span over which you used it. The more frequent you used Suboxone, the longer it is likely to remain in your system upon cessation. Frequent users of Suboxone may take sublingual strips once or twice per day, whereas an infrequent user may take them “as needed.”
Suboxone sublingual tablets are instructed to be taken once daily. However, patient compliance is not always perfect, resulting in some users taking them more or less frequently than once per day. Individuals that take Suboxone sublingual tablets more than once daily will likely end up accumulating more of the drug (and its metabolites), resulting in slower excretion compared to daily users.
Moreover, frequent users often become tolerant to low doses and end up taking high doses – further prolonging excretion. Infrequent users taking Suboxone “as needed” (e.g. twice per week) will likely not accumulate significant amounts of the drug within bodily tissues and probably will not have built up a tolerance to lower doses. As a result, infrequent users tend to clear the drug quicker from their systems when stopping.
In addition to frequency of ingestion, the duration over which an individual has taken Suboxone consistently can also affect elimination half-life. Those that have taken Suboxone at least once daily for a period of 1+ week will likely have longer clearance periods than those who took the drug for less than a week and/or infrequently (e.g. bi-weekly). This is because long-term users will have accumulated peak levels of buprenorphine within their bodily tissues, and are more likely to be taking high doses (as a result of cumulative tolerance).
- Source: http://www.ncbi.nlm.nih.gov/books/NBK64152/
Co-ingestion of other drugs
Co-ingestion of another substance (drug or supplement) could alter your body’s ability to metabolize Suboxone. Alterations in metabolism may serve to either: expedite or prolong clearance of Suboxone. Since the buprenorphine within Suboxone is metabolized primarily by CYP3A4 isoenzymes in the liver, drugs that significantly affect expression of these enzymes will affect its clearance.
Drugs known as CYP3A4 inhibitors are known to prolong clearance of buprenorphine, often significantly. Examples of some of the most potent CYP3A4 inhibitors include: Clarithromycin, Chloramphenicol, Indinavir, Ketoconazole, Nefazodone, and Ritonavir. Should you have taken any of these drugs along with Suboxone, you should expect its elimination half-life to be longer than usual.
Other substances known as CYP3A4 inducers are known to enhance expression of CYP3A4 isoenzymes, thus metabolizing buprenorphine faster. Examples of potent CYP3A4 inducers include: Carbamazepine, Glucocorticoids, Modafinil, Oxcarbazepine, Phenobarbital, Rifampicin, and St. John’s wort. If you have taken any of these substances along with Suboxone, its elimination half-life may be shorter than expected.
Suboxone: Absorption, Metabolism, Excretion (Details)
Suboxone is manufactured in sublingual formats (tablets and films), meaning it is placed under the tongue as a route of administration. Upon placement of Suboxone under the tongue, the active ingredients (buprenorphine and naloxone) diffuse through mucous membranes and enter the bloodstream. The buprenorphine component (of Suboxone) is quickly absorbed through the oral tissue, but its absorption thereafter within the body is slower.
It typically takes between 40 minutes to 3.5 hours to attain peak plasma levels of buprenorphine. Approximately 96% of the ingested buprenorphine binds to proteins and is distributed throughout the body, where it is known to accumulate within bodily tissues due to its lipophilicity. It is then subject to first-pass metabolism in the liver, and is processed primarily by the isoenzyme CYP3A4.
CYP3A4 (and to a lesser extent CYP2C8) facilitates N-dealkylation to convert buprenorphine to its major metabolite “norbuprenorphine.” Norbuprenorphine is estimated to be roughly 20% as pharmacologically active as buprenorphine, acting as a full agonist of mu-opioid receptors and delta-opioid receptors. Buprenorphine undergoes additional glucuronidation via UGT1A1 and UGT2B7 to form additional metabolites such as buprenorphine-3-glucuronide (B3G) prior to excretion.
The metabolite norbuprenorphine is also subject to glucuronidation via UGTA1 and UGT1A3, forming norbuprenorphine-3-glucuronide (N3G) before systemic clearance. Glucuronides formed from buprenorphine and norbuprenorphine are primarily excreted via feces and bile, whereas the remaining 10-30% is excreted through the urine. Fecal excretion contains free form buprenorphine and norbuprenorphine, whereas urinary excretion consists of conjugated forms.
The elimination half-life of buprenorphine is estimated to range between 20 and 73 hours, with an average of 37 hours. This means that most people will have fully excreted the buprenorphine between 4.58 days and 16.72 days after their last dose. Some sources suggest that norbuprenorphine has a longer elimination half-life than buprenorphine, meaning it could stay in the system for longer than 16.72 days before it is fully excreted.
Though the buprenorphine component within Suboxone has a significantly longer half-life than the naloxone component, some may wonder how quickly naloxone is metabolized and excreted. After the naloxone is absorbed through mucous membranes in the mouth, it is distributed throughout the body and exerts an effect within just 5 minutes. It is subject to significant first-pass metabolism in the liver, where it is broken down via glucuornide conjugation.
Hepatic glucuornidation of naloxone generates naloxone-3-glucuornide (N3G) as the principal metabolite. The elimination half-life of naloxone in adults ranges between 30 minutes and 1 hour 21 minutes, indicating that the drug will be fully eliminated within 5.5 to 14.9 hours after ingestion. An estimated 40% of the drug will have been excreted via urinary metabolites within 6 hours post-administration, and up to 70% of all naloxone metabolites will have been excreted within urine after 72 hours of ingestion.
Ultimately it is the buprenorphine and norburprenorphine metabolites that are likely to remain in your system for the longest duration after discontinuing Suboxone. The naloxone component will have been fully excreted (along with its metabolites) long before even half of the buprenorphine has been cleared from your system.
Types of Suboxone Drug Tests
There are various types of drug tests capable of detecting Suboxone, though it is unlikely to be tested for on a standard (SAMHSA-5) drug screening. Typically a more advanced or extensive drug screening will be required to detect Suboxone ingestion. Various types of drug tests capable of detecting the buprenorphine within Suboxone include: urine tests, hair tests, saliva tests, and blood tests.
Urine tests: On a standard urine test, Suboxone will not trigger a false-positive for opioids. This is due to the fact that mainstream urine screenings assess for the presence of opioids via detection of morphine. Most illicit opioids such as heroin and codeine metabolize into morphine, whereas prescription opioid replacement drugs like Suboxone don’t and are unlikely to be detected on a urine screening.
In the event that you are tested specifically for buprenorphine, you can expect the drug to become detectable in your urine within 40 minutes of ingestion and remain present in urine for weeks following your last dose. In high-dose, frequent, and long-term users – it is theoretically possible to test positive for buprenorphine for over 2 weeks post-ingestion on a urine screening. One study found that the total amount of buprenorphine administered over a 12 month period correlated with the amount present in urine samples.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25663675
Blood tests: A blood sample can be taken to determine whether the buprenorphine component of Suboxone is still in your system. That said, blood tests are seldom utilized due to the fact that they are highly invasive, and the window of detection is considered shorter compared to a urine test. One advantage of utilizing a blood test to detect buprenorphine is that it will detect buprenorphine quickly after Suboxone is administered; even quicker than a urine test.
The buprenorphine will peak in the bloodstream in approximately 2.08 hours, making it easily detectable on the day of administration. With each consecutive day of Suboxone sobriety, the detectability of buprenorphine will drop. That said, buprenorphine (and its metabolite “norbuprenorphine”) could remain detectable in a blood sample for days (possibly weeks) after your last dose via high-performance liquid chromatography/mass spectrometry (HPLC/MS).
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15240036
Hair tests: A collection of hair follicles from a person’s head can reveal whether they’ve been using Suboxone. If a person has been taking Suboxone, concentrations of buprenorphine and the metabolite “norbuprenorphine” will be apparent in hair segments. Levels of norbuprenorphine will usually be double those of buprenorphine, and concentrations of each will be substantially greater in proximal (close to the head) and distal (furthest from the head) compared to middle segments.
Among Suboxone users, norbuprenorphine levels in proximal segments average 95.4 pg/mg and buprenorphine levels average 56.5 pg/mg. The threshold of detection for buprenorphine in hair is set at 10 pg/mg – meaning if you test higher than this, you’ll fail. Though it may take days (or weeks) after initial administration to detect buprenorphine in the hair, it is thought to remain detectable for an extremely long duration (1 to 3 months) post-ingestion.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24817054
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24713865
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21301858
Saliva tests: Oral fluid (saliva) samples can be collected to determine whether someone has Suboxone in their system. Since Suboxone is administered via sublingual tablet and/or film – it would be easily detected via an oral fluid test if recently ingested. Suboxone remnants may still remain within a person’s mouth if they just took the drug, resulting in high levels to appear within an oral fluid sample.
If the drug has already been fully absorbed via mucous membranes, it may take slightly longer to detect in oral fluid compared to the blood. However, it should theoretically remain detectable within a saliva sample for days (possibly weeks) after ingestion. Due to the non-invasive nature of saliva tests and improvements in technology to detect specific drugs like Suboxone, they may be more widely utilized in forthcoming years.
Currently saliva tests are most commonly used in scientific research as a means of monitoring patient compliance among those taking Suboxone. Since saliva levels typically correlate with blood-levels of buprenorphine, they allow medical professionals to determine whether a patient is taking the proper dose and committing to treatment.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21219701
Who may get drug tested for Suboxone?
There are a variety of individuals that may get tested for the buprenorphine component within Suboxone. Though assessment of buprenorphine isn’t included on the SAMHSA-5 drug test, additional testing may be requested to increase detection parameters. Individuals that may be tested for buprenorphine include: drug addicts in rehab, criminals, employees, military personnel, and even patients being treated for opioid dependence.
- Athletes: Taking Suboxone isn’t thought to improve athletic performance, but it may still be tested for among athletes. Should an athlete get caught with buprenorphine in their system, he/she may face temporary suspension and/or get fined. If the drug is detected without proper medical permission to be using Suboxone, harsher legal penalization may result.
- Criminals: Since Suboxone can be used to attain a psychological “high,” certain criminals may abuse the drug and/or sell it on an illicit basis. Should a law enforcement agent suspect that a criminal is under the influence of an opioid, extensive testing may be used to detect buprenorphine intoxication. If the criminal is caught with buprenorphine in his/her system, they may be punished with additional sentencing.
- Drug addicts in rehab: Those struggling with drug addiction may take any substance they can get their hands on in attempt to attain a “high.” In some cases, this could mean abusing a prescription drug like Suboxone. Should a drug addict in rehabilitation get caught with unauthorized buprenorphine in his/her system, that individual may be required to stay for a longer duration at the rehab facility.
- Employees: Though most employers will not drug-test for Suboxone, certain companies mandate administration of extensive drug screens. These extensive screens may be used to detect drugs like buprenorphine within Suboxone. Jobs that require sobriety such as those involving operation of heavy machinery or motor vehicles will not tolerate buprenorphine usage. If you are caught with buprenorphine in your system, you could be denied a new job and/or fired from your current job.
- Military personnel: Certain individuals within the military are subject to extensive drug testing capable of detecting buprenorphine. Should an individual get caught with unauthorized buprenorphine in their system, he/she may be delisted without compensation. Most military operations require sobriety of troops due to the fact that a CNS depressant like Suboxone could compromise performance – leading to (potentially fatal) mistakes.
- Patients: Sometimes patients in opioid replacement therapy are tested for treatment compliance. A doctor will request either a blood sample or urine sample for analysis to determine whether any morphine metabolites are present. If morphine metabolites are present, it indicates that the person had been using opioids other than Suboxone. If solely buprenorphine and norbuprenorphine are present in urine at therapeutic concentrations, a medical professional can verify treatment compliance.
Tips to clear Suboxone from your system
There are several ways in which a person could theoretically ensure that Suboxone is excreted as quickly as possible from their system. Understand that the tips listed below should not be implemented without permission from a medical professional. Also realize that efficacy of these tips is subject to significant individual variation.
- Cease usage: The only way to ensure that Suboxone is completely excreted from your system is to stop using it. Individuals that keep taking the drug should expect the drug to remain within their body. The longer it’s been since you’ve last taken Suboxone, the closer you are to complete systemic excretion.
- Increase hepatic blood flow: Enzymes in your liver (CYP3A4) are responsible for metabolizing a majority of the buprenorphine within Suboxone. To ensure that the drug is metabolized and excreted as quickly as possible, you’ll want to maximize hepatic blood flow. The more total blood flow, the faster buprenorphine’s clearance. Supplements like N-acetylcysteine are thought to be effective for this.
- CYP34A inducers: Buprenorphine within Suboxone is metabolized chiefly by CYP3A4 isoenzymes within the liver. Substances that induce activity of CYP3A4 are thought to expedite metabolism and reduce the half-life of buprenorphine. Taking a safe CYP3A4 inducer under medical supervision could facilitate quicker Suboxone excretion.
- Daily exercise: If you are long-term Suboxone user, it’s possible that you’ve accumulated a significant amount of buprenorphine within fat stores throughout your body. Daily exercise, especially in the form of cardio will help you burn fat, thus expediting clearance of buprenorphine. Furthermore, exercise is known to improve circulation and overall physiologic function – possibly indirectly influencing excretion speed of Suboxone.
- Source: http://www.ncbi.nlm.nih.gov/books/NBK64152/
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11153617
Are you trying to clear Suboxone from your system?
If you’ve stopped taking Suboxone and are attempting to clear it from your system, share a comment below. Discuss how long you’ve been on Suboxone, why you decided to stop taking it, and how long you believe it is likely to stay in your system. To help others understand your situation, mention factors such as: your age, the dosage you were taking, whether you have liver problems, and/or whether you take any other drugs.
It is important to understand that there is substantial variation in systemic clearance time of Suboxone. Some people will have excreted the naloxone within several days, but take nearly 10 days to fully excrete buprenorphine and norbuprenorphine. On average, you should expect the buprenorphine to be out of your system in less than 2 weeks.