What is the duration of action of Suboxone?

Suboxone typically lasts up to 3 days. Most doctors ask their patients to take the drug once per day, typically at the same time each day. A person’s weight, metabolism, and history of drug abuse can lengthen or shorten the action of Suboxone. It’s best to work with a doctor on a customized dose, based on your medical history.

Prescription pain management medications are opioid drugs. While they have legitimate medical uses, they are sometimes misused, leading to dependence and addiction, Rehabilitation for those addicted to opiates sometimes includes the use of medications. Suboxone is one of the medications commonly used to lessen withdrawal symptoms and encourage abstinence from illicit opiate drug use.

Suboxone mimics some of the effects of opiates, lessening the brain’s need for the actual opiate drug. This medication is relatively safe and long-lasting, continuing to work for up to three days after being administered.

How long after last use of Suboxone can I take it?

When Can I Take Suboxone® After Opioid Use? Generally, you will need to wait at least 12-24 hours after opioid use to begin treating withdrawal symptoms with Suboxone®. The kind of opioids used — whether short-acting like heroin or long-acting like methadone — will determine how much time you need to wait until you begin taking Suboxone® to treat withdrawal symptoms.

What can make you test positive for Suboxone?

Discussion – Suboxone consists of a formulation of buprenorphine and naloxone (ratio of 4:1) that is widely used for the treatment of patients with opioid use disorder ( 1). When urine from patients on Suboxone is screened by IA, it should test positive for buprenorphine only. It has been reported, though, that some oxycodone IAs, because of cross-reactivity with naloxone, will generate false-positive results ( 2). This issue is assay-specific and cutoff-dependent, so laboratories should exercise care in choosing assays and cutoffs to reduce or eliminate the likelihood of getting false-positive oxycodone results for these patients. When IA results are not concordant with the clinical picture, confirmation testing by mass spectrometry is highly recommended, and in this case showed no oxycodone. Opiate testing by LC-MS/MS often yields quantitative or qualitative results for a group of compounds, which can be very helpful in determining the exact source of the positive opiate result. In this case, an unusual pattern consisting of high concentrations of buprenorphine and naloxone (>1000 ng/mL) and low concentration of norbuprenorphine ( 3). Therefore, quantitative definitive testing by mass spectrometry is essential in cases like this because the ratios of parents to metabolites can help distinguish compliance from adulteration. We recommend that quantitative LC-MS/MS testing be the only method used for assessing adherence in patients on Suboxone, until manufacturers reformulate their IAs to detect buprenorphine metabolites only (without detecting buprenorphine). Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved, Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: J.M. El-Khoury, Clinical Chemistry, AACC. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Research Funding: None declared. Expert Testimony: None declared. Patents: None declared.

What is the half life of buprenorphine?

Mechanism of Action – Buprenorphine is a partial agonist at the mu receptor, meaning that it only partially activates opiate receptors. It is also a weak kappa receptor antagonist and delta receptor agonist. It is a potent analgesic that acts on the central nervous system (CNS).

• The partial agonism at the mu receptor is a unique quality of buprenorphine.
• The feature gives its many unique properties, specifically that its analgesic effects plateau at higher doses, and then its effects become antagonistic.
• Buprenorphine exhibits ceiling effects on respiratory depression, which means that it is safer than methadone for agonist substitution treatment in addiction.

Buprenorphine has high-affinity binding to the mu-opioid receptors and slow-dissociation kinetics. In this way, it differs from other full-opioid agonists like morphine and fentanyl, allowing withdrawal symptoms to be milder and less uncomfortable for the patient.

1. When administered orally, buprenorphine has poor bioavailability because of the first-pass effect.
2. The liver and intestine break down the majority of the drug.
3. Sublingual administration is the preferred route of administration.
4. The absorption is fast, and this route also avoids the first-pass effect.
5. Upon placing the tablet under the tongue, it has a slow onset of action, with the peak effect occurring 3 to 4 hours after administration.

Once in the body, buprenorphine is broken down by the cytochrome CYP 34A enzymes to an active metabolite (norbuprenorphine) with weak intrinsic activity. The average half-life of buprenorphine is about 38 hours (25 to 70 hours) following sublingual administration.

Potent inhibition of the 3A4 enzyme by drugs (such as ketoconazole or protease inhibitors) may cause increased levels of buprenorphine, while inducers of this enzyme (such as carbamazepine, topiramate, phenytoin, or barbiturates) may cause lower levels. The majority of the drug and the metabolite get excreted in the feces, and the kidneys excrete less than 20%.

Because of the slow onset of action and prolonged duration of action, the drug is useful in treating opioid dependence. It may be prescribed on alternate days once the patient has stabilized on the daily dose.

Can I take Suboxone 3 times a day?

Reason 2: Opioid Use Disorder (OUD) – If you are taking buprenorphine (Suboxone®) for OUD, your dose is too low if you are having withdrawal symptoms, The goal of buprenorphine (Suboxone®) is to minimize cravings and weaken withdrawal symptoms, so it is important that your dose is not too low.

What not to take with Suboxone?

What Drugs Can Interact With Suboxone? – If you are taking Suboxone or your doctor is considering prescribing this medication to you, it is important to fully understand if the drug will react negatively when taken with other drugs. This is especially true for drugs that act on the central nervous system.

It is extremely dangerous to take benzodiazepines, like Xanax or Valium, while receiving suboxone treatment. Benzodiazepines and suboxone both depress the central nervous system and can cause impairment, unconsciousness, respiratory failure, coma, or even death if taken together.3 According to data reviewed by the U.S.

Food and Drug Administration, during the period of 2004-2011 the combined abuse of opioids and benzodiazepines significantly increased the rate of emergency department visits and nearly tripled the number of overdose deaths.4 The dangers of mixing these drugs was also demonstrated in findings from a recent study that showed 82% of buprenorphine overdose deaths involved the use of benzodiazepines.5 People are also warned against mixing suboxone and cocaine.

There is evidence that combining these drugs can reduce the effectiveness of suboxone.6 People who combine these drugs demonstrate low motivations to stay clean and are at increased risk for developing a multi-drug addiction, Alcohol is a depressant, and when mixed with Suboxone, it can cause increased depression of the central nervous system.

The effects of mixing alcohol and suboxone can include: 3

• Low blood pressure
• Slowed breathing
• Deep sedation
• Coma
• Death

The findings from one study looking at opioid-associated deaths showed that alcohol was involved in more than half of all buprenorphine poisonings that resulted in overdose death.5

Can you take Suboxone after 8 hours?

How long should you wait before taking Suboxone? You typically have to wait 12-24 hours after last using opioids before you start taking Suboxone as a treatment for opioid use disorder. The exact length of time depends on the type of opioid used. Short-acting opioids, like heroin, take effect more quickly and are eliminated from your bloodstream faster than long-acting opioids, like methadone.

• So, if you use short-acting opioids, you may only need to wait about 12-16 hours before starting Suboxone.
• You may need to wait 17-48 hours if you use intermediate or long-acting opioids.
• This waiting period is necessary because it’s important to start treatment with Suboxone when you are already having early symptoms of opioid withdrawal.

That means the opioid drug is starting to leave your body, causing gradual symptoms. If you take Suboxone when you still have opioids in your system and are not beginning to experience withdrawal, it can trigger sudden and intense symptoms, called precipitated withdrawal.

Suboxone is a combination of the drugs buprenorphine and naloxone. Buprenorphine binds to opioid receptors in the brain, displacing the opioids that are currently attached to these receptors. So, taking buprenorphine after recently using opioids can cause precipitated withdrawal, instead of these opioids slowly losing their effect.

(Naloxone is added to prevent drug misuse.) Your doctor will need to know what type of opioid you used and when you last used it to decide when to start treatment to manage opioid withdrawal. The Clinical Opiate Withdrawal Scale (COWS) or another scale may be used to measure your withdrawal symptoms and determine when to begin treatment.

You may first take buprenorphine alone to manage opioid withdrawal symptoms, and then switch to Suboxone after a day or two. Sometimes treatment begins with taking Suboxone right away. Suboxone comes as a film you put under your tongue (sublingual) to dissolve. You and your doctor will decide whether Suboxone is the right medication for you, based on factors like your medical history and personal preferences.

: How long should you wait before taking Suboxone?

Should I wait 24 hours to take Suboxone?

The first dose of buprenorphine/naloxone should be taken only when signs of withdrawal appear, but not less than 24 hours after the patient last used methadone. Buprenorphine may precipitate symptoms of withdrawal in patients dependent upon methadone.

Can Suboxone be used for pain?

Why Suboxone for Pain May Not Be a Good Idea – When people are in pain, they will do anything to not experience the pain. And that may mean mixing medications, even though it’s a dangerous idea. If you mix Suboxone with alcohol or benzodiazepines such as Xanax, the combination could be fatal.

1. Additionally, the National Alliance of Advocates for Buprenorphine Treatment (NAABT) doesn’t support the use of Suboxone for pain.
2. The NAABT website includes a letter from the Drug Enforcement Administration to a Dr.
3. Heit, who asked about prescribing Subutex or Suboxone for pain.
4. The letter states that the use of sublingual buprenorphine “is not prohibited under DEA requirements.” However, there may be a problem with scheduling and dispensing the various buprenorphine formulations.

Suboxone is FDA-approved to treat opioid use disorder but not chronic pain. Physicians sometimes prescribe it “off-label” to treat pain, but this is not its intended use. Even though it can effectively treat opioid use disorder and prevent individuals from craving opioids, Suboxone still contains an opioid that can cause physical dependence,

Buprenorphine works as an opioid antagonist that limits its pain-relieving effect, which means that it’s unlikely to effectively relieve patients’ pain when they don’t have an opioid use disorder. Because the liver metabolizes buprenorphine (the primary ingredient in Suboxone) so slowly, it is less efficient than other pain medications.

The slow processing may lead people to take more buprenorphine which can lead to an overdose.

Can Suboxone give false positive for opiates?

Testing for Suboxone Use – Depending on the drug panel used, Suboxone may or may not be tested for. Suboxone should not cause false positives for other opioids. While buprenorphine, one of the ingredients of Suboxone, is similar to opioid drugs, it is a different chemical and thus is broken down into different metabolites.

• Metabolites are the chemical result of your body processing the drugs in your system.
• Depending on the drug panel, it may or may not test for buprenorphine and its metabolites.
• Suboxone can be a very effective tool to treat opioid addiction.
• Buprenorphine combined with naloxone in the form of Suboxone can reduce the risk of abuse or misuse, decrease opioid withdrawal symptoms and cravings, and increase safety if overdose occurs.

It has lower abuse potential than buprenorphine alone or methadone.

What is the most common false positive drug test?

Drugs That Can Cause False Positives – Several common medications can lead to a false positive on a drug screen, including but not limited to: brompheniramine, bupropion, chlorpromazine, clomipramine, dextromethorphan, diphenhydramine, doxylamine, ibuprofen, naproxen, promethazine, quetiapine, quinolones (ofloxacin and gatifloxacin), ranitidine, sertraline, thioridazine, trazodone, venlafaxine, verapamil.

Amphetamine (more on this below) and methamphetamine are the most commonly reported false positive. More complex drugs can also show up incorrectly on drug screen results: methadone, opioids, phencyclidine, barbiturates, cannabinoids (see also, a sample case study on marijuana false positives and an ask the expert QA on false-positve marijuana results ), as well as benzodiazepines were also reported in patients taking commonly used medications
.

An OTC nasal inhaler can cause a false positive as well.

What are the side effects for Suboxone?

4.) Suboxone is not without side effects and withdrawal effects. – Side effects of Suboxone may include dizziness or blurred vision, drowsiness, headache, back pain, tongue pain, numbness or tingling, increased sweating, nausea, vomiting, constipation, and insomnia.

How do you reverse the effects of buprenorphine?

If administered in single-dose increments, high doses of naloxone (up to 10 mg) may be needed to reverse the clinical effects of buprenorphine.

What pain killer is the strongest?

Pain Relievers: MedlinePlus URL of this page: https://medlineplus.gov/painrelievers.html Also called: Analgesics, Pain killers, Pain medicines Pain relievers are medicines that reduce or relieve headaches, sore muscles, arthritis, or other aches and,

• There are many different pain medicines, and each one has advantages and risks.
• Some types of pain respond better to certain medicines than others.
• Each person may also have a slightly different response to a pain reliever.
• OTC) medicines are good for many types of pain.
• There are two main types of OTC pain medicines: acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs).

Aspirin, naproxen (Aleve), and ibuprofen (Advil, Motrin) are examples of OTC NSAIDs. If OTC medicines don’t relieve your pain, your doctor may prescribe something stronger. Many NSAIDs are also available at higher prescription doses. The most powerful pain relievers are,

(Food and Drug Administration) Also in

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health. Learn how to cite this page : Pain Relievers: MedlinePlus

How many buprenorphine can you take in 24 hrs?

✹The recommended daily dose for maintenance is 16/4 mg. ✹The maintenance dose ‘is generally in the range of 4/1 mg buprenorphine/naloxone to 24/6 mg buprenorphine/naloxone per day depending on the individual patient. Dosages higher than this have not been demonstrated to provide any clinical advantage.’

What is the ceiling effect of Suboxone?

Suboxone, like all opioids, does cause some sedation and “euphoria”, particularly in patients who are “opioid naive” (do not take opioids regularly). Full opioid drugs will continue to give more and more euphoria at higher and higher doses, and eventually cause so much sedation and respiratory depression that the patient will become somnolent and overdose.

However, unlike pure/full opioids, Suboxone is called a “partial opioid”, and has a “ceiling effect”. The ceiling effect means that Suboxone will produce a certain degree of euphoria and pain relief, but those effects will plateau at higher doses. This means that the patient will not continue to get more and more sedated at higher and higher doses.

This means the risk of over-sedation and overdose are much much lower with Suboxone than with “full” opioids. The ceiling effect is part of what makes Suboxone so safe compared to other opioids.

When is the best time to take buprenorphine?

Quick Answer – Morning is typically the best time to take Suboxone, says the National Alliance of Advocates for Buprenorphine Treatment. A dose early in the day offers protection before you’ve encountered your first drug trigger. The best time of day to take Suboxone is one you can maintain every day.

1. For most people, that’s in the morning.
2. But exceptions exist.
3. Some people feel groggy after morning Suboxone doses, and the problem persists even when they take a lower dose.
4. In cases like this, night doses might be better.
5. Most individuals take Suboxone once a day.
6. However, some individuals may require dosing twice or even three times per day.

You might take doses in the morning and at night in these situations.

What increases the effects of buprenorphine?

Benzodiazepines increase the reward effects of buprenorphine in a conditioned place preference test in the mouse.

Can you work while taking Suboxone?

Dive Insight: – While current illegal drug use is not protected by federal law, the ADA prohibits discrimination against individuals recovering from addiction to illegal drugs, among others. It also places strict limits on employers’ ability to ask job applicants to answer medical questions, take a medical exam or identify a disability such as addiction, the EEOC has said.

• An employer generally may test for illegal drug use at the post-offer stage if it does so consistently, but medically prescribed treatments like Suboxone and methadone and any possible side effects of those treatments must be assessed on an individualized basis, according to the commission.
• Drug abuse reportedly is a widespread problem in the workplace.

A 2018 report suggested that 60% of employers in the U.S. have been affected by at least one instance of opioid abuse in their workforce. And it’s estimated that opioid abuse costs employers billions in lost productivity. In dealing with recruitment and retention issues stemming from drug use, employers have adopted solutions such as seeking out employees with criminal records who are required to refrain from drug use as a condition of their parole or offering drug treatment to applicants who fail an initial screen.

Does Suboxone increase serotonin?

Can A Single Dose Of Suboxone Increase Serotonin? – Yes, a single dose of buprenorphine (Suboxone®) can increase serotonin levels. It has serotonergic effects that are similar to opioids themselves. This doesn’t mean it’s a bad thing. An increase in serotonin levels is often what the body expects if it has been on something like morphine or oxycontin for a while.

What is the onset and duration of action of buprenorphine?

Buprenorphine – Buprenorphine is a semisynthetic opiate that is synthesized from natural alkaloid thebaine found in opium. Buprenorphine was introduced in the early 1980s as an opioid analgesic in Europe and subsequently for the treatment of opioid addiction in France in 1996.

1. Buprenorphine was approved by the US FDA in October 2002 as a Schedule III narcotic for use in treating opioid-dependent men and opioid-dependent women who are not pregnant.
2. Buprenorphine has a significantly different mechanism of interaction with opioid receptors compared with other opioids such as morphine.

Buprenorphine is a potent but partial agonist of μ-opioid receptor, showing a high affinity but low intrinsic activity. High potency and slow off rate (half-life of association/dissociation is 2–5 h) help buprenorphine displace other μ-opioid agonists such as morphine from receptors and overcome opioid dependence issues.

• Buprenorphine is approximately 25–100 times more potent than morphine and has a prolonged therapeutic effect that is very useful to opioid dependance, as well as pain.
• Interestingly, buprenorphine is a potent κ-receptor antagonist, as well as an antagonist for δ-opioid receptors.
• Buprenorphine is a preferred opioid for treatment of pain in patients with renal or liver dysfunction,

Chemical structure of buprenorphine is given in Fig.2.3, Buprenorphine is a lipophilic chiral molecule and has low solubility in water. Compared to 100% bioavailability of buprenorphine after intravenous administration, bioavailability is 49% after administration of sublingual solution and 29% with sublingual tablets.

Sublingual and transdermal formulations tend to show long half-life (20–73 h). With a sublingual formulation, buprenorphine shows onset of effects at 30–60 min after dosing, and the peak clinical effects are observed at 1–4 h. The duration of effect may last for 6–12 h at low dose ( 16 mg). The longer effect at higher buprenorphine sublingual dose may be linked to sustained, effective drug levels for extended duration because of its slower elimination and enterohepatic recirculation.

Buprenorphine has a large volume of distribution, and the drug is strongly protein bound (approximately 96%) mostly to α- and β-globulins. Serum buprenorphine concentration is usually low. Buprenorphine is extensively metabolized in the liver, and the major metabolite, norbuprenorphine, is formed by CYP3A4-mediated N-dealkylation of buprenorphine.

1. In addition, buprenorphine is conjugated with glucuronic acid during Phase II metabolism by the action of UGT2B7 enzyme, while norbuprenorphine is also conjugated with glucuronic acid by the enzyme UDP-glucuronosyltransferase 1A1 in the liver.
2. Buprenorphine is eliminated primarily via a stool (as free forms of buprenorphine and norbuprenorphine), while 10%–30% of the dose is excreted in urine as conjugated forms of buprenorphine and norbuprenorphine.

The plasma levels of conjugate metabolites buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide can exceed the parent drug levels, Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9780128200759000028

Can you take Suboxone after 8 hours?

How long should you wait before taking Suboxone? You typically have to wait 12-24 hours after last using opioids before you start taking Suboxone as a treatment for opioid use disorder. The exact length of time depends on the type of opioid used. Short-acting opioids, like heroin, take effect more quickly and are eliminated from your bloodstream faster than long-acting opioids, like methadone.

• So, if you use short-acting opioids, you may only need to wait about 12-16 hours before starting Suboxone.
• You may need to wait 17-48 hours if you use intermediate or long-acting opioids.
• This waiting period is necessary because it’s important to start treatment with Suboxone when you are already having early symptoms of opioid withdrawal.

That means the opioid drug is starting to leave your body, causing gradual symptoms. If you take Suboxone when you still have opioids in your system and are not beginning to experience withdrawal, it can trigger sudden and intense symptoms, called precipitated withdrawal.

• Suboxone is a combination of the drugs buprenorphine and naloxone.
• Buprenorphine binds to opioid receptors in the brain, displacing the opioids that are currently attached to these receptors.
• So, taking buprenorphine after recently using opioids can cause precipitated withdrawal, instead of these opioids slowly losing their effect.

(Naloxone is added to prevent drug misuse.) Your doctor will need to know what type of opioid you used and when you last used it to decide when to start treatment to manage opioid withdrawal. The Clinical Opiate Withdrawal Scale (COWS) or another scale may be used to measure your withdrawal symptoms and determine when to begin treatment.

You may first take buprenorphine alone to manage opioid withdrawal symptoms, and then switch to Suboxone after a day or two. Sometimes treatment begins with taking Suboxone right away. Suboxone comes as a film you put under your tongue (sublingual) to dissolve. You and your doctor will decide whether Suboxone is the right medication for you, based on factors like your medical history and personal preferences.

: How long should you wait before taking Suboxone?

What is the half life of naloxone?

Monitoring – Patients who overdose on opioids can have not only respiratory depression but also hypotension. These patients should be resuscitated like any other patient and monitored. Additionally, naloxone administration also can trigger an acute withdrawal syndrome, which can present with the following symptoms:

Nausea Diaphoresis Vomiting Tachycardia Cardiac Arrest

In chronic opioid users, naloxone requires slow administration to individuals who are dependent on opioids. All patients who have responded to naloxone should be continuously monitored for at least six to 12 hours since some opioids (methadone, fentanyl, buprenorphine) have a much longer half-life than naloxone.

The half-life of naloxone in adults varies from 30 to 80 minutes. The patient should have vital signs, including pulse oximetry, monitored until obtaining a full recovery. Even after reversing respiratory depression, the patient must be monitored for at least six to 12 hours because the patient may have ingested the longer-acting opioids, which will continue to exert their effects after excretion of the naloxone.

Any patient that requires IV naloxone doses of more than 5 mg should be admitted. For those who completely reverse with 0.4 to 2 mg of naloxone, observation in the emergency room for two to four hours is prudent. If the patient is stable, then discharge is recommended.

Be fully mentally alert with a Glasgow coma scale of 15 Not require further dosing of naloxone in the emergency Have an oxygen saturation of at least 92% on room air Have a respiration rate of no less than ten breaths per minute Have a pulse rate of no less than 50 or no more than 120 beats per minute Have a blood pressure between 110/90 to 140/90 mmHg Be able to tolerate clear liquids, ambulate, and have no withdrawal symptoms Have someone drive the patient home and monitor the patient for the next 12 to 24 hours

Contraindications There are no absolute contraindications to the use of naloxone in an emergency. The only relative contraindication is known hypersensitivity to naloxone. Current Guidelines Because of the current opioid epidemic, recent legislation has been passed in the United States that allows physicians to prescribe naloxone to opioid abusers to reverse the overdose.

Also, more than a dozen states have passed good samaritan laws that permit healthcare workers to prescribe naloxone to the family members or caregivers of opiate abusers. There are now campaigns across the nation to make naloxone easily available to the public, firefighters, police, and other professionals.

Out-of-hospital use Although naloxone is effective in reversing opioid overdose in a hospital setting, its use outside of the hospital is relatively new. Thus not much data are available on its effectiveness. Overall the NAS formula is less effective than the parenteral formulations.

Further, there are no studies that have compared the different routes of administration, the timing of the response, and titration strategies. Naloxone storage Naloxone is stored at room temperature and contained in a protective outer case. This type of packaging makes the product impact-resistant and easy to transport in the ambulance.

Many patients who are addicted to opioids are also prescribed naloxone and may inject the antidote if they feel they have overdosed for home use; the NAS formula is preferred because it eliminates the risk of accidental needle sticks with a contaminated surgeon or needle.

• Plus, the NAS formula avoids the difficulties with the disposal of needles and sharps.
• Discussion Even though naloxone has already saved many lives, the general feeling in the medical community about its universal availability remains debated.
• Some medical experts suggest that making naloxone available over the counter may promote more use of opioids.

Further, some experts feel that the ready availability of naloxone will lead the opioid user to start abusing higher doses more frequently because they know that an antidote is readily available if anything happens. There are also concerns that the average person lacks the training to make a diagnosis of an opioid overdose, and this could lead to misuse of expensive medication.

How long does Sublocade shot last?

Only healthcare providers should prepare and administer SUBLOCADE. Administer SUBLOCADE monthly with a minimum of 26 days between doses. Initiating treatment with SUBLOCADE as the first buprenorphine product has not been studied.