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Important Safety Information (ISI)

SUBOXONE® (buprenorphine HCl/naloxone HCl dihydrate sublingual tablets) (CIII) is indicated for the treatment of opioid dependence.

It is extremely dangerous to take benzodiazepines or other depressants while taking SUBOXONE. A serious overdose and death may occur if benzodiazepines, sedatives, tranquilizers, antidepressants, or alcohol are taken at the same time as SUBOXONE.

SUBOXONE has potential for abuse and produces dependence of the opioid type, with a milder withdrawal syndrome than full agonists.

Cytolytic hepatitis and hepatitis with jaundice have been observed in the addicted population receiving buprenorphine.

Allergic reactions including bronchospasm, angioneurotic edema, and anaphylactic shock have been reported in patients taking buprenorphine.

There are no adequate and well-controlled studies of SUBOXONE (a Category C medication) in pregnancy.

Caution should be exercised when driving cars or operating machinery.

Always store buprenorphine-containing medications safely and out of the reach and sight of children. Destroy any unused medication appropriately.

The most commonly reported adverse events with SUBOXONE include: headache (36%, placebo 22%), withdrawal syndrome (25%, placebo 37%), pain (22%, placebo 19%), insomnia (14%, placebo 16%), nausea (15%, placebo 11%), and constipation (12%, placebo 3%). Please see full Prescribing Information for a complete list.

To report an adverse event caused by taking SUBOXONE, please call 1-877-782-6966. You are also encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full US Prescribing Information for SUBOXONE.

I have read and understood the Important Safety Information.

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Understanding Opioid Dependence

Some essential questions are answered below.

Q.

A.

Opioids are drugs that work in the body the way opium does. Some are made directly from opium (for example, morphine, and codeine), while others are man-made but similar chemically to opium (for example, the painkillers oxycodone, hydrocodone, and fentanyl, better known by such brand names as Oxycontin®, Vicodin®, Percocet® and Actiq®*). The illegal drug heroin is also an opioid.

All of these drugs are extremely powerful. For people with severe pain, opioids are very effective medicines, and most patients treated for pain with opioids do not become dependent on them. For some people, however, opioid dependence is an unexpected side effect of proper pain treatment. The problem comes when someone is unable to stop using the drug after the pain passes.

*All brand names above are the property of their respective owners.

Q.

A.

Dependence on opioids—prescription pain medicine and heroin—has been defined as a long-term brain disease by the World Health Organization and the National Institute on Drug Abuse. It is a treatable medical condition that is caused by changes in the chemistry of the brain that occur as a result of the use of opioids. It may have started with medicine that your doctor prescribed for serious pain, or with recreational drug use with prescription pain medicine or heroin. Regardless of how you became dependent, once dependence has developed it is considered a disease that requires treatment.

Q.

A.

A person who shows 3 or more of the following behaviors over a 12-month period is most likely opioid-dependent:

  • Opioid tolerance
  • Withdrawal symptoms occur when opioids are not used
  • Taking other drugs to help relieve the withdrawal symptoms
  • Taking larger amounts of opioids than planned and for longer periods of time
  • Persistent desire to or unsuccessful attempts to quit
  • Spending a lot of time and effort to obtain, use, and recover from opioid use
  • Giving up or reducing social or recreational activities; missing work
  • Continued use of opioids, regardless of negative consequences
Q.

A.

The development of opioid dependence causes complex, long-term, changes in the structure and functioning of the brain. The significant changes to brain "circuitry" have led addiction, medical, and scientific experts to classify it as a disease that interferes with normal brain functioning.

Typically, the changes that cause opioid dependence will not correct themselves right away, even though the misuse of opioids has stopped. In fact, these changes can trigger cravings months and even years after a patient has stopped using opioids. Consequently, overcoming opioid dependence is not simply a matter of eliminating drugs from the body.

Q.

A.

There is a part of the brain that we refer to as the "reward circuit." This is the area of the brain that, among other things, regulates pain and pleasure. Basic life functions—such as eating and sex—stimulate receptors in the brain's "reward circuit" to release dopamine, a chemical that produces an intensely pleasurable feeling known as "euphoria."

It doesn't take long to learn that certain activities will be "rewarded"—that is, that they will prompt dopamine release and pleasurable sensation. This positive reinforcement is the brain's way of encouraging behavior important for survival.

The ability to activate the reward circuit accounts for some drugs being viewed as potentially addictive. Opioids are among those drugs capable of activating the reward circuit to release dopamine and reinforce drug-taking behavior. Activating the reward circuit, together with the changes in the structure and functioning of the brain, have several powerful results.

One result of this euphoria is that drug-taking behavior is rewarded, thereby increasing the chances that the behavior will be repeated.

A second result of this reward is that the brain begins to think drug-taking is actually necessary for survival. To the brain, just the fact that an activity is rewarded at all means that activity must be important for survival.

A third result is that, by the time a person develops opioid dependence, his or her brain no longer functions normally without opioids.

A fourth result is that opioid-dependence can impair the mechanism by which information from certain areas of the brain—namely, those involved with judgment and caution—is received.

Additionally, the motivation to obtain opioids may come from:

  • Physical pain and discomfort caused by withdrawal symptoms
  • Increasing anxiety due to powerful, unsatisfied opioid cravings
  • Stress resulting from the brain's fear that the current lack of opioids presents a threat to its survival

Taken together, all of these results help explain the behaviors associated with opioid dependence.

Q.

A.

The initial decision to take a drug, whether as a prescribed medication or as a "street" drug, would be considered under voluntary control. However, when someone develops a dependence on that substance, the person's ability to exert self-control can become seriously compromised. Brain imaging studies from drug-dependent individuals show physical changes in areas of the brain that are critical to judgment, decision-making, learning and memory, and behavior control. Scientists believe that these changes alter the way the brain works, and may help explain the compulsive and destructive behaviors of drug dependence.

So, even though, logically, a person may know that opioids are not essential for life, as long as those parts of the brain in charge of survival behavior still believe opioids are necessary, they may override "higher reasoning." Furthermore, to an opioid-dependent brain, not having enough opioids to satisfy cravings or suppress withdrawal is comparable to not having enough food to satisfy hunger.

The need to obtain opioids can become more important than that person's safety because opioid-dependence can impair the mechanism by which information from certain areas of the brain—namely, those involved with judgment and caution—is received. The brain responds by taking whatever steps are necessary to see that its opioid "hunger" is met, which usually means pursuing opioids with all the drive of a basic instinct.

Q.

A.

Medicine is important for managing both the short- and the long-term effects of opioid dependence. Over the short term, medication can help to relieve the opioid cravings and withdrawal symptoms that occur when use of heroin or opioid pain medicine is discontinued. Medication can be important over the long term as well.

The CSAT Clinical Guidelines for the Use of Buprenorphine recommend that patients stay on medication after they have "detoxed" from their drug of abuse. This gives patients time to learn new skills that can help them cope with cravings and other triggers that might otherwise make them vulnerable to relapse.

Q.

A.

Since it is long-term, it is like other chronic illnesses, such as diabetes, asthma, or heart disease. It shares a lot in common with these other types of illnesses:

  • It can be successfully managed, but not "cured"
  • Both medication and behavior change can be helpful
  • It has a genetic basis—it runs in families
  • People can have periods of time when they are symptom-free as well as periods of time when they are symptomatic

With Type II diabetes, for example, people need to learn to exercise and eat right, which is the behavior part of change, in addition to taking medication to control their blood sugar. Sometimes, if people with diabetes do exercise and eat right, they can reduce or end medication. However, sometimes, even when they have changed their behavior, they can still have episodes of high blood sugar, so they stay on medication too. And, for those who don't modify their behavior appropriately or eat right, medication treatment is still available to help minimize how often they experience symptoms of high blood sugar.

The same holds for opioid dependence. With opioid dependence, there are also behavior changes that can reduce or end the need for medication therapy. But, sometimes, even those who have done everything they can to improve their lives might still experience overwhelming cravings and long-term withdrawal symptoms or other symptoms that put them at risk for re-using, and so may need to continue medication therapy for optimal treatment. Cravings and withdrawal symptoms can continue because some of the changes in their brains that resulted from the opioid dependence may be slow to recover, or permanent.

Q.

A.

Most people who use opioids do not become opioid-dependent. This suggests that, while the reward circuit is responsible for opioids' addictive potential, opioid dependence most likely involves additional factors.

Exactly why some people, and not others, become dependent on opioids (or any addictive substance) is not totally understood. However, certain factors appear to increase the likelihood of dependence, including:

  • Risk-taking or novelty-seeking personality
  • Psychiatric disorders (eg, depression, bipolar disorder)
  • Stress (high stress seems to increase the desire to use drugs)
  • Properties of the drug itself (eg, how quickly it creates a "high," how long the effects of the drug last)
  • Genetic factors
  • Lastly, substance abuse, which can lead to dependence, is often highly influenced by societal norms and peer pressure.
Q.

A.

Scientists estimate that genetic factors account for between 40% and 60% of a person's vulnerability to dependence, including the effects of environment on gene expression and function. Adolescents and individuals with mental disorders are at greater risk of drug abuse and addiction than the general population.

Q.

A.

Treatment of chronic diseases involves changing deeply imbedded behaviors, and relapse does not have to mean treatment failure. The chronic nature of the disease means that relapsing to drug use can occur. Relapse indicates the need for treatment to be reinstated or adjusted to a more intensive level of care until the person is again stable and drug-free.

Science has taught us that stress, cues linked to the drug experience (eg, people, places, things, mood), and exposure to drugs, are the most common triggers for relapse, so strategies need to be developed to help minimize or avoid these triggers. Counseling and group therapy or self-help groups are strongly recommended to help develop these strategies.

Q.

A.

In addition to functioning as a reward, dopamine is also the brain's way of ensuring that the experience itself will not be easily forgotten. Dopamine release activates the areas of the brain involved in memory formation to record details about the environment where the event occurred.

Which details the brain chooses to record can range from the obvious (where the incident occurred, who was there) to the obscure (a billboard passed on the way, the temperature outside). There is no way to know ahead of time what details the brain has stored. But whatever they were, when those circumstances are encountered in the future, they will trigger memories of the good feelings produced by dopamine, and, often, a desire to recreate that experience. The technical term for these memories is "conditioned associations," but most people familiar with opioid dependence refer to them as "triggers."

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This site is sponsored by Reckitt Benckiser Pharmaceuticals Inc. and intended for residents of the United States.
SUBOXONE® and Here to Help® are registered trademarks of Reckitt Benckiser Healthcare (UK) Ltd.
This site is provided for educational and informational purposes only and is not intended
as a substitute for direct consultation with a qualified mental health professional.
Patient quotes are hypothetical.
© 2009 Reckitt Benckiser Pharmaceuticals Inc.

Important Safety Information (ISI)

SUBOXONE® (buprenorphine HCl/naloxone HCl dihydrate sublingual tablets) (CIII) is indicated for the treatment of opioid dependence.

It is extremely dangerous to take benzodiazepines or other depressants while taking SUBOXONE. A serious overdose and death may occur if benzodiazepines, sedatives, tranquilizers, antidepressants, or alcohol are taken at the same time as SUBOXONE.

SUBOXONE has potential for abuse and produces dependence of the opioid type, with a milder withdrawal syndrome than full agonists.

Cytolytic hepatitis and hepatitis with jaundice have been observed in the addicted population receiving buprenorphine.

Allergic reactions including bronchospasm, angioneurotic edema, and anaphylactic shock have been reported in patients taking buprenorphine.

There are no adequate and well-controlled studies of SUBOXONE (a Category C medication) in pregnancy.

Caution should be exercised when driving cars or operating machinery.

Always store buprenorphine-containing medications safely and out of the reach and sight of children. Destroy any unused medication appropriately.

The most commonly reported adverse events with SUBOXONE include: headache (36%, placebo 22%), withdrawal syndrome (25%, placebo 37%), pain (22%, placebo 19%), insomnia (14%, placebo 16%), nausea (15%, placebo 11%), and constipation (12%, placebo 3%). Please see full Prescribing Information for a complete list.

To report an adverse event caused by taking SUBOXONE, please call 1-877-782-6966. You are also encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full US Prescribing Information for SUBOXONE.