Drugs for Treating Heroin Users: A New Abuse Problem in the Making?

“Evidence is mounting that certain drugs used to treat heroin users are themselves being sold on the streets – and may even be a ‘gateway’ to heroin or opioid use. As some experts herald their value for treating addiction, others ask if the ‘cure’ is making things worse.

More than a decade ago, the FDA partnered with a British company to develop Suboxone, a new treatment for addiction to opioids. But that effort has had highs and lows, experts say. Lifesaving to some opioid abusers, Suboxone and generic drugs like it have not helped others to whom they have been prescribed – in part, these experts say, because of poor oversight of how the opioids are dispensed and used.

Those drugs have also ended up where the U.S .government hoped they wouldn’t: on the street, where they are sold in the same illicit subculture in which heroin and prescription painkillers are peddled.”

http://www.csmonitor.com/USA/Society/2014/0530/Drugs-for-treating-heroin-users-a-new-abuse-problem-in-the-making

Source: Christian Science Monitor – May 30, 2014

News From the States

Medication-Assisted Treatment for Substance Use Disorders: Research and Practice Training Session

SAMHSAThis full-day training session will precede the 75th Annual Meeting of the College on Problems of Drug Dependence, which will be held June 15–20, 2013 at the Hilton Bayfront Hotel in San Diego from 8:30 AM to 4:30 AM. Registration and CEUs are free.

Sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA) and the National Institute on Drug Abuse (NIDA), the training will provide practitioners, clinicians, clinical supervisors, healthcare providers, researchers, and other participants the opportunity to learn the latest information and best practices on medication-assisted treatment (MAT) for substance use disorders (SUDs). Nationally renowned researchers and experts will present on topics such as:

  • Pain management and prescription opioid addiction.
  • Agonist and antagonist medications to treat opioid dependence.
  • Adolescents and young adults—treatment for opioid abuse.
  • Veterans and MAT.
  • Smoking cessation with SUD patients.
  • Integrating MAT and primary care.
  • A state’s response to prescription drug abuse.
  • A county’s approach to MAT.
  • Integrating MAT into a 12-step program.

This training will provide information on how MAT is being used to improve opioid dependence treatment outcomes, across a variety of settings and populations.

Register at: http://www.seiservices.com/samhsa/cpdd2013/Registration.aspx
Source: The Substance Abuse Mental Health Services Administration and the National Institute on Drug Abuse – May 2013

Bob Newman is Retiring, But You Haven’t Heard the Last From Him

BobNewmanphotoLegendary methadone treatment advocate Robert G. Newman, MD, is retiring. But, he hastens to add, he is not leaving the field. “What I’m leaving,” he told AT Forum in February, “is the office.”

Dr. Newman announced via a January 26 e-mail that he would be giving up his “formal role” as director of Beth Israel’s Baron Edmond de Rothschild Chemical Dependency Institute. He will continue to work through June, but Hindy Bernstein, his assistant of the past 25 years, will be leaving in April. “Hindy is leaving me for Florida,” he said. Although he will no longer have the financial support of Beth Israel, he will continue advocacy efforts.

An Advocate

“The challenges are at least as great today as they were 40 years ago when I started my advocacy work,” Dr. Newman said. He will continue to be a fly in the ointment, but he does want to see more “noise” from the rest of the opioid treatment program (OTP) community.

His days will continue to begin and end the way they have for years, he told AT Forum. “I go to the Internet, I get the Google alerts, which very often have some particularly horrendous feature that I’m obliged to respond to.”

There is a lot of “bad news” for Dr. Newman to blog, write letters to the editor, and send e-mails about. And he does so very articulately. For example, some states are cutting off methadone treatment arbitrarily, trying to limit it to one or two years. Regulators are confounding addiction and dependence, not recognizing that maintenance medication is treatment, not a “substitute” for heroin. Unbelievable as it is that this non-science is going on today, some 50 years after medication-assisted treatment (MAT) has been proven effective, and in the face of federal officials, Dr. Newman sees it happening. And he isn’t going to be quiet about it.

NIMBY

NIMBY—the “not in my back yard” phenomenon in which even people who claim to support MAT don’t want programs in their neighborhoods—is illegal, violating the Americans with Disabilities Act (ADA). But despite the various ADA wins that OTPs have achieved, they are never “precedent-setting,” and therefore need to be fought over and over again. “This is terribly frustrating to me,” said Dr. Newman.

Dr. Newman said the opioid-treatment field can help with this fight. “There are many reasons for NIMBY, and some of those reasons have to do with the field, how we have allowed our treatment, our patients, our services to be viewed,” he said. “It isn’t just misperception on the part of communities and politicians. Some of the anti-methadone- patient bias reflects the way the field has chosen to isolate itself and adopt and embrace unique practices that make this treatment separate.”

 Office-based Methadone

 Dr. Newman is glad that buprenorphine has been made available to OTPs and to office-based opioid treatment (OBOT) providers, as a treatment tool for caring for opioid dependence. He notes that more than 40 years ago he proposed that private physicians be permitted to offer methadone maintenance, in addition to OTPs. And now that buprenorphine can be utilized in OBOT, why not methadone, he asks rhetorically. Dr. Newman also notes the extremely limited willingness of office-based physicians to become “waivered” to prescribe buprenorphine. “I think some of the practices of programs are so foreign to what is done in every other field of medicine that medical colleagues view this as something that is from Mars and refuse to get involved in any form of opioid-dependence treatment.”

In fact, the requirement that patients go to a clinic every day is a barrier to care. Dr. Newman is skeptical about the effect of the Affordable Care Act (ACA) on OTPs in particular. “I have seen repeated references to the notion that under the ACA, there’s going to be a sudden upsurge of demand for addiction treatment,” he said. “Increased demand, maybe,” he said. “But how is that demand going to be met? You can have all the insurance you want, but an awful lot of people who need treatment will avoid OTPs because of the requirements and the stigma, and there are not that many OBOT providers.”

Nevertheless, he noted that hundreds of thousands of patients do go to OTPs for MAT, which shows how motivated these patients are. “How many people would have the motivation to deal with obesity, smoking, hypertension, or a great many other medical problems if the treatment regimen required many months of daily attendance and a host of other demands? The fact that there are 300,000 people enrolled in MAT is amazing.”

 Methadone Safety and Dosing

With an appropriate dosage schedule, methadone is an extremely safe medication, said Dr. Newman. But he warned that some OTPs give induction increments that are too great. The federal regulations state that the dose on the starting day must not be more than 40 milligrams—the first dose has to be no more than 30, and an additional dose that day can be 10, said Dr. Newman. But after that, there are some programs that raise the dose too quickly. “Some programs have induction protocols of 30, 40, 50, 60, 70,” with the dose going up daily, he said. The rule of thumb—“start low, go slow, aim high”—needs more of an emphasis on “go slow.”

 Federal Exclusions

Finally, Dr. Newman would like to see more support for methadone treatment at the federal level. The insurance plans of the federal Department of Veterans Affairs and the Department of Defense have an exclusion against methadone and buprenorphine maintenance treatment, something Dr. Newman has long railed against. “Tom McLellan (then deputy director of the federal Office of National Drug Control Policy) and other very high-level officials have said the exclusion is bad, and that they were trying to change it,” said Dr. Newman. “But it persists, and that’s inexcusable and shameful. “

What Dr. Newman wants advocates to do is to speak up. “Silence equals death,” he said, citing an oft-used slogan of AIDS activists years ago. And he is not going to be silent. “There are a lot of windmills still out there.”

Reckitt Benckiser Pharmaceuticals Inc. Receives FDA Response to Citizen’s Petition

Reckitt Benckiser Pharmaceuticals Inc. (RBP) announced that the U.S. Food and Drug Administration (FDA) has denied a Citizen’s Petition filed by the Company.  In the Citizen’s Petition, RBP presented a new evaluation of pediatric exposure data and recommended that the FDA adopt more stringent packaging standards and increased educational interventions to help reduce the number of children exposed to buprenorphine-containing products used to treat opioid dependence.  The FDA concluded that the safety data presented by RBP did not warrant these additional measures, deciding instead that existing labeling and safety programs were sufficient.

RBP is disappointed with the decision but will continue to work with the FDA on safety enhancements.  RBP remains committed to maintaining its own high level standards for safety, including the use of child-resistant, unit-dose packaging for its buprenorphine-based opioid dependence treatment products.  It will therefore carry on with the decision to discontinue the sale and cease distribution of SUBOXONE® Tablets (buprenorphine and naloxone) Sublingual (CIII) in the United States as of March 18, 2013, in light of the analysis evidencing an increased risk of pediatric exposure.

“As a pioneer in opioid dependence treatment, Reckitt Benckiser Pharmaceuticals Inc. strongly believes that child-resistant, unit-dose packaging and increased educational interventions are in the best interest of public health and safety, and we encourage other manufacturers to proactively implement these additional safeguards,” says Tim Baxter, M.D., Global Medical Director, Reckitt Benckiser Pharmaceuticals Inc.

The communication from the FDA also informed RBP that two manufacturers (see related article below) have now received approval to produce generic SUBOXONE Tablets.  The details of these manufacturers’ proposed safety programs have not been provided.

http://www.dailymarkets.com/stock/2013/02/25/reckitt-benckiser-pharmaceuticals-inc-receives-fda-response-to-citizens-petition/

Source: PRNewswire/Reckitt Benckiser Pharmaceuticals Inc. – February 25, 2013

Sharp Rise in Buprenorphine-Related Emergency Department Visits from 2005 To 2010

According to a new Substance Abuse Mental Health Administration (SAMHSA) Drug Abuse Warning Network (DAWN) report, Emergency Department (ED) visits involving buprenorphine increased substantially from 3,161 in 2005 to 30,135 visits in 2010 (Figure 1). This trend likely reflects the increased availability of buprenorphine after the Food and Drug Administration approved its use for treatment of opioid dependence in 2002, and the increasing number of physicians who subsequently became certified to prescribe it.

Figure 1. Emergency Department (ED) Visits Involving Buprenorphine: 2005 to 2010

Most buprenorphine-related ED visits fell into one of three types of visits: patients seeking detoxification or substance abuse treatment, adverse reactions to medications, or nonmedical use of pharmaceuticals. Nonmedical use includes taking more than the prescribed dose of a prescription medication or more than the recommended dose of an over-the-counter (OTC) medication or supplement, taking a prescription medication prescribed for another individual, being deliberately poisoned with a pharmaceutical by another person, or misusing or abusing a prescription medication, an OTC medication, or a dietary supplement.

In 2010, 52 percent of buprenorphine-related ED visits involved nonmedical use of pharmaceuticals, 24 percent involved patients seeking detoxification or substance abuse treatment, and 13 percent involved adverse reactions to medications (Figure 2).

Figure 2. Emergency Department (ED) Visits Involving Buprenorphine, by Type of Visit: 2010

Demographic Characteristics

In 2010, most buprenorphine-related ED visits involving nonmedical use of pharmaceuticals involved male patients (66 percent). Patients aged 26 to 34 accounted for the highest proportion of visits for nonmedical use (38 percent), followed by patients aged 18 to 25 (24 percent), aged 35 to 44 (15 percent), and aged 45 to 54 (13 percent).

Drug Combinations with Buprenorphine

In 2010, 41 percent of buprenorphine-related ED visits involving nonmedical use of pharmaceuticals involved buprenorphine only (Figure 3). In the remaining 59 percent of these visits, another drug was involved. More specifically, pharmaceuticals were combined with buprenorphine in 43 percent of visits The most common types of pharmaceuticals were benzodiazepines, which are commonly prescribed to treat anxiety and insomnia (27 percent of visits). A specific benzodiazepine, alprazolam (Xanax®), was combined with buprenorphine in 12 percent of visits. Narcotic pain relievers other than buprenorphine were involved in 12 percent of visits; more specifically, 6 percent of visits involved the narcotic pain reliever oxycodone and 3 percent of visits involved an unspecified opiate.

Figure 3. Drug Combinations among Emergency Department (ED) Visits Involving Buprenorphine,
by Type of Visit: 2010

 

The report can be accessed at: http://www.samhsa.gov/data/2k13/DAWN106/sr106-buprenorphine.htm

Source: Substance Abuse Mental Health Administration (SAMHSA) Drug Abuse Warning Network (DAWN) – January 29, 2013

OTPs Can Now Dispense Buprenorphine Take-Homes with No Waiting Periods

As of January 7, 2013, opioid treatment programs (OTPs) can now dispense buprenorphine take-homes, with no predetermined waiting period for stable patients. The Substance Abuse and Mental Health Services Administration (SAMHSA) at last issued its final rule giving OTPs the welcome flexibility this past November, and the rule was published in the Federal Register December 6, 2012. Fears of diversion were probably the driving force behind the delay in the final rule; the proposed rule was issued in June 2009.

Because Schedule III substances—like buprenorphine—have a lower potential for abuse compared to Schedule II substances—like methadone—there is justification for the less-restrictive rules on dispensing buprenorphine, according to SAMHSA.

Of course, states can have stricter rules. Some require OTPs to be open 7 days a week, and the idea of buprenorphine take-homes isn’t even on their radar screens. Still, the final rule is a very important first step for OTPs and their patients.

Most OTP physicians (80 percent) have already completed the DATA training and obtained the required waivers, according to SAMHSA. OTPs will not have a cap on how many patients they can treat with either buprenorphine or methadone. However, for take-homes, OTPs will still be “required to assess and document each patient’s responsibility and stability to handle opioid drug products, including buprenorphine products,” SAMHSA said in the final rule.

At this important juncture in the history of OTPs, accompanying articles in this issue take a look back at the development of buprenorphine and methadone for treating patients with opioid use disorders, and the differences between the two medications. We also report thoughts from leaders in the field as to what the new rule is likely to mean to OTPs and their patients.

Buprenorphine vs. Methadone

Buprenorphine and methadone, both being opioids, activate the opioid (mu) receptors on nerve cells. And both drugs have long half-lifes, meaning that they’re long-acting medications. The half-life can vary from 24 to 60 hours for buprenorphine, and from 8 to 59 hours for methadone. (The half-life is the amount of time a drug stays in the body before its concentration in the plasma drops by half. A drug’s half-life can vary from patient to patient.)

The long half-lifes of buprenorphine and methadone account for their usefulness in treating opioid dependence. Simply put, these drugs lack the peaks and troughs that are associated with short-term opioids, like heroin—swings in drug plasma levels that can cause overdose and withdrawal symptoms.

But there are key differences between buprenorphine and methadone.

Full Agonist vs. Partial Agonist

Buprenorphine is a partial agonist; methadone, like heroin, is a full agonist. It is by their actions on opioid receptors that opioids achieve their analgesic (pain-killing) as well as their addictive effects.

Methadone, as a full mu opioid agonist, continues to produce effects on the receptors until either all receptors are fully activated, or the maximum effect is reached.

Buprenorphine, as a partial agonist, does not activate mu receptors to the same extent as methadone. Its effects increase until they reach a plateau. At that level, opioid-addicted patients can discontinue opioid use without experiencing withdrawal. Buprenorphine reaches its ceiling effect at a moderate dose, which means that its effects do not increase after that point, even with increases in dosage.

Like all opioids, buprenorphine can cause respiratory depression and euphoria, but its maximal effects are less than those of full agonists. The benefits of this from an overdose perspective constitute the safety profile of buprenorphine—a lower risk of abuse, addiction, and side effects than with full agonists.

For people who are not addicted to or dependent on opioids, the effects of partial (buprenorphine) and full (methadone) agonists are indistinguishable. However, at a certain point, the increasing effects of partial agonists reach maximum levels. For this reason, people who are dependent on high doses of opioids are better suited to treatment with a full agonist, such as methadone.

Buprenorphine, like methadone, has a serious potential for drug-drug interactions. It must be used cautiously with other medications, in particular benzodiazepines, other sedatives, opioid antagonists like naltrexone, and opioid agonists.

Buprenorphine

Methadone

Heroin

Partial agonist Full agonist Full agonist
Long half-life (24 to 60 hours) Long half-life (8 to 59 hours) Short half-life
Ceiling effect; good safety profile No ceiling effect (useful in patients dependent on high doses of opioids) No ceiling effect

Formulations of Buprenorphine

In October 2002, the Food and Drug Administration (FDA) approved the buprenorphine monotherapy product, Subutex, and a buprenorphine/naloxone combination product, Suboxone, for treating opioid addiction.

Subutex is no longer sold in this country. It has been replaced by generic buprenorphine. Suboxone, a sublingual tablet (designed to dissolve under the tongue), comes in two dosage forms. Suboxone film was approved by the FDA in 2010. The sublingual film dissolves faster than the tablet, and is individually wrapped in unit-dose, child-resistant pouches. According to the manufacturer, Reckitt Benckiser, Suboxone film is clinically interchangeable with the tablet.

Last fall, Reckitt Benckiser voluntarily removed its Suboxone tablets from the market, citing a few pediatric overdoses. But it protected its hold on the Suboxone market by retaining the film formulation. The patent on the tablets had long expired; the patent on the film runs until 2023. Patients, of course, had to be switched to the film, unless their physicians wanted to switch them to generic buprenorphine. At the same time that Reckitt pulled the tablets, it filed a Citizen’s Petition with the FDA, calling on all buprenorphine products to be sold in childproof packaging.

The effect of these moves by Reckitt on the buprenorphine marketplace are not clear, said Nicholas Reuter, MPH, who was senior public health analyst with SAMHSA’s Center for Substance Abuse Treatment (CSAT) when this story was written (he retired on January 31, 2013). “Submitting a Citizen’s Petition doesn’t mean the FDA has to accept it,” he said. In addition, in November 2012 the FDA accepted Orexo’s New Drug Application for Zubsolv, a buprenorphine-naloxone combination. Zubsolv could well be the first generic competition to Suboxone. And on December 17, 2012, Titan licensed Probuphine, its buprenorphine implant, to Braeburn Pharmaceutical for exclusive commercialization in the U.S. and Canada. “The buprenorphine marketplace is looking at different formulations,” noted Mr. Reuter. “There could be a generic competitor [for Suboxone] tomorrow.”

Making the Decision: Methadone vs. Buprenorphine

Aside from the dosage issue, there is no “cookie-cutter” approach for deciding what patient gets buprenorphine and what patient gets methadone. Philip L. Herschman, PhD, chief clinical officer of CRC Health Group, pointed out that different patients react differently to different medications. “Some feel better on buprenorphine, some feel better on methadone,” he said. CRC has been using generic buprenorphine in its OTPs on the same basis as methadone. The extent to which CRC will be able to give buprenorphine take-homes will depend in large part on state regulations—just because the federal government has approved the plan doesn’t mean states will.

“Buprenorphine is great, but it’s not for everybody,” said Walter Ginter, CMA, project director of the Medication Assisted Recovery Support (MARS) project. He doesn’t think the final rule is going to make a big difference for most patients. He noted that few patients go to methadone maintenance as their first course of treatment.

In fact, Mr. Ginter can speak as an expert on subjective effects in a personal way: he has been maintained on both medications—buprenorphine during its development in the 1990s, when he was a study subject, and then methadone. He has been on a high dose of methadone for years, and says “I don’t think I’m clouded out.” Indeed, he is one of the most energetic and articulate advocates in the field. It comes down to a matter of personal preference, he said. “With methadone, you’re never sick and you’re never high, but you do get the serum peaking four hours after the dose,” he said. “I think Suboxone is too much the same, with no ups or downs.”

Still, there are OTPs that do switch patients from methadone to buprenorphine, titrating very carefully downward for patients on doses of 80 milligrams or more of methadone before switching to buprenorphine, said Mark Parrino. MPA, president of the American Association for the Treatment of Opioid Dependence (AATOD). In general, if a patient has been using opioids for a longer period, or has a higher tolerance, methadone would be more appropriate. The reason is that buprenorphine’s ceiling limits those higher-dose equivalents.

Publishers Note: Nicholas Reuter, MPH joined Reckitt Benckiser in February 2013 as a Treatment Manager.

History of Buprenorphine

 Buprenorphine has been in active use for 10 years as a treatment medication for opioid addiction.

As explained by Nicholas Reuter, MPH, senior public health analyst with SAMHSA’s Center for Substance Abuse Treatment (CSAT), the development of buprenorphine was preceded by the development and approval by the Food and Drug Administration (FDA) of levo-alpha-acetyl-methadol (LAAM). The government supported the development of LAAM, but the medication “couldn’t generate enough income from patient use to be sustainable,” he said.

“At the time, there was a lot of discussion about the treatment gap,” he told AT Forum. There were at least 2 to 3 million people who needed treatment for opioid addiction, and only 150,000 or fewer could get into Opioid Treatment Programs (OTPs). “The thinking was that we needed to develop an office-based model,” said Mr. Reuter.

Buprenorphine had been approved for addiction treatment in other countries, Mr. Reuter said, and the molecule is interesting because it is a partial agonist, which gives it a ceiling effect. This means that the risk of overdose is attenuated. “Taken in increasing amounts, it causes dysphoria [anxiety, depression, unease],” noted Mr. Reuter.

People on Capitol Hill were working to see how buprenorphine could be developed as an office-based treatment for opioid addiction, and this led to the development of DATA 2000, said Mr. Reuter. “It was set up as an experiment.” Safeguards were built into the law, so that if treating patients in the physician’s office with narcotic drugs did not turn out to be a good idea, the law could be rescinded. “We were required to do a formal analysis.”

The “experiment” worked, and in 2002 the FDA approved buprenorphine for the treatment of opioid addiction.

Why Not More OTPs?

Why didn’t SAMHSA just increase methadone slots in OTPs, if there was a need for more treatment? First of all, it’s not that easy to increase the number of OTPs, said Mr. Reuter, noting that almost everyplace a program tries to open up, there is a NIMBY battle from the local community. But perhaps more important, there were concerns about methadone overdoses. It turned out that the overdoses were mainly related to pain prescribing, but that was not known at the time. That’s because the increase in pain prescribing coincided with the rule allowing more flexible methadone take-home doses.

But SAMHSA was in a difficult position, nevertheless. “Here you have people saying methadone is a dangerous drug, too many people are dying from it, and we have to look at how it’s used,” said Mr. Reuter. “Methadone mortality was such a significant concern. We would hear it every day.”

While there has been an increase in the number of OTPs in the past decade, there is still a treatment gap, said Mr. Reuter. There were 900 OTPs ten years ago, and now there are 1,260. The number of patients treated in OTPs has gone from 170,000 In 1998 to about 300,000.

Instead of expanding some office-based models for methadone, the government decided to look at buprenorphine—in large part because of problems with methadone mortality, which peaked in 2001, said Mr. Reuter.

Buprenorphine in Practice

Something similar has happened with buprenorphine’s early years—in spite of all of the agency collaboration. “What’s interesting is that as physicians got more experience in treating opioid addiction, they realized that there is a high relapse rate, and maintaining the patient is better than withdrawing the patient,” said Mr. Parrino. This doesn’t mean that every patient will need to be on medication for life.

But by increasing access to buprenorphine, DATA 2000 did not necessarily provide access to counseling and other comprehensive treatment services, said Mr. Parrino. “As far as we know, many patients did not receive counseling in addition to the medication prescribed, did not receive routine toxicology tests to guide clinical decision making, and appeared to divert buprenorphine take-home medication,” he told AT Forum. “Without question, treatment access was increased significantly because patients who never would have sought treatment in the OTP, or simply felt more comfortable receiving such care in a physician office setting, did get access to treatment. But what kind of treatment did they receive?”

Buprenorphine Prescribing Trends

It’s easy to find the number of physicians who are certified through the DATA waiver process to prescribe buprenorphine, but much more difficult to find out how many of them are actually prescribing, or how many patients they have, or whether they are providing counseling or drug testing.

According to the Drug Enforcement Administration’s ARCOS data, over 190 million dosage units of buprenorphine were distributed to pharmacies in 2010, said Mr. Reuter. That’s almost five times the 40 million distributed in 2006. Only 1.1 million dosage units were distributed to OTPs during 2010. Almost 800,000 individuals got prescriptions for buprenorphine from office-based physicians in 2010—five times the 140,000 estimated in 2006.

SAMHSA measures the number of prescribing physicians by how many submit applications to get certified to prescribe buprenorphine. Currently, that’s about 23,000, according to Mr. Reuter. But that doesn’t mean that they are all prescribing—far from it. In fact, the number of physicians prescribing buprenorphine has gone down; fewer physicians are prescribing to more patients, and there is a clear need for more access to buprenorphine.

In 2005, there were 22,000 physicians certified to prescribe buprenorphine under DATA 2000. Of these, almost 5,200 requested to treat up to 100 patients, according to the final rule. In 2009, when the DEA stepped up its investigations of buprenorphine-prescribing physicians, to make sure they were adhering to 100-patient caps, some physicians objected, and surrendered their certificates. Mr. Reuter noted that some of these doctors (about 2,000) had obtained the certification but not gotten any patients, and didn’t want to be bothered with the inspections.

As of September 2012, about 3.9 million patients had been treated with Suboxone, said Tim Baxter, MD, global clinical director of Reckitt Benckiser, which makes the Suboxone brand of buprenorphine.  Of the 23,000 physicians who are waivered to prescribe buprenorphine, 12,000 have actually prescribed it—“many have written only one prescription,” said Dr. Baxter. In fact, there aren’t enough physicians prescribing it. “Initially the number of prescribers went up, and then it flattened out,” he said. Many active prescribers are now fully booked. “With the 100-patient limit, it’s harder for patients to find a prescriber.”

Buprenorphine Diversion

Abuse and diversion of buprenorphine are a concern to us and the FDA, said Mr. Reuter. The 2010 DAWN national data showed an increase in buprenorphine reports in the emergency department.

There are concerns about increases in buprenorphine abuse and diversion, which has paralleled the prescribing increase in the buprenorphine mono formulation, the one without naloxone. The naloxone is what prevents people from being able to get high from melting down and injecting the medication.

One problem is that the mono formulation has been available in generic versions for three years. Generic versions are less expensive than Suboxone, and prescribing of mono buprenorphine has increased steadily.

According to the final rule, HHS “is not aware of compelling evidence to support the assertion that more OTPs than office-based physicians will dispense mono buprenorphine.” But controls already in place regarding OTPs—much more intense controls than those regarding office-based physicians—“will mitigate diversion issues in OTPs with either buprenorphine formulation,” the final rule states. In addition, “the risk for buprenorphine diversion from buprenorphine dispensed by OTPs in accordance with this final rule will be less than the risk of diversion associated with office-based settings.”

If an OTP patient gets a 30-day supply of methadone, or, under the new rule, buprenorphine, that patient is “still subject to drug-testing requirements, still subject to counseling, and still has a treatment plan,” said Mr. Reuter. “On the other end of the spectrum are the buprenorphine prescribers who could prescribe a 30-day supply of Suboxone or buprenorphine, with no requirements for drug testing or counseling,” he said. “That may explain why there is an escalating abuse and diversion of buprenorphine.”

Buprenorphine Not a Miracle Cure

Treatment with buprenorphine is effective, said Mr. Reuter. Medication-assisted treatment has expanded, even in parts of the country where it wasn’t available, such  as Wyoming and North Dakota. Those states don’t permit OTPs. “But the success has to be looked at in terms of the real world, in which people relapse,” he said. “It’s not a miracle cure, and I never thought it would be. To my mind, it’s expanded treatment capacity, but it’s not a cure. And now we see increasing abuse and diversion.”

Mr. Parrino thinks the reason buprenorphine has been successful is that it is not “stigmatized,” the way methadone is. Interestingly, the earliest prescribers of buprenorphine were using it primarily as a withdrawal agent, rather than a maintenance agent, he said. Many of these patients undoubtedly relapsed; as a huge NIDA clinical trial showed, more than 9 out of 10 patients who were tapered off buprenorphine, relapsed.

See comment from Robert Newman, MD in comment section. 

Reference

Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004.

Suboxone® Sales Estimated to Reach $1.4 Billion in 2012—More Than Viagra® or Adderall®

Sales data from the first three quarters of 2012 indicate that Suboxone retail sales in the U.S. will likely reach $1.4 billion this year—nearly a ten-fold increase over the $137.1 million in sales in 2006. Suboxone currently has the 28th highest retail sales of all prescription drugs in the U.S., up from 198th in 2006. Suboxone sales will likely continue to increase in light of new SAMHSA regulations allowing Opioid Treatment Programs (OTPs) to dispense a multiple days’ supply of take-home buprenorphine, the main ingredient in Suboxone, to eligible patients without having to adhere to previous length of time in treatment requirements. The steady and rapid increase in Suboxone sales suggests that the drug is being widely adopted in the treatment of opioid dependence, likely because of its effectiveness and because it can be prescribed in both private physicians’ offices and OTPs.

Further information is available at: http://www.cesar.umd.edu/cesar/cesarfax/vol21/21-49.pdf

 Source: Cesar Fax – December 10, 2012 Vol. 21, Issue 49

Federal Rule Provides Flexibility in Dispensing Buprenorphine for Opioid Addiction Treatment in OTPs

The Substance Abuse Mental Health Services Administration (SAMHSA) issued a Federal rule to allow patients being treated through an opioid treatment program (OTP) to receive take-home supplies of buprenorphine from an OTP in a more flexible manner. Buprenorphine is a medication used in opioid addiction treatment. The regulation takes effect on January 7, 2013.

Under the rule change, OTPs will be permitted to dispense buprenorphine to eligible patients without having to adhere to previous length of time in treatment requirements. Currently, OTPs require a person to be in treatment a certain amount of time before being given a multiple days’ supply of medicine to take home.

The change in the rule will not affect requirements for dispensing methadone. SAMHSA based the change in the restrictions for dispensing buprenorphine on several factors. These include differences in the abuse potential between methadone and buprenorphine, as well as the actual abuse and mortality rates (buprenorphine is lower in each instance).

For more information on the rule, go to: http://www.ofr.gov/OFRUpload/OFRData/2012-29417_PI.pdf

The Federal Register notice can be accessed at: https://www.federalregister.gov/articles/2012/12/06/2012-29417/opioid-drugs-in-maintenance-and-detoxification-treatment-of-opiate-addiction-proposed-modification

Source: The Substance Abuse Mental Health Services Administration – December 6, 2012

The Beginning of the End of the Abstinence Rule?

“The reaction to the news last week that Hazelden will be using medication-assisted treatment—including the maintenance drug, buprenorphine (Suboxone), potentially indefinitely for some patients—has been intense. “Hell froze over,” one tweeter responded, expressing shock that the granddaddy of abstinence-based treatment could make such a big change. “It’s about time,” said Dr. Charles O’Brien, director of the University of Pennsylvania’s prestigious Center for Studies on Addiction, and one of the field’s most eminent researchers. The head of the National Institute on Drug Abuse, Dr. Nora Volkow, also praised the decision.”

http://www.thefix.com/content/hazelden-maintenance-suboxone-opiate-painkiller8546

Source: TheFix.com – November 8, 2012

Reckitt to Discontinue Suboxone Tablets in U.S.

Reckitt Benckiser plans to withdraw its Suboxone heroin treatment tablets in favor of a film version in the United States over the next six months due to the higher risk of children getting hold of the tablets.

The press release can be accessed at: http://www.rb.com/site/RKBR/Templates/MediaInvestorsGeneral2.aspx?pageid=1328&cc=GB

See related Blog: http://janaburson.wordpress.com/2012/09/30/reckitt-benckiser-to-stop-manufacturing-suboxone-tablets/

Source: Reuters.com – September 25, 2012

Majority of Buprenorphine-Certified Physicians Think Buprenorphine Is Easier to Get Illegally Than Methadone

Physicians who are certified to prescribe buprenorphine are increasingly likely to perceive diversion and abuse of the drug, according to a survey funded by the manufacturer as part of a national post-marketing surveillance program*. Nearly one-half (46%) of physicians certified to prescribe buprenorphine in 2009 knew of buprenorphine products being bought or sold on the street, compared to 27% in 2005. In addition, a majority (81%) of the physicians surveyed believed that buprenorphine was easier than methadone to buy on the street in their community in 2009, a 56% increase from 2005 (see figure).

Forty-four percent reported that they knew someone who used illegal buprenorphine/naloxone to manage opioid withdrawal, 34% for maintenance until entering treatment, 17% to try out its effect, and 7% to get high (data not shown). The authors suggest that “the increase in diversion may be driven by the increase in abuse” as evidenced by the increasing percentage of treatment applicants who said they knew of buprenorphine being used to get high (from 5% in 2005 to 21% in 2009; see CESAR FAX, Volume 21, Issue 25). However, the increase in diversion may also “be driven by therapeutic demand, suggesting treatment expansion may be necessary. Finding a balance between diversion and abuse of a medication versus expanded treatment remains a challenge”.

Perceptions of Buprenorphine Diversion/Misuse, Physicians Federally Certified
to Prescribe Buprenorphine
(n=8,194 from 2005 to 2009)

*Conducted by an independent contractor for Reckitt Benckiser Pharmaceuticals, the Surveillance of Diversion and Abuse of Therapeutic Agents (SODATA) utilizes several national indicators of diversion and abuse combined with a survey of applicants to substance abuse treatment programs and a survey of CSAT-certified physicians. A total of 8,194 quarterly surveys were conducted with randomly-selected physicians federally-certified to prescribe buprenorphine from 2005 to 2009.

See Wish, ED, Artigiani, E, Billing, A, Hauser, W, Hemberg, J, Shiplet, M, and DuPont, R, “The Emerging Buprenorphine Epidemic in the United States,” Journal of Addictive Diseases 31(1):3-7, 2012 for more information on buprenorphine diversion and abuse.

Source: Adapted by CESAR from Johanson, C-E; Arfken, C. L.; di Menza, S.; and Schuster, C. R., “Diversion and Abuse of Buprenorphine: Findings from National Surveys of Treatment Patients and Physicians,” Journal of Drug and Alcohol Dependence 120:190-195, 2012. For more information, contact Chris-Ellyn Johanson at cjohans@med.wayne.edu.

Harsh Cameron Douglas Sentence Sparks Appeal, Support

Not offered drug treatment, Douglas relapsed while in prison and was caught in possession of a small amount of heroin and Suboxone.

But, unusually, Douglas was also prosecuted for drug possession by a prisoner, and even more unusually, he was hammered hard at sentencing. Federal District Court Judge Richard Berman nearly doubled his original drug trafficking time, sentencing him to an additional 4 ½ years in prison. Prosecutors had asked for at most an additional two years.

“Tacking on more prison time for a person who is addicted to drugs because they relapse behind bars goes against fundamental principles of medicine, inflicts unnecessary suffering and undermines both safety and health,” said Dan Abrahamson, director of legal affairs for the Drug Policy Alliance.  “Such a response only fuels the vicious cycle we see daily across the country of drug-dependent persons being imprisoned while sick, coming out sicker, and then returning to jail even quicker — at huge expense to everyone.”

http://stopthedrugwar.org/chronicle/2012/may/21/harsh_cameron_douglas_sentence_s

Source:  StopTheDrugWar.org  – May 21, 2012

 

Drug Users, Treatment Providers, and Law Enforcement Officers Describe Increasing Suboxone Misuse in Ohio

Since 1999, the Ohio Substance Abuse Monitoring Network (OSAM) has been monitoring local substance abuse trends. Their most recent report, covering January to June 2011, indicates that the “availability of Suboxone remains high in all regions, with the exception of Toledo where it remains moderately available.” Obtaining Suboxone is described by another user as “super easy; like candy machines, a dime a dozen.” According to a treatment provider, Suboxone “is becoming easier to get than methadone.” Following is a summary of Suboxone use in Ohio, in the words of users (U), treatment providers (TP), and law enforcement officers (LE).

How Is Suboxone Obtained? 

“You’ve got people at [12-step] meetings handing them [Suboxone] off. They’re being sold like any other drug” (TP). “When they prescribe it …, they prescribe a lot of it, and people don’t use the whole prescription. They [users] would then sell it on the street” (LE). “They’re [heroin addicts] getting Suboxone and turning around and selling it” (U). “People pick up prescriptions [for Suboxone] and call [their dealer] and sell them” (U). “The dealers will give them [users] a free Suboxone with their heroin. Customer satisfaction.” (TP).

Why Is Suboxone Used?

Fight Withdrawal: “[Some users] don’t want to get off [opioids] for good. They just want to not be sick, so they have Suboxone stashed away for when they feel sick” (TP). “They [opiate addicts] use it … like Tylenol 3, to use till they can get a fix. [Suboxone is] a drug of convenience” (TP). “Some start off using it …to assist with withdrawal, but find that they like how it feels and become addicted” (TP). “I quartered them [Suboxone] …to take the bare minimum, so I wouldn’t be sick, but that way I could still use an opiate; I would buy them …to come off other stuff, but it never worked that way. ‘Cuz you could get high off Suboxone if you hadn’t had any opiates in a couple of days …If you are addicted to opiates, you take the smallest piece of Suboxone—it makes you feel normal” (U).

Get High: “If you are clean [opioid free], you will get very high from Suboxone” (U). “For a buzz … can snort Suboxone, as long as you don’t have other opiates in the system” (U, p. 50). “If you are not addicted to opiates and you take a Suboxone, it’s very, very strong.  It can make you high for three days” (U). “People … will use Xanax a half-hour before Suboxone and will get high. Some clients say the effects are as good as, or better than, that of OxyContin®” (TP). “[A] lot of people are being introduced to opioids through Suboxone now because, if they were not Suboxone users, the buprenorphine …the active agent in Suboxone is giving them the opiate effect, and now they’re looking for stronger opioids. So now it’s …a gateway drug to opioid addiction” (TP).

Avoid Detection: “Participants also reported that individuals who need to avoid detection of drug use on urine drug screens (probationers) use Suboxone because it is often not screened” (Report). “[Suboxone is] the institutional drug of choice” (U).

How Is Suboxone Being Used?

“People typically put them …under their tongue, or they chew them up. I’ve actually witnessed a couple people shoot [inject] them up; I would eat the full 8 mg Suboxone” (U). “I snorted it … when I would take it. It made me not sick” (U). “Well, I shoot [Suboxone] in my neck, so, um, it goes straight to you, you know” (U). “I do know a few people that when switched to the films [Suboxone strips], they say that those are a lot easier to shoot up [inject]. Yeah, ‘cause they dissolve in water; they dissolve completely, and I’ve heard people say that those actually work really well” (U).

http://www.cesar.umd.edu/cesar/cesarfax/vol21/21-02.pdf

Source: CESAR FAX (University of Maryland) – January 16, 2102

Nearly 50 Attica, New York Inmates Falsely Test Positive for Suboxone Use

A total of 57 inmates tested positive for the use of Suboxone, a drug containing buprenorphine, a medication used to treat opiate addiction.

Inmates testing positive were subject to disciplinary hearings that resulted in many cases, solitary confinement, the loss phone use and commissary privileges, loss of family visitation and loss of accrued “good time status”, which can affect parole hearing outcomes.

After nearly a month of complaints, the Superintendent of Attica contacted the manufacturer of the drug testing equipment, who, after testing, found it to be mis-calibrated, leading to the false-positive results.

As a result, 48 of the 57 prisoners who tested positive for Suboxone will have their positive test reversed and have imposed sanctions reversed.

http://www.wkbw.com/news/Nearly-50-Attica-Inmates-Falsely-Test-Positive-for-Opiate-Use-137827278.html

Source: Buffalo, New York WKBW.com  – January 21, 2012

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