Archive for the ‘Buprenorphine’ Category

Subcutaneous Buprenorphine Injections for Treatment of Opioid Use Disorders

 

 

 

 

 

I’ve blogged in the past about studies conducted on CAM2038, a new preparation of buprenorphine that can be given in a subcutaneous injection weekly or monthly. I think this delivery system holds great promise for the treatment of opioid use disorder.

Earlier this year, pharmacokinetic data from healthy volunteers showed that blood levels with the subcutaneous injections equaled the levels provided by sublingual means. This data supports the idea that the injections should provide therapeutic levels in patients with opioid use disorder. [1]

Later this year, a Phase II study was published in JAMA Psychiatry. Weekly subcutaneous preparation of buprenorphine was administered to 47 subjects with opioid use disorder. These patients were not seeking treatment, but had agreed to take part in this study, and all were diagnosed with opioid use disorder, either moderate or severe.

These subjects were given dose of either 24mg or 32mg one week apart, and had complete suppression of opioid withdrawal at both doses. The subjects were then challenged with varying doses of hydromorphone, and had sustained blockade of response to the hydromorphone. [2]

The six-month implant, brand name Probuphine, hasn’t been widely prescribed. As I predicted, the confusion over cost, insurance coverage, and implantation regulations have so complicated Probuphine’s use that mainstream medical providers aren’t considering its use. Also, it’s only indicated for patients on 8mg or less of sublingual buprenorphine, and patients have concerns about what will happen if it doesn’t work well. They ask if their insurance companies would pay for supplemental buprenorphine if the implant doesn’t work as well for them. I don’t know for sure, but I’m guessing they would not pay for supplemental medication.                                                                                                                                                                                                                                                                                                                                                                                                                 My biggest concern with Probuphine was that patients may be less inclined to come for counseling sessions if they have had a six-month implant that keeps them feeling normal. They have no monthly incentive to see their physicians. Many physicians require counseling as a condition for ongoing monthly prescription for sublingual buprenorphine.

I like the idea of injections for weekly or monthly buprenorphine. If it works as well or better than sublingual buprenorphine, it could be the solution to some difficult problems.

  • It would save time for my patients on buprenorphine at the opioid treatment program. One of the complaints we hear is of the regulations surrounding treatment in our setting. Unlike in the office-based setting, buprenorphine prescribing at the opioid treatment program demands we follow the sometimes onerous rules of both state and federal laws governing opioid treatment programs.
  • It would resolve our diversion dilemma.But injections can’t be diverted, so far as I’m aware.
  • Because buprenorphine has a high street value in my community, patients are sometimes tempted to spit out their medication to sell it, or even to inject it into themselves. We don’t want this, given the high rates of complications with intravenous use. We don’t want patients to sell medication because it hurts our reputation in the community. We don’t want to be known as suppliers of illicit buprenorphine.
  • It would be a godsend for patients who have to go to jail unexpectedly.
  • Most of the time, jails won’t bring incarcerated patients to the OTP for their daily dose of buprenorphine (or methadone), so they suffer opioid withdrawal and are at risk for relapse upon being released, with increased risk of overdose death. But if we can give them a monthly or even weekly shot, it will keep them feeling better, and serve as a blocker if they do leave jail and use illicit opioids like Opana or oxycodone or heroin.
  • Patients wouldn’t have to think about taking medication each day; with the injections they wouldn’t have to take a dose of anything each day, just show up for weekly or monthly injections given to them by a medical professional
  • Subcutaneous injections are much less complicated to administer than Probuphine, with rods that require a minor surgical procedure to implant, then explant six months later.The FDA plans to discuss this new preparation of buprenorphine at their advisory committee meeting November 1, 2017. Several days prior to this meeting, data to be discussed at this meeting should be available online for interested readers. [3]If this new option is approved by the FDA, it can give us yet another tool with which to treat patients, always a good thing.
  • 1. Albayaty et al., Advanced Therapeutics, 2017, Feb; 34 (2)

 

  • 2.Walsh et al., JAMA Psychiatry, 2017;74(9):894-902.

 

Advertisements

Maximum Daily Dose of Buprenorphine

Hser et al., 2014, Addiction

 

 

 

 

 

I’d like to thank my readers for their patience during my recent break from blogging. Now that I’m rested, it’s time to start barbequing some sacred cows.

First on my list: limiting the dose of sublingual buprenorphine to 16mg per day.

Recently I’ve heard from physicians who have been told 16mg of sublingual buprenorphine is the highest daily dose that should be prescribed, because studies show that opioid receptors in a human brain are saturated at that dose in most people. While this is true, limiting all patients to 16mg or less neglects research from real life patients.

Some governmental agencies have gone as far as forbidding daily doses higher than 16mg. For example, the Virginia Board of Medicine passed a regulation earlier this year that the highest dose that physicians could prescribe was 16mg per day. In Tennessee, patients can’t go above 16mg per day unless they are seen by an addiction specialist physician.

However, the FDA has approved doses up to 24mg SL per day. Who is right? Did the FDA get it wrong? Are patients who want to go higher than 16mg all drug seekers? Or do all such patients plan to sell their excess medication?

If you read the REMS document created by the manufacturer of Suboxone film, it says the target dose should be no higher than 16mg per day, and that doses higher than 24mg haven’t been shown to provide additional benefit. That leaves a question mark about dosing between 16 and 24mg.

The American Society of Addiction Medicine (ASAM) issued a statement addressing the tendency of state prescription monitoring programs to assign MME (morphine milligram equivalents) values to buprenorphine doses. In that statement, issued earlier in 2017, they said, “The US Food and Drug Administration (FDA) approves dosing to a limit of 24 mg per day. There is some evidence regarding the relative efficacy of higher doses.” [1]

If ASAM says 24mg is OK for some patients, and the FDA has already approved that dose, that’s good enough for me…assuming the patient truly needs a higher dose.

Some patients do better on a dose of 24mg than on 16mg. I work at an opioid treatment program where we observe the patients taking their doses on site, and we pay close attention to any attempt at diversion of the dose. Therefore, we have no question about whether a patient is taking less than the dose I’m prescribing.

When I see new patients within a week or two of admission, I ask how they are feeling. Some patients dosing at 16mg per day of buprenorphine describe symptoms consistent with opioid withdrawal by late evening. I increase their dose above 16mg when I also see physical signs of withdrawal, like large pupils, sweaty palms, and the like. Many patients feel improvement to the point we don’t have to consider switching to methadone.

I increase these patients’ doses because I am sure they are getting their full dose each day, and because I see signs of withdrawal with my own eyes. I know experts say a dose of 16mg is “supposed” to block all the opioid receptors according to studies of this drug, and I believe that is true for many patients. I also think there are patients for whom increasing the dose above 16mg provides benefit, and can eliminate the need to switch to methadone.

Not that there’s nothing wrong with methadone. It has a proven track record, but it does have more medication interactions than buprenorphine, and is more dangerous with certain medical problems.

Methadone patients were under-dosed for years, when physicians had the misperception that no patient needed more than 70mg per day to treat withdrawal. With further studies and information, we know that’s not true, and best evidence shows most patients need between 80-120mg, and sometimes much more than that.

I think in years to come, we will see that by limiting patient doses to 16mg, we are under-dosing some buprenorphine patients.

Why are so many agencies trying to keep buprenorphine doses low?

First, the U.S. has a “less is more” attitude regarding medication-assisted treatments for opioid use disorder. Given the existing bias against these medications, of course some peoples’ attitudes will be grudging acceptance of the medications, but trying to limit the doses to be as low as possible.

Second, there’s the very real concern about diversion of buprenorphine. The more buprenorphine that’s being prescribed and dispensed, the more that may end up being diverted to the black market. I know this is true.

However, opinions can differ regarding the potential harm of providing more buprenorphine to the black market. Some experts might think since buprenorphine is one of the safest opioids manufactured, increased black market access could help save lives. Though many more people embrace harm reduction now than ten years ago, we are not yet in a place where the law-and- order types would allow a serious conversation about this.

Third, I’m worried that some decisions about dose maximums for buprenorphine may be driven by cost. In a state where many patients prescribed buprenorphine products are on Medicaid, higher doses would cost the state more. The same would be true for managed care organizations and the insurance companies and the like. I hate to sound cynical, but financial concerns often drive medical decisions.

By now you know my opinion; if a patient dosing with buprenorphine 16mg SL per day reports withdrawal symptoms and has physical signs that match these symptoms, I’m willing to increase the dose to 20 to 24mg per day. We have a pretty good study, by Hser et al., 2014, that shows higher treatment retention rates with higher doses. Plus, the FDA has already approved doses up to 24mg per day. [2]

I’m cautious about take home dose in patients at the opioid treatment program. If the patient has a history of injecting drugs, I’d like them to have more time in stable recovery before granting take homes. For patients on 24mg per day, I may do more frequent pill counts and bottle recalls, as a precaution against drug diversion. But I’m not sure a patient on 16mg is any less likely to sell part of her prescription than a patient dosing at 24mg.

  1. https://www.asam.org/advocacy/find-a-policy-statement/view-policy-statement/public-policy-statements/2016/10/11/public-policy-statement-on-morphine-equivalent-units-morphine-milligram-equivalents
  2. Hser et al., “Treatment Retention among Patients Randomized to Buprenorphine/naloxone Compared to Methadone in a Multi-site Trial,” Addiction, 2014, Jan; 109(1) 78-87.

 

Buprenorphine in the Primary Care Setting

 

 

 

 

 

I was asked to participate in a project to help primary care doctors provide buprenorphine in office-based settings. This grant, awarded to some very smart people at the University of North Carolina, uses the ECHO model to help physicians in the community become more comfortable with treating patients with opioid use disorder in their offices.

This ECHO model, originally conceptualized at the University of New Mexico, uses a hub-and-spoke model to connect experts at UNC and other locations with primary care doctors at their North Carolina locations. The ECHO model can help not only the physicians and physician extenders, but also nurses, social workers and other staff members who are a part of patients’ treatments, using teleconferencing.

Other hub-and-spoke models have placed physicians and the hub and patients at the spokes, so this is a little different. It’s also different from telemedicine, since the participants at the hub and spoke are all care providers, not providers and patients.

It’s a great program, and gives free continuing medical education hours to the physicians who participate, at the same time they get help with problematic situations in their practice.

Our group is prepared. We’ve done practice sessions and we’ve gotten comfortable with the technology (no small achievement for me!).

Now all we need are providers to participate.

We’ve had some interest, but of course would like to reach as many providers as possible. We had some brainstorming sessions about how to get more participants. We would like to reach primary care providers who have a waiver to prescribe buprenorphine, or who may be interested in prescribing.

As it turns out, many physicians who get the waiver to prescribe buprenorphine don’t end up prescribing, or only prescribe to a few patients. These providers could see more patients with opioid use disorder, and help our nation’s situation with the treatment gap.

This treatment gap is the number of people who need treatment compared to the number of people who are able to receive it. At present, experts estimate that only about 20% of people who need treatment for opioid use disorder actually get it. Of course, some of the remaining 80% aren’t yet interested in treatment, but many are desperate for help, and can’t access it.

Due to changes in the DATA 2000 law, physician extenders like nurse practitioners and physicians assistants will be allowed to prescribe buprenorphine to treat opioid use disorder, after they take a 24-hour course. Of course…many extenders in my area have been prescribing buprenorphine for years, off-label “for pain” with a wink and a nod, but the new law will allow them to be legitimate prescribers. This may expand the number of prescribers a great deal, and help to close the treatment gap.

So why do providers, after getting the training to be able to prescribe buprenorphine, not end up prescribing?

A study done by Walley et al., published in the Journal of Internal Medicine, 2008, surveyed all 356 physicians in Massachusetts who were waivered to prescribe buprenorphine. The study was done in 2005, so that was relatively early in the history of office-based treatment. Out of that total, 235 responded to the survey. Of the 235 that answered the survey, 66% had prescribed at least once, and 34% had never prescribed buprenorphine.

Of the non-prescribers, around half said they would prescribe if some barriers were removed. Nearly a third of these doctors felt like they had insufficient office support. Other barriers, in rank of descending importance, were insufficient nursing support, lack of institutional support, insufficient staff knowledge, low demand for services, and payment issues. So this study showed physicians didn’t feel like they had the support staff that they needed.

Of the physicians who were already prescribing buprenorphine in their office-based practices, the biggest barriers, in descending order of importance, were payment issues, insufficient nursing support, insufficient office support, insufficient institutional support, and pharmacy issues.

Some additional tidbits of data emerged from this study. For example, psychiatrists were less likely to prescribe buprenorphine than were primary care physicians, and physicians in solo practice were more likely to prescribe than those in group practices.

I suspect it’s easier to implement changes to medical practice when you are the boss and the lone provider. In groups of physicians, it’s probably harder to change the status quo to take on new projects and ideas, even when more support staff are presumably available.

This trend, where many of the physicians waivered to prescribe buprenorphine don’t end up prescribing, or prescribe for very few patients, has continued through the last fifteen years.

A study from 2014 by Hutchinson et al., published in the Annals of Family Medicine, looked at 120 physicians in Washington State who received training in 2010 and 2011, to prescribe buprenorphine for opioid use disorder. Out of the 120 providers trained, 92 participated in the post-training survey. Of those providers, some were excluded because they were still in their residencies, or were prescribing buprenorphine before they took the course, leaving 78 physicians newly qualified to receive a waiver to start prescribing buprenorphine for opioid use disorder

Of these 78 physicians, only 64% actually applied for the waiver. Of these 50 physicians, only 22 actually ended up treating at least one patient with buprenorphine. In other words, only about a fourth of physicians who could start prescribing to treat opioid use disorder actually did so. Of these 22 physicians, half prescribed for only three or fewer patients.

Physicians in a practice where there was already another physician prescribing buprenorphine were significantly more likely to actually start prescribing than physician in practices where no other physicians prescribed. Younger physicians were more likely to prescribe buprenorphine than older physicians. Fewer than half of these physicians were willing to have their names listed on SAMHSA’s buprenorphine treatment locator site. (http://buprenorphine.samhsa.gov)

Another study by DeFlavio et al., Rural Remote Health, 2015, was done with an anonymous survey of all of Vermont’s primary care doctors. As it turns out, 10% were buprenorphine prescribers, while 80% said they saw patients addicted to opioids. The barriers that these physicians saw for buprenorphine treatment were inadequately trained staff, insufficient time, insufficient office space, and cumbersome regulations.

Interestingly, Vermont also used a “hub and spoke” model, where experts at the hub stabilize patients newly starting buprenorphine, and after stabilization they transfer to the “spokes” which are primary care providers who continue the prescribing for these patients. This model seemed to work well for the patients and physicians who participated.

As of today, SAMHSA’s website (https://www.samhsa.gov/programs-campaigns/medication-assisted-treatment/physician-program-data accessed 6/6/17) says there are almost 38,000 physicians with waivers to prescribe buprenorphine from an office setting to treat opioid use disorder. Around 3200 have permission to treat up to 275 patients; nearly 9000 can treat up to 100 patients, and around 26,000 can treat up to thirty patients.

In other words, if all of these physicians were prescribing to their maximum, and were located in areas with the highest rates of opioid use disorder, we’d have enough manpower to treat all patients who wanted help.

But these providers aren’t at their maximum.

How can we convince these doctors to prescribe for more people? How can we recruit new providers, who will follow through with a commitment to treat people with opioid use disorder? How can we remove the barriers, which largely appear to fall under the category of insufficient support to give good care?

Some smart people have been working on this for some time, and we now have several models available to assist buprenorphine providers help patients with opioid use disorders.

“Collaborative Care Model,” also known as the Massachusetts model, uses nurse care managers to expand access to treatment. This model is based on how patients with other difficult chronic diseases are managed, such as diabetes and HIV infection. In other chronic illnesses, nurse care managers help the patient with day-to-day care management. This helps the physician know what is going on with the patient and gives the doctor much-needed support to manage the health of these patients.

Studies done on this model showed that patients did as well or better than patients managed only by physicians. This program expanded into community health centers, and the numbers of waivered physicians participating increased by 375%, though this was at a time when buprenorphine was first taking off anyway. The patients treated under this model also had significantly fewer hospital stays.

In this model, nurse managers were doing much of the medical management: doing inductions, doing follow-up on patients, and troubleshooting any problems the patients were having. Providers participating in the model mentioned that RNs can’t charge as much for the care they provide as physician extenders or physicians, so that’s a possible problem.

This year at the American Society of Addiction Medicine’s annual conference, Dr. Andrew Saxon spoke during a session which addressed how to engage practitioners to treat opioid use disorders. He treats patients in the Veterans Administration system, and describing an intriguing method that he called “academic detailing” that they use at the VA.

He said that pharmaceutical companies have already found a model that works, when it comes to getting doctors to prescribe new medications. These companies hire charming people to go to doctors’ offices to spend time talking with the physicians and physician extenders, explaining the new medication and giving them brochures with information.

Dr. Saxon started doing the same thing with VA doctors. Experienced providers make an appointment to speak with a doctor, and bring him or her information, perhaps bring lunch, and generally talk about the process and pleasures of treating opioid use disorders in an office setting. This one-on-one approach appears to work well, and the VA increased treatment availability a great deal using this approach.

The VA made a slick brochure, called “Opioid Use Disorder Provider Guide” which is a pretty good summary of information needed by providers starting to prescribe buprenorphine. Since it’s in the public domain, you can access this document at: https://www.pbm.va.gov/PBM/AcademicDetailingService/Documents/Opioid_Use_Disorder_Educational_Guide.pdf

I think this academic detailing idea is a winner. It makes sense – pharmaceutical companies wouldn’t have used this method for years if it didn’t work.

To veer off-topic for a moment…it strikes me that I’ve been trying to “detail” local providers for five years, not to get them to prescribe, but just to get them to stop telling patients to get off buprenorphine and methadone. It would be a huge relief if local doctors encouraged these patients, rather than belittling them.

I exaggerate, of course. There are many physicians in my area who are great to work with, but I guess the more difficult doctors tend to stand out in my mind.

Maybe local doctors need detailing from a physician with credentials and/or clout. Perhaps I lack the credibility or personal charisma that makes other doctors listen to me. I’d like to enlist that kind of doctor to “detail” in my area.

Back to the topic at hand.

The VA isn’t the only agency that’s created guidelines.

The American Society of Addiction Medicine (ASAM) has had a similar document, composed by experts as a guide for prescribers: https://www.asam.org/docs/default-source/practice-support/guidelines-and-consensus-docs/asam-national-practice-guideline-supplement.pdf

There’s also information published by SAMSHA (Substance Abuse and Mental Health Services Administration):

https://store.samhsa.gov/product/Medication-Assisted-Treatment-of-Opioid-Use-Disorder-Pocket-Guide/SMA16-4892PG

However, the last time I tried to download this one, there seemed to be a glitch.

So there’s plenty of information available for new prescribers, and there’s a nationwide support network called PCSS MAT, for Providers’ Clinical Support System. It’s an organization dedicated to training and mentoring medical providers in the treatment of opioid use disorders with medication-assisted therapies.

If you go to their website, (http://pcssmat.org/) you can access archived trainings about various topics relating to MAT. They have online modules, podcasts, and basic information. It’s possible to be connected with a one-on-one mentor with experience treating the disease. This helps the provider feel connected and supported, particularly with difficult issues that often arise.

So currently, there’s a ton of data and support for providers who want to treat patients with opioid use disorders, more than there’s ever been before.

With our ECHO UNC launch, providers can get specific recommendations for managing complex patients (with patient privacy protected, of course). Their staff can learn how to support the prescriber, and it’s all free, paid for under grant money. The prescriber can even earn continuing education credit hours, so it’s a win-win-win prospect for them.

I’ll keep my readers updated about how it’s going.

If you are a provider or know a provider who’d like to take advantage of this opportunity to learn, get help with issues that are vexing you, and get free credit hours for doing so, send me an email so I can connect you with the ECHO UNC hub. The technology is free and easy to use.

New Way to Dose Buprenorphine

FluidCrystal technology

 

 

We all know that Probuphine in now available. It’s a depot preparation of buprenorphine that can be implanted beneath the skin to release buprenorphine for six months. It finally came to market last year, and we are awaiting news of how well it is working.

Soon we may have another choice: weekly and monthly depot injections of buprenorphine. I blogged about this in an entry posted July 30, 2013.

In essence, this new subcutaneous injection of buprenorphine was invented by Camarus Pharmaceuticals, a small Swedish company that invented a nanoscale drug delivery system, as they say on their website. This “Fluidcrystal” injection containing buprenorphine comes in preparations of varying doses, and can be dosed once per week or once per month, depending on the preparation.

The liquid substance containing buprenorphine is injected subcutaneously (under the skin), where it forms a gel. Then a capsule-type substance surrounds it, allowing buprenorphine to be released into the body over time. Started weekly, the dose can be adjusted to meet patient needs. Eventually, the patient can move to once-monthly injections. The matrix of material is biodegradable, and eventually completely absorbed by the body.

This subcutaneous injection of medication has a very low viscosity, meaning it can be given with small needles that cause less pain to the patient. The medication is already pre-mixed, making it convenient for medical providers, and it is stable at room temperature for up to three years.

Initial trials of this medication have been intriguing; they show a fast delivery of medication, giving rapid onset and a steady blood level over one week or one month, depending on the preparation given. Safety data was pretty good; other than some headache and a low rate of inflammation at the injection site, it was well-tolerated. Because of the Fluidcrystal technology, if an addict attempts to inject this substance into a vein, it will form a deposit at the injection site, blocking the vein.

I’m excited by this medication. First, with daily buprenorphine dosed sublingually, some patients relapse. They may decide to stop taking the buprenorphine for a few days so that they can use their opioid of choice and get high again. True, they have to do a little more planning to relapse than if they were not on buprenorphine, but relapse rates are still too high. The depot forms make relapse less likely, I think, because compliance is assured once the medication is injected.

Second, with the depot forms of buprenorphine, the patients don’t have to think about taking something to treat their addiction. They don’t have to think about their medication at all, and their addiction doesn’t have the chance to urge them to take more of their medication than prescribed. Thankfully with buprenorphine there is a ceiling to its opioid effect, so that patients already on a blocking dose of sublingual buprenorphine won’t usually feel any intoxication from taking more of their medication.

Third, we’ve seen increases in the amount of buprenorphine being diverted to the black market, as the total amount prescribed has increased. Politically, this diversion threatens buprenorphine availability. One only need to look at regulations like what was passed by Virginia’s medical board to see the limits being placed on this life-saving medication, due to concerns about diversion. Law enforcement officials and politicians believe buprenorphine is a desirable street drug. Of course, research shows most people using illicit buprenorphine are trying to prevent withdrawal, and not using it to get high.

With this subcutaneous injection, I think it’s highly unlikely to be diverted, or at least much less likely that film or tablet to be diverted.

Because the dosing interval is every one week to every one month, medical providers can still see the patient once per month, and can provide counseling as a condition of continued treatment. With the six-month depot placement of Probuphine, it’s unlikely the patient will voluntarily return monthly for counseling visits, once they get the medication implanted. The more frequent and simpler administration of this form of buprenorphine appears ideal to me.

According to the Drug Addiction Treatment Act of 2000, the FDA must give approval to any form of buprenorphine that’s to be used to treat opioid addiction. At present, the sublingual form of buprenorphine and the implantable form of buprenorphine known as Probuphine have FDA approval. Other forms of buprenorphine in patch (Butrans) or injectable form are illegal for a doctor to prescribe to treat opioid addiction. this new subcutaneous injection of buprenorphine therefor must be approved by the FDA before it can be legally used to treat patients with opioid use disorder.

According to the manufacturer’s website, Phase 3 trials are concluded. According to a company press release, a double-blind, double dummy controlled trial of the weekly and monthly injections were found to be “non-inferior” to sublingual buprenorphine. That phrase is something drug manufacturers have to prove before a new drug is allowed to be approved by the FDA. The new drug must show it’s at least as good as the old drug. Additional data is rumored to show that it’s superior to sublingual buprenorphine, though I haven’t been able to find and read the original data yet.

This is a medication I would be excited to use in my practice. Instead of a surgical procedure, all I would need to do would be give a subcutaneous injection of this new product. How easy! My patient could see me as often as needed, and could see her counselor the same day she gets the injection, thus remaining established in a counseling program, too.

I am eager for the FDA to review this drugs study and approve it, if appropriate.

Medical Board Action Against Telemedicine Buprenorphine Physician

Telemedicine

 

 

 

Telemedicine is all the rage these days. For medically underserved areas, telemedicine could help reduce physician shortages and provide care to people without medical specialists in their area.

As appealing as the idea may be, physicians must be careful to conform to their states’ medical board regulations.

Of course, buprenorphine can now be prescribed in the office setting to treat opioid use disorders. Even with the increased prescribing capacity DATA 2000 gave us, less than a quarter of people who need treatment for opioid use disorder receive it. In fact, modifications to DATA 2000, passed last year, allow buprenorphine prescribers to have up to 275 patients at a time, if they fulfil various criteria. Also, physician extenders can now get certification to prescribe buprenorphine after taking proper training.

But what about telemedicine? Can it be used to meet the demand for opioid use disorder treatment in underserved areas? We now have clearer guidance, thanks to a recent ruling by the NC Medical Board.

Here’s the condensed story:

A physician, who lived and practiced in the middle of the state, also prescribed Suboxone via telemedicine for patients in the Western part of the state. The medical board was displeased this physician didn’t examine his patients in this second location in person, prior to initiating the Suboxone. The physician stated he felt buprenorphine could be prescribed safely without an in-person exam, but the board didn’t agree.

The medical board faulted the physician for not giving adequate attention to patients’ use of other drugs, and their mental health history. The board said patients were not examined for track marks or withdrawal signs, and that the physician accelerated their doses too quickly. Patients were seen every four weeks from the start, and the medical board opined that was not frequent enough in early treatment.

In other words, there were clearly other issues besides the lack of initial face-to-face contact, but this lack was cited as a departure from the standard of care.

I’ve been contacted by at least a half dozen mental health agencies who wanted to hire me to start treating patients with opioid use disorder with buprenorphine, using telemedicine. I’ve turned them all down, mainly because it wasn’t good medical care, and also because I didn’t want to do anything to violate medical board’s telemedicine policy. They have had published guidelines surrounding telemedicine since 2010, and update it periodically. You can read it here: http://www.ncmedboard.org/resources-information/professional-resources/laws-rules-position-statements/position-statements/telemedicine

You will note that the policy says “This evaluation need not be in-person if the licensee employs technology sufficient to accurately diagnose and treat the patient…”

So it is a little confusing, in view of their recent ruling against a doctor prescribing buprenorphine.

In September of 2016, another Addiction Medicine physician got a public letter of concern from the NC Medical Board, for using the telephone to stay in contact with a patient who had moved out of state. I only know the circumstances of the case from what the medical board listed in their public letter of concern, but I do know the physician. He is well-trained, cautious, and has excellent judgment.

His patient of over three years moved out of state and couldn’t find a new buprenorphine prescriber. So his NC doctor agreed to continue to prescribe for him, and did phone sessions with this patient every two weeks for thirty minutes at a time. He issued buprenorphine prescriptions for only two weeks at a time. This happened over several years without a face-to-face visit. Apparently the physician enlisted the aid of a local pharmacist to do medication counts, and the medical board opined this was “insufficient.”

Wow. This ruling should give every physician a reason to avoid telemedicine. Because I think that doctor did a good thing. Every patient should have such a doctor, willing to go the extra mile to help. I don’t think the physician’s actions were “insufficient” in any regard, though I’ll admit I’m probably not what our NC medical board considers an expert.

I’ve used pharmacists to do pill counts for me if the patient says he is out of town when called for a pill count. Sounds like I’m going to have to stop doing that, given the medical board’s statement.

At least once at an opioid treatment program, I was pressured to admit patients using telemedicine.

Several years ago, I had surgery for a broken leg. At the time, I worked for two opioid treatment programs. One was located an hour away, and the other was two hours away. Driving was going to be cumbersome, of course.

As soon as I was able, I called the program managers of each to let them know I might be out of work for the next week or two. At the first OTP, the program manager said I should take all the time I needed, and intakes could be postponed. Obviously, this is not an ideal situation, since we want to admit patients as soon as possible, but this was one of those things that were out of our control. I was still available by phone, of course.

At the second, the program manager said being out of work for several weeks was “not acceptable.” The program manager pushed me to admit patients via Skype or other technology. I refused, citing quality of care issues. In retrospect, I made the right decision.

I hear about “Doctor on Demand,” advertised by Dr. Phil on his show, and I wonder how these doctors get around this telemedicine issue. These doctors aren’t examining patients face to face on the first visit. Also, to practice medicine in NC, you must have a NC license, and surely all these doctors don’t have NC licenses.

I sent an email to Doctor on Demand asking about these issues. They sent me an email back, saying someone would be in contact with me. This was about four weeks ago and I haven’t heard anything else. I’ll let you know what they say in the unlikely event that they do contact me.

In the meantime, I think all physicians, and specifically buprenorphine prescribers, need to be very careful with telemedicine. Given these two recent rulings by the NC Medical Board, we could be cited for improper medical practice. Telemedicine seems like it could be a wonderful way to get care to people with opioid use disorders who live in remote places, but physicians need to protect their medical licenses first, or we won’t be able to prescribe anything to anybody.

 

 

Suboxone Manufacturer Sued for Anticompetitive Practices

Pharma Lies

 

 

 

I read a brief news item online about the drug manufacturer getting sued, but I didn’t get detailed information until I read last week’s issue of Alcoholism and Drug Abuse Weekly (ADAW).

Here’s the scoop: the Attorneys General for thirty-six states are suing Reckitt-Benckiser (RB, now called Indivior), because the company attempted to block generics from entering the market after RB’s patent for sublingual buprenorphine products expired.

Reckitt-Benckiser manufactured Suboxone and Subutex, which were the initial buprenorphine products that came to market in 2002, after the DATA 2000 law was passed.

As a reminder, before DATA 2000 was passed, it was illegal to treat opioid use disorder in an office setting with an opioid prescription. Doctors have gone to jail for this. Before DATA 2000, opioid treatment programs (OTP) were the only setting where prescribing (methadone was the only approved medication) for opioid addiction was permitted, and these OTPs have always been strictly regulated by multiple governmental agencies.

The FDA has approved only one medication, buprenorphine, to be used under DATA 2000, and only the sublingual form was approved. Then earlier this year, a second form of buprenorphine was approved to treat opioid addiction: the six-month, sustained release implantable rods impregnated with buprenorphine, known as Probuphine.

Buprenorphine taken by other routes of administration aren’t covered by DATA 2000, and therefore can’t be used to treat opioid addiction. These forms include the name brands Butrans patch, Belbucca oral film, and IV/IM buprenorphine used for pain control.

Reckitt-Benckiser’s patent for sublingual buprenorphine tablets was set to expire around 2008. Years before that, RB worked on finding a different delivery system, and the film version of Suboxone came out in mid-2010. This new form had its own patent, so that RB was the only company that could manufacture and sell that form of their medication.

However, since their sublingual tablet had come off patient, other drug companies could make generics, which would bring down the price to consumers of this life-saving medication.

But the Attorneys General allege RB tried to block the release of the generic tablets. RB told their drug salespeople to tell doctors that children were dying from ingesting buprenorphine tablets, and that the risk of prescribing this form of treatment was too great. They said the safest way to treat patients was with the film, which comes individually wrapped in a foil packet. And remember, only RB manufactured this film.

On May 12, 2012, I blogged about Reckitt-Benckiser’s attempt to persuade me to prescribe only the film. In that blog post, I describe how the drug representative told me that sublingual tablets were now suddenly too dangerous to prescribe, due to pediatric overdoses. She also told me it was much better for patients to be prescribed the film, since people addicted to pills could be triggered by tablets.

Her credibility took a big hit that day, because she’d promoted the hell out of her company’s tablet form of Suboxone and Subutex to me for years. I called her out on the inconsistency and disingenuousness of her statements, promulgated by her company, and I blogged about it.

At her next visit, she told me she was “disappointed that I chose such a public forum to describe our conversation.”

It was the first time someone chastised me for something I wrote on my blog, and I was elated. I felt like a real journalist!

She hasn’t visited my office since, and I haven’t missed her. She’s a nice lady, which is the only reason I put up with her in the first place. Right or wrong, I‘ve always found drug reps to be tedious.

I harbor no illusions about what drug reps do. Their job is to sell their product. When I worked in primary care, I was lied to on a regular basis by drug reps. For example, when the drug rep for a company that sold Prempro told me that estrogen replacement therapy reduced the risk of breast cancer. I remember being shocked into silence as I frowned at him, wondering if he thought I was really, really stupid.

Back to the point of this blog. So in 2012, R-B tried to prevent the generic from coming onto the market by saying the pediatric overdose problem was so bad that only the films (still under patent with R-B) should be prescribed

The lawsuit alleges consumers had to pay higher prices due to RB’s efforts to block generic tablets. These states want Indivior, formerly Reckitt-Benckiser, to pay back billions of dollars of profit obtained through unfair practices.

The lawsuit alleges the company manufactured claims of pediatric safety as a way to manipulate doctors into switching their patients over to the film, instead of continuing to prescribe the tablet form of the medication, which would have generic versions coming onto the market soon.

The drug company, as well as the company that developed the film technology, both say they did nothing wrong, and that their product has saved countless lives.

So…what is the price difference for different forms of buprenorphine? I did some current comparisons for my area on www.goodrx.com, recording the lowest price on the site for people with no insurance. Here are the results:

Generic buprenorphine: dose of 16mg per day, #60 tabs: $133

Generic combination product, buprenorphine/naloxone, dose of 16mg per day, #60 tabs: $243

Name brand Suboxone Film, same dose of 16mg per day, #60 films: $455

Name brand Zubsolv, dose of 5.7mg, two per day, #60 tabs: $455

Name brand Bunavail buccal film, 4.2mg, two per day (highest recommended maintenance dose) #60 films: $455

I’m sure readers find it remarkable, as I do, that all three of the name brand forms are the same price. It’s also interesting that the cheapest form, generic buprenorphine monoproduct, is only 28% of what the name brands all cost.

Here’s something more fascinating – BlueCross/Blue Shield of NC requires prior authorization for every one of their covered patients who are prescribed buprenorphine. For years, this insurance company will ONLY authorize payment for the name brand Suboxone in film form. They refuse to pay for the cheaper generic, either mono or combination forms.

I don’t know why BC/BS decided to only cover the name brand Suboxone films.

I could understand if they wouldn’t pay for the monoproduct, due to concerns that it’s more desirable on the black market, and the insurance company may not want to contribute to this problem. But why do they object to the generic combo product? Perhaps they worked out a special, cheaper deal, or perhaps they were swayed by drug manufacturer patter.

It’s hard for me to see that Reckitt-Benckiser/Indivior did anything different than what other drug companies do routinely. Of course their drug salespeople exaggerated the danger of pediatric exposure to buprenorphine tablets in an effort to influence doctors to prescribe only the films. But their claims were so weak and transparent that it would be a gullible doctor indeed who fell for the company line.

And since when do doctors accept what a drug company salesperson tells them at face value? I’m not saying outright lying by drug company representatives should ever be OK, but…it happens.

The drug companies make big bucks, but they counter by saying they spend so much money in research and development of new drugs, and if it weren’t for their work, we wouldn’t have all these new medications that we have that are extending peoples’ lives.

That’s somewhat of a legitimate point, but at what point do we say the drug companies are making adequate profits or excessive profits? And at what point does an exaggeration about a medication become a lie?

 

To Taper or Not To Taper…

aaaaaaaaaaajudgy cat

 

Below is a comment responding to my last blog post, and my answer to it. I thought this aspect of buprenorphine treatment was so important that it’s worth a blog of its own.

While I wholeheartedly disagree with a decision not to stock any buprenorphine products at a pharmacy, I understand what led to it. The area has a troubling pattern of buprenorphine use to maintain dependence instead of being tapered to actually treat the dependence and help the patient. A pharmacist should be able to refuse prescriptions that are being prescribed and/or used inappropriately without having to fall back on a blanket “we no longer stock it” statement. Ensuring that patients who are being gradually tapered to treat dependence or bring treated for pain have a harder time getting their medication is not an acceptable way to lessen the abuse.

         Posted by janaburson on July 28, 2016 at 8:56 pm  edit

Aha!! You may be on to something. Maybe these pharmacists think, like you do, that buprenorphine should be tapered, instead of being used as a maintenance medication. When it first came out, I think many of us hoped we could taper people off of it quickly. However, more & more studies are showing that the patients who stay on buprenorphine do the best. By best, I mean not dying, no illicit opioid use, can hold down a job, finish school, be a good parent, etc.
People who taper have a high relapse rate. Relapses can be deadly. Our opioid overdose death rate is already too too high. Let’s not make it worse by insisting opioid use disorder be treated like a short-term illness, rather than the chronic disease that it is.
Having said that, patients are different, and taper may be appropriate in selected patients. But it’s not a quick process and it takes time to get the counseling and make life changes.
Would you tell a diabetic, who is not eating right or exercising, that they should taper off metformin, since if they changed their behavior, they would not need medication?

I forget there are still people who think buprenorphine should only be used temporarily, as a detoxification medication. I’m not saying that’s always wrong. A minority of patients may do well with only a taper, but most patients with opioid use disorder do better if they stay on buprenorphine long-term.

Does that mean these patients should never taper off buprenorphine? I’m not willing to say that either. We don’t have enough information from good studies to show us how long is long enough.

We do have studies now that tell us tapering off buprenorphine after a few months of stabilization isn’t going to produce best outcomes for most patients.[1, 2, 3]

We also know active opioid use disorder is associated with a high mortality risk.

Some people do misuse buprenorphine, and shouldn’t be kept on this treatment. Those patients will do better with another form of treatment, perhaps methadone.

Let’s take what we know about opioid use disorder and its treatment with buprenorphine, and apply it to an imaginary disease that has no moral judgment attached. Let’s call our disease “Syndrome X.”

We know Syndrome X causes a great deal of emotional, physical, and spiritual suffering. It can occur in anyone, and has a high mortality rate. It can be effectively treated with a medication that is relatively safe, and does not cause euphoria when used correctly. However, the medication can cause some withdrawal if it’s stopped suddenly.

While on medication, patients with Syndrome X feel normal, unlike how they feel off medication. On medication, these patients are more likely to be in better physical health, mental health, and are more likely to be employed. They are more likely to be productive members of their families and their communities.

The studies of patients with Syndrome X show pronounced reduction of death rates while patients are on medication, as well as lower rates of infectious diseases. We also know from studies that if patients with Syndrome X are tapered off their medication, their death rates increase anywhere from three times to sixteen times compared to if they stayed on their medication.

Who in their right mind would ever recommend tapering the medication? Who would say to their loved one, “You’ve got to get off of that stuff. You just need to be strong.” Or, “Isn’t it time you stop using that crutch?”

It’s only because of the stigma this country has against people with substance use disorders that tapering off a life-saving medication is even an issue. If we were talking about any other chronic illness, there would be a loud clamor for every person to be able to get on and stay on that medication. In fact, doctors not prescribing a medication with as much benefit as buprenorphine has for opioid use disorder would be accused of malpractice.

I don’t push my patients to taper off buprenorphine. If that is their desire, I’ll do everything I can do to help them. I tell them what I’ve seen work in my other patients, work with them on relapse prevention, and encourage them to go slowly, to give their brain time to adjust as their dose comes down.

I’ve had many patients taper successfully, and most of them did this after at least a few years of stability on buprenorphine. When I see new patients, I tell them this isn’t (usually) a quick fix that they can do in a few months and be cured forever. A few lucky patients are able to taper quickly but I think we now have studies showing this isn’t the situation for most people with opioid use disorder.

How about this: leave the timing of the taper up to the patient and their doctor.

If you aren’t one of these two people, maybe you don’t get to have an opinion on when or even if a taper should be attempted.

1.Fiellin et al, See comment in PubMed Commons belowJAMA Intern Med. 2014 Dec;174(12):1947-54.

This study concluded “Tapering is less efficacious than ongoing maintenance treatment in patients with prescription opioid dependence who receive buprenorphine therapy in primary care.” The taper arm of the study was started after six weeks of stabilization, with a three week taper. Patients on the taper were offered medication to help withdrawal symptoms and also offered naltrexone treatment. Patients who tapered were significantly more likely to have opioid-positive drug screens compared to the patients who remained on buprenorphine maintanence. Patients on maintenance were significantly more likely to remain in treatment for addiction counseling that the patients were tapered.

2.Marsch et al,  See comment in PubMed Commons belowAddiction. 2016 Aug;111(8):1406-15.

This study of fifty-three young people aged 16 to 23 were enrolled in a double-blind, placebo-conrolled trial. Subjects enrolled in the arm of the study where buprenorphine was tapered over fifty-six days were signigicantly more likely to have opioid-negative drug screens and continued participation in treatment compared to subjects given twenty-eight day tapers

3.Weiss et al, Prescription Opioid Addiction Trial

“Adjunctive Counseling During Brief and Extended Buprenorphine-Naloxone Treatment for Prescription Opioid Dependence: A 2-Phase Randomized Controlled Trial.”  Archives of General Psychiatry 2011.

This study of prescription pain pill users found that taper off buprenorphine after stabilization shows a high relapse rate.