Archive for the ‘Buprenorphine’ Category

Access to Buprenorphine Will Expand; News About CARA

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Last week, the Department of Health and Human Services (HHS) announced it was raising the limit on the number of patients each doctor can treat for opioid use disorder with buprenorphine, from the present cap of 100 patients to 275 patients. However, each doctor must first meet criteria and complete an application procedure to be approved for this higher limit.

Initially, HHS wanted to increase the limit to 200 but for some reason ended up with 275. It’s still an arbitrary number, and opioid use disorder remains the only disease to have patient enrollment limits legislated for physicians.

HHS still wants physicians to meet extra requirements before they are approved to accept 275 patients, as I blogged about in my May 8, 2016 post:

  • Have professional coverage for after-hours emergencies.
  • Provide case management services
  • Use electronic medical records
  • Must use that practitioner’s state prescription monitoring program
  • Accept third-party insurance
  • Have a plan to address possible diversion of prescribed buprenorphine medication
  • Re-apply for permission to treat up to 275 patients every three years
  • Supply yearly reports about their practice and their buprenorphine patients

For some of the reasons I names in my May 8th blog, at this time I’m not planning to request permission to treat more than 100 patients.

This measure by HHS is a good and positive thing, and will help more desperate people get treatment. Just because I have a few objections to several HSS’s requirements doesn’t mean other doctors will feel the same way. I expect many physicians treating opioid use disorder will undergo the procedure to expand their patient limit.

 

Meanwhile, both the House of Representatives and the Senate passed the Comprehensive Addiction and Recovery Act (CARA) as of last week, and the bill is going before the President for his signature.

This bill, considered weak by some members of the House, contained only a fraction of the requested money to treat addiction. However, other advocates for addiction treatment say even a weak bill is better than none.

CARA’s content addresses the following:

Expand availability of naloxone to law enforcement and first responders, in order to quickly reverse opioid overdoses and prevent deaths. I think our own Project Lazarus helped get this ball rolling many years ago, and I’m so grateful my OTP has had support from them to give our patients naloxone kits!

Expand education and prevention efforts toward teens, parents, and aging people to prevent drug abuse and promote treatment and recovery.

Encourage states to improve their prescription monitoring systems. I hope some of that money will be directed to interoperability, meaning it will be easier to access a neighboring state’s prescription monitoring program. I also hope the Veteran’s administration will start reporting their data about prescribed controlled substances, too.

Prohibit the Department of Education from rejecting financial aid for people who have had past drug offences. I didn’t know people with drug offences on their record were denied governmental financial aid. If we want people to improve themselves and their life situations, why would we deny help for them? So this measure in CARA is great.

Expand resources to identify and treat incarcerated people with substance use disorders using evidence-based treatments.

Great idea, about forty years late.

Expand drug disposal sites to keep leftover meds out of the hands of children.

Just a question I’ve always had…Of all the tons of medication which have been collected at these disposal sites, has anyone ever studied how much controlled substances are collected?

Launch a “medication assisted treatment and intervention demonstration program.”

Not sure exactly what this will look like, but good luck with all of that.

I feel like I’ve beaten my head against the brick wall of prejudice and stigma against MAT in my community for four years. All I have is a headache…and resentment towards the medical community. I’d be very happy if someone else wants to take over for a while.

Launch a program to promote evidence-based treatment of opioid use disorder.

Well, yeah. it needs to happen. Actually it needed to happen about fifteen years ago, but whatever.

Director money towards law enforcement, to get people with substance use disorders help, rather than incarceration. CARA wants law enforcement to be able to work with addiction treatment services.

I indulged a private snicker at that last one. What a change from only a few years ago.

About six years ago, I was trying to educate people about medication-assisted treatment of opioid addiction. I thought I could help educate law enforcement personnel about addiction treatment, since they encounter it so much. I used the internet to find a journal for law enforcement.

I wrote to the editor, offering to write an educational article for their publication about opioid addiction treatment. My hopes weren’t especially high, but I wanted to give it a shot.

I was surprised when the journal’s editor took the time to call me in person. I was so excited!

Then the editor started talking to me like I was a naughty child. He asked what made me think it was appropriate to waste his time with such a query letter. He said I should have known better than to think any of his readers would be interested in the kind of thing I was offering to write, and he was calling to see what kind of person would be so unwise as to think otherwise.

I was stunned. I regret my reaction to him. I was so taken aback that I started apologizing to him, and said I was so sorry for bothering him and wasting his time.

In reality, he behaved like an asshole. If he didn’t want to waste time, he could have passed on the urge to call me to tell me how stupid he thought I was.

I wish I would have stuck up for myself in that conversation. I like to think I would handle it differently today.

Anyway, now, six years later, the government earmarked money to help law enforcement learn about opioid use disorder treatment.

While writing this article, I’ve come to realize I have bitterness towards people in law enforcement, medical fields, judicial, etc…when they denigrated my efforts to educate them about medication-assisted treatment for opioid use disorder.

I don’t want this bitterness. It’s too hard on me. It’s a weight that interferes with my enjoyment of life, and I’m going to release it.

The tide has begun to turn. We have legislation addressing the terrible opioid addiction problem we have, and money earmarked to help the problem. I want to be able to work with people who may have said bad things about medication-assisted treatment of opioid use disorders in the past. I want to work with those people without feeling resentment and without indulging in sarcasm.

Probuphine Implants: Impractical?

Probuphine

The more I learn about Probuphine, the less I think it will be practical for use in the average office-based opioid use disorder treatment setting. I predict it will be a specialty medication implanted by a few practitioners who take referrals from other doctors.

Braeburn Pharmaceuticals is sponsoring conferences for doctors to learn how to insert Probuphine, the form of buprenorphine that’s implanted under the skin like Norplant, the birth control medication. This medication is marketed by Titan Pharmaceuticals. Probuphine consists of four slender rods that are inserted just under the skin at the upper arm. These rods release buprenorphine over six months, when they have to be removed, and new rods implanted.

I wasn’t sure I wanted to do Probuphine implants, but I liked the idea of being able to do it, so I asked to attend one of their conferences to learn the procedure.

Alas, the company says only doctors who have performed minor surgical procedures over the past ninety days are eligible to learn to be an implanter of Probuphine. I can still prescribe it if I take the course, their letter says, but I’d have to refer to someone else to implant Probuphine.

Huh? I thought I could prescribe it already, since I have an “X” number. Maybe not.

If I can prescribe it but I can’t administer it, why would the patient see me at all? Why not just go directly to the doctor who can prescribe and implant?

I looked around the room during my recent addiction medicine conference and tried to imagine how many of these specialists had done surgical procedures over the past three months. There was one surgeon, and a few obstetricians, so I decided three out of sixty or so of the doctors who presently prescribe buprenorphine.

Even if the FDA approves Probuphine in May, I have a hard time imagining how Probuphine could be used in a typical office-based buprenorphine practice.

Because besides the implantation conundrum, who pays for it? Drug company representatives were unable to answer questions about the cost.

And how does the implant, the implanting physician, and the patient all arrive at the appointment time? Is the doctor expected to order the implant, store it in her office, and hope the patient shows up for the implantation? Surely we couldn’t give a prescription to the patient to take to a pharmacy for the implant, so I’m not sure how that’s going to work.

Won’t this medication need prior approval? Representatives from the drug’s manufacturer say “no,” but I have a hard time believing that.

I picture one or two sites in North Carolina that will have the resources to do the implants and probably keep them in stock, perhaps at a hospital pharmacy. Maybe the teaching hospitals will have the resources to do this.

Also, the Probuphine delivers drug levels equivalent to six to eight milligrams of sublingual buprenorphine, so patients at higher probably won’t be considered.

I’m starting to doubt the practicality of Probuphine at an average addiction medicine physician’s office.

Buprenorphine: Current Practices

NCSAM

I just got back from the NC Society of Addiction Medicine annual conference. (Yes, I’ve been to several conferences lately.) One of the sessions I attended was a lively discussion of the current practices in office-based prescribing of buprenorphine, for opioid addiction.

The session was run by two experienced, knowledgeable addictionologists, who mediated topics and shepherded the dialogue. One physician works in North Carolina and the other in Tennessee. The room was packed with at least fifty people, most of us doctors who prescribe buprenorphine for addiction.

Deliberations were collegial but we didn’t agree on all issues, of course. Dissenting opinions were respected and debated.

The first topic I can recall was about how often buprenorphine patients need to be seen. Most practitioners agreed that new patients needed to be seen at least weekly initially. As stability develops, we gradually extend the time between visits to one month. One doctor opined that no patient should be allowed to go any more than one month between physician visits. When the moderator asked if anyone disagreed, I raised my hand, and the moderator asked me to explain.

With some trepidation, I told the audience that I had a super-stable group of patients in my practice. I inherited most of them from another physician who was one of the first in the area to prescribe buprenorphine. This group of patients all have over five years of stable and relapse-free recovery. A few have been in stable recovery for nearly ten years. These people work, and have happy and productive lives.

So yes, I do allow these patients to go two months between visits.

No one booed or hissed me, but I got the feeling I’m doing something with my patients outside the realm of normal for most doctors prescribing buprenorphine. Thankfully, the moderator made the point that we should use our clinical judgment and adjust treatment to best fit each situation, which made me feel better.

I was mulling this over later, and maybe I do have an unusual group of patients, who have been stable on MAT for so long. Some of these patients elected to stay on sublingual buprenorphine because they are doing so well on it, and they fear relapse if they taper off of it. Others plan to stay on buprenorphine because they developed addiction as a complication of chronic pain treatment. Happily, the buprenorphine works as well for their pain as it does for their addiction, so we get the two birds with the one stone.

There’s another unusual thing about these super-stable patients: almost all of them are deeply involved in 12-step recovery. Many were in Alcoholics Anonymous prior to their opioid addiction. They developed addiction to opioid pain pills after receiving prescription opioids for an acute or chronic pain condition. Once they started on buprenorphine to treat the opioid addiction, they continued going to Alcoholics Anonymous (a few go to Narcotics Anonymous).. Other patients didn’t start going to AA until after they entered MAT on buprenorphine.

I’ve had many people write comments to my blog, furious when I even mention 12-step recovery and MAT in the same sentence. But I have living proof in my practice of multiple patients on medication-assisted treatment of opioid addiction who have been able to make 12-step programs work for them.

Getting back to the conference…we spent much time discussing the monoproduct buprenorphine versus the combination product buprenorphine/naloxone. All of us agreed there’s a need for caution with prospective patients who insist they can take only the monoproduct (this is the equivalent of the brand name Subutex), because it does have a higher street value than the combination product.

Of course, there are people who inject the combination product (Suboxone film, Zubsolv, etc.), but overall, people seeking to inject buprenorphine are much more likely to prefer plain buprenorphine. Black market prices are higher for the monoproduct than the combination product, underscoring the preference for monoproduct.

One outspoken doctor said the monoproduct should rarely if ever be prescribed. Another doctor echoed my feelings on the matter when he said something to the effect that some patients really do have a bad reaction to the naloxone in the combination products, and if we are cautious, we can prescribe the monoproduct. However, the general opinion was that financial reasons weren’t sufficient to take the risk of prescribing the monoproduct.

I disagree with that, but kept quiet, already feeling like maybe I’m a bit too liberal.

I have had patients, stable on a buprenorphine combination product (usually brand name Suboxone films), who suddenly lost their health insurance. If such patients had negative drug screens for years, and no history of intravenous use, I switched them to the generic monoproduct because it’s the cheapest buprenorphine product on the market. These patients could not have stayed in treatment if I’d made them stay on the much more expensive brand names. Most of those patients prefer the films, and when they got new insurance, asked to switch back to the films.

I did not suspect these patients would sell their medication for profit. You have to know them, but these patients had stable jobs and no leanings toward criminality. And I am by no means a gullible person.

Since then, a generic combination product came onto the market. Still more expensive than the monoproduct, it’s less expensive than all the name brands.

Next we discussed how to deal with patients who say they are allergic to naloxone, and thus can’t take the combination product (Suboxone, Zubsolv) but only the monoproduct (Subutex).. Patients usually don’t mean an actual allergy, but rather intolerance to naloxone. These patients report headache, nausea, etc. when they ask their physician to prescribe the monoproduct. Of course, this raises suspicion with physicians that such patients plan to misuse the medication by injecting or snorting.

Should physicians just accept what patients say at face value, or should we say sorry, I only prescribe buprenorphine in combination with naloxone? After all, there’s no way to “prove” a headache or nausea. There’s no test we can order that will give any useful information. One doctor said he sent such patients to a neurologist for evaluation of the headache, or to a gastroenterologist to decide the cause of nausea. He says most patients fail to follow through, and so he weeds such prospective patients out of his practice that way.

An audience member suitably questioned this habit, asking how could a specialist be expected to determine if a medication caused headache or nausea? I think it’s kind of a sneaky way to get rid of patients who want buprenorphine monoproduct.

I have the same fears when fielding new calls from prospective patients. I’ve instructed my patient contact representative (who is also my office’s licensed professional counselor, after-hours contact person, pharmacy liaison, licensed clinical addiction specialist, prior approval wrangler, and fiancé) to tell these people that I do not prescribe the monoproduct to new patients. I have no problems saying “no” upfront to these patients, and try to explain why I’ve made this decision for my private practice (even though, as above, I have prescribed it for patients I know very well).

I use the monoproduct in the opioid treatment program where I work, because those patients dose with us every day until they have a period of stability. The dosing nurses roughly chop the tablets, to minimize diversion, and patients stay on-premises until the medication has dissolved, also to make diversion more difficult. These patients don’t get any take home doses until we feel they have stabilized.

We also discussed how long to keep patients on buprenorphine. The bottom line is that no one knows. Best outcomes are seen in patients who stay on buprenorphine, since there’s still a high relapse rate back to opioids in patients who stop buprenorphine. I ask my patients periodically if they wish to start a slow taper, if they’ve been stable for over a year. I don’t push them to taper if they’re not ready, but if they are, I recommend they taper slowly. From the discussion at this meeting, it sounds like most of my colleagues do the same.

We discussed the maximum daily dose of buprenorphine. According to studies, a daily dose of 16mg saturates most of a patient’s opioid receptors, and increasing the dose to 24mg only gives about a 4% increase in the number of covered opioid receptors. Some doctors say this shows buprenorphine should never be dosed more than 16mg per day.

However, about a third of the doctors in the room raised their hands when the moderator asked if they had any patients who seemed to require 24mg per day to stabilize.

I didn’t interject anything into the discussion, but I just went to a session at the national ASAM meeting where this same topic was discussed. While it’s true that basic pharmacology would indicate 16mg is probably the just as effective as 24mg in most patients, several studies have shown better patient retention in treatment when higher doses (24-32mg per day) are used.

It’s possible this isn’t a physiologic effect, but more of a mental process. We can’t be sure. But for whatever reason, if my patient does best at 24mg, I’ll allow her to stay on that dose.

For patients on higher doses, we need to make sure they aren’t diverting some of their medication. Patients sometimes ask for a higher dose than they need, in order to get enough medication to treat a friend, family member, or significant other. Some doctors call this “piggy-backing.” Even though it means a suffering addict is getting treatment, the piggy-backer won’t get any counseling. Also, law enforcement types use examples of diversion to demonstrate that buprenorphine is a bad street drug, contributing to the stigma against patients doing well in their treatment. Diversion threatens the whole concept of office-based treatment program.

All in all, we had two hours of lively interaction on the finer points of office-based prescribing of buprenorphine. I don’t think all doctors will agree about everything, but it’s nice to hear what other physicians are doing, to make sure I am not too far out of line with the standard of care.

A Non-random, Completely Biased Study of Patient Perception of Quality of Care in an OBOT Practice.

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In recent blog entries, I’ve discussed the pros and cons of allowing buprenorphine-prescribing physicians to have more than one hundred patients at a time. In my view, increased access to treatment of opioid addiction is essential, and could be accomplished by allowing OBOT (office-based opioid treatment) doctors to see more patients than the current limit of one hundred. But many people argue that quality of care will go down and “Suboxone mills” will sprout like noxious weeds across the country, just like pain pill mills did in previous decades.

I’ve begun to agree that some sort of oversight of quality of care for buprenorphine doctors will be needed. But what would this look like? What do quality OBOT practices look like? What do poor OBOT practices look like?

I decided to ask a few of my patients.

I asked them if they felt they were getting good care from me, and they all said yes. Then I asked them why they felt that way. I was putting them on the spot; even if they didn’t think they were getting good care, would they tell me? Probably not. But still, their answers were interesting and revealing, and could help define quality care.

All of the half-dozen patients said something to the effect that their perception of quality of care involved the amount of time they spent with the doctor, and that they felt like they were being heard.

One patient, in solid recovery for about four years, has seen two other OBOT physicians before me. He said, “The other doctors didn’t ask me questions like you do. I was just there to get a prescription written and then see a counselor.” He felt his previous doctors were in a hurry to write the prescription and shuffle him off to the counselor. Another patient, who came to office-based buprenorphine from methadone at an opioid treatment program, also complained that he rarely saw his doctor at the OTP. He was seen on admission, and then once or twice over the next two years while he was on methadone maintenance. I see him every month and he likes this; he says he has more opportunities to ask questions about his care.

Of all the debate thus far about how to regulate the quality of care of an office-based buprenorphine practice, I don’t recall much said about the duration of the physician encounter with the patient. Yet my patients said this was the most important aspect of their treatment.

My patients may be on to something. After all, if the doctor spends fifteen or twenty minutes with each patient, the practice could hardly be a pill mill, because the amount of time in each workday is limited. Of course, it’s possible to spend fifteen minutes with each patient and still do a poor job, but much less likely, I think.

Pills mills run on volume. These places see many patients through each day, spending little time with each. So quality care may mean spending time with our patients, among other things like periodic drug testing, referral for counseling, and film/pill counts.

Most doctors don’t have formal training in counseling techniques, but many of us have counselled patients for years, even in other fields of medicine. I know in primary care I dealt with helping patients make behavioral changes like following dietary restrictions, losing weight, taking blood pressure medication regularly, etc. Since switching to Addiction Medicine, I’ve had training on counseling techniques like cognitive/behavioral therapy and Motivational Interviewing. I’m fortunate to be engaged to a MINT-certified trainer, (Motivational Interviewing Network of Trainers) and have learned a great deal from him. I’m not as good as he is, but I like to think I can do a bit of helpful counseling during my visits with patients, which complements his counseling sessions with these same patients.

Let’s consider time spent with the physician as a quality indicator for good office-based buprenorphine treatment, and as a way to avoid buprenorphine “mills.”

Expanding Access to Buprenorphine

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My last blog post stimulated some lively debate, and I thought this topic deserved further discussion. However, I would like to ask commenters to talk about the issue and please refrain from mentioning specific names of previous commenters. Please and make your points in a thoughtful and respectful manner. Thanks for your cooperation.

Given our present epidemic of opioid addiction and opioid overdose deaths, authorities are considering lifting the 100-patient limit for physicians who prescribe buprenorphine from office-based settings. Some people in the addiction treatment field oppose expanding access to buprenorphine in the office setting, saying some of these patients don’t get the counseling that they need, but only medication. They say there aren’t enough regulations to prevent shady physicians from opening buprenorphine mills.

Experts on both sides of the debate make good points. It’s a tough topic, but let’s explore the issues further.

1. “You don’t provide enough counseling.”

Weirdly, this used to be a main complaint against OTPs, but now OTP personnel are directing the same complaint toward office-based buprenorphine physicians.

Is there any data to help us decide how much counseling is enough for opioid-addicted patients who are started on medication, either buprenorphine or methadone?

The POATS trial gives some information on this topic. (Weiss et al, 2010, http://ctndisseminationlibrary.org/protocols/ctn0030.htm )

POATS showed that opioid-addicted patients maintained on buprenorphine/naloxone were likely to reduce illicit opioid use during treatment with the medication, but most relapsed after being tapered off the medication at twelve weeks. So this part of the study supported keeping patients on medication longer, just like the older data with methadone for heroin users. No surprises so far.

Now comes the interesting part: POATS showed similar outcomes for patients getting standard medical management versus standard medical management plus fairly intense counseling. The group with added counseling didn’t do any better than the standard medical management group.

However, the standard medical management consisted of an hour-long first visit with the doctor, and a fifteen- to twenty- minute visit per week for the first four weeks, then every two weeks.
This may be more than an average buprenorphine doctor provides in real life. It’s a little more than I do for my office-based patients. My first visit with new patients is one hour, and usually I see them back in one week for a twenty-minute visit. But then, if they are doing well, I see them every two weeks, until the patient is established in counseling. After that, if all is going well, I cut down to monthly visits. I conclude that the average buprenorphine doctor may have to increase visit frequency to get the results seen in the POAT study.

The group with enhanced counseling treatment got 45 minutes with a counselor twice per week for the first four weeks, then twice per month. At present, patients of OTPs must have two counseling sessions per month, even at the beginning of treatment. Opioid clinic opponents say twice per month isn’t even close to enough counselling, and use this point as a reason to say opioid treatment programs deliver bad care.

The POAT study was relatively short. Twelve weeks may not be long enough to detect an improvement in patients getting enhanced counseling. We know life changes usually don’t happen quickly. Maybe it is unfair to say the counseling didn’t help, because the patients weren’t followed long enough.

Now let’s look at interim methadone. Interim methadone was proposed as an alternative to long waiting lists for patients to enter an opioid treatment program. People were concerned about the welfare of opioid addicts who wanted help, but had to wait for a treatment slot to open. Interim methadone is a short-term, simplified treatment where methadone medication is started for the opioid addict, until the patient can be admitted to an OTP. With interim methadone, some counseling given, but only for emergency situations. Drug screening is still done, but is more limited than for OTP patients. These interim patients can transition to a traditional opioid treatment program when a slot opens for them.

It appears that starting just methadone, with limited other services, still helps the patients. Studies show these patients are less likely to continue to use heroin, are less likely to commit crimes, and more likely to enter a full-service OTP when admission is offered. [1]

Would “interim buprenorphine” work as well? I don’t think there are any studies to give us data, but it seems logical that it would.

2. “Just apply to be an OTP”

Government officials have said that if office-based physicians wish to see more than one hundred buprenorphine patients, the physician should apply to become an opioid treatment center.

When I first read this suggestion, I laughed, because it sounded so silly to me. Well-intentioned though this statement might be, it starkly exposed a lack of knowledge of the average physician’s economic circumstances.

I don’t know many doctors like me who have the necessary capital to do this. Some professionals in the field estimate it takes starting capital of around a quarter of a million dollars. I’ve seen one OTP fold due to inadequate financial support and management, and another escape closure by a narrow margin. These days, it takes deep pockets to afford the eighteen to twenty-four month process to establish an OTP. Getting the certificate of need alone can take years. (Just look at Crossroad’s struggles to get a CON in Eastern Tennessee, an area with arguably more opioid addiction per capita than most other states!)

OTP sites must be approved by multiple agencies: the DEA, CSAT, SOTA, and local authorities to name a few. The pharmacy has to meet strict regulations, as do personnel. If you want to accept Medicaid, that’s another avalanche of regulation and paperwork.

I’m not saying it’s impossible for a physician to open an OTP, but I am saying that it would cost so much that most doctors who treat opioid addiction wouldn’t consider it. I could be wrong – maybe my colleagues are making a whole lot more than me…

3. “In it for the money.”

Experts in the field who work for opioid treatment programs oppose expansion of office-based treatment, saying doctors charge exorbitant fees for their patients. Sadly, in some cases, they are right. But many office-based doctors charge reasonable fees. If we allowed doctor to treat more than one hundred opioid-addicted patients at one time with buprenorphine, wouldn’t that reduce demand for services? And when demand decreases, shouldn’t cost of treatment drop too?

For example, let’s take a community where one buprenorphine doctor is price gouging, and charging $500 per month for only one doctor’s visit. The second buprenorphine doctor charges $250 per month for the same service plus addiction counseling. Both are at their one- hundred patient limit. If both were allowed to increase the number of their patients, wouldn’t the second, more reasonably-priced doctor get some of the more expensive doctor’s business?

Conversely, some advocates for office-based treatment say that opioid treatment programs are upset because they have lost money in recent years. They accuse organizations like AATOD of wanting to limit further expansion of office-based programs because it cuts into their business. With more access, more patients would abandon OTPs for these less restrictive programs

DATA 2000 changed the landscape of opioid addiction treatment. OTPs aren’t the only option for patients seeking treatment for their opioid addiction.

My point is, both OTPs and buprenorphine doctors can accuse the other group of being in it for the money. But as I pointed out in my last blog…no medical treatment in this country is free.

4. “My medication is better than your medication.”

Patients entering opioid addiction treatment often ask me, “Which is better, buprenorphine or methadone?” I say, “Both.” Each has its advantages, and I’ve discussed this in previous blog entries. Briefly, buprenorphine is safer, since there is a ceiling on its opioid effects, but it’s more expensive. Patients on buprenorphine also seem to leave treatment prematurely more often than methadone patients. This isn’t a good thing, since the majority of these patients relapse back to illicit opioid use.

Methadone, as a full opioid agonist, may be more difficult to taper off of, and maybe fewer patients leave treatment prematurely because of that feature. Methadone has been around for fifty years now, with a proven track record. It works, and it’s dirt cheap. Methadone does have more medication interactions, but those can usually be managed if all the patient’s doctors communicate with each other.

Buprenorphine isn’t strong enough for all opioid addicts. Because it’s a partial agonist, there’s a ceiling on its opioid effect. This property means it’s much safer than methadone, but it doesn’t work for everyone.

Buprenorphine is safer than methadone, which to me is its best quality. I’ve started hundreds of patients on buprenorphine and never had an induction death. Sadly, I cannot say the same of methadone. I am not saying overdose death is impossible with buprenorphine…I’m saying it’s much less likely, and that’s worth a lot to me.

Buprenorphine’s superior safety profile is one reason it was approved for use in an office setting. Methadone is riskier to prescribe from an office, because misuse and diversion is more likely to be fatal with this drug. That’s why buprenorphine has fewer restrictions on it. Neither medication is good or bad; the difference between the medications is pharmacologic, not moral.

Next week, I’ll describe my OTP, where we provide methadone, buprenorphine under the OTP license, and buprenorphine under my office-based license, all on the same premises. I think we’ve created a continuum of care that’s able to meet the needs of patients as their recovery evolves.

At our program, it’s not one program versus another. Difference patients need different things, and the same patient may need different things at different points in recovery.

1. Schwartz et al, “A Randomized Control Trial of Interim Methadone,” Archives of General Psychiatry, 2006

New Buprenorphine Product: Bunavail

Manufacturer's ad

Manufacturer’s ad

Until this month, only buprenorphine in the sublingual form was FDA approved for the treatment of opioid addiction. This includes commonly known brands like Suboxone and Zubsolv, and generic buprenorphine both with and without naloxone added.

But earlier this month, the FDA approved Bunavail (B-YOU-na- vail), a buprenorphine product that is absorbed through the mucosa of the cheek. This method of delivery is termed “buccal.” The company making Bunavail says the product has an adhesive, which they call “BioErodible MucoAdhesive,” that improves absorption through the cheek mucosa. This product has twice the bioavailability of Suboxone film, and that’s the selling point for this new product.

Bioavailability is the percent of the drug that is absorbed into the bloodstream out of the total amount of the drug that is administered. If a drug is injected, by definition it has 100% bioavailability. Other routes of administration have less than 100% bioavailability because not all of the drug is absorbed orally, or due to the first-pass metabolism seen with some drugs like buprenorphine. When using a route of administration with lower bioavailability, more of the drug must be given to achieve the same blood level as when the drug is injected.

Buprenorphine has poor gastrointestinal availability. If a drug company made an oral tablet to be swallowed, less than 10% of the drug would be absorbed into the bloodstream. Sublingually (under the tongue), bioavailability of buprenorphine is said to be anywhere from 30 to 50%, and can be influenced by things like the pH of oral secretions (an acid environment interferes with absorption, which is why we tell patients not to drink any soft drinks, coffee, or tea for fifteen minutes prior to dosing).

So what does Bunavail’s higher bioavailability mean on a practical level? Bunavail’s films contain less buprenorphine than Suboxone, but deliver the same blood level. And if the blood level’s the same, the effect of the drug is the same. In other words, individual patients should feel the same.

Other than that, I can think of a few potential advantages. With higher bioavailability, fewer grams of buprenorphine would be prescribed, and fewer grams of buprenorphine that could make it to the black market.

Since less of the drug is needed per unit dose, perhaps the price will be lower. I have no information about the costs of this new product…but I’m going to make a wild prediction that Bunavail won’t be significantly cheaper than Suboxone. Zubsolv has higher bioavailability but I don’t think it’s significantly cheaper than its competitors.

The makers of Bunavail are making a big deal about the inconvenience of sublingual forms of buprenorphine compared to their new product, which sticks to the side of the cheek. In an interview on Bloomberg News, one of their scientists said patients taking Bunavail can talk and swallow while their medication is dissolving, something that can’t be done with their sublingual competitors.

OK, maybe that’s an advantage…but what are we talking about, five or ten minutes at most? I don’t know if patients will think that’s a big selling point, but time will tell.

On their website, the manufacturers caution, “Do not switch from BUNAVAIL to other medicines that contain buprenorphine without talking with your doctor. The amount of buprenorphine in a dose of BUNAVAIL is not the same as the amount of buprenorphine in other medicines. Your doctor will prescribe a dose of BUNAVAIL that may be different than other buprenorphine-containing medicines you may have been taking.”

To me this means I will have to be careful if I have a patient who wishes to switch buprenorphine products. However, the package insert says that 4.2/.7 mg of Bunavail is equal to Suboxone 8mg/2mg. The package insert goes on to say that patients should be started at 2.1mg and increased in increments of 2.1mg until a maintenance dose of 8.4mg is reached, though patients may go as high as 12.6mg

The insert also says not to tear or cut the film. Manufacturers of Suboxone say the same thing about their film, though cutting those films is fairly standard practice. I think that since the drug company hasn’t done any testing of their products when cut or torn, they can’t say for sure that it’s OK.

The company behind Bunavail, BioDelivery Sciences International Inc. (BDSI) has several other unique products. For example, they already market Onsolis, which is fentanyl also in a buccal (absorbed through the cheek) film. They’re also in phase 3 trials now with another buprenorphine product that uses the special mucoadhesive they developed, but it will be marketed for moderate to severe chronic pain. No information is available yet regarding the doses contained in this product.

Bunavail is expected to be marketed to doctors the last quarter of this year.

Choices

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Today’s blog is more a ramble of my recent musings than a march toward a specific point.

Over the last few weeks I’ve been working out of town, covering an opioid treatment program for a doctor who is out on sick leave. At my usual work sites, about half of the patients who come for admission at these OTPs specifically request to be started on buprenorphine (better known as Suboxone, Subutex). At these new sites, many patients are opposed to buprenorphine, and want to start on methadone.

That’s fine with me. Methadone has been around for fifty years now, and we have reams of data to show it works. I have no problems starting these patients on methadone, but I’m curious about the resistance opioid addicts have towards buprenorphine in this area of the state, as opposed to my “home” opioid treatment program.

Some addicts bought Suboxone or Subutex illicitly, and when they took it, they got sick. Because of their bad experiences, they are much opposed to trying buprenorphine again. I try to explain that because buprenorphine is a partial opioid with a higher affinity for opioid receptors than their usual opioids of abuse, their prior experience probably occurred because they took the buprenorphine too soon. If they took it before they were in withdrawal, it caused precipitated withdrawal. I try to explain that I can help them start buprenorphine at the right time, to avoid precipitated withdrawal.

Other patients entering opioid treatment programs say they want methadone because they also suffer from chronic pain. I used to go along with that, and agree with them, because I believed methadone would also treat their pain in addition to their addiction, and do it more effectively than buprenorphine. But recent studies call that into question, and show that patients with both addition and chronic pain got as much pain relief with buprenorphine as with methadone. Also, there’s some evidence that full opioids like methadone actually increase chronic pain in some patients, due to hyperalgesia.

A few patients said they still felt a little bit of euphoria from methadone, and preferred it over buprenorphine for that reason. I appreciate the honesty of those patients, and I think that is true to some extent, but in most cases, the euphoria subsides as tolerance for methadone increases. It is rare for patients on methadone to continue to feel euphoria from it if they are on maintenance for more than a few months.

I’m proud to work for a company that has pushed for its opioid treatment programs nationwide to incorporate treatment options other than methadone, even though there’s less of a profit margin for OTPs who prescribe buprenorphine. That’s because methadone, which has been around for years, costs pennies to dose, but buprenorphine costs much more.

Also, as a regional manager for this company pointed out to me, buprenorphine patients spend less time in treatment and come in & out of treatment more than methadone patients. Treatment retention isn’t as good for buprenorphine patients.

Is that a bad thing? Probably, yes. Studies show better outcomes with better treatment retention. It’s certainly worse for the bottom line of the opioid treatment program, which makes it even more admirable for OTPs to offer buprenorphine.

In my usual neck of the woods, I see patients come into treatment for buprenorphine who say they would never consider methadone, due to the stigma. Those are patients who would not enter treatment if we didn’t offer buprenorphine, and I’m happy we can reach them.

Buprenorphine is much safer than methadone, and has fewer side effects with other medications. And if patients do well in treatment, they can get take home doses much more quickly than with methadone, because of the increased safety.

Most patients on buprenorphine don’t feel the intense withdrawal that patients on methadone feel, if they miss days of treatment. This quality of buprenorphine is probably why patients on buprenorphine leave treatment more frequently than patients on methadone. They don’t feel as bad if they miss treatment for days at a time.

Many addicts at my new OTP site ask for methadone because of recommendations from their friends. I don’t hear as much talk about buprenorphine at the new OTP, so maybe addicts haven’t heard of some of the specific benefits.

I’m just happy their friends recommend treatment in any form.

Readers, why do you think patients starting treatment on medication-assisted treatment prefer methadone to buprenorphine?

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