Archive for the ‘Buprenorphine’ Category

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?

Celebrity Overdose Deaths

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Recently, the overdose death of a beloved celebrity restarted discussion of addiction treatment in the mainstream media. I have mixed feelings about such discussions.

On the one hand, I don’t think it’s appropriate for outsiders to comment on whether the celebrity got the best available treatment. It feels reckless for someone to say he should have had this treatment or that, without being privy to the personal medical history of the celebrity. Those details can make a big difference in deciding the most appropriate treatment. Of course in hindsight we can say the treatment chosen didn’t work… but as I’m painfully aware, even the best evidence-based treatments can have disastrous outcomes in individual patients.

On the other hand, celebrity deaths can focus the public on pertinent addiction issues facing society. For example, the death of 1980’s basketball star Len Bias helped change public perception about the risks of cocaine use. Mr. Bias, the second overall draft pick of the NBA in 1986, was the picture of physical health. When this young man died of a cardiac arrhythmia from cocaine use, people stopped looking at cocaine as a harmless party drug. There was a shift to a more realistic view of cocaine as a potentially addictive drug that can cause serious medical problems, including death, even in young healthy people. It’s possible Len Bias’s death, untimely and tragic, saved some number of young people from experimenting and becoming addicted to cocaine.

I am thankful that some light is being shed on the treatment of opioid addiction, even though the cause of this examination is due to a celebrity death. Perhaps something good can come of tragedy.

Realistically, are opioid addicts, including celebrities, being told of all evidence-based treatments for the disease? I don’t have facts or figures, but I’m confident the answer is a resounding “No.”. Most Minnesota model, 12-step based inpatient drug rehabs still discourage patients with opioid addiction from considering methadone or buprenorphine, even though medical evidence proves such treatments to be the most successful. Is this ethical? I don’t think so.

In a recent article from Alcoholism & Drug Abuse Weekly (Feb 10, 2014) on this same topic, even the deputy director of the White House Office of National Drug Control Policy Michael Botticelli says, “For people with opioid dependence, MAT should be the standard of care.”

So how are Minnesota Model facilities, opposed to MAT, able to maintain accreditation if they don’t inform patients of all evidence-based treatments? It’s unethical. Our first obligation is to do the right thing by our patients, based on scientific data.

This wouldn’t be allowed in any other field of medicine.

FDA Approves Zubsolv, New Brand of Sublingual Buprenorphine

aaaaaazubsolv

Suboxone is getting competition from the generic preparations of buprenorphine/naloxone, and now another name-brand preparation has just been approved by the FDA.

It’s called Zubsolv, and the manufacturer, Orexo, says it takes less time to dissolve, is a smaller tablet, and tastes better. The company added a menthol taste. They also say their preparation has higher bioavailability, and the tablets come in two strengths: 5.7/1.4 buprenorphine to naloxone ratio, and 1.4/.36 ratio. The lower doses of buprenorphine per tablet are due to the higher bioavailability. Also, each tablet is contained in unit dose packaging, to reduce the risk of pediatric exposures.

Interestingly, the package insert says not to switch from one buprenorphine preparation to another, because other tablets have different amounts of buprenorphine than Zubsolv. That’s a problem for established patients. I’d like the manufacturer to give prescribers some information on how blood levels of their tablets compare to blood levels of other preparations of buprenorphine. I guess new patients could be started on Zubsolv.

On the company’s website, they claim that nine out of ten people prefer Zubsolv to Suboxone.

This medication should be available in pharmacies by September of this year.

I’m glad for every new buprenorphine product that’s released to the market, because I hope it brings the price down. Lower cost of medication means more opioid addicts could afford treatment.

I’m curious to see how this new preparation will be greeted by patients on buprenorphine.

New Forms of Buprenorphine for Opioid Addiction Treatment

depot injection of buprenorphine

depot injection of buprenorphine

At this year’s American Society of Addiction Medicine conference, researchers talked about innovative ways to dose buprenorphine (formerly known as Suboxone) that may be available in the future.

One of the new products doesn’t yet have a trade name. Researchers call it “CAM 2038.” It’s made by Camurus 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 into the body over time. The capsulized gel makes the medication time release. 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.

This form of buprenorphine is in Phase II trials in Germany now, so it will be some time before it’s even considered in the U.S. for FDA approval. Per the Drug Addiction Treatment Act of 2000, without this FDA approval, it can’t be used to treat opioid addiction. As we know, the buprenorphine implant (Probuphine) was turned down for approval by the FDA earlier this year, likely because the implants didn’t deliver a high enough dose of buprenorphine to patients.

Initial trials with CAM 2038 don’t appear to have this problem. The company’s initial studies 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 into the vein, it will form a deposit at the injection site, blocking the vein.

Reckitt-Benckiser, the company who makes sublingual brand name Suboxone and Subutex, is developing a medication using a depot technology called Atrigel. Buprenorphine is put into the Atrigel preparation, a precipitation polymer that must be mixed before being injected. This delivery form of buprenorphine is also in Phase II trials now. RB apparently bought exclusive rights to use the Atrigel technology about four years ago.

These injectable depot forms of buprenorphine may be superior to sublingual forms of buprenorphine in the treatment of opioid addiction for several reasons:

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. But the disease of addiction is always telling the addict, “More!” so injectable forms thwart that urge completely.

Third, we’ve seen recent increases in the numbers of emergency department visits due to buprenorphine. Pediatric exposure remains a huge concern. Unlike pills which must be swallowed to have an effect, children who put the sublingual forms in their mouths will absorb the medication. Any pediatric exposure to buprenorphine is too much; unfortunately there have been a few pediatric deaths as well. With depot forms of buprenorphine, I don’t see how pediatric exposure would be possible.

Fourth, and probably politically most important, diversion of buprenorphine into the black market is getting much attention from press and law enforcement officials. More people are being arrested with illicit buprenorphine tablets and films, and law enforcement personnel believe buprenorphine is a desirable street drug. Of course, research shows most people using it illicitly are trying to prevent withdrawal and not trying to get high. The actual proportion of this medication getting into the black market hasn’t really risen; it’s being prescribed much more, so there’s more buprenorphine to be diverted. But diversion makes buprenorphine look like a desired street drug, and puts the DATA 2000 program at risk. I don’t see how a depot injection can be diverted, though I don’t doubt someone will try.

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, only the sublingual form of buprenorphine has that FDA approval. Other forms of buprenorphine in patch (Butrans) or injectable form are illegal for a doctor to prescribe to treat opioid addiction. If these new preparations of buprenorphine get approved, there will be a second delivery form that can be used in patients with addiction.

I like the idea of these depot injections. I’ve decided I don’t want to learn to do the minor surgery required to place Probuphine implants, but I can already do intramuscular and subcutaneous injections. Plus, I’d be seeing the patients once a week or once a month, rather than every six months with the implants. That’s more opportunity to keep track of what is happening with the patient’s addiction treatment counseling, a key component of recovery from addiction.

I’m looking forward to more research on these new forms of treatment.

How to Switch from Methadone to Buprenorphine (Suboxone)

Change Can Be Good

Change Can Be Good

I’ve helped about thirty or forty people switch from methadone to buprenorphine. Some were patients at my office, where I do office-based treatment with buprenorphine (formerly known as Suboxone or Subutex), and some have been patients at one of the two opioid treatment programs where I work.

Most of the time, the transition goes smoothly; however, around fifteen percent of the time, the patient doesn’t feel right on buprenorphine and goes back to methadone. I haven’t found a way to predict who will do poorly with buprenorphine.

Most of these patients had been in treatment for months or years, and were trying to taper their methadone dose. These patients heard that since buprenorphine is a partial opioid, it’s easier to taper off of than methadone. For the most part, that seems to be true, but everyone’s different.

Some patients switched because they wanted a medication that wasn’t as “heavy” as methadone. Most patients say they feel lighter, or less medicated, or more normal, on buprenorphine as compared to methadone.

Buprenorphine seems to have fewer medication interactions. For patients with complicated medical problems on many medications, it’s a better choice. It’s also a better choice for patients who have prolonged QT interval syndrome (condition of the heart) from methadone.

Also, restrictions on take home doses for buprenorphine when it is prescribed at opioid treatment programs aren’t as strict as rules for methadone, because buprenorphine is much safer than methadone. Patients switch to buprenorphine to get take homes more quickly, particularly helpful if they live a great distance from their treatment program.

In January of 2013, the federal government dropped the time in treatment requirement for take home doses for buprenorphine. With methadone, a patient has to be doing well with negative urine drug screens for a minimum of ninety days before getting extra take home doses. According to the new federal law, buprenorphine patients can get take homes regardless of time in treatment, so long as they meet all the other seven requirements for take homes. (These are: negative drug screen including alcohol, no ongoing criminal activity, regular clinic attendance, absence of serious behavioral problems at the clinic, stability of home environment, assurance that take-home doses can be stored safely, and rehabilitative benefits to the patient outweigh risk of diversion).

Some states have more restrictive regulations than federal law. In that case, the opioid treatment program has to follow the more restrictive of the two laws. In my state of North Carolina, time in treatment regulations still apply. However, I can petition the state opioid treatment authority for early and extra take home doses for patients who are doing well, and those requests are nearly always granted.

Some patients switch to buprenorphine at the opioid treatment program to prepare for transition to an office-based buprenorphine program. Office-based treatment is better for patients who have made progress on their recovery, and need less oversight with dosing of their medication. It’s an excellent step for stable patients.

Buprenorphine is a partial opioid and methadone is a full opioid. And buprenorphine has a higher affinity for opioid receptors. This means that it sticks like glue to the receptors, and if there’s methadone on the patient’s opioid receptors, buprenorphine will toss it off, throwing the patient into withdrawal. That’s a simplistic explanation, but you get my drift. This is why patients on methadone have to be in at least moderate withdrawal before taking the first dose of buprenorphine. Otherwise, the patient will be miserable, in withdrawal, with little to be done to ease the situation.

I ask patients to taper to about 30 or 40 milligrams of methadone per day prior to making the switch. I recommend tapering by about 5mg per week, or more slowly if needed. If I’m in the opioid treatment program on Mondays, I ask the patient to take her last dose of methadone on Friday, and then skip Saturday and Sunday. I see her first thing on Monday and evaluate the degree of withdrawal. By then, this patient has gone without methadone for seventy-two hours, and should be in at least moderate withdrawal. We check vitals signs (blood pressure, heart rate, etc.) and check a COWS (clinical opioid withdrawal scale) score. I talk with the patient and do a quick exam. If she’s in enough withdrawal, we start buprenorphine, usually at 4mg. If possible, we have the patient stay for an hour or return in an hour so we can see how she’s feeling. Sometimes we give a second dose on that first day.

Here are some issues I’ve seen in patients making the switch from methadone to buprenorphine:
-Coming down too fast on the methadone dose. Don’t zoom from 115mg to 40mg in a week or two and expect the transition to buprenorphine to go well. It probably won’t. I tell patients that if you’re going to expend time, money, and energy in making the switch, do it the right way, and optimize your chance for success.
-Not planning ahead for the increased cost of buprenorphine. In most clinics, buprenorphine costs more than methadone. If it’s not financially feasible over the long term, it’s best to stay on methadone.
-Expecting to take buprenorphine for a few weeks and then taper off with no withdrawal. Most people do not have this experience. Even the taper off buprenorphine can take months and be difficult. Besides, getting off opioids is one thing; staying off is another. I tell patients not to taper off buprenorphine unless they are ready. Have they spent the time getting counseling against relapse? Have they changed friends, and put distance between them and people still using drugs? Do they work around people using drugs? Do they have a chronic pain condition that will require opioids intermittently? If so, what’s the plan to avoid relapse?
- If buprenorphine lasts longer than methadone, don’t be tempted to miss days without telling your counselor what is going on. Some patients on buprenorphine are able to dose three times per week, so talk to your doctor about setting this up instead of missing days on your own.
-DO NOT attempt to divert medication. At one treatment center, we’ve detected many patients trying to “save” part of their dose for later use. I think most are telling the truth, but some are probably selling their medication. I can’t tell who is selling and who is saving doses for later. If we have a problem with patients selling their medication in the community, our treatment program can get a bad reputation in the community and even get closed down. So we have to act on any attempt to divert medication, and at times may even have to dismiss a patient from treatment, which I hate to do. So don’t divert medication.
-Don’t feel bad if buprenorphine doesn’t work for you. No medication works for everyone. If methadone did work, go back to it. Methadone has been around for forty years and has a proven track record.

I’m happy to work for two opioid treatment programs who offer both buprenorphine and methadone. It’s a little more difficult to offer buprenorphine, and the profit margin is likely much slimmer than treatment with methadone, but it’s the state of the art treatment. I fear some methadone clinics are going to get left behind with their “methadone only” mindset. Methadone will always be needed, but now we need to have other choices readily available for patients seeking treatment. Soon, I think we will see opioid treatment centers also offer naltrexone/ naloxone, medications that can prevent opioid relapse in patients who have completed withdrawal from opioids.

Combining Medication-Assisted Treatment and 12- Step recovery: One Patient’s Success Story

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A few weeks ago, I posted a few articles about 12-step recovery. Several readers became very upset, even saying that if I was pro-12-step, I couldn’t really be an advocate for medicated-assisted treatment of opioid addiction. That’s their opinion, and I honor their views, though I heartily disagree with them.

Now I’d like to present an interview I did with a very successful Suboxone patient who did find help from 12-step meetings.

JB: Please tell me about your experience with pain pill addiction and your experiences with buprenorphine (Suboxone).

XYZ: For me, my opiate addiction got so bad, I was taking two hundred and forty to three hundred and twenty milligrams of OxyContin per day, just to stay normal. It had gotten really, really bad. And it started out with a reason. I had kidney stones, and I was in all this pain, but then it got to the point where it solved some other problems in my life and it got out of hand. I tried a lot of different things. I went to detox, and they helped me, but it was…it was almost like I never came out of withdrawal.

JB: How long were you off pain pills?

XYZ: Even after being clean for thirty or sixty days, I would still feel bad. Bowels, stomach…really all the time.

JB: Did it feel like acute withdrawal or just low grade withdrawal?

XYZ: No…I’d try to fix it myself, sometimes, and I would just put myself back where I was. It got to the point where I was making myself sicker and sicker and sicker. And then I got off of it, and stayed off of it for a hundred and twenty days, I guess…but still just sick. Just miserable, and not feeling right. I was miserable. I wouldn’t eat, I was losing weight…

It [buprenorphine] gave me something that replaced whatever was going on in my head physically, with the receptors. It took that [prolonged withdrawal] away, to the point that I felt well. All that energy I would spend getting pills…and I was going to the doctors almost daily. Because taking that much medicine, nobody would write me for that much, so I had to doctor shop.

My only life was going to the doctors, figuring out what pharmacy I could use. I had a whole system of how many days it could be between prescriptions, what pharmacy to go to. It was sick. I was just trying to not get sick.

JB: And you were working during that time?

XYZ: Yeah! I was working, if you want to call it that. I wasn’t a very good employee, but I held a job. I was a regional vice president for “X” company. I traveled a lot, so I had new states where I could see new doctors. That was bad. When I came off the road, I owed $50,000 in credit card bills.

JB: And your wife didn’t know about it?

XYZ: No. It all came tumbling down. And I had gotten into trouble, because they were company credit cards, and they wanted the money back! So, all of the sudden my wife found out that not only do I have a pain pill problem, but we’re $50,000 short, and I wasn’t very ethical in the way I got the money, because it really wasn’t my credit, it was my company’s credit card.

JB: So addiction made you do things you wouldn’t do otherwise?

XYZ: Absolutely. I lied to people, I took money from people, I ran up credit cards tens of thousands of dollars, and really put my family in serious jeopardy at that time. But buprenorphine took away that whole obsessive-compulsive need for pills, made me feel better, and took away all the withdrawal symptoms at the same time. I didn’t worry about it.
To be honest, I was such a hypochondriac before. I haven’t been sick in years now. I haven’t had a backache or headache that ibuprofen didn’t cure [since starting recovery]. I was fortunate it was all in my head. I would milk any little thing. I had two knee operations that probably could have been healed through physical therapy, but I was all for surgery, because I knew I’d get pain pills.

JB: That’s the power of addiction!

XYZ: Yes. Finally I did some research about buprenorphine, online. Actually, I had some good family members, who did some research and brought it to me, because they were concerned for me, and they brought it to me and said, “Hey, there’s a medicine that can help. Call this number,” and I found places out there that would do it [meaning Suboxone], but my concern was the speed that a lot of them were doing it. A lot of them said, OK come in, and we can evaluate you, and after a week you’ll be down to this, and after a month you’ll be down to this.

This was in 2005. And when I asked them what their success rate is, it wasn’t very high. It was something like twenty percent of the people who were doing it [succeeded]. So when I’d finally gotten a hold of “X,” [receptionist for Dr. H], she saved my life over the phone. Because she said, you can come tomorrow, and she said that whatever it takes, they’ll work with you. And I felt good about going to a place where it wasn’t already determined how long it would take. Because I already knew how I was feeling after I would come off of opiates. I didn’t want to do that again.

I saw Dr. H. and felt better within twenty-four hours, although it took a little while to get the dosage right. I think we started off at a lower dose, then we went up on the dose and it kept me so level. I had no symptoms. It cured my worst withdrawal symptoms, my stomach and my bowels.

There’s always a kind of stigma in the rooms [12-step recovery meetings] because I’d been in NA for a little bit of time then [he’s speaking of stigma against medication-assisted treatment]. You realize who [among addicts in NA] is die-hard, one way to do recovery, and who is willing to be educated about some things and understand that there’s more than one way to skin a cat.
And I was fortunate that I had a sponsor at that time, and still do, who was willing to learn about what exactly it was, and not make me feel guilty about it. It wasn’t necessarily the way he would do it, but he was a cocaine addict, so he didn’t understand that whole part of it.

He said, “Your family’s involved, you’ve got a doctor that’s involved, your doctor knows your history. If all these people, who are intelligent, think this is an OK thing, then who am I to say it’s not going to work?” He was open-minded. And there are not a lot of people I would trust right off the bat [in recovery], that I would tell them. [that he’s taking Suboxone]. I’ve shared it with some people who’ve had a similar problem, and told them, here’s something that might help you. I always preface it with, [don’t do] one thing or another, you’ve got to do them together. You have to have a recovery program and take this medicine, because together it will work. Look at me. I’m a pretty good success story.

One of my best friends in Florida called me, and I got him to go see a doctor down there, and he’s doing well now. He’s been on it almost eleven months now and no relapses.

To me, it takes away the whole mental part of it, because you don’t feel bad. For me, it was the feeling bad that drove me back to taking something [opioids] again. Obviously, when you’re physically feeling bad, you’re mentally feeling bad, too. It makes you depressed, and all of that, so you avoid doing fun things, because you don’t feel good.

Once I trained myself with NA, how to get that portion of my life together, to use those tools, not having any kind of physical problems made it that much easier to not obsess.

JB: So, how has your life improved, as a result of being on buprenorphine?

XYZ: Well, the most important thing for me is that I’ve regained the trust of my family. I was the best liar and manipulator there was. I’d like to think of myself as a pretty ethical and honest person, in every aspect of my life, other than when it came to taking pills.

JB: So, you regained the trust of your family, felt physically better…

XYZ: I gained my life back! Fortunately, I had enough of a brain left to know it had to stop. Once I started on buprenorphine, it gave me back sixteen hours a day that I was wasting. That’s when I decided I really don’t want to jeopardize my recovery, by going out and looking for a job again [he means a job in corporate America, like he had in the past], because I’ve got this thing, this stigma…they’re going to check a reference and I’m screwed. I’m not going to get a job doing what I was doing for the same amount of money.

My brother had enough faith in me that it was worth the risk of starting this business [that he has now] together. My wife and I started on EBay, making and selling [his product], and slowly grew it to the point that, three years later, I’m going to do over two million dollars in sales this year, I’ve got [large company] as a client, I’ve got [large company] as a client, I’m doing stuff locally, in the community now, and can actually give things back to the community.

JB: And you employ people in recovery?

XYZ: Oh, yeah. I employ other recovering addicts I know I can trust. I’ve helped some people out who have been very, very successful and have stayed clean, and I’ve helped some people out who came and went, but at the same time, I gave them a chance. You can only do so much for somebody. They have to kind of want to do it themselves too, right?

JB: Have you ever had any bad experiences in the rooms of Narcotics Anonymous, as far as being on Suboxone, or do you just not talk to anybody about it?

XYZ: To be honest, I don’t broadcast it, obviously, and the only other people I would talk to about it would be somebody else who was an opioid addict, who was struggling, who was in utter misery. The whole withdrawal process…not only does it take a little while, but all that depression, the body [feels bad]. So I’ve shared with those I’ve known fairly well. I share my experience with them. I won’t necessarily tell people I don’t know well that I’m taking buprenorphine, but I will let them know about the medication. Even though the information is on the internet, a lot of it is contradictory.

It’s been great [speaking of Suboxone] for someone like me, who’s been able to put a life back together in recovery. I’d tell anybody, who’s even considering taking Suboxone, if they’re a true opioid pill addict, (I don’t know about heroin, I haven’t been there), once you get to the right level [meaning dose], it took away all of that withdrawal. And if you combine it with going to meetings, you’ll fix your head at the same time. Really. I didn’t have a job, unemployable, my family was…for a white collar guy, I was about as low as I could go, without being on the street.
Fortunately I came from a family that probably wouldn’t let that happen, at that point, but who knows, down the road… I had gotten to my low. And that’s about it, that’s about as much as I could have taken.

It [Suboxone] truly and honestly gave me my entire life back, because it took that away.

JB: What do you say to treatment centers that say, if you’re still taking methadone or Suboxone, you’re not in “real” recovery? What would you say to those people?

XYZ: To me, I look at taking Suboxone like I look at taking high blood pressure medicine, OK? It’s not mind altering, it’s not giving me a buzz, it’s not making…it’s simply fixing something I broke in my body, by abusing the hell out of it, by taking all those pain pills.

I know it’s hard for an average person, who thinks about addicts, “You did it to yourself, too bad, you shouldn’t have done that in the first place,” to be open minded. But you would think the treatment centers, by now, have seen enough damage that people have done to themselves to say, “Here’s something that we have proof that works…..”

I function normally. I get up early in the morning. I have a relationship with my wife now, after all of this, and she trusts me again. Financially, I’ve fixed all my problems, and have gotten better. I have a relationship with my kids. My wife and I were talking about it the other day. If I had to do it all over again, would I do it the way I did it? And the answer is, absolutely yes. As much as it sucked and as bad as it was, I would have still been a nine to five drone out there in corporate America, and never had the chance to do what I do. I go to work…this is dressy for me [indicating that he’s dressed in shorts and a tee shirt]

JB: So life is better now than it was before the addiction?

XYZ: It really is. Tenfold! I’m home for my kids. I wouldn’t have had the courage to have left a hundred thousand dollar a year job to start up my own business. I had to do something. Fortunately, I was feeling good enough because of it [Suboxone], to work really hard at it, like I would have if I started it as a kid. At forty years old, to go out and do something like that…

JB: Like a second career.

XYZ: It’s almost like two lives for me. And if you’re happy, nothing else matters. I would have been a miserable, full time manager, out there working for other people and reaping the benefits for them and getting my little paycheck every week and traveling, and not seeing my wife and kids, and not living as well as I do now.

I joke, and say that I work part time now, because when I don’t want to work, I don’t have to work. And when I want to work, I do work. And there are weeks that I do a lot. But then, on Saturday, we’re going to the beach. I rented a beach house Monday through Saturday, with just me and my wife and our two kids. I can spend all my time with them. I could never have taken a vacation with them like that before.

JB: Do you have anything you’d like to tell the people who make drug addiction treatment policy decisions in this nation? Anything you want them to know?

XYZ: I think it’s a really good thing they increased the amount of patients you [meaning doctors prescribing Suboxone] can take on. I’d tell the people who make the laws to find out from the doctors…how did you come up with the one hundred patient limit? What should that number be? And get it to that number, so it could help more people. And if there’s a way to get it cheaper, because the average person can’t afford it.

The main thing I’d tell them is I know it works. I’m pretty proud of what I’ve achieved. And I wouldn’t have been able to do that, had I not had the help of Suboxone. It took me a little while to get over thinking it was a crutch. But at this point, knowing that I’ve got everybody in my corner, they’re understanding what’s going on…it’s a non-issue. It’s like I said, it’s like getting up and taking a high blood pressure medicine.

I originally interviewed this patient in 2009, for a book that I wrote. Since that time, he and his family have moved to the west coast, but I’ve stayed in contact with him. He’s been in relapse-free recovery for over eight years, he’s still on Suboxone, and still happy. He has excellent relationships with his wife and children, and his business has thrived and continues to grow.

He’s an excellent example of how a recovering addict’s life can change with the right treatment. For this person, Suboxone plus 12-step recovery worked great.

Good News for Opioid Addicts: Reckitt’s Requests Rejected by the FDA

aahuzzah

This week’s issue of Alcohol and Drug Abuse Weekly ran a front page article about the FDA’s recent ruling on Reckitt Benckiser’s requests. Reckitt, the manufacturer of buprenorphine (Suboxone and Subutex), had submitted a Citizen’s Petition to the FDA, asking them to refuse to approve any form of buprenorphine that didn’t have additional child-resistant safety measures.

Last year, Reckitt said they were taking the tablet form off the market because of increased risk for pediatric exposure with tablets as compared to the newer film form of Suboxone. Cynics (like me) said this was an attempt to hide profit motives behind claims of concern for children. The film is still under patent, while the patent for the tablet form had already expired. This Citizen’s Petition was felt by some (like me) to be an additional smokescreen, invented to prevent the release of a generic competitor.

In their ruling at the end of February of this year, the FDA said the scientific and regulatory concerns raised by Reckitt’s petition weren’t valid. They said there was no proof of Reckitt’s claim that the unit-dose packaging of the film reduced pediatric exposures. The FDA noted that the new REMS (Risk Evaluation and Mitigation Strategy), put in place for buprenorphine and other opioids, could have caused the decline in pediatric exposures. The FDA has also made efforts to educate physicians about overdose potential in children. The FDA also pointed out that many drugs dangerous to children are packaged in bottles, rather than unit –dose packaging. Also, the FDA pointed out that Reckitt received the pediatric overdose information two years before they announced they would voluntarily stop making the tablets due to pediatric overdose concern. This delay undermined their claim of making the change for patient safety.

The FDA criticized Reckitt for making these safety claims, yet still selling the tablets. In fact, the FDA has asked the Federal Trade Commission, the FTC, to investigate the United Kingdom-based Reckitt-Benckiser for possible anticompetitive business practices.

I admired Reckitt Benckiser when they first released Suboxone. At last, a drug company was willing to take a chance on manufacturing a medication to treat addiction. Since drug addicts often don’t have insurance or money, this is not usually a lucrative market. They took a financial risk. They funded, or helped to fund, many of the training programs doctors needed to get licensed to prescribe Suboxone. Reckitt provided free treatment for a few indigent patients per doctor with their Here to Help program. They provided telephone support to addicts entering Suboxone treatment, at no cost, though few addicts used this benefit.

But over the last few years, Reckitt Benckiser has lost credibility with me. I feel they’ve become heavy-handed, and have pressured doctors to prescribe only the films, saying it’s less likely to be sold on the black market and less likely to be misused than the tablets. That may be true, but some patients don’t like the film, and would leave treatment if it’s the only available medication. And many addicts have written in to this blog, claiming to be able to dilute and inject the films more easily than the tablets. At the same time, the prices of the Suboxone tablets skyrocketed, in an attempt to force patients to switch to films. Reckitt of course also discouraged doctors from prescribing the less expensive generic monoproduct buprenorphine, which costs less than half of the name brand manufactured by Reckitt.

Then there was that whole pediatric overdose issue. After that, my opinion of Reckitt fell. They lost credibility with me.

The two drug companies that make the generic form of Suboxone say their tablets should be available in pharmacies within a month. Actavis, based in New Jersey, is the third largest manufacturer of generic medications. The other manufacturer, Amnel Pharmaceutical, is also based in New Jersey and is the 7th largest generic manufacturer. Amnel’s press release describes their tablet as being cheaper than Suboxone, with a “pleasant orange flavor.”

I can’t wait to see how much these generics will cost. I’d expect them to be a little more expensive than the generic monoproduct buprenorphine. In my area, that generic sells for around three to four dollars per pill, less than half what the name brand Suboxone costs now.

The release of these two generics will likely mean more patients will be able to afford addiction treatment. The more affordable treatment becomes, the more patients will take advantage of help for their addiction.

Huzzah for the FDA! This was a good decision.

Reckitt-Benckiser to Stop Manufacturing Suboxone Tablets

This week, officials of Reckitt-Benckiser, the pharmaceutical company that manufactures Suboxone and Subutex, announced its plan to stop manufacturing Suboxone tablets. The drug company says the tablets will be phased out over the next six months. According to their press releases, the company decided to discontinue manufacture of Suboxone tablets, “Because of strong evidence that the tablet form of Suboxone is linked to significantly higher rates of pediatric exposure as compared with…the film.”

Reckitt Benckiser says they are basing their action on data from the Poison Control center from September that showed there were around 8 times as many accidental Suboxone exposures in children with tablets versus films. They say they are taking action in the interest of public health.

The drug company says that since the films and tablets are clinically interchangeable, patients presently taking tablets won’t be adversely affected.

In the most recent issue of Alcohol and Drug Abuse Weekly, a spokesman for the company said per 10,000 Suboxone patients, there were .71 pediatric exposures to the film and 6.25 pediatric exposures to the tablets. These numbers were statistically significant. (1)

I believe their data. It makes sense that children would have a harder time opening one of those foil packets of Suboxone film than opening a prescription bottle of tablets. Plus, with a bottle there’s more than one dose available for ingestion, while one packet yields only one potential dose. The tablets also have an orange-y smell and taste, and may be more appealing to young children than other types of pills.

I also think Reckitt Benckiser’s film is a better product than their tablet. Most of my patients do prefer the film, saying it dissolves faster and tastes better.

However…maybe I’m too cynical when it comes to drug companies, but I don’t believe pediatric exposure is the only reason the drug company is ceasing manufacture of the tablets. I think it’s also a financial decision. The film’s patent doesn’t expire for more than ten more years, while the tablet’s patent has already expired. The Reckitt Benckiser rep for my area told me months ago that the company was considering taking the tablets off the market.

I think the recent data about pediatric overdose with tablets gave RB a great excuse to pull their tablets off the market, “For the kids…” The drug company would be open to criticism if they pulled the tablets for a purely financial motive, but who could criticize a drug company for trying to prevent the death of children? I do wonder how pediatric overdose rates of Suboxone tablets compares with other prescription opioids, but after scouring the internet can’t find that information.

I wondered how RB’s decision will affect my patients. I’m worried about a small number of my patients who, for whatever reason, didn’t like the films. These patients are all doing great in their recovery, and show no sign of medication diversion. They aren’t “bad” patients trying to scheme a way to misuse medications. Many of them have been in stable recovery, assisted by Suboxone tablets, for more than three years. All tried the film when it was released, and found it lacking. Some patients didn’t like how the films were crumbling, a problem that seems to have resolved over the last six months. I have about twenty-five people in my practice who prefer Suboxone tablets to films.

Today in my office practice I saw three patients of these patients. All of them, by the way, keep their medication locked up and safely away from children. I explained the situation to them, and told them I would like to switch them to the film, because the tablets were going to be phased out over the next six months. Two grudgingly said they would switch but wanted to wait until it was absolutely necessary. The third said he’s prefer to switch to the generic buprenorphine tablets, because he hated the film and didn’t feel like it worked nearly as well.

Overall I don’t like to prescribe generic buprenorphine in the office, because it has higher street value and is easier to misuse. Since the generic buprenorphine has no naloxone in it, it can be injected. I don’t usually prescribe it unless the patient has no insurance, is stable in their recovery with no recent IV drug use, and can’t afford name brand Suboxone. In my area, the generic buprenorphine tablets are less than half the cost of either Suboxone film or tablet. For some patients, being able to buy the cheaper generic has made it possible for them to afford to remain in treatment. Their other option would be to go to the methadone clinic, and many patients prefer treatment in an office setting, obviously.

My patient today has been in recovery for three years. He has a sponsor, goes to 12-step meetings several times per week, has never had a positive drug screen the whole three years, has a stable home, wife, kids, and also finds time to help his aging parents. I’m going to prescribe generic buprenorphine tablets for him.

This won’t be the right answer for all my patients. Some will have to try the Suboxone films again, and I hope that will work for them.

Because of this pediatric overdose information I’m going to ask every patient – on films or tablets – how they store their medication, to make sure it’s safe.

http://www.alcoholismdrugabuseweekly.com/

Barring Healthcare Professionals from Working while on Buprenorphine

While buprenorphine has been prescribed for many patients over the last 10 years, there’s still controversy about whether healthcare professionals should be allowed to work while on buprenorphine.

In an article in March 2012 Mayo Clinic Proceedings, Hamza and Bryson  cite studies that support their conclusion that medical professionals should not be allowed to work while taking buprenorphine as maintenance for opioid addiction. The authors say studies show that people taking buprenorphine have some impairment when performing safety-sensitive tasks that are required in practice as a physician. (1)

I read this article with great interest, since I have been prescribing buprenorphine and telling my patients they won’t be impaired while taking a maintenance dose. Wanting to know if I am misleading patients, I scrutinized the studies cited in this paper.

I’m not sure the authors’ conclusions are backed up by the studies they cite.

The most worrisome misinterpretation was the Schindler et al study. The Mayo study by Hamza and Bryson interpreted the Schindler study thusly: “significant differences were found between them [methadone and buprenorphine groups] and the controls.” But when I read the original study, the authors’ conclusion was really the opposite: “The synthetic opioid-maintained subjects investigated in the current study did not differ significantly in comparison to healthy controls…” (2)

Hmmm…I’m confused.

When I looked at other articles cited by Hamza and Bryson, I discovered that what I read didn’t match Hamza and Bryson’s conclusions of what I read.

Three of the studies cited in the Mayo article (Pickworth et.al., Jensen et. al., and Zacny et.al.) all looked at healthy volunteers who were given buprenorphine, then tested to see if they were impaired. In other words, these test subjects weren’t opioid dependent. All three studies showed impairment, and I don’t doubt it, because opioid-naïve subjects would be expected to feel a great deal of opioid effect with their first dose of buprenorphine. But studies of opioids-naïve subjects given buprenorphine don’t seem applicable to opioid-addicted patients on buprenorphine for maintenance.

The Rapeli et al study looked at methadone and buprenorphine patients in early recovery, so these groups would be expected to be different than those on established maintenance therapy.

Soyka et al compared opioid addicts on buprenorphine and methadone at 2 weeks, then at 8-10 weeks. This study also had a control group. The patients on methadone and buprenorphine had impaired cognition on testing compared to the controls, but they improved with length in treatment. This study was randomized but not blinded. This means patients and researchers knew who was on methadone, buprenorphine, and who was a control subject. Interestingly, in a later letter to the editor defending their conclusions, Hamza and Bryson mistakenly claimed the study was double-blinded, but clearly it was not.  Also the study was relatively small, since only 46 patients completed the study. The purpose of the study was to see if methadone was more impairing than buprenorphine. The authors of the Soyka study didn’t conclude the buprenorphine group was impaired to the point they were unable to work, only that they performed better than methadone patients.

One study, by Messinis et al, did compare abstinent heroin addicts on naltrexone with opioid addicts on maintenance buprenorphine, and showed the buprenorphine group had more cognitive impairment than the naltrexone group in cognitive functions. To me, this is the main study that speaks to the actual issue of impairment. It gives a basis to require more studies be done. However, the small size of the study, 18 patients, limits the impact of this study. (3)

The ideal study to resolve this issue would be a double blinded prospective study of opioid-addicted healthcare professionals who are randomized either to abstinence-base treatment or buprenorphine maintenance treatment. Then cognitive abilities can be compared at various times during recovery, like 3 months, 6 months, 1 years, and 2 years. Such a test is unlikely to be done, since most addicted professionals enter abstinence-based recovery, and have a high rate of success.

I do think medication-free recovery is the ideal. I acknowledge that’s my bias, even though I strongly believe medication-assisted treatment is a life-saving option. But then, medication-free treatment is the ideal for all diseases. If a patient can achieve good blood pressure control by changing her diet and exercise, I think most of us would agree that’s a superior outcome to taking blood pressure medication to achieve the same result.

Most doctors and dentists have the resources to afford the prolonged inpatient treatment needed for medication-free recovery. The monitoring required for continued licensure is additional leverage and accountability that most opioid addicts don’t have after leaving inpatient treatment. These factors produce excellent recovery rates in these healthcare professionals, much better than that achieved by the average opioid addict.

But no recovery works for everyone. If a healthcare professional has failed traditional abstinence-based recovery, but is able to do well on medication-assisted recovery with buprenorphine, is the data strong enough to say such a recovering person on a stable dose of buprenorphine can’t work in healthcare?

We must be careful about this decision. If the decision is going to be based solely on patient safety, and not on a bias against medication-assisted recovery, then healthcare professionals on opioids for acute or chronic pain must also logically be removed from the workforce, unless we can prove they don’t have cognitive deficits from prescribed opioids. And what of other medications, like benzodiazepines, which are more likely than opioids to cause impairment?

If professional monitoring boards rely on the evidence cited by this study to refuse to allow healthcare professionals on buprenorphine to return to work, they leave themselves open to accusations inconsistent safety standards if they allow other healthcare professionals to work while being prescribed opioids or benzodiazepines.

It would be a mammoth task to monitor every healthcare professional who is prescribed a controlled substance. But if a professional on stable a dose of buprenorphine can’t work safely, how can we assume a surgeon who takes legitimately prescribed opioids for back pain is safe to work?

Frankly I suspect most of the posturing about the dangers of healthcare workers on buprenorphine is really an attempt to remove medication-assisted recovery as a treatment option for healthcare professionals. I don’t know if the mayo article authors, Hamza and Bryson, have any underlying bias against medication-assisted treatments, or perhaps biases favoring abstinence as the only worthy treatment goal. I don’t know these two people at all. But my impression is that they have taken a sweeping position supported by shaky evidence. The studies they cite are evidence enough to call for larger studies, but don’t seem adequate in themselves to deny a potentially life-saving treatment to a healthcare professional.

  1. Hamza H, and Bryson E, “Buprenorphine Maintenance Therapy in Opioid-Addicted Health Care Professionals Returning to Clinical Practice: A Hidden Controversy, Mayo Clinic Proceedings., 2012, 87(3);260-267
  2. Schindler SD, et al, “Maintenance therapy with synthetic opioids and driving aptitude, European Addiction Research, 2004; 10(2):80-87acol.
  3. Messinis et al, “Neuropsychological functioning in buprenorphine maintained patients versus abstinent heroin abusers on naltrexone hydrochloride therapy”. Hum. Psycholpharm. 2009;24(7):524-531
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