Archive for the ‘buprenorphine patch’ Category

Suboxone Manufacturer Sued for Anticompetitive Practices

Pharma Lies

 

 

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

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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.

Is Suboxone available in a patch?

No, not to treat addiction. At least, not yet.

 

However, buprenorphine, the active ingredient in Suboxone, is now available in the U.S. in a transdermal patch for use in patients with pain. It’s being marketed under the brand name Butrans by Purdue Pharma, the fine folks who also make OxyContin.  Transdermal buprenorphine has been available in Europe since 2001, under the trade name Transtec.

 

The patches are meant for patients with nearly constant moderate to severe pain. Each patch is meant to be worn for seven days, making it one of the longest-acting opioid patches on the market. Butrans comes in three strengths: 5mcg/hour, 10 mcg/hr, and 20 mcg/ hour. This means that at the highest dose, the patient gets nearly half a milligram over twenty four hours.

 

The patches have been inadequately studied  for use in patients with addiction, and they aren’t approved for this purpose.  I did find one open label study of nine patients, all physically addicted to opioids. In an inpatient setting, they were allowed to go into opioid withdrawal,  then they were given a patch containing buprenorphine that lasted for three days. During that time, their withdrawal symptoms were improved. The symptoms decreased by about 50%, and did return somewhat after the patch was removed. The patch used in this study was said to have released 1.9 mg per day of buprenorphine, about four times more than the highest strength of the brand Butrans.

  

I hope more clinical trials are done with this delivery system of buprenorphine. I’m curious to see if a patch of some strength can be used successfully to treat addiction. I have patients who can get down to 1 or 2 milligrams of Suboxone per day, and still have a difficult time stopping completely, due in part to physical withdrawal symptoms. These Butrans patches deliver much less medication than that each day, and I wonder if it would be just enough medication…

  

1.      Lanier RK, Umbricht A, Harrison JA, Nuwayser ES, Bigelow GE, Evaluation of a transdermal buprenorphine formulation in opioid detoxification., Addiction, 2007 Oct; 102(10): 1648-56.