I have shared my thoughts about ‘Suboxone Film,’ a product that serves only one purpose:  to block generic competition from entering the Suboxone market.  Below I’ve copied a Bloomberg article that discusses the current nature of the buprenorphine/naloxone business, and the efforts by RB to prevent market penetration by generics– something that would lead to price reductions for healthcare consumers.

Unfortunately, the Bloomberg article overlooks the most significant threat to the profits of Reckitt-Benckiser.  This threat is mitigated only by the ignorance of many of the physicians who prescribe Suboxone.  The threat to profits consists of a simple fact that RB does not want anyone to realize:  that the generic equivalent of Suboxone is already available, in the form of orally-dissolving tablets of buprenorphine.

I encourage physicians who doubt my comments to do their own ‘due diligence’ and break out their old pharmacology textbooks.  I have a hard time understanding how people who graduated from accredited medical schools can get things as wrong as they do with this issue.  I sometimes present opinions, but not with this post.  The facts about buprenorphine and naloxone that I’m about to describe are described in any pharmacology textbook— e.g. Goodman and Gilman—and are not in dispute in any way.

Suboxone consists of buprenorphine plus naloxone.  Naloxone is an opioid antagonist that is added to reduce diversion of Suboxone in the form of intravenous injection of a dissolved tablet.  Naloxone is NOT ACTIVE when not injected.  The molecule is poorly absorbed through the oral mucosa because of the molecule’s size and poor lipid-solubility.  Instead, naloxone is swallowed, absorbed from the small intestine, and totally destroyed at the liver before reaching the systemic circulation through a process called ‘first pass metabolism.’

I suspect that some physicians confuse naloxone with the similarly-named substance naltrexone, an opioid antagonist (blocker) that IS orally active. There is NO naltrexone in Suboxone.

All of the beneficial aspects of Suboxone come from the partial agonist buprenorphine.  The ceiling effect of buprenorphine causes a reduction in cravings through a process that I’ve described in earlier posts.  Naloxone, on the other hand, does absolutely nothing to reduce cravings, to increase safety, to reduce euphoria, etc, provided that the medication is not injected.

The confusion surrounding buprenorphine essentially consists of intellectual laziness or intellectual dishonesty by the physicians who prescribe the medication and the pharmacists who dispense it.  I realize that not all doctors are cut out to be ‘physician scientists’ who understand pharmacology in great detail.  But I am particularly disappointed that the large organizations that supposedly oversee the science of addiction treatment have dropped the ball on this issue. I don’t know why groups like ASAM and SAMHSA don’t get it– whether the problem is ignorance, or whether there are mutually beneficial relationships between these organizations and RB that encourage the organizations to foster ignorance among
patients and doctors.  I don’t belong to the organizations primarily for this reason– and I blame ASAM and SAMHSA for the current status of addiction treatment as the ‘no science zone’ of modern medicine.

 A few examples of intellectual laziness: 

Example 1:  Physicians who prescribe Suboxone often say that one shouldn’t use buprenorphine ‘because it doesn’t have the opioid blocker and therefore….’ (add whatever here– it causes euphoria, it is addictive, it isn’t safe– any or all of these comments). The statement is partially correct. Generic buprenorphine does not have the opioid blocker naloxone— but naloxone is irrelevant to the actions of Suboxone!

There are TWO opioid blockers in Suboxone, but only one is clinically relevant—the one that is in both Suboxone and generic buprenorphine.  What is the relevant ‘opioid blocker’ that IS
in both Suboxone and generic buprenorphine?  Buprenorphine!   As a partial agonist, buprenorphine has antagonist properties that are responsible for ALL of the effective clinical properties of Suboxone.

Example 2:  Refusing to consider the cost of medication as a factor that determines access to treatment.  Some docs make ‘fear of diversion’ the only factor in determining what to prescribe.  Discussions with hundreds of opioid addicts over the years have convinced me that buprenorphine is rarely a drug of choice.  Rather, it is used by addicts who are sick and tired and want a break from using without withdrawal, or by addicts who have no money or access to agonists.  In such cases, buprenorphine or Suboxone are equally effective– and equally diverted.  When I ask addicts new to treatment about their injecting habits, I often ask whether they injected buprenorphine or Suboxone.  The typical response is either ‘can you do that?’ or ‘why would I do that, since heroin is cheaper?’

In my area, an 8 mg tab of buprenorphine costs as low as $2.33.  This low cost should be part of the equation for choice of medication, just as it is for other illnesses.  Does anyone doubt that there are some people kept from treatment by a price differential of 300%?!  Is it ethical to fear diversion so greatly that treatment is effectively withheld– for a condition with the fatality rate of opioid dependence?!   I’m sure readers know my answer, especially when there are effective ways to reduce diversion, such as close monitoring of prescribed doses, a ‘no replacement’ policy, and drug testing, among others.

Example 3:  There is some question whether the naloxone in Suboxone does anything to reduce diversion. Buprenorphine patients on my forum  who have injected Suboxone in the past have claimed that they did not experience withdrawal from either Suboxone or buprenorphine, consistent with what I would expect from combining a low-affinity antagonist with a high-affinity partial agonist.

Note: Injecting ANYTHING is in essence taking your life in your hands, and I strongly encourage anyone in such a position to seek treatment immediately.   Really—don’t do it.

Example 4:  Insurers generally refuse to cover generic buprenorphine (the generic form of the RB drug Subutex), even though it is much cheaper than Suboxone.  The one time they WILL cover Subutex or buprenorphine is for women who are pregnant or nursing.  The argument is that we shouldn’t expose the fetus/infant to one more drug (naloxone), since that drug isn’t necessary to the actions of Suboxone.  I agree with the argument, and wonder why it is extended only to the fetus?  Why does mom or dad have to be exposed to an extra substance(naloxone) that isn’t necessary to the actions of Suboxone?

I struggle to understand the insurance issue, as I would expect that someone at some major insurer would know enough about pharmacology to save money on Suboxone by favoring generic buprenorphine.

The ultimate of silliness is that the State of Wisconsin requires that people on Medicaid use only Suboxone FILM.  Getting Abilify for a patient is virtually impossible without first using a variety of older, cheaper medications… but the squishy arguments in favor of Suboxone Film push the med up the formulary chain past an alternative that sells at a fraction of the cost.  The film/Medicaid situation is doubly dubious, as we have the arguments for buprenorphine over Suboxone, and the even less-sound argument for Suboxone Film being favored over the tablet.

RB apparently convinced the state that for Medicaid patients, only the film was safe– and that the film should be required instead of the tablet form of Suboxone, placing future generics at a great disadvantage.  It is especially impressive that RB accomplished this feat after selling a million units of the tablets themselves!  I can picture the person making the point:  ‘the tablet is unsafe…. Starting NOW!’

I’m going to write all night if I don’t wrap this up.  To summarize, the Bloomberg article below describes why RB is winning the battle with generics, but the writers of the article, along with most doctors, miss the bigger issue– that misplaced fears, intellectual laziness, and misinformation have protected Suboxone sales from a much greater foe-– generic buprenorphine.  If doctors, states, and insurers ever get their acts together and prescribe according to science, brand name Suboxone profits will go down the toilet faster than the cleaning products made by RB.

The Bloomberg piece:

Reckitt Benckiser Kicks Heroin Tablet Habit With Film: Retail

By Clementine Fletcher

Reckitt Benckiser Group Plc may be kicking its heroin problem.

After losing U.S. patent protection in 2009 for its Suboxone tablet, designed to help heroin users quit, Reckitt Benckiser has said that the entrance of a generic competitor could erode pharmaceutical sales and profit by 80 percent (note by JJ:  What a shame?!  Consider the benefit of such a price reduction for addicts in need of treatment!).

Reckitt Benckiser, which gets most of its revenue from selling home and personal-care products like Lysol cleaners and Durex condoms, has faced calls to sell the business before a generic comes to market. Instead, the London-based company aims to divert the showdown by switching users to a film form of the drug — one whose last patent doesn’t run out until 2025 (note by JJ:  NOW do you see why they made the film?!)

To get people to make the switch, Reckitt Benckiser is thinking more like a consumer company than a pharmaceutical one. It’s drawing on a marketing technique first pioneered by Coca- Cola Co. more than 100 years ago: coupons. By offering up to $45 a month toward a user’s co-payment in the U.S., the company is making the film version, which looks like a Listerine Pocketpak, close to free. That offers patients who get part of the bill subsidized by health insurance little incentive to transfer to a generic pill once it appears on the market.

“They’ve done a good job of making a silk purse out of a not very compelling situation,” said Martin Deboo, an analyst at Investec Securities Ltd. in London.

Reckitt Benckiser’s shares have risen 55 percent in the last five years, outpacing Unilever and Procter & Gamble Co. Under Chief Executive Officer Bart Becht, who stepped down last month, the company more than doubled sales in a decade. The stock has dropped 3.7 percent this year, compared with Unilever’s 4.7 percent gain and P&G’s 1.2 percent gain.

Drugs Growth

The company is due to report third-quarter results tomorrow and will probably say revenue adjusted for purchases and asset sales rose 7 percent at the drugs division, analysts led by Andy Smith at MF Global in London estimate, compared with a 3.9 percent increase for the rest of the business. Profit likely rose 0.9 percent to 430 million pounds, they said.

The film version of Suboxone, introduced in September 2010, accounted for 41 percent of the drug’s U.S. sales by the end of the first half (note by JJ:  Thanks, Wisconsin Badgercare!). That surpassed the company’s own expectations, Becht said on an Aug. 30 conference call arranged by Sanford C. Bernstein. Becht was succeeded by Rakesh Kapoor, a company veteran.

Generic Delay

The film “has been a phenomenal success,” Becht said, according to a transcript of his remarks. “To make the business completely sustainable, we would like to have a share which is clearly much higher than where we are.” He added that the company aims to grow that share every month.

Right now, time is on his side. Teva Pharmaceuticals Industries Ltd., the world’s biggest maker of generics, began the year saying it might launch a Suboxone copy in 2011. Now the company has backed off, saying it no longer expects the product to win regulatory approval this year.

Biodelivery Sciences International Inc., another drugmaker going after Suboxone, said a study comparing its own version of the drug to a placebo failed to show a statistical difference in the treatment of chronic pain. A test in patients addicted to opioids, which include heroin and codeine, is scheduled to begin
later this year. Titan Pharmaceuticals Inc. on Aug. 31 said it’s preparing to seek approval of an upper-arm implant that would deliver buprenorphine, one of
the active ingredients in Suboxone, directly into the bloodstream (note by JJ:  the ONLY active ingredient in Suboxone!)

‘Massive Benefit’

“This delay has been a massive benefit,” said Andrew Wood, an analyst at Sanford C. Bernstein. “With every day that goes by, RB has an extra day to convert users.” Suboxone is either harder-than-expected to copy or generic-drug makers are having second thoughts about targeting addicts, according to Bernstein.

About 1 million people in the U.S. are addicted to heroin, the National Institute on Drug Abuse estimates. As many as 325,000 people use Suboxone to quit the drug or painkillers, says Pablo Zuanic, an analyst at Liberum Capital in London.

The medicine combines buprenorphine, a painkiller derived from the opium poppy that shares some of its properties, with naloxone, a chemical that blunts
withdrawal symptoms (note by JJ:  This is simply WRONG.  BLATANTLY WRONG.  Really–  an opioid antagonist BLUNTING withdrawal symptoms?  Shame on the writers!). The film sells for about $4.63 to $8.23 a dose at Walgreens stores, according to Liberum, depending on its strength and pack size. That means the strongest dose costs about $247 a month.  (note by JJ—a pharmacy near my practice sells generic buprenorphine dissolvable tabs, 8 mg, for $2.33 per tablet—a medication that works EXACTLY the same way IF NOT INJECTED INTRAVENOUSLY)

More than half of people on Suboxone use private insurance with co-pay, Zuanic says. Reckitt Benckiser offers $45 towards co-pay for the film, he said, meaning an insured patient who’d contribute $50 to the cost of the drug may end up spending $5.

‘Near Zero’

“The actual cash cost for some patients buying the film with private insurance could be near zero,” Zuanic said in a note to clients this month. (note by
JJ:  but we are all paying the cost in higher insurance premiums, and some insurers, notably Humana, have draconian policies that stop covering—forcing instant withdrawal- if a patient receives a prescription for a sleep medication such as Ambien, so many people are left paying cash).

Meantime, Suboxone is only becoming more important to Reckitt Benckiser. The drugs division, whose sales grew five times as quickly as the main business last year, accounted for almost 9 percent of sales and 24 percent of profit, up from 7.6 percent and 20 percent in 2009. Sales at the unit will probably rise 12 percent to 829 million pounds ($1.3 billion) this year, according Nomura International Plc estimates.

The maker of French’s mustard is even considering making an injectable Suboxone and developing new products for cocaine, alcohol and cannabis addicts.
The plan has met skepticism.

“We’re quite a long way from having any visibility on these products,” said Julian Hardwick, an analyst at Royal Bank of Scotland Group Plc in London. “Are they products that will work? Which will get approval?”

Prescription drugs are perceived as a bit of a misfit in the home of Vanish stain removers and Finish dishwasher tablets.

Misfit

“Reckitt Benckiser is basically a home and personal-care company with over-the-counter pharmaceuticals,” said Carl Short, an analyst at Standard & Poor’s in London. The drugs unit is “always going to be something that looks like it doesn’t fit with the rest.”

Reckitt Benckiser may look at selling the unit, which Becht himself has said is “not the No. 1 strategic part” of the company, once a generic form of Suboxone reaches pharmacy shelves, analysts said. (note by JJ:  i.e. after all of the profit has been wrung from suffering addicts).  But the company’s marketing savvy, coupled with delays in the launch of a generic, are giving Kapoor time to settle into his new job.

“This is a big job and he is coming in after someone’s done it for some considerable time and very well,” said Julian Chillingworth, who helps manage about 16 billion pounds in shares at Rathbone Brothers Plc, including Reckitt stock. “You wouldn’t want to come in as a CEO into a very successful business and start selling things off on the cheap.”

Not Time

Analyst valuations range from 2 billion pounds to 6.3 billion pounds, according to four estimates compiled by Bloomberg News. Estimates diverge because it’s hard to value the business without knowing how Suboxone sales will resist the generic challenge and whether the shift to film can counter some of that impact.

“Until you get generic competition for the tablet, I think it’s unlikely that prospective buyers would give you the full value for the business,” said Hardwick of RBS. “Now is not the time to sell.”

–With assistance from Naomi Kresge in Berlin. Editors: Celeste Perri, Marthe Fourcade.

I recently received a question about stopping Suboxone (buprenorphine)…. I deleted the message but I remember the bulk of it, and I have a copy of my response. I thought that someone else out there may find it useful, so here it is:

The question:

I have decided to go off Suboxone after that was recommended to me by almost everybody. My doctor told me to taper off by going down to 2 mg per day, and then take 2 mg every other day, then every third day, and stopping after I get to every 4th day. I followed those instructions and I am taking it every other day, but I am now getting sick every other day. Is this a good way to stop Suboxone, or do you recommend another way?

My response:

I’m not certain who is giving you advice. More and more, the standard of care is to keep people on buprenorphine for at least a year, and many people stay on ‘remission treatment’ indefinitely– just as we do for other chronic illnesses. There is no evidence or truth to the idea that ‘it is harder to stop buprenorphine the longer you take it’; tolerance does not increase after reaching a plateau, usually in a month or so, and I have found that patients are more successful at stopping buprenorphine the further they get from the period of active use. There is no significant toxicity from the medication when it is taken properly; it is far safer than medications used to treat other illnesses, such as hypertension, elevated cholesterol, asthma, diabetes, or arthritis– let alone other potentially fatal illnesses like cancer.

If you DO go off buprenorphine, the method you described won’t generally work because of the pharmacokinetics of the drug. The plasma half-life of buprenorphine is 2-5 hours, but the elimination half life is over 30 hours. The volume of distribution of the drug increases with dose because of dose-dependent protein binding. Finally, the ceiling effect creates a non-linear relationship between blood level and pharmacologic effect. The practical result of these factors is that larger doses of buprenorphine produce opioid effects that last longer than smaller doses. A typical buprenorphine pain dose of 50-100 micrograms lasts for 6-8 hours, but in the super high doses used for addiction (8 mg equals 8000 micrograms), the opioid effects last much longer- allowing for once per day dosing.

As the dose is lowered, the effects of buprenorphine become shorter in duration. So the person tapering buprenorphine need to not only take smaller amounts each day, but must also divide that daily amount into two, then three, then maybe even four doses to avoid withdrawal symptoms at the end of the dosing interval.

On my forum, SuboxForum, people discuss the ‘liquefied taper method’– a method that I believe I was the first to describe, where a tablet of Suboxone is dissolved in a small amount of water, and doses are administered by drop from a medicine dropper or TB syringe. Any small medicine bottle and the included dropper can be used. I would suggest taking the time to calculate the microgram per milliliter concentration, and using the dropper to dose known amounts.  A TB syringe is more accurate, as it has the amounts marked on the side. For this purpose, a ‘cc’ is the same as an ‘ml’. There are 1000 micrograms per milligram (mg). I’ll leave the rest of the calculations to you!

Another option might be to use ‘Butrans’, a buprenorphine skin patch, after tapering to a low sublingual dose. The biggest patch releases 500 micrograms (or 0.5 mg) per day, and there are a couple smaller sizes with the smallest patch releasing 0.1 mg per day or 100 micrograms. One could taper down to a quarter of an 8 mg tab per day, and then change to the 0.5 mg patch. That sounds like a big drop, but only a small percentage of the sublingual dose of buprenorphine is absorbed– some estimates as low as 15% of the dose. By that estimate, a 2 mg sublingual dose of buprenorphine would be comparable to 0.5 mg of transdermal buprenorphine.

I wrote Butrans might be used because under current law, doctors cannot prescribe Butrans to treat addiction—and I assume that includes tapering off buprenorphine. Federal law that allows for use of controlled substances to treat opioid dependence (DATA 2000)—an exception to the Harrison Act— only allows use of medications that are indicated for opioid dependence. At the present time, Butrans is indicated for treating pain, and not for treating addiction. By my understanding of the law, doctors can use Butrans to taper patients off buprenorphine only if the indicated use for the buprenorphine is any condition other than addiction.

But again, do give some thought to whether you should be stopping buprenorphine, as the relapse rate for opioid dependence is, unfortunately, very high.

I’m not sure about the make-up of readers of this blog.  I know that there are about 20,000 page views each month, but I don’t know how many are by people addicted to opioids, people taking buprenorphine, family members of addicts, or physicians who prescribe buprenorphine.  If you fall into that latter category– i.e. if you prescribe buprenorphine, or if you prescribe other medications to treat opioid dependence such as Vivitrol or methadone– consider joining the group at linkedin.com called ‘Buprenorphine and other medication-assisted treatment of opiate dependence.’  If you already belong to LinkedIn, you can simply follow this link to join: http://www.linkedin.com/groupRegistration?gid=2710529

I have always resisted separating those who prescribe buprenorphine from those who are prescribed the medication.  I have avoided, for example, placing a ‘doctors’ section’ at SuboxForum, as I don’t want there to be two separate discussions.  Clearly, each group would benefit from the wisdom of the other.  But there are some physicians who want to discuss prescribing habits, techniques, and science with other docs, who are not comfortable discussing some topics in the ‘presence’ of their patients.

Non-docs, please don’t flame me for this decision;  I’ve wrestled with it, and have made this decision, at least for now.   Frankly, the discussions at SuboxForum are far more interesting than anything that has come up so far at the linked in site!    But some docs who prescribe buprenorphine are isolated out there, perhaps even looked down on by their peers for working with addiction– and that is a crying shame.    I want to get those docs some support.  My goal ultimately is to bring the two sides together, so that docs can talk to addicts and realize that they are the same species as the rest of their patients!

Thanks all,

JJ

Many of you are familiar with my e-book, ‘User’s Guide to Suboxone,’ that has been available for sale on the web.  The copy that is sold through that site is ‘print-protected’ and copy protected;  a password is required to open the document and it cannot be printed– at least not without a bit of digital trickery. 

e-book about buprenorphine

I was just looking through the book, and realized that it ain’t that bad– I’m no Hemingway, but I think that it contains some good ideas, and the words are spelled correctly.   The chapters are listed at the end of this post.

I plan to upgrade ‘the forum’ in the near future, and part of that process includes raising money for a web designer.  My friend Jim will always be the ‘right-hand guy’ with the programming, but I can only ask for so much free help before feeling guilty!  So if anyone out there has considered making a donation, now is the time…. because a $5 donation will get you a copy of the e-book, User’s Guide to Suboxone, sent as an e-mail attachment that unlike prior forms can be printed.  I do ask that you respect the copyright, and if you want a dozen copies for your treatment center, send me a note to work out a discount– rather than simply making 11 copies.

Instead of automating things this time around, if you want a copy of the printable e-book I’ll have you use the donation button on the right side of this web site.  Just make a donation of $5 or more, and I will use the e-mail address that you use for the PayPal or Google Checkout donation to send the book as an attachment.  I’ll get it out within a day or two.  Proceeds will go to the new SuboxForum– the more I raise, the nicer I hope to make it!  As always, thank you all for your support.

List of Chapters:

A Caution

Introduction

Introducing Buprenorphine

Practical considerations

High Tolerance at Induction

Precipitated Withdrawal

Pain control

Surgery

Pregnancy

Length of Maintenance

Tapering

Other Medications While On Buprenorphine

Other Drugs of Abuse

Benzodiazepines

Other Medications

Buprenorphine Side Effects

Twelve Step Meetings

Future trends

I have written about this topic multiple times, but perhaps a summary is appropriate.  More and more evidence and clinical experience suggest that buprenorphine is best considered a long-term ‘remission agent’ for opioid dependence.  Such a conclusion would have been obvious years ago if not for the hesitancy to do what has been suggested by addictionologists for decades, and treat opioid dependence as a DISEASE.  While many people pay lip service to addiction being a chronic illness, the reluctance, particularly by AODA counselors, to fully accept a medication for the condition is clear evidence of the stigma that continues to force addiction into the realm of ‘character.’   AODA counselors would do well to do some serious soul-searching on this issue– at least in my opinion.

While remission therapy with buprenorphine will likely become the standard treatment for opioid dependence, there will be some cases where tapering off buprenorphine is appropriate.  The problem in such cases is that the taper process causes withdrawal, which stirs up all of the self-disgust, fear, and shame that predispose an addict toward relapse.  As I have discussed, a long-term injectable formulation (such as Probuphine, currently in the FDA approval process) would be useful for tapering off buprenorphine.  The final piece of the equation would be effective treatments for opioid withdrawal. 

A number of medications are rumored to help reduce the symptoms of opioid withdrawal.  I’ll mention a few of the medications that I have used to treat withdrawal, or that I have read about in scientific studies or case reports.

- Clonidine is the ‘standby’ agent for treating opioid withdrawal.  The medication reduces CNS excitation by effects at alpha-2 adrenergic receptors, causing less release of epinephrine and norepinephrine by central and peripheral nerve terminals.  Symptoms of withdrawal are reduced by about a third, and the primary side effect is sedation.

- Some medications target specific components of withdrawal;  Imodium (generic name loperamide) reduces bowel cramping and diarrhea; benzodiazepines reduce anxiety (but are themselves addictive); ibuprofen and acetaminophen reduce muscle aches and headache; stimulants or wellbutrin reduce fatigue (perhaps for severe symptoms, but use of stimulants would be considered controversial at best).

- Proglumide is an antagonist of two classes of receptors for a gastro-intestinal hormone called ‘cholecystokinin’, or CCK.  Proglumide used to be used in the US and elsewhere to treat gastric ulcers, before more effective medications like histamine blockers were developed (e.g. cimetadine).  There are a number of chemicals structurally related to proglumide that have similar actions, that include enhancing analgesia caused by opioids, treating Parkinsons disease, and enhancing the release of growth hormone.  Proglumide appears to ‘reset’ tolerance to opioids in people who are physically dependent, and also to reduce symptoms of withdrawal.  Proglumide appears to have dropped of the face of the planet;  if you search for the medication you will find it available in chemical supply houses in China, but not available through pharmaceutical companies.  I recently received contact from a person claiming that  proglumide is available through a company based in Pakistan, but I have not yet verified the information.  Stay tuned.

- I recently came across an article with some fairly convincing evidence that symptoms of withdrawal are reduced by the anti-anxiety medication buspirone.  A study found that self-reported withdrawal symptoms of opioid addicts were greatly reduced by treatment with buspirone, which is a pretty safe, inexpensive medication that is not itself addictive.

- Ondantreson is an anti-nausea medication used during chemotherapy and surgery.  I have seen several studies demonstrating a reduction in opioid withdrawal from the medication, which like buspirone is fairly safe and is not addictive.  Ondantreson is, however, more costly.

I have treated patients in withdrawal using gabapentin, specifically to reduce sweating and hot flashes.  I do not know if it works, or if the people who liked it were getting a placebo response.  I have not seen reports in the literature showing this benefit.

- I have mentioned the recent approval of transdermal buprenorphine, called ‘BuTrans.’  This formulation provides a lower range of doses of buprenorphine, in the tens to hundreds of micrograms (one tablet of Suboxone contains 8000 micrograms of buprenorphine).  This lower dosed formulation may find usage for tapering.

Do you have other suggestions for treating opioid withdrawal?  If so, please share them in the comments below or over at SuboxForum.  Of course, these medications must NOT be taken ‘on the street,’ but rather should be discussed with your physician if and when the time comes to taper off buprenorphine.

Thanks all,

JJ

Something I haven’t yet come across:

Acesulfame Potassium

Well, i’ve been clean with the help of Suboxone for 14 months now. Throughout my treatment I’d been getting tongue blisters and ulcers at least two at a time. I’ve probably had them six to eight different times in this 14 month period. I realized something wasn’t right, and started investigating, trying to figure out what the problem was. I watched the foods I ate and the things I drank. Nothing seemed to work; they just kept coming back. So, the only thing I could think of was the Suboxone.  I read the pamphlet that comes with the medication. The artificial sweetener in Suboxone (Acesulfame K sweetener) is what I am allergic to. I have been allergic to artificial sweeteners my entire life. I had been taking a medicine I’m allergic to for 14 months! I admit, i should have done more research from the start. But I was so desperate for relief that i would have done anything to get rid of withdrawal. I also checked the ingredients in Subutex. It does not contain Acesulfame K sweetener. I went to my next doctor appt. and told my doctor my findings. My doctor was a complete jerk. When I brought up pretty much the only option I had and asked ‘could you switch me to Subutex?’  He said he usually only uses Suboxone but because of my allergy there wasn’t any other choice.  I said ‘will you write the prescription so that i can get the generic just in case Subutex isn’t covered?’  He said, ‘nah I really don’t want you taking generic.’ I said, ‘do you mind going to check and see if you can find out whether Subutex is covered?’ he leaves for a few minutes, comes back and says ‘nope it doesn’t cover it.’ Then he says, ‘ I’ll go ahead and write it so that you can get generic.’ He was very angry. I can only guess it was because the generic is made by another company.I could take this discussion in any of several different directions.  But instead of getting angry tonight at doctors who may have hostility for addicts (or perhaps addicts who perceive something else as hostility–  I wasn’t there, so I don’t know what happened), let’s look at the issue of allergy to the artificial sweetener in Suboxone, and the issue of prescribing brand vs. generic and Suboxone vs. Subutex.  For people who are interested, I took the discussion in an entirely different direction on the forum, where I took Reckitt-Benckiser to task for their limited number of slots in their patient assistance program.

Some background:  Brand Suboxone and Subutex have been the only bupe game in town until last fall, when a generic version of Subutex appeared on the scene.  Access to the medication has been a constant frustration since then, as distribution gets backed up and the price continues to rise– now almost double the initial price of about $2.50 per 8 mg tablet.  People in Wisconsin can generally find the generic by ordering it ahead of time at Walgreens– a company I am loathe to refer people to, but that at least has been able to get the medication.  That is if one of their pharmacists doesn’t decide to tar and feather you and post you on the wall along with those other darn drug addicts!

The generic version of Suboxone entnered the market about a month ago thanks to Teva pharmaceuticals, a large generic company that SHOULD be able to meet demand, but that so far does not have tablets on the shelves in Wisconsin.  The hope of many people, of course, is that the advent of generics will bring down the price of buprenorphine.  That SHOULD happen, provided that doctors don’t fall for whatever anti-generic nonsense is thrown their way by the sales force for Reckitt-Benckiser.

This is the point, by the way, where a company’s ‘true colors’ show.  Reckitt-Benckiser makes a big deal of talking about how they are NOT about the money– they are all about HELPING ADDICTS, and really don’t hardly notice that their company profits continue to surprise to the upside, pushing the stock price higher.  And I’m sure it is completely by accident that the price of Suboxone is so high, and that the high price has gone higher by about 50% over the past two years, at a time when everything else in the world is getting cheaper.  I figure that somebody accidentally moved a decimal point,  just like that crazy day in the stock market a month ago.  They probably THINK that Suboxone sells for $0.60 per tablet, not $6.00!

I’m sorry for sounding annoyed.  My anger stems from my suspicion that RB ISN’T just about saving lives.  Don’t get me wrong– I love capitalism.  But only when ruled by honesty, especially in the healthcare sector.  I have heard and read comments from the sales reps from Reckitt-Benckiser that suggest a concerted plan to tarnish competitors in a way not done by other companies about other generics.  I do not know what happened to their plan for a listerine-strip type of product, individually packaged, but they clearly planned to attack their own formulation just as soon as they got approval for the new product.  But so far, the dissolving SL tablet in a multi-dose vial appears to be just fine!  Watch for that to change. 

Reckitt-Benckiser is also playing up the diversion-potential of Subutex, even though they know that the vast majority of diversion cases consist of addicts self-treating their addiction, taking the tablet by the usual sublingual route– NOT injecting it.  But it protects the sales of Suboxone if the doctors and pharmacists (and DEA) are under the impression that prescribing Subutex is taking a big risk.  Is Subutex ever injected?  Of course.  But only a small fraction of diverted Subutex ends up used that way.  For the most part, Suboxone and Subutex are the same medication– except until recently one had a generic and the other did not.  I even suspect that some RB reps deliberately allow confusion over how Suboxone works– i.e. not explaining that Subutex contains EVERYTHING necessary to treat opioid dependence that is present in Suboxone.  Some docs think that the naloxone in Suboxone adds to the opioid blockade (it does not, when taken sublingual) or reduces cravings (it does not).

I did some reading on the artificial sweetener in Suboxone, and the writer is on the right track– and I hope he is prescribed the medication that he needs, rather than suffer with mouth sores.

I encourage physicians to take all factors into account as they take on this nasty illness.  On one hand, I resist the complaint that ‘I can’t get help because Suboxone is too expensive’ because active using is always much more costly– even before considering the costs to one’s occupation or to one’s relationships.  But physicians have long-relied on generics to increase availability of life-saving medications that otherwise would be beyond reach for many people– particularly during a nasty recession. 

Makers of generic buprenorphine, please continue your good work, and good luck to the new products entering the market– for example Butrans, which was approved a few days ago, and Probuphine, a long-term injectable form of buprenorphine that I suspect will be a great help for the final stage of buprenorphine remission treatment, i.e. stopping treatment with buprenorphine.  Let’s hope the FDA recognizes the demand for that delivery system.

JJ

Over a year ago I wrote about the transdermal formulation of buprenorphine available in Europe called ‘Butrans.’  One problem with the treatment of opioid dependence using buprenorphine has been the limited dose options available;  while 2 and 8 mg sublingual tablets are fine for maintenance, they are wholly inadequate when it comes to tapering off buprenorphine.  The ‘wall’ of withdrawal symptoms that people discover as they taper past 2 mg is a product of the ceiling effect of buprenorphine– so useful on the way up, but so challenging on the way down!  At 2 mg, the level part of the dose/response curve ends, and each decrease in dose causes a drop in opiate effect and a drop in tolerance… and so an increase in (albeit temporary) misery.  Smaller doses of buprenorphine would be very useful at that point, say 2 mg of buprenorphine in a scored bar about a cm long, so that people could measure consistently-sized doses like 2 mg, 1.8 mg, 1.6 mg, and so on.  I have described a ‘liquefied taper method’ that some people have used with success, as described on the Forum, to consistently measure smaller and smaller doses for an effective taper.

Of course the remaining problem with any opiate taper is that the person must suffer through some degree of discomfort and craving, while at the same time holding a vial filled with the doses that would make things whole.  Most opioid addicts really struggle at 3 AM under those conditions!.  I’ve been excited about the newer products coming down the pipeline, including the transdermal product Butrans and also an injectable form of buprenorphine called Probuphine.  The latter in particular would be useful for tapering, as the addict could get a slowly-dissolving shot of buprenorphine and then go about life as it wears off, without having a vial of more buprenorphine on the nightstand.  I don’t know if Butrans will have any usefulness for tapering buprenorphine– if it did, such use would be ‘off-label’ as the medication is approved for treatment of pain, NOT for addiction treatment.

Here is the link to the Purdue news release: 

http://www.purduepharma.com/pressroom/news/20100701.htm

The old days

I worked for several years as the medical director of a residential treatment center in Wisconsin, leaving the position several weeks ago.   On my last evening in the place I took a moment to look around and think about how addiction treatment has changed in the past decade.  I looked at the pictures of the patients in their charts, who were mostly in their late teens or early 20’s.  The most common class of ‘drugs of choice’ were opioids, including oxycodone, heroin, methadone, morphine, and hydrocodone.  I thought about the different but similar program that I attended ten years ago, filled mostly with addicts and alcoholics in their 30’s and older.  I wonder if Bill W would have come up with the same twelve steps, had his target been not 50-year-old alcoholics, but teenage heroin addicts! 

On the walls around me were posted sheets of paper, and on them were lists of ideas from a brain-storming session about how to remain competitive in the modern era of addiction treatment.   I scanned the 20-some pages for mention of buprenorphine, and found the medication mentioned only once, under ‘challenges.’  On the other hand there a number of ideas related to marketing, endowment funding, and public image.  What I saw in that room essentially summarized the problems with traditional treatment in an era of buprenorphine.  It also validated my decision that it was time to move on.  

When I was an anesthesiologist I went through a period of frustration over the American Heart Association’s ACLS treatment guidelines, or more specifically over how they were implemented by the hospital where I worked.  The guidelines provide easy-to-remember steps to use when treating victims of cardiac arrest.  As an anesthesiologist, my education and training taught me to think ‘physiologically;’ if my patient on the OR table went into cardiac arrest, my training allowed me to quickly decide the likely cause, the appropriate medication for that problem, and the proper dose of medication based on body composition, patient age, other medications, medical history, fluid balance, etc.  ACLS guidelines were not initially devised for anesthesiologists, but for paramedics and other medical professionals who had less critical care training and experience.  To keep things simple enough to remember, the ACLS guidelines provide general medication and dose recommendations based on averages, not tailored to specific conditions or patients.  The dose of epinephrine listed in the protocol is 1 mg, whether the patient is a 20-y-o male athlete or a 95-y-o woman.  That dose may or may not be appropriate for either a 20-y-o or a 95-y-o–  but it is certainly not the correct dose for both!  But that’s OK, because we were just talking ‘guidelines,’ not hard and fast rules. 

The problem began when nursing educators started teaching ACLS classes not only to paramedics, but to physicians as well.  I attended those classes—I had to, just as most physicians who are part of networks are required to do every three years.  In most courses I attended, physicians who asked about optimizing doses based on patient characteristics were told to stick to the algorithm so that people didn’t get confused.  The result, of course, was to dumb down the classes, and to dumb down the people taking the classes.  The issue comes down to whether to trust that individual doctors will be able to think and get it RIGHT, or to assume that they will get it wrong and therefore give them easy-to-memorize instructions.  I could go off and extrapolate to modern society as a whole, but I’ll try to control myself!  The problem with telling docs to avoid thinking and to instead just follow the protocols is that the guidelines are SO generalized that they almost guarantee failure.  

Successful resuscitations are relatively uncommon, making it difficult to come up with treatment guidelines that are clearly good or clearly bad.  Over the years, ACLS guidelines have changed in drastic ways.  Some interventions recommended as beneficial were later found to make things worse.  It is hard enough to decide if standardized, dumbed-down guidelines are beneficial, so you can imagine how hard it would be to determine if a single doctor’s care was good or bad. 

What I took issue with was the push for consistency, and the effect of that push on patient care.  After a cardiac arrest and resuscitation in the hospital, the chart was reviewed by quality assurance and by a committee that included the people who taught the ACLS courses.  No problem so far.  But if a doctor deviated from the ACLS protocol, things got silly.  The doctor would be asked to provide reasons for deviating from protocol, including support from the literature for the deviation.  But the literature focuses on whether the ACLS protocols themselves are of any value, so there are few studies of non-ACLS approaches.  There are no studies of the effects of using 750 micrograms of epinephrine instead of 1 mg in a cardiac arrest in a 54-y-o man on beta-blockers, having hernia surgery, who is slightly dehydrated and has a history of mitral stenosis!  

Initially the ACLS protocols were designed to help people with less knowledge of physiology provide adequate treatment.   But over time, the protocols became the final authority on treatment.  So if a patient with an intelligent physician has a heart attack in the cath lab, the doc now has to make a decision.  Is the doctor going to give medications and doses of medication specifically geared toward this one patient—and then be hung out to dry by the hospital QA department (which is run by nurse educators who don’t understand this issue)?  Or should the doctor just turn his brain off and follow the ACLS protocols, guaranteeing that there won’t be any calls for explanations?  The irony is that a doctor who never successfully resuscitates a patient will never run into trouble, provided that the ACLS algorithms are followed—he/she may even get an award!  But the doc who saves an occasional patient by THINKING and figuring out the perfect treatment is likely to run into all kinds of trouble!  If you were the patient with that smart doctor, and you were facing low odds of survival, would you rather have the standardized, one-size-fits-all approach that rarely works?  Or would you want your doc to risk getting written up by using the new medication that he read about that he thinks would fit your condition, but that isn’t on the protocol sheet? 

How do we get back to addiction treatment?  About 100 years ago some people came up with the twelve steps.  I don’t know the history of early AA as well as many, but the steps were devised for the patients of the time, who were mainly middle-aged alcoholics, mostly Caucasian, and mostly male.  The steps have stood the test of time, and are now applied to many different substance addictions, and even to non-substance disorders such as eating disorders and pathological gambling.  Do they work for those conditions?  Sometimes.  Like cardiac arrests, the conditions treated by the twelve steps tend to have very low success rates for ALL treatment strategies, so the steps don’t have to work very well to be as good as anything else.  I have great respect for the twelve steps, but some have imparted them almost magical qualities that can be used to fix anything! 

Some addiction treatment centers are fixated on the steps not as a treatment tool but as a special entity, so that they seem to favor ‘purity of sobriety’ over saving lives.  As a fan of the steps myself, I too see ‘sobriety’ in a biased way, making it all the more difficult to describe this concept.  Bear with me—maybe my point will be clearer if I ask a few questions.  I encourage you to come up with your own answers, and to discuss this topic at the forum. 

What is the point of treatment?  When a patient enters a treatment program, how should them measure success?  If everyone is hugging each other and going to meetings at the end of 30, 60, or 90 days, is that enough?  If 85% of those ‘successful treatments’ are using after one year, should the treatment center feel good about the job they are doing? 

At the forum, we try to avoid discussions about ‘who is more clean’ because there really is no answer to the question.  Today I surfed past a silly TV program where the Real Housewives of New Jersey were divided into two groups, arguing with each other over who was meaner, who lied first, who said what to who… all shouting over each other.  Do they really think that one side will ‘win?’  That’s how I feel about ‘who is more recovered’ arguments.  And I am gratified that most of the discussions at the forum show far more class and intelligence than that particular topic!  My questions here are not intended to go down that path; these questions are to make the point that there are bigger issues than ‘whose recovery is better.’ 

Which of the following outcomes should a treatment center prefer?  Patient A leaves treatment totally free of all substances after 30 days of a 30-day program. He enters a halfway house and leaves after 90 days, still clean.  After six months he stops attending meetings.  Three months later his friend from his home town pays him a visit, and after drinking a few beers and taking a couple 80’s for old time’s sake he dies in his sleep.  Patient B leaves treatment after 21 of 30 days and against the counselors’ advice finds a doc who prescribes buprenorphine.  After a month on buprenorphine he takes a couple 80’s with an old friend, and doesn’t feel anything from taking them.  The next month he takes an extra buprenorphine tab every now and then, so that he runs out early.  He doesn’t call his doc, and instead gets sick for a day or two at the end of the month.  He even takes some methadone to ‘treat’ the withdrawal, but it doesn’t really do anything.  After four months he has talked to his doc about these things several times, and is starting to get used to—and enjoy–not feeling high.  At eight months an old friend visits and gives him a couple 80’s.  He knows that they won’t do anything, so he passes on them.  Or maybe he is having a rough day and he gives in one last time—but they don’t do anything. 

I am not implying that a patient necessarily does better with buprenorphine (although I do think that it is the case that patients do better with buprenorphine!).  My point is to show two types of ‘recovery,’ and to ask, which patient of the two is doing better?  MY answer is that the second person is better off, because he is ALIVE.  I would think that most people would agree—that it is better to be alive than dead.  But some of the attitudes I have witnessed among traditional counselors make me think that they are so intent on a twisted version of ‘perfection’ that they would feel better about the first patient!  I was speaking with the CEO of a hospital recently who said that if hospitals had a 15% success rate for other diseases, they would be viewed as dismal failures.  But in recovery, there seems to be an attitude that the failure rate is acceptable—as long as someone lives.  I hope that buprenorphine prompts movement toward a new paradigm where it is no longer acceptable, accepted, or ‘a given’ that many people die. 

The steps were designed, in my view, with the help of divine intervention.  They sometimes offer the gift of sobriety to a suffering alcoholic who has reached rock bottom.   There have been attempts to use them to achieve sobriety from other substances, including opioids, and they sometimes help a desperate opioid addict.  But it is much more difficult, and rare, for a teenage opioid addict to accept ‘powerlessness’ than for a jaundiced, middle-aged alcoholic to do the same.  Like the ACLS algorithms, the steps are a ‘one-size fits all’ approach to treatment.  Like the algorithms, they can be a valuable tool.  But for both the algorithms and the steps, the point should NOT be on the purity of the treatment approach; the point should be whether lives are being saved, and whether an imperfect approach that uses out-of-the-box thinking might save a few more. 

The REAL challenge facing traditional treatment centers will be to let go of their old ideas of ‘perfect sobriety’ and to use the treatment tools that have the best chance of keeping addicts alive.  Doing so should not be that difficult;  all they need  do is look at the faces of the young addicts entering their programs, and ask themselves, honestly, how many will be alive after a few years?  The honest counselors at traditional, non-buprenorphine programs should be humbled, and even ashamed, by what they know about those numbers.

Some of you may be up on ‘affiliate marketing’.. for those who aren’t, there are many variations on the idea out there. I now have it set up for my e-book and audio recordings and a few people are already taking advantage of it. The basic idea is that an ‘affiliate’ gets a percentage– 30% in this case– of sales of the products. Since my e-book goes for about ten bucks, the affiliate share is little over three dollars. Other products sell for $10 – $20.

It costs nothing to be an affiliate, and once you are set up there is no action required on the affiliate’s part except receiving money in a PayPal account. To set it up, follow instructions at this page.  There are a number of affiliate sites out there; my particular program uses E-Junkie.

As you can read here (the link is http://addict-ed.com/affiliates), there are many ways to set up a program that once established will bring in regular earnings. I describe a couple ways to do it at the site listed, including using Facebook, YouTube, or sending links via e-mail. It really all comes down to traffic and contacts; if you have access to a number of people with interest in opiate dependence, you might do very well. If you are a physician, you could make the information available to your patients using your own ‘hop-link’ as described on the affiliates page. There are affiliate programs out there where the information that is sold is very generic or of little value; I have had good feedback about the educational value of these recordings and about the e-book. One of the recordings, entitled ‘how long are you going to take that stuff,’ has been particularly useful for friends and family of people taking buprenorphine.

I hope to get a couple other products into the affiliate program soon. Thank you to any of you who are willing to give the program a try!

For those of you who prefer watching to reading, here is a video with a few thoughts about why will power is NOT any kind of strategy for staying clean.  As I describe, believing in will power is not only unhelpful;  it even INCREASES one’s chance for relapse, and serves as a frequent justification for the using that leads to full-blown relapse.  Please share comments at Buprenorphorum.com.