Archive for the ‘Misuse of Suboxone film or tablet’ Category

Treatment Implications for Intravenous Buprenorphine Use

Hokey Pokey

 

 

During the admission of new patients for opioid use disorder treatment, I ask about prior use of all drugs. I include the medications we use for treatment. I’ve done this since I started working at opioid treatment programs (OTPs) fifteen years ago.

Over the last few years, more patients say they’ve used illicit buprenorphine in the past. At first, I saw patients who were using it sublingually (under the tongue), as recommended, though still illicitly. Most of them wanted to see if this medication would work for them before they committed to the time and expense of entering a treatment program.

Over the past six months, I’m seeing more and more new patients who say they’re using buprenorphine intravenously. This past month, I’d estimate that a fourth of the patients who use buprenorphine illicitly are injecting it. Only a few said they snort buprenorphine.

This presents a big wrinkle to the treatment process.

I see why people use intravenous buprenorphine. It has low sublingual bioavailability, at around thirty percent. That means injecting two or three milligrams gives the same blood level as eight milligrams sublingually. In the short term, people injecting buprenorphine feel like it saves them money. In the long term, I’m certain it will cost more than they can imagine.

Buprenorphine tablets and films were not designed to be injected. Pills and films have fillers in them, and they aren’t sterile. Heating a mixture prior to injection will kill off some of the bacteria, so that’s a harm reduction practice. Using a filter can remove some of the particulate matter, also reducing the potential for harm. However, heat and filters can’t remove all the risk of injecting.

People on the internet insist the bioavailability of snorted buprenorphine is higher than sublingual use, but I doubt that. Either way, you bypass the liver because it crosses to the bloodstream via the veins of the nose or tongue. Plus, alkaline environments increase absorption and bioavailability for this drug, and the mouth is more alkaline than the nose.

Of course there is another reason people with opioid use disorder inject or snort their medication. Their brains associate the act of injecting or snorting with pleasure and euphoria, and can become addicted to the process and feeling of both means of ingestion.

Due to the ceiling on buprenorphine’s opioid effect, it is… arguably… one of the safest opioids a person could inject. But intravenous use is never safe.

Here’s only a partial list of complications from intravenous drug use:

  1. Overdose resulting in death, brain damage from low oxygen, stroke or heart attack from prolonged low oxygen
  2. Pulmonary edema (lungs fill with fluid)
  3. Skin abscesses and cellulitis
  4. Endocarditis (infection of heart valve that is life-threatening)
  5. Deep vein thrombosis (blood clot)
  6. Septic thrombophlebitis (infected blood clot)
  7. Contracting infections: HIV, Hep C or B
  8. Bacterial infections and abscesses in weird places like the spine, brain, joints, spleen, muscles, or eye
  9. Necrotizing fasciitis – rapid, “flesh- eating” infection, also botulism
  10. Pneumonia
  11. Septic emboli – when infected clots break off and go to the lungs, brain from infected heart valves
  12. Fungal blood/eye infections – (seen frequently when pills mixed with saliva are injected)

I have seen patients with every one of these complications. Most of them were in the distant past, when I was an Internal Medicine resident during the late 1980’s, but not all of them. Over the past six months, I’ve seen two patients with spinal abscesses from injecting drugs, though not necessarily buprenorphine.

The last time I posted about intravenous use of buprenorphine (November 2015), Dr. Wartenberg M.D. (pioneer in the addiction treatment field) wrote about the mitochondrial disease, which has caused liver failure, in European IV buprenorphine drug users. This disorder is specific to buprenorphine

So what are the treatment implications for a new patient who has injected buprenorphine?

First of all, these patients aren’t appropriate for office-based practices, even if the physician plans to prescribe the combination product with buprenorphine/naloxone. Clearly there are some patients who inject combination products and monoproducts. Granted, it’s less common, but it still occurs. There’s usually not enough oversight available at office-based practices to treat more complicated patients. I think they should be referred to opioid treatment programs, where they can be offered treatment with methadone.

What if the patient refuses methadone for some reason, or their risk with methadone is at too high from a medical view? Should patients with a history of injecting buprenorphine ever be treated with buprenorphine?

I think they can be – with great caution and daily dosing, on-site at the opioid treatment program.

At our OTP, we ask all buprenorphine patients to sit in a designated area while their dose dissolves. It usually takes around ten minutes, and they are watched by program personnel. Before they leave, each buprenorphine patient shows one of the staff their mouth, to show the medication is completely dissolved. It does feel a little “police-y” but we had a high incidence of diversion until we started this close observation.

If a patient tries to spit out their medication, they meet with me. I’m rarely willing to continue to prescribe buprenorphine if it appears they are trying to divert their medication. I meet with the patient and we discuss the option of methadone. If they refuse methadone, we try to refer them to another form of treatment.

If a patient with a history of injecting buprenorphine wants treatment with buprenorphine, I tell him I’m willing to give it a try, but that he can’t expect take home doses for a very long time, after months of observed dosing and stability. So far, this approach seems to be working. These patients are getting counseling, and haven’t attempted to divert their medication, so far as we can see. I’ve checked these patients for track marks, which in all cases appear to be healing, with no new marks.

When/if to grant these patients take homes remains a huge question. I don’t want to unduly burden a patient by insisting he must come every day forever, but I also don’t want to give the patient take home doses that could lead to a relapse back to intravenous use.

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.

Update on Suboxone Films

In the past, I’ve blogged about how some of my patients were having problems with their Suboxone films. When they opened the foil packets, the films were broken into pieces or so fragile they broke when handled. But now over the last two or three months, my patients tell me the films are no longer breaking or fragile, making them easier to use.

I’m glad. The Reckitt Benckiser drug company, manufacturer of Suboxone, wants doctors to switch patients to film because it dissolves faster, is easier to use, is less dangerous to children because the package is so hard to open, and it’s less likely to be snorted. They also say it’s harder to divert and has less value on the black market. And they say tablets are more likely to trigger patients who were addicted to tablets.

There’s validity to much of that, but I believe the biggest reason they want patients to switch is because their patent on the film runs for at least seven more years. Call me cynical.

About half of my patients who tried the film didn’t like it. Nearly all were patients in good recovery, stable for months to years, and if they wanted to tablets rather than the film, I was OK with that. When the film became crumbly, a few more patients wanted to switch back to the tablets.

Now, I’m more enthusiastic about the films. I can prescribe the film with more confidence since they no longer crumble. I prefer to use the films for patients tapering off Suboxone. I know the drug company says the films (and tablets) shouldn’t be cut, but of course everyone has been cutting both. With sharp scissors, the films can be cut into equal and small portions, ideal for a gradual taper of the dose.

I have more success with tapers in patients taking the film. In my next blog, I’ll talk about some of the “recipes” for taper my patients and I have used.