Injection of Transmucosal Buprenorphine Products

As I’ve said before on this blog, may people find my site by googling phrases like “inject buprenorphine,” so obviously people want information about that topic. I know what I’ve seen in my patients, but that’s anecdotal information, so I searched online for more scientific information.

Morbidity and Mortality Weekly Report, otherwise known as the MMWR, is published by the Centers for Disease Control and Prevention (CDC). In their August 14, 2020 issue, they discussed emergency department visits for complications from injecting buprenorphine products meant to be used sublingually (under the tongue). This formulation is the most frequently prescribed form of buprenorphine. [1]

The authors of the MMWR cited several studies pertinent to the topic. First, a study by Geller et al. looked at emergency department visits resulting from nonmedical use of prescription opioids. Of the 598 cases observed by one health system between 2016 to 2018, around one-third of those emergency department visits were for the treatment of intravenous use of sublingual buprenorphine products.

Of the patients who had complications from injecting buprenorphine products, two-thirds were male, and the average age was 33. Most of these visits (85%) involved the combination product buprenorphine/naloxone. In two thirds of the cases, patients were treated and released from the emergency department or left against medical advice, so most of these patients were not admitted to the hospital.

 In around a third of these patients, other non-pharmaceutical drugs were involved, such as cocaine or heroin.

In another study of one hundred and one emergency department cases of injection of buprenorphine products,  most of those patients had either skin abscess or cellulitis, but around 6% had serious infections such as endocarditis (infected heart valve), sepsis (blood infection) or septic arthritis (bacterial infection of a joint space). These last ailments usually require prolonged hospitalization and treatment with antibiotics.

The MMWR article concluded by saying buprenorphine is an important component of the public health response to opioid use disorders, and that patients may benefit from syringe exchange programs, information about infection prevention practices, and linkage to recovery support services.

I’ve written about the intravenous use of buprenorphine products in past blogs (January 15, 2017 and November 1, 2015). Clearly, medication meant to be used under the tongue is not safe to inject. This medication isn’t sterile, and besides the actual buprenorphine, there are fillers and other substances in the tablets and films that aren’t meant to be injected into veins. These substances can clog the veins, causing clots, or cause infections that can lead to abscesses.

For one thing, buprenorphine mono- and combo- tablets are made with a substance called “amidon” which is a starch that helps the tablet hold its shape. This substance appears to cause specific findings when injected through the skin into veins and may cause the inflammation and irritation we see in patients who inject this product.

So why do people inject buprenorphine? There are several reasons, chief among them being buprenorphine’s poor sublingual bioavailability. Injection of a drug means, by definition, that 100% of the drug makes it to the person’s bloodstream. Sublingual use of buprenorphine, either in the monoproduct or combination product form, has at best around 40% bioavailability. Patients buying buprenorphine on the street often feel that they are wasting money if they use tablets sublingually as the medication was intended and are tempted to inject buprenorphine to make it go farther.

But there are other reasons. Some patients get just as addicted to the “rush” of injecting as they do to the actual drugs. Some people feel a euphoria as soon as they start the act of injecting – preparing the needle, etc. – even before the drug is in their bloodstream. This yearning for intravenous use can be a difficult part of the addiction to defeat. I’ve had many patients in treatment who still feel an obsession to inject their buprenorphine, even though we could increase their sublingual dose to provide a therapeutic blood level.

As the information from MMWR shows, people are injecting both the monoproduct and the combination product, though the monoproduct has higher black-market value and is more desirable than the combination product.  As the study showed, 85% of the patients presenting to the emergency department after injecting buprenorphine used the combination product.

I’ve asked patients how they can inject a product that’s supposed to put them into withdrawal. Most of them shrug and say they still get a drug effect, and that if it makes them sick, it’s for a short time only. This puzzles me, since I was sold on the idea that patients could not inject the combination product without serious adverse side effects. Or maybe that’s why the people who injected the combination products went to the emergency department – they felt sick with precipitated withdrawal?

From the MMWR data, I conclude that injection use of buprenorphine occurs frequently. On the one hand, it’s probably safer then injecting heroin, now loaded with either pure fentanyl or various percentages of fentanyl and its analogues. On the other hand, injection of buprenorphine carries increased medical risk seen with any type of intravenous drug use, plus the tablets appear to be particularly caustic to veins and other soft tissues and can cause serious health issues.

At our opioid treatment program, we used to do observed dosing with buprenorphine products just like we do with methadone. Pre-COVID, we asked our patients to sit in a designated area while their dose dissolved. We did this so that patients wouldn’t be tempted to leave our facility with medication in their mouth then spit it out in the parking lot so that they could inject it.

I’ve had a few patients tell me that they were able to do this despite our precautions, and they got substantial infections. This is probably because ordinary human saliva contains some bacteria that causes big problems when injected into the bloodstream

Since COVID, we allow patients to leave our facility as soon as they place medication under their tongues, to reduce the time patients are exposed to other patients. However, if a certain patient has struggled with intravenous buprenorphine use in the past, I’ll ask that patient to stay in the dosing cubicle until he has completed dissolved the medication, so that he won’t be tempted to inject medication. And the patient won’t get take home doses until he makes significant progress in recovery, to the point he’s not at risk of injecting medication.

Upon admission, if a patient admits to past intravenous buprenorphine use, I’ll talk to that patient about starting methadone instead of buprenorphine. Methadone isn’t often injected, at least not for pharmacologic reasons, since it has such good oral bioavailability.

I do not think patients who inject buprenorphine products are appropriate for office-based treatment practices. I think those patients need to be referred to opioid treatment programs, where we have the experience and ability to address this situation. I know some good practitioners who disagree with me about this idea, feeling that any treatment at all is preferable to no treatment. I understand their thinking is based on harm reduction principles, but I also know that with other chronic medical illnesses, we refer the most complicated patients to specialists. The specialists at treating opioid use disorder should be found at opioid treatment programs.

After all, OTPs have been treating opioid use disorders with medication for decades, long before our recent opioid crisis.  I’ve come to realize that even office-based providers of buprenorphine rarely refer patients to OTPs. Incredibly, many office-based providers hold the same stigma towards OTPs as other medical professionals, and this needs to change.

But that’s a topic for a whole other blog.

13 responses to this post.

  1. Posted by soraya kamran on November 30, 2020 at 1:59 am

    “I think those patients need to be referred to opioid treatment programs, where we have the experience and ability to address this situation…..” Not sure it follows – does it not depend on the provider and the infrastructure around the provider? Unless I misunderstand. Some OTPs are just oral liquid mills as well – I think it depends on the program and existing ancillary support. I currently work in two OTP’s and I also provide OBOT both in person and telehealth, privately and in larger programs so I see it all. I think the advantages are the ancillary services…. but then again the daily engagement with people at various stages of treatment in OTP’s in itself can be harmful to recovery.

    Reply

    • Yes, I’d agree it does depend on the provider and support staff. If an OBOT provider can do daily observed dosing I guess that would serve well. But I don’t think most OBOTs can or will do that.

      Reply

  2. Posted by Stuart Gitlow on November 30, 2020 at 3:17 am

    If you go back in time to the point where the thought of adding naloxone to buprenorphine came about to reduce likelihood of patients injecting their sublingual buprenorphine, the original hypothesis called for a 4:1 ratio. This was then tested to determine that efficacy was no worse than that obtained with the mono product. After all the very expensive testing was complete, everyone (both at the pharmaceutical company and in the field) recognized from experience during the trials that the 4:1 ratio was insufficient to truly reduce injectable use. It really needed to be closer to 3:1, or perhaps even 2.5:1. But that would have meant redoing all the very expensive testing. So it didn’t happen. In the meantime, the manufacturer was very successful in promoting the bup/nal product as being “better” and “safer” than the mono product, so successful that guidelines were developed around it. As a result, physicians have prescribed the far more expensive bup/nal (and of course they have no choice, because if they don’t, they’ll find themselves in hot water either civilly or criminally) even though there’s really little advantage. The guidelines themselves are based upon a hypothetical that, from the very start, was known not to have actual support from the data.

    Let’s go on to the point you made about referring to OTP’s. There are many reasons OBOTs do not commonly refer patients to OTPs, but the primary one is the complete absence of any feedback from the OTP to the OBOT. At least in my area, each time we’ve referred patients to the OTP, we’ve never heard anything back. Did the patient get there? Did the doctor receive our information? Did they even appreciate the referral? Nothing. Every other doctor to whom I refer patients calls me up and we discuss the case. Not the OTP doc. Not ever. Not in any community I’ve worked in. Your point is well taken about referring patients who are found to be injecting their buprenorphine. However, I’ve never had a patient tell me he or she was injecting buprenorphine beyond the rare “I tried it once long ago,” and no lab test known will differentiate IV from SL use.

    Reply

    • Thanks Stuart for that history. Very interesting.
      Sounds like communication should improve in both directions. I do call OBOT providers, if only to let them know their previous patients have found their way to the OTP and to ask them for information. Sometimes I get to talk to the prescriber and sometimes I have to leave a message and don’t get called back.
      Sounds like we have silos within silos, not sure what the answer is, other than all of us using the common curtesy to pick up the phone.

      Reply

    • Posted by Zac Talbott on November 30, 2020 at 8:03 pm

      The lack of coordination between OTPs and OBOTs lays equally at the feet of both types of providers. Owning and operating OTPs across several states, we never once had an OBOT reach out to us. All but 1 in 1 town never returned our calls to collaborate around individualized patient needs. To lay the blame at the feet of OTPs alone doesn’t match the reality of my subjective experience nor those of the seven regional “stand alone” OBOTs I oversaw just this last year. The OBOT physicians in these 7 programs that treated more than 2600 patients across two states all overwhelmingly used words like “methadone” or “methadone clinic” with disdain and disgust (few even knew what an OTP was or that the majority of OTPs offer at least 2 of the 3 FDA-approved meds). They would have NEVER referred to an OTP, even after more than a year of education from people like – speaking of names in this thread – Dr Alan Wartenberg, who I brought in precisely because he is one of the most objective experts on the two medications when it comes to his equal praise AND condemnation of both.

      This is a problem with both OTP and OBOT providers, not an OTP problem as it is framed above.

      Reply

      • Posted by Stuart Gitlow MD on November 30, 2020 at 8:36 pm

        I’m starting to wonder if some of the problem might be a competitive perception. For my own practice, where I offer buprenorphine but not methadone (because I’m not an OTP), my partner doc and I view the methadone providers as being an essential part of the team. Some patients who don’t do well on buprenorphine might do better on methadone. We always refer them over, but I wonder if the docs who work for large companies providing OBOT services do the same, or if methadone providers who also provide buprenorphine would do the same. If the corporate concept is that the alternative is competitive, that might filter down to the docs.

        Similarly, it would help if lines of communications were more open. Outreach from the OTP (e.g. “Hi….we’re in your area, are open to patients, and here’s a phone number you can use to quickly reach us so you aren’t trapped in voicemail”) would be welcome. OBOTs could do the same with OTPs.

      • Posted by Zac Talbott on November 30, 2020 at 10:28 pm

        There is definitely an impact on both the OTP and OBOT models from the significant influx of mergers and acquisitions, especially by private equity and venture capitalist groups whose business model is grow, slim down, and flip for a profit in a few years. The “mom and pop” providers and shops – or folks in research/University/hospital systems – are also the ones that are most likely to be found in these comment sections. How do we spur these conversations across the country in OBOTs and OTPs that are a part of all different business models? Additionally, how do we finally put to bed the inaccurate notion of OTPs as “methadone clínics?” The vast majority of OTPs not offer methadone as well as Buprenorphine (to circle back to the main point of this post). These are the challenges that face our field. Additionally, we have to wrestle with the reality that explosive growth due to the opioid crisis, while great, has often outpaced the ability to recruit, train, and retain quality providers.

  3. Posted by Matthew McClure on November 30, 2020 at 3:49 am

    To echo Stuarts comment. The OTP’s near me won’t even take a physician referral. They don’t accept any information nor have I ever had one send me an ROI. If I call, ‘the patient has to call.’ They won’t even take down the information. If I request information I will get a MAR, but never any clinician notes.
    As far as expertise? Give me a break, any warm body with a degree is accepted here.

    Reply

  4. Posted by Alan Wartenberg MD on November 30, 2020 at 2:00 pm

    I am an “OTP doc”, as Stuart puts it (and hi, btw), and my problem is I never get return calls from internists, family physicians and others whom I very conscientiously reach out to, when they have information on my patients. The group of programs I work with (or rather worked, since I have left to enter lockdown) takes ALL physician referrals, and we send back notes when patients are, or are not admitted. Psychiatrists chief complaint about other physicians is that they never return phone calls or letters/emails, and other physicians’ chief complaint about psychiatrists is that THEY never return calls etc. If we had interconnected EHR systems, with appropriate privacy features, it would be a hell of a lot easier to communicate. Also, I have seen a considerable amount of injection of methadone in my 40 years in the business. While it does have very good oral bioavailability, it also has a 50% hepatic first pass, which is why parenteral doses are 1/2 of oral doses and vice versa.

    Reply

    • Posted by Stuart Gitlow MD on November 30, 2020 at 5:27 pm

      Hi, Alan! I think part of the problem is expectations. Back when we had written prescriptions, we had a direct phone number printed on the prescription so that the pharmacist, if he or she had any questions, would have their calls answered at once by the doctor. No voicemail, no waiting. I can’t tell you how many times I answered the phone only to have the pharmacist immediately say, “Oh, I got a wrong number,” and hang up. I’d call them back and they’d say, “I assumed it was a fake prescription because no real physician actually answers his office phone himself.”

      Reply

    • Thanks as always Alan for your input.

    • Does the sugar in liquid methadone interfere with injection?
      You mentioned you are in lockdown – hope you are OK and don’t have “the COVID”!!
    • Reply

  • Posted by Andre Benson on November 30, 2020 at 5:27 pm

    As I remember it, back in the early 70s the oral formulation of the analgesic pentazocine (Talwin) was not a controlled substance. It became an abused drug by iv injection. They made it a controlled substance but not surprisingly the iv use continued. They then added naloxone to the pentazocine (Talwin Nx) which stopped the iv abuse.
    Why was this approach with buprenorphine not equally effective?
    The affinity of buprenorphine for the mu opioid receptor is higher than the affinity of naloxone for the mu opioid receptor. I believe with pentazocine the naloxone affinity is dominant. Buprenorphine is known to have one of the highest affinities for the mu receptor. The manufacturer was aware of this and in their literature about buprenorphine
    they state that naloxone may not readily reverse bup overdose (or higher doses may be needed).

    Reply

  • “ I do not think patients who inject buprenorphine products are appropriate for office-based treatment practices. I think those patients need to be referred to opioid treatment programs, where we have the experience and ability to address this situation.”
    👏🏼
    Yes, yes, and yes. There’s a true need for better collaboration and coordination of care between OTPs and OBOTs, with referrals based on patient need and individualized situation going both ways.

    Reply

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