Posts Tagged ‘subutex’

Using High-dose Buprenorphine Induction in the Emergency Department for Patients with Opioid Use Disorder

In my last blog post, I talked about the new idea of micro dosing buprenorphine in patients who have not yet stopped using full opioids, to switch them to buprenorphine products without going through a time of opioid withdrawal.

I was surprised at the response to that blog. I now feel about micro dosing buprenorphine like I did about sex in high school: everybody but me seems to be doing it and they are having a great time. I’m envious.

In this blog post, I’m going to review a study of “high dose” buprenorphine induction done in an emergency department setting. This study was done on patients already in withdrawal, in contrast to the micro dosing studies.

This recent article, by Herring et al., describes the outcomes of patients with untreated opioid use disorder who were started on doses of buprenorphine that were higher than 12mg sublingual per day while in the emergency department. [1]

This study described 366 encounters of patients with opioid use disorder in the emergency department of one large urban hospital in Oakland, California. The study was done because the authors suspected that the usual buprenorphine induction, which takes several days, could discourage the most fragile patients. They felt an accelerated induction process that could achieve therapeutic buprenorphine blood levels within four hours, and that a quicker process could be more likely to engage patients in further treatment. They hoped to increase both the magnitude of withdrawal suppression as well as the duration.

As a side note, it’s important for emergency departments to provide treatment for opioid use disorder. We know that ED-initiated buprenorphine treatment is lifesaving and cost effective. All the following organizations have recommended ED initiation for opioid use disorders: the American College of Emergency Physicians, the U.S. Surgeon General, the National Institute of Drug Abuse (NIDA), and the Substance Abuse and Mental Health Services Administration (SAMHSA). Now that there is no requirement for an “X” number (as of April 2021), any physician with a DEA number can legally prescribe for patients. Some ER providers protest that they don’t have anywhere to refer these patients. However, many Emergency Departments with many referral options still don’t prescribe, as it is in my little town.

Of the patients in this study, 23% were homeless and 41% had co-occurring psychiatric diagnoses. Around 44% were black, and 15% Hispanic, and 54% of all the patients had no prior formal treatment for their opioid use disorder. The type of study was a retrospective chart review.

The patients were excluded from the study for certain criteria: those with recent methadone use, impending surgery, current intoxication with alcohol, benzodiazepines or other sedatives, post-overdose reversals, serious acute medical issues including kidney failure or respiratory distress.

Those not excluded were asked about time since last use. Patients had to be at least 12 hours from last use of heroin or fentanyl, 24 hours from last use of long-acting opioids, and 72 hours from last use of methadone. These patients were given a COWS (Clinical Opioid Withdrawal Scale) score and those scoring less than 8 were not dosed but were re-checked in 1-2 hours. Those scoring above 8 were given a first dose of 4-8mg of buprenorphine sublingually and re-assessed about 30-60 minutes.

Then patients either underwent standard induction or high-dose induction.

For patients who had improvement in their withdrawal symptoms and no barriers to same-day dispensed buprenorphine were given a total of 8-12mg in the emergency department and a prescription for 16mg SL per day until they could get a follow-up appointment. These were the standard dose patients.

High-dose induction patients were re-assessed 30-60 minutes after their first 4-8mg of buprenorphine, but then were given an additional 8-24mg every 30 minutes until relief of withdrawal or 32mg total. This protocol was done for patients with heavy opioid tolerance, scores of more than 8 after the re-assessment, and for patients who couldn’t reliably fill a buprenorphine prescription, whatever their reason might be. They were also sent home with a prescription for sublingual buprenorphine at a dose of 16mg per day until a follow-up appointment.

Precipitated withdrawal occurred in only .8% of these patients, a very low incidence. Nearly all those cases occurred within the first 8mg of buprenorphine given. Precipitated withdrawal was unrelated to high-dose buprenorphine. Median stay in the emergency department was only 2.4 hours, showing opioid withdrawal can be treated relatively quickly even under trying circumstances. None of the patients needed Narcan rescues, and there was no significant reduction of respiratory rate at doses higher then 28mg.

Three of the study patients had serious adverse events. One patient had diabetic ketoacidosis, and another patient returned to the ED in opioid withdrawal and had to be hospitalized for acute heart attack. None of these three events were felt to be due to buprenorphine, but I would have liked more information about whether that second patient could have had precipitated withdrawal. Some of the study patients were admitted to the hospital for treatment of medical illnesses that included infections such as abscesses and cellulitis, exacerbation of COPD (chronic obstructive pulmonary disease) and other conditions.

Between 10-18% of study patients did return to the ED if they were unsuccessful at accessing follow-up treatment with buprenorphine. I think that’s a remarkably low percentage. This shows this team of providers did a great job at referring patients.

The authors concluded that present dosing guidelines requiring multi-day buprenorphine inductions are unduly burdensome, particularly for patients who are homeless or have few financial resources to access treatment.

They felt the high-dose protocol was shown to be safe, at least for patients without serious illness or sedation from other drugs. The patients’ opioid withdrawal was addressed quickly and didn’t take much time to achieve, with an average stay of 2.4 hours in the ED. They felt this method of accelerated dosing helped removed barriers to treatment and that a higher dose lasted longer and extended the duration of action of buprenorphine.

I wish all ED providers could read this study. They might become convinced opioid use disorder can be treated without extreme burden on their time, with significant rewards.

I did have a few thoughts about the study.

I wish the authors would have told use what the primary opioids of use were in these patients. I suspect it was mostly heroin or fentanyl or both, but that data wasn’t included. If the primary opioid patients had been using was oxycodone or some other short-acting opioid, it could make a difference in the results.

Many patients were excluded from the high-dose option, so the degree of safety shown in this study may not apply to the type of patients that were excluded. For example, patients who received Narcan after an overdose were not included, and neither were patients who were using alcohol or benzodiazepines. The patients who are revived from an overdose may be the most important ones to get into treatment the quickest, since a history of opioid overdose is the leading predictor of future fatal overdose. This study doesn’t help us with this set of patients.

I’m appreciative of the study authors and I think this is an important study that supports induction of buprenorphine in selected patients who come to the Emergency Department for care.

  1. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781956

New Form of Suboxone: Dissolving Film

Yesterday the FDA approved a new delivery system for the medication buprenorphine. Reckitt Benckiser, the drug company that makes the brands Suboxone (a combination pill of buprenorphine and naloxone) and Subutex (containing only buprenorphine), is now approved to manufacture and sell Suboxone in the form of a thin film that is placed under the tongue to be absorbed. According to early studies, patients think the film tastes better, dissolves more quickly, and is easier to use. I don’t yet have any information on the relative cost of this new film.

Since it was just approved, it’s not likely that a generic form of the film will be available for many years.

 This film of buprenorphine, the active ingredient, can’t be obtained as a generic, and it may be a few weeks before it appears in retail pharmacies.

 I’m hoping the sublingual (under the tongue) film will be harder to snort or inject, because there are reports of addicts misusing the Suboxone and Subutex tablets. And every addict misusing the name brands or the generic of buprenorphine who comes to the attention of law enforcement endangers the existence of the buprenorphine program.

 In the past I worried about prescribing Subutex, the form of the drug that doesn’t contain naloxone, or the newer generic buprenorphine, which also doesn’t contain naloxone. But apparently, some addicts are able to inject Suboxone, and the naloxone in it doesn’t put them into withdrawal. At least, they don’t go into intolerable withdrawal.

 It just shows me again that people are so different in the way they react to medications.