Rapid Induction Therapy for Opioid-Use Disorder Using Buprenorphine Transdermal Patch: A Case Series



 

Daniel Saal, MD1; Frank Lee, MD1

Perm J 2020;24:19.124 [Full Citation]

https://doi.org/10.7812/TPP/19.124
E-pub: 03/13/2020

ABSTRACT

Introduction: Opioid dependency is a major epidemiologic problem with profound morbidity and mortality. Despite the availability of effective treatments, there are often overwhelming barriers to those treatments.
Case Presentations: We present a case series involving a novel approach to the induction phase of buprenorphine or buprenorphine-naloxone therapy using transdermal buprenorphine. This approach has been demonstrated in inpatient settings but has not been widely explored in the outpatient setting. We demonstrated that a range of patients, from the highly medically complex to relatively straightforward cases, benefited from this approach.
Discussion: We believe that this approach can be used in a wide range of patients to transition from opioid use to buprenorphine therapy without the patient having to experience withdrawal or wait to start treatment. This should reduce the risk of lack of return for follow-up as well as decrease the dropout rate caused by patients being unable to tolerate withdrawal symptoms.

INTRODUCTION

Opioid dependency is a serious, life-threatening, and costly problem. There are highly effective tools for treating and managing opioid dependency, but there are major barriers to getting patients to a stable regimen of treatment. One of the best approaches for many opioid-dependent individuals is buprenorphine or buprenorphine-naloxone maintenance therapy.1

Buprenorphine is a partial agonist with a high affinity at the µ receptor. As such, if a person is currently intoxicated with opioids and ingests buprenorphine, that individual will go into precipitated withdrawal. This is a particularly acute problem in those who are using longer-acting opioids such as methadone.2 Precipitated withdrawal symptoms are not only uncomfortable but also often scare the patient away from further treatment with buprenorphine-naloxone and eliminate this viable path to a greatly improved life.3 There is also concern on the part of clinicians that they will have to manage precipitated withdrawal, affecting the likelihood that they will offer buprenorphine to their patients. To avoid this phenomenon, patients must be no longer taking opioids or be in substantial withdrawal before starting buprenorphine therapy.

Often, during the attempt to have the patient enter moderate opioid withdrawal to be induced with buprenorphine-naloxone therapy, the severity of opioid withdrawal symptoms leads to opioid relapse. The relapse event has a high risk of accidental overdose.4 Paradoxically, the attempt to treat the condition may actually increase the mortality risk. Hence, a more reliable and safe method for induction therapy is needed.

Kornfeld and Reetz5 published the idea of using a buprenorphine transdermal patch to “induce” patients in the inpatient setting to buprenorphine treatment. There is an additional case report on inpatient induction therapy with transdermal buprenorphine by Raheemullah and Lembke6 in 2019. We have used variants of these protocols in a number of cases in both the inpatient and outpatient settings.

The following is a summary of 5 of those cases. Our goal in presenting these cases is to encourage the use of this approach. It is our belief that this approach to induction obviates the need to have a patient in withdrawal to start buprenorphine treatment. It also opens the possibility of starting a buprenorphine regimen at the point of intake even if the patient has used opioids in the parking lot on the way into the clinic. This approach will allow a more comfortable transition, will decrease the likelihood of patients avoiding the withdrawal process and not attempt to get on a buprenorphine-naloxone regimen, and will allow us to treat individuals who cannot emotionally or physically tolerate withdrawal. Furthermore, it will allow induction therapy to start immediately after the patient presents to the physician regardless of the patient’s withdrawal status.

The goals of the approach are as follows:

•  more successful buprenorphine-naloxone induction dosing

•  reduced number of failed attempts for induction therapy

•  reduced precipitated withdrawal symptoms during induction therapy

•  reduced risk of precipitated withdrawal relapse and accidental overdose.

This report is important because it presents this approach to buprenorphine induction therapy in both the inpatient and outpatient settings. Most inductions of buprenorphine treatment are performed in the outpatient setting.

CASE PRESENTATIONS

Case 1

A 63-year-old woman with spinal muscle atrophy was bedbound, had a tracheostomy, and used a percutaneous endoscopic gastrostomy (PEG) tube for feeding. She was dealing with a bedsore and associated osteomyelitis that had not healed because of her lack of mobility. The patient was receiving hydromorphone, 4 mg every 3 hours, via the PEG tube and fentanyl, 100 µg/d, via a patch to manage her ongoing pain. However, the palliative care team noted that she was overusing her opioids and had at times in the past had multiple practitioners supplying opioids, and the team members realized she had an opioid-use disorder. On a deeper review of the medical record, it was noted in 2003 that the patient had a history of “alcohol abuse” (term used by the patient at the time) resulting in liver damage. Also noteworthy was that in 2003 she was assaulted by her reportedly intoxicated husband while she was wheelchair bound.

The treatment team (palliative care, addiction specialists, and a standing group that reviews cases) convened and then met with the patient to offer a pain management plan that would be safer in opioid exposure and less likely to cause continuing and increasing opioid tolerance. It was clear that she had a substantial opioid-use disorder. Furthermore, in the case of a patient who may ultimately die of respiratory failure, ongoing full-agonist opioids are not an optimal approach. The team implemented the management plan in the hospital (Table 1).

In this case we used a relatively high-dose buprenorphine patch (20 µg), beginning on day 2, because the patient was on a notably high morphine milligram equivalent at the start of the induction phase. The patient’s dose of hydromorphone was reduced on day 2 to 4 mg every 4 hours and continuously tapered every day thereafter. Sublingual buprenorphine was added to the regimen on day 4. By day 8, the patient was able to remove the buprenorphine patch and to discontinue hydromorphone therapy. The patient remained stable on a regimen of buprenorphine-naloxone sublingual film and tapered the dose from 16 mg to 12 mg at 6 months after induction.

This patient did remarkably well over the longer term. One of her home care physicians noted:

I am pleasantly shocked that she is doing so well. A social worker following her [up] from home health just checked in yesterday and notes a large difference in her well-being on buprenorphine-naloxone. [Another home care physician] was also equally shocked. I am so glad we did this.

Case 2

A 58-year-old married man with a history of alcohol addiction from his 20s to his 50s presented to our addiction medical clinic in 2012. He had an average daily intake of 20 to 23 of the hydrocodone-acetaminophen tablets (10/325 mg), which were prescribed for his foot and leg pain. We had him go through the standard withdrawal and induction protocol for buprenorphine-naloxone. He started at a daily dosage of 8 mg and 2 mg, respectively, but because he was taking carbamazepine (Tegretol) and likely was not getting enough effect from the buprenorphine-naloxone, the buprenorphine-naloxone dose was raised to 16 mg daily. He remained in remarkably stable condition for 5 years.

In late 2017, he fell off a ladder and fractured his foot. His foot required surgical repair with hardware placement, and the surgical team stopped his buprenorphine-naloxone maintenance therapy and went back to full-agonist opioid therapy. Subsequently, his physicians were unable to wean him off the morphine and oxycodone-acetaminophen for more than 6 months. The physicians managing his pain medications asked for our help. At the time the patient was taking 1 oxycodone-acetaminophen tablet (10/325 mg) daily and morphine at a dosage of 15 mg twice a day. He had been attempting to taper off the opioid regimen but was having too much pain and withdrawal.

The patient was given a buprenorphine transdermal patch (10 µg/h) on day 1. The opioid-tapering plan, which was to begin on day 2, is shown in Table 2. However, the patient did not take the full dose of morphine on day 1 as recommended and had uncomfortable withdrawal symptoms. Specifically, the patient reported in a message to the prescriber that he had chills, low energy, and poor appetite. By later that day, however, he had taken 15 mg of morphine and was feeling better.

Ultimately the patient returned to his original buprenorphine-naloxone dosage of 8/2 mg twice daily. After the transition back to buprenorphine-naloxone, the patient reported in a scheduled phone visit that he was having “an amazing day” and later emailed.

Just an update, the [buprenorphine-naloxone] is working great. My pain is less than when I was on the morphine and [oxycodone-acetaminophen]. It’s unbelievable. My mood is better, and I can even walk better.

The patient continued to do well on buprenorphine-naloxone maintenance therapy and returned to his baseline in compliance. He continued to have mechanical issues and some pain in his foot but was not using opioids for more than 3 months. At that time, he had to return to the hospital for further surgery and was restarted on an opioid regimen.

Case 3

A 56-year-old man had a long history of opioid dependency. He had been in prison for 20 years and after his release returned to heroin use. He entered a methadone maintenance treatment program and was given up to 30 mg of methadone daily when he decided to try to take buprenorphine-naloxone instead. By that point he had been receiving methadone for 3 weeks. He entered our clinic about 48 hours after his last dose of methadone. On the intervening days he had been using kratom (Mitragyna speciose), which has similar effects to opioids.

On examination, he was in minimal withdrawal, so we believed that a standard sublingual induction dosing might induce precipitated withdrawal. He was given a buprenorphine transdermal patch, 10 µg/h, on day 1. During the next 2 days, he continued to use both kratom and heroin but by day 3 reported that he was not having any feelings of withdrawal. Three days after applying the buprenorphine patch, we added 8 mg of oral buprenorphine-naloxone to the transdermal regimen. He reported stopping use of other opioids, which was confirmed by his urine tests (of note, we cannot test for kratom). On day 4 after starting to apply the patch (day 7 off the methadone regimen), he removed the patch and reported no withdrawal symptoms or cravings from that point. He has successfully been maintained on a sublingual regimen of buprenorphine-naloxone, 8/2 mg daily, with no ongoing issues (Table 3). As of 1 year of treatment, regular urine toxicology results have confirmed no other drug use.

Case 4

A 34-year-old single woman with a history of ankylosing spondylitis diagnosed at age 16 years was referred to the addiction medicine recovery program from our chronic pain treatment program. She had been started on opioid treatment after her ankylosing spondylitis diagnosis and had escalated her dose over time to a maximum regimen of fentanyl, 125 µg/d, transdermally and morphine, six 15-mg tablets daily. An attempt to taper her opioid doses was started at the pain treatment program, but the patient was not able to follow the plan. What triggered her referral to the addiction program was a pattern of inconsistent reports of her level of use, behaviors such as changing the fentanyl patches sooner than needed, and the use of cannabis. This pattern, combined with the team uncovering a history of inhalant abuse starting at age 10 years, indicated that she had a possible or likely substance use disorder.

We met with the patient and decided to offer her buprenorphine. During the meeting, the patient gave a more consistent picture of her actual use at the time, which was fentanyl, 62.5 µg (the patient was cutting patches in half to allow daily application) and morphine sulfate, 7.5 mg twice a day. She had, in fact, self-tapered her dose but was also running out of medication because she had not informed her physicians of her actual use pattern.

Even though she had been receiving fentanyl, it was at a lower dose than in the first case in this series, and we believed that 10 µg/h of transdermal buprenorphine would be a sufficient starting dose. We were aware that we might need to increase the dose, but determined did not need to (Table 4).

By day 4 the patient reported that she had some limited body aches but was feeling better than expected. She noted on day 14 that she was “doing great.” On each of the subsequent appointments she noted that she was more energetic and could think more clearly than she had in a long time. To date, the patient is doing well in treatment and in her personal and professional life.

Case 5

A 72-year-old man with chronic abdominal pain had previously been in our buprenorphine-naloxone (Suboxone) maintenance program but decided to leave the program. He returned because he felt that he might have better pain relief from buprenorphine-naloxone. We had several discussions with the patient that we did not expect the buprenorphine-naloxone to relieve his abdominal pain unless it was caused by withdrawal. During his time away from our program, the patient was getting an opioid from an Internet supplier. We believe that the name and dose of the opioid was “tapentadol 100 mg.” However, given its unregulated path to the patient, it is not clear what he was, in fact, taking. We discussed with the patient that the interaction between an unknown opioid and buprenorphine-naloxone would be hard to predict. It was our suspicion that, if this was actually tapentadol, it would have opioid properties and, when mixed with sublingual buprenorphine-naloxone, could result in precipitated withdrawal. The protocol we used is described in Table 5.

The patient continued to have abdominal discomfort, which was treated with ondansetron. He was able to discontinue his opioid use.

19.124

DISCUSSION

The common theme of these cases is that we avoided weaning the patients off their opioids until they were comfortably on a buprenorphine regimen. This could be accomplished by slowly introducing buprenorphine during the course of 24 to 48 hours via a buprenorphine transdermal patch. This approach is not novel, but this is the first known published report in which the technique is proposed as a general method independent of setting and medical complexity. The patch eliminates the risk of precipitated withdrawal because it essentially internally cross-tapers the patient from an opioid to the buprenorphine. Mechanistically this is most likely because of the higher affinity of the buprenorphine and the slow entry into the patient’s body. As the buprenorphine diffuses through the skin, subdermal fat, into the bloodstream, into cerebrospinal fluid, and ultimately to the µ receptors, it slowly displaces the other opioids, occupies the receptor, and blocks further access to other opioids. By the time we taper the patient’s hydromorphone, hydrocodone, and oxycodone doses, there is a limited number of receptors for the full-agonist agents to bind to.

The lethality of opioid-use disorders need not be stated. Opioid replacement therapies greatly reduce that mortality. However, the first weeks of trying to get on a buprenorphine regimen are notably at-risk times for death.7

In the future, the use of transdermal buprenorphine to transition people from full-agonist opioids to buprenorphine or buprenorphine-naloxone may open the door to multiple applications that were previously very challenging or off-limits. The most common use would be in the buprenorphine-naïve, opioid-dependent patient who presents with too high a blood level of opioid to perform an induction at the time of presentation. For many of these patients we postpone the induction phase and hope that they will return in withdrawal so that we can perform an induction. For patients who have received buprenorphine in the past, we sometimes send them home to self-induce when they get into enough withdrawal. This approach often fails because patients are not always a good judge of when to self-induce or they simply change their minds in the face of the early discomfort of withdrawal. The potential exists to simply apply the buprenorphine patch in the office and then follow-up in the next 24 to 48 hours to initiate sublingual treatment with buprenorphine or buprenorphine-naloxone. Even if the patient continues to use opioids on those first and second days, the buprenorphine will gradually enter the body and displace the full agonists. Not only is this potentially more humane, but it also should reduce the lack of return for follow-up, which is a major issue.

Certain groups of patients in particular can benefit from this approach. Patients with chronic pain who experience terrible pain flares when they are no longer taking opioids also do not need to go through withdrawal to transition to buprenorphine treatment. This population is particularly sensitive to withdrawal and rebound hyperalgesia.

Future applications could also include opioid-dependent pregnant women who, to date, have typically been sent to a methadone clinic. Buprenorphine has been shown to be as good or better than methadone for the mother and newborn.8,9 However, the withdrawal experience in pregnant women is considered a risk for fetal distress. Although we found nothing in the literature about this to date, it is logical that transdermal buprenorphine could be used to transition from full-agonist opioids because this approach does not require a withdrawal phase. This could be a radically improved approach and would limit the risk of the transition of the patient to a methadone clinic. Often methadone is administered at a self-standing outside clinic so there is the risk of patients not presenting for follow-up. Starting buprenorphine in the clinic at the point of diagnosis would clearly improve compliance and reduce barriers to treatment.

Conclusion

The use of transdermal buprenorphine is not novel. We present an expanded approach to its use in a wide range of settings and with patients who range in medical complexity. Our cases demonstrate that the approach is generalizable to many different clinical situations. It is our hope that the approach described will lower barriers and increase access to a potentially life-saving and quality-of-life-improving treatment.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.

Acknowledgments

Kathleen Louden, ELS, of Louden Health Communications performed a primary copy edit.

Author Affiliations

1 Addiction Medicine Recovery Program, Santa Clara Medical Center, CA

Corresponding Author

Daniel Saal, MD ()

How to Cite this Article

Saal D, Lee F. Rapid induction therapy for opioid use disorder using buprenorphine transdermal patch: A case series. Perm J 2020;24:19.124. DOI: https://doi.org/10.7812/TPP/19.124

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Keywords: buprenorphine transdermal patch, opioid dependency, opioid-use disorder, rapid induction therapy

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