#22 Low Key Pearls for Low Dose Bup

September 14, 2023 | By Era Kryzhanovskaya

Audio

Video

With Amelia Goff FNP and Eleasa Sokolski, MD

Accelerate your knowledge on low-dose buprenorphine starts for individuals with opioid use disorder. We cover the physiology of how low-dose starts work, different 4-7 day protocols, and how to troubleshoot challenges patients may face.  We’re joined by Dr. Eleasa Sokolski, MD (Oregon Health and Sciences University) and Amelia Goff, MSN, FNP (Oregon Health and Sciences University).

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Production Partner: ACAAM

The Curbsiders Addiction Medicine are proud to partner with  The American College of Addiction Medicine (ACAAM) to bring you this mini-series.  ACAAM is the proud home for academic addiction medicine faculty and trainees and is dedicated to training and supporting the next generation of academic addiction medicine leaders. Visit their website at acaam.org to learn more about their organization.

Show Segments

• Intro, disclaimer, guest bio:  0:55
• Guest one-liner: 5:10
• Case from Kashlak: 9:05
• Buprenorphine and fentanyl:  10:20
• Methods to start buprenorphine: 16:00
• 4-day low-dose buprenorphine protocol:  18:20
• Buprenorphine formulations: 22:30
• Counseling patients on low dose start: 26:10
• Patient population considerations: 28:20
• Troubleshooting;  30:15
• Outpatient low dose starts:  36:55
• Take Home Points:  45:14
• Outro:  50:48

Low Dose Buprenorphine Pearls

1. Fentanyl is lipophilic, and individuals with heavy, regular use who want to start buprenorphine may need to wait longer periods (> 24 hours) before initiating their first dose to decrease the risk of precipitated withdrawal.
2. Low-dose buprenorphine starts generally occur over 4 – 7 days: Slowly introducing buprenorphine while continuing the full-agonist opioid allows individuals to transition to buprenorphine without experiencing severe withdrawal. 
3. Low-dose buprenorphine starts may work well for patients who have previously experienced precipitated withdrawal, have acute pain management needs, or have not successfully transitioned to buprenorphine using traditional protocols. 
4. Be sure to counsel patients that you will manage their withdrawal and cravings during the low-dose process, as well as explain the rationale behind the protocol
5. Many different low-dose protocols can be used in the hospital and outpatient setting.  Check with the hospital formulary to see which buprenorphine products are available for use. 
6. In the outpatient setting, due to regulations, most patients will need to cut sublingual films or tabs of buprenorphine for the low-dose protocols.
7. If an individual is having challenges with the low-dose protocol, consider slowing down the protocol (e.g., repeating a day) or consider increasing the full agonist opioid. 
8. In the outpatient setting, try to provide patients with written instructions, and provide frequent touch-points. 

Low Key Pearls for Low Dose Bup – Notes

Buprenorphine Pharmacology

Buprenorphine is a partial agonist, with high affinity at the mu-opioid receptor. As such, if someone with physiologic opioid dependence takes buprenorphine when a full agonist opioid is still in their system, it can cause precipitated withdrawal as the buprenorphine will displace/”kick off” the full opioid agonist due to its higher binding affinity. 

Individuals regularly taking non-prescribed fentanyl often need to stop using it for a longer period of time than other short-acting opioids, because it has lipophilic properties (Shearer, 2022). Due to its lipophilicity, fentanyl sticks around in the body longer and there may be more time needed to allow fentanyl to leave the body before initiating buprenorphine in some patients (Varshneya, 2022). A three-compartment model can be used to describe plasma fentanyl decay as its distribution goes between the plasma (central compartment), organs/tissues (peripheral distribution compartment), and adipose (deep distribution compartment) (Encinas, 2013). 

In Dr. Sokolski’s expert opinion, patients using fentanyl regularly are at higher risk of precipitated withdrawal if they take buprenorphine within 24 hours from their last use, but some patients may need to wait 48-72 hours after their last fentanyl use before taking buprenorphine. 

More research is needed in this area. Based on urine drug testing, it can take an average of 7.3 days for fentanyl to clear from a urine drug test. For its metabolite norfentanyl, average clearance times can be even longer – 2 weeks on average (Huhn, 2020). 

Starting Buprenorphine for Opioid Use Disorder

There are three ways to start buprenorphine, the traditional start, low-dose start, and high-dose start. Traditional buprenorphine starts involve stopping the full agonist opioid and waiting for generally moderate withdrawal symptoms before taking the first dose of buprenorphine. In patients who are unable to stop full opioid agonists, such as individuals being treated for acute pain, low-dose initiation of buprenorphine is another option to avoid periods of withdrawal. Using this low-dose approach, low doses of buprenorphine are administered and slowly increased each day while the full opioid agonist is continued.  

Types of Low-Dose Buprenorphine Initiations

Low-dose starts work by slowly introducing small doses of buprenorphine that increase over several days, and continuing the full agonist opioid during that time (De Aquino, 2021). Once an individual reaches a therapeutic dose of buprenorphine the full opioid agonist is stopped. Keeping both the full opioid agonist and buprenorphine on at the same time helps prevent opioid withdrawal, opioid cravings, and provides the ability to manage acute pain. 

There are a number of different low-dose protocols for initiating buprenorphine. They vary in length and the types of buprenorphine formulations used (Cohen, 2021). Dr. Sokolski and Amelia Goff, FNP utilize a 4-day low-dose protocol in the hospital setting as their protocol of choice (Sokolski, 2023). See the infographic below. Of note, in the OHSU protocol, the patch can be–and often is, in expert opinion–removed on day 4.  On the last day, the patient can go to whatever buprenorphine dose is effective for them (up to 32mg of buprenorphine). The benefit of a 4-day protocol is that it may make it more feasible to complete this process during a hospital admission, compared to a 5-7 day protocol.

Buprenorphine Formulations

The choice of buprenorphine formulation to use for low-dose starts often varies depending on what is available on hospital/local formularies and insurance coverage. Below are the different formulations of buprenorphine, along with references of low-dose buprenorphine protocols that can be utilized with each formulation

• Buccal: dissolves in the cheek, FDA-approved for chronic pain, often expensive (Adams, 2023, Weimer, 2021)
• Patch: FDA-approved for chronic pain and changed Q7 days. Reaches steady state around day 3, often expensive (Sokolski, 2023, De Aquino, 2021). In the OHSU protocol, the patch can be and is often removed on day 4. 
• Intravenous: can be available in some hospital settings (Murray, 2023, Thakrar, 2022)
• Sublingual films or tablets: commonly available, may require patients to cut the films or tabs. Different hospital pharmacies may not allow for the cutting of these medications (Brar, 2020)

Counseling Patients on Low Dose Initiations

Start by discussing how withdrawal and pain will be addressed while starting buprenorphine. Be sure to offer adjunctive medications such as clonidine, loperamide, and hydroxyzine. Dr. Sokolski likes to use an analogy to explain the process to patients. She describes a traditional start as jumping out of a 3rd story window: you need to wait, then all of a sudden after the jump and withdrawal symptoms start, you are given a high dose of buprenorphine. A low-dose start is more like walking down the stairs to the first floor: a much more gradual, “step-wise” transition. For some patients, the window analogy can be triggering to previous trauma or experience; consider phrasing around jumping into a cold lake (precipitated withdrawal) versus gradually dipping toes into the lake (low-dose start). 

Amelia likes to use the car analogy. It’s like you are driving in a super fast car at 100 mph. Using a low dose start is like slowly lifting your foot off the gas pedal until you get to a speed that is comfortable: A gentle process. This is in contrast to what happens in precipitated withdrawal: Taking a too-high dose of buprenorphine while on full-agonist opioids is like slamming on the brakes and having your body lurch forward with the sudden deceleration from full agonist to partial agonist opioid. 

Patient Population Considerations

In Dr. Sokolski’s expert opinion, for individuals on more than 80mg of methadone, low-dose starts are worthwhile AND may be more challenging. In these patients, opting for a longer low-dose protocol such as over 7- 10 days may be preferred.  In addition, patients who are using a lot of non-prescribed fentanyl may have a more challenging time starting buprenorphine in general, and need extra attention and care in using the low-dose protocol as well. Furthermore, some patients just want to get on buprenorphine quickly, particularly those who are only on regulated short-acting opioids, who can generally wait 12 hours and complete a traditional buprenorphine start. 

Patients who are expected to have a shorter hospital stay (i.e., days-long instead of weeks-long) may be better served by a rapid low-dose protocol to ensure that they reach a therapeutic dose of buprenorphine prior to discharge. 

*Using low-dose buprenorphine initiations for birthing people who have opioid use disorder is an area of ongoing research and deserves increased study informing more nuanced recommendations.*

Some individuals may benefit from injectable, extended-release buprenorphine. This first requires stabilization on sublingual buprenorphine at doses of 8mg or higher. Low-dose, traditional, or high-dose buprenorphine protocols can all be used as a bridge to extended-release buprenorphine. 

Troubleshooting low-dose initiations 

Dr. Sokolski highlights that in the 4-day protocol, day 3 can be challenging as it requires frequent nursing care. She highlights that nursing communication is key to avoiding missed doses. If someone does miss some of the does, they will repeat that day of the protocol. Be sure to involve stakeholders to make this protocol successful in the hospital. Get buy-in from nursing, pharmacists, and clinicians. Be sure to provide education to any interprofessional team members that are involved in this process. Consider approaching this with a quality improvement mindset as well as building a protocol or order set within your EMR to help facilitate.

Amelia highlights that it’s important to control opioid withdrawal and cravings during this process. One option is to increase the dose of the opioid agonist, utilize adjuncts (clonidine, hydroxyzine, trazodone, ondansetron, tizanidine, etc), or slow down the buprenorphine protocol. Address fear and anxiety that patients may be experiencing in the hospital. 

Low dose starts in the outpatient setting  

Low-dose protocols can be done in outpatient settings (Brar, 2020) including via telehealth as an option to start buprenorphine. However, unlike the hospital setting, full opioid agonists cannot be prescribed for OUD in the outpatient setting per the Harrison Narcotic Tax Act. This means patients will continue using non-prescribed opioids during the low-dose initiation. There are also limitations with which buprenorphine formulations can be utilized in the outpatient setting. Since the buprenorphine patch and buccal tablets are not approved for the treatment of OUD they cannot be used in the outpatient setting strictly for the low-dose starts. 

When doing outpatient low-dose starts, patients are often counseled to split tablets or cut films for the lower starting doses (Reindel, 2019). Partnering with pharmacies can be helpful in developing bubble or blister packs containing the appropriate buprenorphine doses to complete a low-dose protocol (Accurso, 2021). 

When this isn’t possible, it’s helpful to provide written patient instructions. Consider asking them to check off the steps needed each day.  During the low-dose protocol, try to follow up with patients as often as your clinic can. Daily touch points with a staff member (nurse, pharmacist, peer recovery specialist, etc..) are ideal. At a minimum, checking in on day 3 or 4 is recommended. 

Take Home Points

• Be sure to adequately treat acute withdrawal, cravings, and pain for patients with opioid use disorder during their hospital stay who are undergoing a low-dose buprenorphine initiation
• It is important to educate patients on the low-dose protocol and pharmacology of the process. Involving patients in the process is important for building trust. 

Links

1. Project ECHO – Oregon; Oregon ECHO Network is opening up their Substance Use Disorders in Hospital Care – ECHO (oregonechonetwork.org) for national participation; fall program starts 9/13/23, winter and spring programs are also open to participants across the US. 
2. American Society of Addiction Medicine (ASAM)

Goal

Listeners will learn to utilize low-dose buprenorphine initiation in the treatment of opioid use disorder (OUD) in outpatient and inpatient settings. 

Learning objectives

After listening to this episode listeners will…

1. Recognize the spectrum of definitions of, approaches for, and evidence supporting low-dose buprenorphine initiations for opioid use disorder.
2. Identify patients who may be appropriate for a low-dose buprenorphine initiation. 
3. Develop an approach to deciding if a rapid or slower low-dose buprenorphine initiation would be most appropriate to discuss with a patient based on history and care settings.
4. Describe common challenges (and opportunities to overcome them) with low-dose buprenorphine initiation. 

Disclosures

Dr. Sokolski and Amelia Goff, FNP report no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Kryzhanovskaya E, Sokolski E, Goff A, Leyde S, Chan CA “#22 Low Key Pearls for Low Dose Bup with Dr. Sokoloski and Amelia Goff, FNP”. The Curbsiders Addiction Medicine Podcast. https://thecurbsiders.com/addiction September 19th, 2023