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).
Claim free CME for this episode at curbsiders.vcuhealth.org!
By listening to this episode and completing CME, this can be used to count towards the new DEA 8-hr requirement on substance use disorders education.
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.
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).
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.
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.
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.
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.
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 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.
Listeners will learn to utilize low-dose buprenorphine initiation in the treatment of opioid use disorder (OUD) in outpatient and inpatient settings.
After listening to this episode listeners will…
Dr. Sokolski and Amelia Goff, FNP report no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
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
Producer: Era Kryzhanovskaya, MD
Show Notes, Infographic, Cover Art: Carolyn Chan, MD, MHS & Kenny Morford, MD
Hosts: Carolyn Chan, MD, MHS and Era Kryzhanovskaya, MD
Reviewer: Sarah Leyde, MD
Showrunner: Carolyn Chan, MD, MHS
Technical Production: PodPaste
Guest: Dr. Eleasa Sokolski, MD and Amelia Goff, MSN, FNP
Got feedback? Suggest an Addiction Medicine topic. Recommend a guest. Tell us what you think.
We love hearing from you.
Yes, you can now join our exclusive community of core faculty at Kashlak Memorial Hospital along with all the perks:
Close this notice to consent.