Best Practice of the Month
Low-dose Buprenorphine Initiation: What, Where, Why, How, and For Whom?

Buprenorphine is one of three medications approved for the treatment of opioid use disorder (OUD). It is a partial opioid agonist with a high binding affinity at the opioid receptor, so if a high dose of the medication is given too soon after opioid use, it will precipitate withdrawal. For this reason, buprenorphine initiation has traditionally been recommended:

  • 8–24 hours after last opioid use
  • Once an individual is in at least moderate withdrawal
  • With a first dose of 4mg to 8mg, which is titrated up over the course of 1-2 days

As fentanyl has become the predominant opioid in the illicit market in most parts of the country, concerns are increasing that the traditional dosing approach is causing precipitated withdrawal. Fentanyl is stored in fat cells, and chronic use leads to tissue stores and prolonged excretion from the body.[i] The current hypothesis is that this prolonged excretion among people who have been chronically using fentanyl may be causing more precipitated withdrawal.[ii],[iii]

 

What is low-dose initiation?

What is low-dose initiation?

Low-dose initiation (sometimes referred to as “microdosing”) is an alternative buprenorphine initiation approach in which an individual takes very low buprenorphine doses, which are titrated up to therapeutic levels over the course of multiple days. With this initiation method, full opioid agonists (including nonpharmaceutical opioids) can be continued as buprenorphine is initiated and titrated up. These small doses of buprenorphine will very slowly displace the full opioid agonist, which minimizes opioid withdrawal symptoms and avoids precipitated withdrawal.2

Where can low-dose initiation be offered?

Low-dose initiation can be offered in inpatient and outpatient settings.2,3

Why offer low-dose initiation?

Why offer low-dose initiation?

This approach avoids the need for an individual to be in opioid withdrawal prior to initiating buprenorphine and also minimizes the risk of precipitated withdrawal symptoms. Published data describing the frequency of buprenorphine-precipitated withdrawal in the era of a predominantly illicitly manufactured fentanyl supply are limited, but a recent study found that only 1 percent of patients initiated on buprenorphine in 28 U.S. emergency departments experienced precipitated withdrawal, despite high prevalence of fentanyl use.[i] However, fear and distress associated with opioid withdrawal can be a barrier for patients considering buprenorphine, so low-dose initiation can be a good alternative for some patients.3

 

How do you prescribe a low-dose initiation?

How do you prescribe a low-dose initiation?

Multiple protocols exist, and most vary from 3– 7-day overlap initiation protocols, meaning buprenorphine is initiated while the individual continues to use other opioids (including nonpharmaceutical opioids). This resource from CA Bridge describes 3- and 7-day cross-taper dosing schedules (see page 2), and this resource from New York State Office of Addiction Services and Supports provides a summary of 2 different outpatient protocols for low-dose buprenorphine initiation (see page 8). Note that both resources provide dosing protocols utilizing the buprenorphine transdermal patch; however, the buprenorphine patch is not Food and Drug Administration approved for the treatment of OUD and, therefore, is not legal to use for OUD treatment in the outpatient setting. Consequently, in the outpatient setting, film or tablet splitting is the most accessible and cost-effective method.2

For whom would you recommend low-dose initiation?

For whom would you recommend low-dose initiation?

Traditional buprenorphine initiation remains the clinical standard of care in most settings, but low-dose initiation can be particularly helpful when a patient has intolerance to withdrawal, and/or past buprenorphine initiation attempts have precipitated withdrawal. Low-dose initiation can be offered to any patient, but it is important to note that this approach requires daily dose changes and typically requires splitting films or tablets, which can be confusing. For this reason, the following considerations for outpatient settings are recommended: 2

  • Provide clear instructions with daily or near-daily check-ins with a member of the health care team
  • Provide a patient dosing guide/handout
  • If possible, partner with a pharmacy to provide a blister pack to help with a dosing schedule

A recent, retrospective, outpatient case series reported on the outcomes of 12 patients who were prescribed a low-dose buprenorphine initiation using a 3-4 day overlap protocol. Eleven patients (92 percent) picked up their prescription; 7 (58 percent) returned for follow-up; and, of those, only 1 reported any withdrawal symptoms, which were mild.3

In conclusion, low-dose buprenorphine initiation is an alternative to traditional dosing that minimizes risk of precipitated withdrawal and reduces opioid withdrawal symptoms. Although dosing can be confusing for patients, this can be mitigated through patient education, handouts, frequent check-ins, and pharmacy supports.

References

[i] Huhn AS, Hobelmann JG, Oyler GA, Strain EC. Protracted renal clearance of fentanyl in persons with opioid use disorder. Drug Alcohol Depend. 2020 Sep 1;214:108147. https://doi.org/10.1016/j.drugalcdep.2020.108147. Epub 2020 Jul 2. PMID: 32650192; PMCID: PMC7594258

[ii] Cohen SM, Weimer MB, Levander XA, Peckham AM, Tetrault JM, Morford KL. Low dose initiation of buprenorphine: a narrative review and practical approach. J Addict Med. 2022 Jul-Aug 01;16(4):399-406. https://doi.org/10.1097/ADM.0000000000000945. Epub 2021 Dec 23. PMID: 34954746

[iii] Suen LW, Lee TG, Silva M, Walton P, Coffin PO, Geier M, Soran CS. Rapid overlap initiation protocol using low dose buprenorphine for opioid use disorder treatment in an outpatient setting: a case series. J Addict Med. 2022 Sep-Oct 01;16(5):534-540. https://doi.org/10.1097/ADM.0000000000000961. Epub 2022 Feb 10. PMID: 35149614