(55) Fentanyl to Buprenorphine < 24 Hours - Rapid Microinduction Buprenorphine Initiation

Background & Introduction: Buprenorphine is first-line treatment for opioid use disorder. Low dose initiation protocols (AKA micro-induction) were developed to help patients initiate buprenorphine often in the setting of prolonged and protracted fentanyl use which alters fentanyl pharmacokinetics such that standard induction protocols are associated with higher rates of precipitated withdrawal. Typical low-dose initiation is completed over several days (range of 4-8 days) where buprenorphine is slowly titrated up from sub milligram doses. We hypothesize that low-dose initiation can be completed in many patients much quicker than the several days current protocols and have developed a ‘rapid’ low-dose initiation for patients that are not concomitantly receiving full opioid agonists and have usually had 12 hours since last fentanyl use. This protocol is useful for patients that don’t want to continue using other opioids during micro-induction or where time does not permit slower administration over days and where getting the patient fully onto a ‘blocking’ dose of buprenorphine is priority (e.g., history of opioid use despite buprenorphine). It prompts the question on balance of appropriate dose and rate of buprenorphine administration to avoid precipitated withdrawal -perhaps we can go much quicker than the several days most low-dose initiation protocols employ?

Case Description: 38-year-old female with use of counterfeit oxycodone tablets containing fentanyl is seen in an outpatient addictions treatment clinic. She has prior experience of precipitated withdrawal with standard initiation of buprenorphine and has heard the clinic offers “micro-induction” initiation. She is concerned she might have to continue using until she is at the right buprenorphine levels (per “Reddit”). UDS is positive for fentanyl and THC. She is started on buprenorphine using a rapid low-dose initiation which she tolerates well, after an initial delay of 24 hours due to insurance issues. She is maintained on 8/2 mg SL BID.

38-year-old G5P4 woman is at 32 weeks gestation. She has a history of intranasal fentanyl use up to 10 x daily and has had intermittent prior treatment with buprenorphine. She’s also experienced precipitated withdrawal but agrees to rapid low-dose initiation after initially telling nursing she was concerned she would need to leave to use to self-treat withdrawal. A rapid low-dose initiation is completed on the Obstetrics unit approximately 36 hours prior to a successful delivery (expedited due to maternal complications non-related to buprenorphine initiation). She tolerates the 300 mcg x 2, 1/0.25 mg x 2, 2/0.5 mg x 1 to 8/2 mg SL BID each two hours apart without experiencing withdrawal symptoms or other adverse effects from buprenorphine.

24-year-old male with history of IVDU and fentanyl/cocaine dependence presents to the hospital with cellulitis and undergoes a rapid micro-induction initiation of buprenorphine about 12 hours after his last fentanyl use. He has mild opioid withdrawal symptoms that he says are not from precipitated withdrawal but from standard fentanyl withdrawal. These dissipate as his buprenorphine is increased to 8/2 mg SL TID.

30-year-old M with polydrug dependence including opioids with intermittent buprenorphine treatment in the past presents to the hospital after an ATV crash. A standard low-dose initiation is planned after he receives escalating doses of full agonists in the ED and in the Trauma ICU but he refuses the buprenorphine. On HD 4 he abruptly decides to stop the full agonists and asks if he can, “get on buprenorphine before leaving the hospital.” He completes a rapid low-dose initiation which was completed four days after last fentanyl use (“1-2 bundles/day”) and 12 hours after last full agonist use of oxycodone 30 mg PO q 4 hours. After initiation of buprenorphine, he decides to stay and continue to receive care in the hospital.

Conclusion & Discussion: We describe four patients that tolerated a protocol involving a fixed escalation of buprenorphine that involving giving two doses at each level two hours apart (300/300/1/1/2 mg doses) before escalation up to either 4/1 mg SL QID or 8/2 mg SL BID or TID depending on the patient response and request. The outpatient started with 250 mcg (1/8th of a 2/0.5 mg film) followed by 500 mcg (1/4), 1 mg and then full 2 mg film each given two hours apart x 2 except the 2 mg film which the patient took once before escalating to 8/2 mg dosing. While comparison to standard low-dose initiation should be performed this protocol is particularly useful when rapid titration up to full buprenorphine dosing is the goal and the patient or setting is not ideal for continuing full opioid agonists concomitantly, as is typically done during standard micro-induction protocols over several days. Emergency Department patients may be particularly ideal candidates to initiate a rapid low-dose initiation protocol so they are at full dose prior to discharge yet the dosing does not become a resource burden keeping patients in the Emergency Department for prolonged administration periods.

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2.) Silverstein SM., Daniulaityte R., Martins SS., Miller SC., Carlson RG. "Everything is not right anymore" Buprenorphine experiences in the era of illicit fentanyl. Int JU Drug Policy. 2019 December; 74: 76-84.

3.) Schult R., Maynard KM., Corelli JM., Rapport S., McKinney B., Clarkson T., Wiegand TJ., Malcho J., Acquisto NM. Low-dose initiation of buprenorphine in hospitalized patients on full agonist opioid therapy. A retrospective observational study. Journal of Addiction Medicine. 2023 Aug 18. doi: 10.1097/ADM. PMID: 37594850.