Opioid overdose after extended-release buprenorphine injection: a case report

KEYWORDS:

• Extended-release buprenorphine
• opioid overdose
• illicit fentanyl
• supplemental buprenorphine

Background

Buprenorphine is a partial µ-opioid agonist used to treat opioid use disorder (OUD) (1). It has a lower risk for overdose due to its ceiling effect and higher binding affinity at the µ-receptor (1,2). Buprenorphine is available in multiple formulations including daily sublingual (SL) and a monthly injection (XR-Bup) which is available in two doses, 100 mg and 300 mg. According to the manufacturer, XR-Bup 300 mg should be administered during the first two months, however subsequently may continue at either 300 mg or 100 mg (3). Its formulation allows increased medication adherence through the lack of missed medication and reduces the possibility of diversion. It also allows for consistent plasma levels of buprenorphine which stabilizes the patient’s condition. However, XR-Bup can be cost prohibitive. One study cites $1700 for the 300 mg dose (4). Conversely, the cost of monthly sublingual buprenorphine can be approximately $550 (5).

It is recommended that prior to initiation of the first monthly XR-Bup injection, the patient should be pretreated with at least 8 mg of sublingual (SL) buprenorphine once daily for a week (6). In this case and with patient consent, we describe a patient who received the monthly XR-Bup injection and had two subsequent opioid overdoses within four weeks of that injection.

Case description

This case occurred in southern New Jersey where fentanyl is the main street opioid. DW is a 38-year-old male with a 12-year history of OUD. He injected 6–10 bags of fentanyl daily. He had been stable in recovery for 8 months on SL buprenorphine 8 mg three times daily (TID). He restarted using fentanyl intermittently and skipping SL buprenorphine doses. It is unlikely that DW was taking his medication daily while using fentanyl and more plausible that he was skipping doses and using more fentanyl, until he stopped taking his buprenorphine. In September 2022, he received his first monthly XR-Bup 300 mg injection and supplemental SL buprenorphine 8 mg TID. He, subsequently, admitted to skipping all supplemental SL buprenorphine.

16 days and again 25 days after the injection, DW experienced an overdose. Both times he received naloxone with positive effect. DW had had multiple attempts at buprenorphine induction, however, he was never able to continue taking his buprenorphine beyond day one or two. This was due to previous precipitated withdrawal and inability to tolerate the fentanyl washout period. He had previously attempted microinduction, however he reported severe anxiety around day 3–4 and returned to use. Despite not taking the buprenorphine, he continued to engage in outpatient and various inpatient treatment, both detox and long term.

Discussion

To our knowledge, this is the first case report of a patient who had a fentanyl overdose shortly after receiving an XR-Bup injection. The current recommendation of pretreatment with daily SL buprenorphine before receiving the XR-Bup injection would be ideal, however many patients in our clinic are too unstable in their use disorder. Our clinic is affiliated with a large academic center located in New Jersey. 85% of our patient population is insured via Medicaid and about 5% are uninsured. Our clinic defines instability as patients who have inconsistent cadence of visits, low or nonexistent buprenorphine/norbuprenorphine levels by comparison to the prescribed amount, and/or adulterating urine samples over a duration. This period varies based on the provider, however at a minimum, patients do not demonstrate their instability before 6 weeks. The instability of our patients is often due to housing, food, and income insecurity which often leads to diversion. Some patients find it difficult to travel to our clinic and maintain the consistency required to develop sobriety. Others are simply not taking their buprenorphine. Most however, are hesitant to wait the fentanyl washout period to avoid precipitated withdrawal. As a result, patients are left with XR-Bup as their only option for continued treatment for OUD. Unstable patients are sent to our Emergency Department where they receive XR-Bup without pretreatment. They are discharged post injection with 8 mg of buprenorphine SL TID until their follow up.

Patients such as DW, theoretically have other options other than buprenorphine. They may choose referral to a methadone clinic, inpatient care, or ultimately may choose nothing. Brixadi, a new injectable extended-release buprenorphine medication, may be administered weekly for patients who have been pretreated with a single transmucosal buprenorphine dose. A monthly version is also available for patients who are already being treated with buprenorphine (7). Patients may find the weekly injection objectionable, and cost may be a barrier.

While it may be indirect reasoning to provide daily SL buprenorphine after XR-Bup to patients who were too unstable to take it in the first place, we have found that once the patients receive the injection, they are no longer hesitant to take SL buprenorphine. Our patients continue the injections monthly and are limited to this timeframe by the insurance companies. Some patients’ payors limit their care to either injectable or sublingual formulation, but not both.

A limitation of our case report is the unknown level of buprenorphine/norbuprenorphine present at the time of each overdose. We also do not know the exact potency of the fentanyl. According to a 2022 report disseminated by the Pennsylvania Attorney General, in 2021, the concentration of fentanyl in Philadelphia which is the main supply for our patients, was found to be 27.30%, and the concentration of heroin was found to be 7.40% (8).

We know that our patient received XR-Bup and his risk of fentanyl overdose should have been minimal. However, with the increasing potency of the fentanyl, it is likely that XR-Bup alone is not as effective against overdose.

Conclusion

It is our belief that the XR-Bup injection by itself is not protective against fentanyl overdose, especially in the early months. This injection should be supplemented with sublingual buprenorphine until the patient develops stability and buprenorphine/norbuprenorphine levels reach their peak. This would be useful not only to the stable patient who is pretreated with buprenorphine prior to injection to prevent cravings and withdrawal; however, it would be moreso beneficial for the unstable patient who needs extra protection from the risk of fatal overdose.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.