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Hello Colleagues,
Precipitated withdrawal (PW) is a deterrent to initiating MOUD for both patients and providers. Experiencing PW can turn an ambivalent patient further from accepting medication, as can the need to experience withdrawal simply to start treatment. Having a medication at the ready, without the need to wait for withdrawal to ensue, is of great appeal. In this multicenter study conducted in EDs, investigators enrolled patients with minimal to mild opioid withdrawal, i.e., COWS of 0-7, and gave them a dose of weekly injectable buprenorphine, CAM2038 (brand name Brixadi) at 24mg (16mg SL “equivalent”)- without prior sublingual dosing. Woah.
Why would the investigators believe this could be successful?... Onset of action. The authors state that CAM2038 blood levels rise more slowly than sublingual, “reaching 1.6 ng/mL in 4 hours compared with 5.6 ng/mL in sublingual dosing”. (SL dose unclear). With this, they proceeded.
One hundred patients enrolled, 70 tested positive for fentanyl on a point of care (POC) test, and 7 patients experienced PW. All of these were in the positive fentanyl group. Five of the seven had a COWS 0-3, and two had a COWS of 4-7. This translates to a risk of PW in fentanyl-positive patients with a COWS 0-3 = 18% and COWS 4-7 = 5%. However, 39 of the 100 had buprenorphine in their initial urine.
It is wonderful to have a new potential approach to initiation, along with data that we can use to make decisions and counsel patients. But as we do that, it is important to consider the influence of the 39% with positive bup. Based on a previous study by this group and knowledge of related pharmacology, we know that the presence of BUP can mitigate the incidence of PW. So, while patients with fentanyl-positive POC fentanyl and COWS 4-7 had a 5% incidence of PW in this study, that is likely an underestimate among patients who are negative for buprenorphine. And, for those with fentanyl-positive POC and a COWS of 0-3, it seems worth waiting until more withdrawal symptoms set in, as the risk of PW is at least 18%.
Overall, this is great information and opens the door to treating people earlier in withdrawal with a long-acting medication absent sublingual lead-in. However, given that many patients had buprenorphine “on board,” these numbers should probably be considered underestimates of PW risk for patients who have not taken any buprenorphine in the last 4-5 days.
Please read on for a deeper dive.
Andrea Truncali, MD, MPH
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