This material covers changes in the clinical use of buprenorphine that have occurred within the last several years. We're going to begin by reviewing the standard induction protocols. We've asked in the past that patients show signs of mild to moderate opiate withdrawal that you use an opiate withdrawal scale to measure that. That you begin with either a two or a four milligram buprenorphine naloxone dose. Patients can be re-dosed in two hours if opiate withdrawal has not been diminished by the first dose. Our target dose for the first day was eight milligrams, but we could go to 12 milligrams in areas where patients were using fentanyl. And then it would be possible the second day to increase the dose to 12 milligrams as the target dose of induction. We initially recommend that patients come back and be seen the second day and the dose be adjusted according to patient need. Most of the patients are going to stabilize using this model between 12 or 16. But you're probably going to have to go higher in areas where fentanyl is being used. FDA has approved buprenorphine in a dose range of up to 24 milligrams daily. And whenever you hear me using the word buprenorphine, I'm really referring to the buprenorphine naloxone combination. So we're talking here about a combination of 24 milligrams buprenorphine and six milligrams naloxone. Now, our early recommendations for induction included specific detail depending on what drug the patient was addicted to. If they were using heroin, we recommended that they abstain from any drug use for 16 hours before you initiate the buprenorphine. If they were using opioid pharmaceuticals, we recommended that you sustain from any drug use for a full 24 hours before attempting induction. And if they've been on methadone for any period, we're suggesting that the methadone dose be reduced slowly. And you may have to work with a methadone clinic to gradually bring them down to 30 milligrams. Once they're stabilized on 30 milligrams, and that usually would take about one to two weeks at that dose, then switch them to an initial dose of 15 milligrams for the first day, no methadone the next day. So you got one day at 15 milligrams, no methadone for one day. And then the next day, you can begin the induction of buprenorphine. So you gradually reduce the methadone, get it down, miss one day, and then start the buprenorphine. We're recommending that the patient have a moderate cow score of 8 to 10 before they receive the first dose of buprenorphine. For patients who've been using fentanyl, we recommend that a cow score of at least 13 to 15 would be a safer target before you begin to initiate buprenorphine. And that it would avoid precipitating withdrawal if you make sure that the cow score is in the moderate range or higher. You can rapidly escalate the dose to at least 12 milligrams if needed by the end of day one. So these were our earlier recommendations. In the next couple of slides, I'll get to the sections on high-dose and low-dose protocols, which are the revised recommendations for induction. I also would mention home inductions. These were relatively infrequent 5 or 10 years ago. Now they're becoming very common. And it's been our experience that home induction can be considered with almost any patient, particularly those who've had any prior experience taking buprenorphine. In this situation, we would recommend a rapid induction to medications, and that should be a high priority. You would continue with weekly office visits as possible until the patient is stable in treatment. So you would see them at home or send them home, maintain telephone contact with them over the next couple days, see them back in your office weekly until their treatment, and in the meantime, continue monitoring with telephone calls. Many practices are using home inductions in the pandemic, and they have found that they work extremely well. I think over the last 10 years, the patient population has become much more familiar with using buprenorphine, so patients are relatively experienced on how the drug works. You need, of course, to review the issues of precipitated withdrawal and how to take buprenorphine correctly, but patients generally are not naive about buprenorphine, so it's easier to proceed with a home induction. So now I'll get to the procedures for high-dose and low-dose initiation. This has probably been the most radical change in induction procedures in the last few years. Low-dose induction, or something that is called microdosing, was first developed in Bern, Switzerland in 2010. Sometimes referred to as the Bernice method. It's initiation of low-dose methadone while the patient is still using opioids, or the dose of a full agonist. So the patient really does not have to experience withdrawal, and it can be a way of switching them from their street drugs or prescribed pharmaceuticals on to buprenorphine without requiring that they go through withdrawal. It's accomplished by a gradual increase of buprenorphine starting at a very low dose, and I'll give you more details on that in a second. Once you have a sufficient accumulation, usually by the seventh day in those protocols, you can switch to buprenorphine just in the standard dosing mechanism, starting with BID dosing, and you can stop all the illicit or other prescribed opioids. This is an example of European protocols. They are available to clinicians in Europe, and they have lower doses of buprenorphine tablets available, or sublingual tablets available. So you can see they're able to start with a 0.2 milligram tablet on one day, repeat that the second day, go to 2.8 tablets the third day, 4.8, the fourth day, the fifth day up to five milligrams, up to seven milligrams, then eight milligrams. For two days, it's seven and eighth day, and then on the ninth day, they're up to 12 milligrams. So we see a rapid increase of buprenorphine over a 12-day period. And here, the patients were using heroin, and you can see that they continued using the heroin they were on for the first two days, and then they were asking the patients to reduce the heroin they were using, getting that down to 0.5 milligrams a day by the fifth day, and then stopping it completely. So what you've basically done is start with a low dose of buprenorphine, increase it rapidly to a 12-milligram dose at the end of nine days, and at the same time, reduce heroin gradually over a five-day period, and then stop the heroin. And with this method, they described no particular problem with withdrawal symptoms. So this is a very effective way to initiate buprenorphine. Now, this is a U.S. protocol, because in this country, we do not have the pharmaceutical availability of such a low dose of buprenorphine. And here, they were using film strips, and people have either done initiations by taking this sublingual tablets and splitting them into small pieces, which may be a little bit more difficult to do, or using the smallest film strip available and cutting that into thirds or quarters. But the effort was to begin with 0.5 milligrams once a day, and then go to 0.5 twice a day, then 1 milligram a day, then 2 milligrams a day, and then 3 milligrams, 4 milligrams, and up to 12 milligrams by day seven. Here, the Phenol was being used. Now, SAMHSA does not endorse telling a patient to keep using Phenol, but this is what clinicians were seeing, that if the patient continued using their street drugs for several days, they were able to do that. And at this point, where you're getting to a full buprenorphine dose, they can stop the heroin and Phenol, and they should not experience withdrawal symptoms. Now, this slide describes high-dose or macro-dosing. This procedure has become very common in the last year. It's primarily used in emergency rooms, so it's not done in a private office setting. At least the bulk of experience looking at it has been the induction of patients in the emergency room in hospitals that are well-prepared to deal with opiate withdrawal. You give a large dose of buprenorphine, larger than you would use in conventional dosing, often beginning at 4 milligrams, rapidly going to 16, or even in some cases beginning with 16 milligrams. Rapid increase of the dose is the T, is the target. In some cases, the target dose is 24 milligrams. In other situations, it's been as high as 32 milligrams or higher. I would have to say with both the micro-dosing protocols and the macro-dosing protocols, there is no one standard protocol that is accepted. Nothing has been officially endorsed by SAMHSA or the FDA.

clinical use

buprenorphine

induction protocols

dosing recommendations

home inductions