Posts Tagged ‘maximum buprenorphine dose’

Maximum Daily Dose of Buprenorphine

Hser et al., 2014, Addiction






I’d like to thank my readers for their patience during my recent break from blogging. Now that I’m rested, it’s time to start barbequing some sacred cows.

First on my list: limiting the dose of sublingual buprenorphine to 16mg per day.

Recently I’ve heard from physicians who have been told 16mg of sublingual buprenorphine is the highest daily dose that should be prescribed, because studies show that opioid receptors in a human brain are saturated at that dose in most people. While this is true, limiting all patients to 16mg or less neglects research from real life patients.

Some governmental agencies have gone as far as forbidding daily doses higher than 16mg. For example, the Virginia Board of Medicine passed a regulation earlier this year that the highest dose that physicians could prescribe was 16mg per day. In Tennessee, patients can’t go above 16mg per day unless they are seen by an addiction specialist physician.

However, the FDA has approved doses up to 24mg SL per day. Who is right? Did the FDA get it wrong? Are patients who want to go higher than 16mg all drug seekers? Or do all such patients plan to sell their excess medication?

If you read the REMS document created by the manufacturer of Suboxone film, it says the target dose should be no higher than 16mg per day, and that doses higher than 24mg haven’t been shown to provide additional benefit. That leaves a question mark about dosing between 16 and 24mg.

The American Society of Addiction Medicine (ASAM) issued a statement addressing the tendency of state prescription monitoring programs to assign MME (morphine milligram equivalents) values to buprenorphine doses. In that statement, issued earlier in 2017, they said, “The US Food and Drug Administration (FDA) approves dosing to a limit of 24 mg per day. There is some evidence regarding the relative efficacy of higher doses.” [1]

If ASAM says 24mg is OK for some patients, and the FDA has already approved that dose, that’s good enough for me…assuming the patient truly needs a higher dose.

Some patients do better on a dose of 24mg than on 16mg. I work at an opioid treatment program where we observe the patients taking their doses on site, and we pay close attention to any attempt at diversion of the dose. Therefore, we have no question about whether a patient is taking less than the dose I’m prescribing.

When I see new patients within a week or two of admission, I ask how they are feeling. Some patients dosing at 16mg per day of buprenorphine describe symptoms consistent with opioid withdrawal by late evening. I increase their dose above 16mg when I also see physical signs of withdrawal, like large pupils, sweaty palms, and the like. Many patients feel improvement to the point we don’t have to consider switching to methadone.

I increase these patients’ doses because I am sure they are getting their full dose each day, and because I see signs of withdrawal with my own eyes. I know experts say a dose of 16mg is “supposed” to block all the opioid receptors according to studies of this drug, and I believe that is true for many patients. I also think there are patients for whom increasing the dose above 16mg provides benefit, and can eliminate the need to switch to methadone.

Not that there’s nothing wrong with methadone. It has a proven track record, but it does have more medication interactions than buprenorphine, and is more dangerous with certain medical problems.

Methadone patients were under-dosed for years, when physicians had the misperception that no patient needed more than 70mg per day to treat withdrawal. With further studies and information, we know that’s not true, and best evidence shows most patients need between 80-120mg, and sometimes much more than that.

I think in years to come, we will see that by limiting patient doses to 16mg, we are under-dosing some buprenorphine patients.

Why are so many agencies trying to keep buprenorphine doses low?

First, the U.S. has a “less is more” attitude regarding medication-assisted treatments for opioid use disorder. Given the existing bias against these medications, of course some peoples’ attitudes will be grudging acceptance of the medications, but trying to limit the doses to be as low as possible.

Second, there’s the very real concern about diversion of buprenorphine. The more buprenorphine that’s being prescribed and dispensed, the more that may end up being diverted to the black market. I know this is true.

However, opinions can differ regarding the potential harm of providing more buprenorphine to the black market. Some experts might think since buprenorphine is one of the safest opioids manufactured, increased black market access could help save lives. Though many more people embrace harm reduction now than ten years ago, we are not yet in a place where the law-and- order types would allow a serious conversation about this.

Third, I’m worried that some decisions about dose maximums for buprenorphine may be driven by cost. In a state where many patients prescribed buprenorphine products are on Medicaid, higher doses would cost the state more. The same would be true for managed care organizations and the insurance companies and the like. I hate to sound cynical, but financial concerns often drive medical decisions.

By now you know my opinion; if a patient dosing with buprenorphine 16mg SL per day reports withdrawal symptoms and has physical signs that match these symptoms, I’m willing to increase the dose to 20 to 24mg per day. We have a pretty good study, by Hser et al., 2014, that shows higher treatment retention rates with higher doses. Plus, the FDA has already approved doses up to 24mg per day. [2]

I’m cautious about take home dose in patients at the opioid treatment program. If the patient has a history of injecting drugs, I’d like them to have more time in stable recovery before granting take homes. For patients on 24mg per day, I may do more frequent pill counts and bottle recalls, as a precaution against drug diversion. But I’m not sure a patient on 16mg is any less likely to sell part of her prescription than a patient dosing at 24mg.

  2. Hser et al., “Treatment Retention among Patients Randomized to Buprenorphine/naloxone Compared to Methadone in a Multi-site Trial,” Addiction, 2014, Jan; 109(1) 78-87.