First Posted 2/15/2013
A recent exchange with a reader:
I have been on buprenorphine for 5 yrs. Recently my doctor stated that my u/a t looked like I have been ‘loading my meds.’ He said my levels where ‘backwards’ and that would happen if I took just a few doses just before my appt. My doc had me come back in two weeks to go over my next u/a, and again it came back funky. So my doc starts having me take my meds in front of the nurses on a daily basis. Two weeks later with supervised u/a’s, my urine comes back the same. My doc looked perplexed but kind of ignored the results like I was still doing something to mess with the results. I had to come in again for another urine test and it finally came back normal. My numbers were fine after that, and all was good until last week.
I went to my normal monthly check up and the u/a showed NO buprenorphine in my system. My doc looked at me like I am the biggest liar. I am perplexed. I am taking my meds daily. I don’t know what is going on and I need to figure it out soon before my doc kicks me out of the program. What could be wrong with the test, that is says that I have no buprenorphine in my body?
There are several directions we could go with this issue. One aspect is whether it is always fair to believe the results of drug tests over the word of our patients. I understand the reasons for testing, but I think that doctors sometimes lose the forest (the patient’s addiction problem) on account of the trees (quantitative testing). This patient has been on buprenorphine for five years; I would hope to have sufficient trust established with patients after that period of time, such that the lab results wouldn’t be seen as the only answer. There can be problems with any laboratory test. Drug tests are one tool– not the ultimate arbiter of truth.
Most people metabolize buprenorphine a certain way, leading to the build-up of a chemical called norbuprenorphine. I assume that by ‘backwards’ the doctor is saying that the buprenorphine level is higher than the norbuprenorphine level, whereas with daily use of buprenorphine the opposite would be true. As your doctor said, if a person takes one dose of buprenorphine and is tested an hour later, buprenorphine would be present, with only small amounts of the metabolite norbuprenorphine.
Urine tests for any substance are affected by many variables, including the actions that different parts of the kidney have on certain substances. Some substances are concentrated at the kidneys, making urine testing more sensitive than blood testing. But other substances might be re-absorbed by the kidneys to a varying degree, depending on hydration status, nutritional and dietary factors, hormonal factors, and personal genetics. Because of concentration and reabsorption effects, the drug levels from urine tests are not accurate indicators of drug levels in the bloodstream.
In addition, the metabolic pathways for certain substances might be changed by the presence of other substances. For example, if the enzyme that turns buprenorphine into norbuprenorphine is blocked or occupied by other substances, the pathway may change such that metabolites other than norbuprenorphine are formed—- including metabolites that won’t show up unless they are specifically tested for.
I asked the patient:
Are you taking any other medications? Are you able to get the actual lab results showing the details of the test?
I thank you for responding to me. I am on many medications because I have fibromyalgia among many other things. My list of meds:
Prozac 20 mg; Provigil 200 mg; Clonidine 0.1 mg 4x’s a day; Amlodipine 5mg once a day; Nabumetone 500mg 2x’s a day; omeprazole 20mg once a day; Ambien 10mg per day; Relpax when I have a migraine; Buspirone 10mg about 2x’s a day; Subutex 16 mgs per day. I also take diphenhydramine 50 mgs at bedtime when needed to help sleep, and Vitamin D3-1000 iu once per day. I take this because my blood tests showed it was low.
I asked to see my results and my doctor told me that I didn’t need to see them; that he had told me what it said and that it should be enough for me to know.
The receptionist in the office is getting the number to the lab for me. Do you have any questions that I should ask? What should I know? I am going to ask for a copy of my labs at my next visit. I am nervous that my doc will just stop prescribing. This medication has saved my life and I don’t know where I would be without it. Please help me make my doctor believe in me again. I know that is a lot to ask but I’m in trouble. Where can I turn? There aren’t any Suboxone docs in my area taking new patients.
(A couple thoughts)
Over my 20 years as a physician, I’ve come across times when tests were mistakenly trusted over the word of patients. At a maximum security prison for women where I worked as a psychiatrist, for example, many women were disciplined for diverting clonazepam, until a call to the lab revealed that testing wasn’t reliable for that medication.
Over time, we learn more and more about how the metabolism of one medication impacts other medications. One such interaction was apparent in this person’s case.
The most obvious interaction from your list is that Provigil is an ‘inducer’ of cytochrome 3A4, the enzyme that breaks down buprenorphine. A person taking Provigil develops greater amounts of that enzyme in the liver, which results in faster metabolism of buprenorphine. The first step in metabolism of buprenorphine is conversion to norbuprenorphine, so levels of buprenorphine and norbuprenorphine would be affected by Provigil, in unpredictable ways.
From the program that I use to search for interactions: buprenorphine
Coadministration with modafinil (the racemate) may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. Modafinil and armodafinil are modest inducers of CYP450 3A4, and pharmacokinetic studies suggest that their effects may be primarily intestinal rather than hepatic. Thus, clinically significant interactions would most likely be expected with drugs that have low oral bioavailability due to significant intestinal CYP450 3A4-mediated first-pass metabolism (e.g., buspirone, cyclosporine, lovastatin, midazolam, saquinavir, simvastatin, sirolimus, tacrolimus, triazolam, calcium channel blockers). However, the potential for interaction should be considered with any drug metabolized by CYP450 3A4, especially given the high degree of interpatient variability with respect to CYP450-mediated metabolism. Pharmacologic response to these drugs may be altered and should be monitored more closely whenever modafinil or armodafinil is added to or withdrawn from therapy. Dosage adjustments may be required if an interaction is suspected.
That is just one of many possible interactions. When a person takes multiple medications, there are often other, less predictable interactions. Some medications also interfere with the testing of other medications. You may know that there are chemicals available on the internet to block the testing for certain compounds; some medications do the same thing.
I can’t thank you enough for even responding to me…… You are a very kind man! I hope this helps me. I am very scared my doctor will take me off my meds.
But then she wrote again:
I wanted to send you an update. My doctor wouldn’t even look at the conversation we had. I guess for whatever reason, he refuses to look deeper into the issue. It is sad when a doctor has had a patient for over 5 yrs and he won’t look into this further. I don’t ever have dirty u/a’s. I don’t drink, I don’t smoke marijuana, I only take what he prescribes to me. He refuses to look further into the matter so much that it is clouding his judgment. He won’t even test me another way. He states urine test are the most accurate but there is something wrong because I know that I take my meds. He refuses to do another supervised dosage week because he doesn’t have the manpower.
I know in his eyes that all I am is a drug addict but I deserve respect. Why would a man who believes in science have such a closed-minded view? I would think he would at least want to discover what is happening. There has to be more patients like me that are being thrown away because we don’t fit a certain mold. When he throws me out of treatment on Monday, I have nowhere to go. There are large waiting lists to see a doctor in my area. I can’t go back on the streets for medication. I don’t have any of those friends left in my life. I am in so much trouble.
I don’t know why I felt the need to vent to you but my hope was to find one person that believes me in hopes that this problem could be addressed someday, somehow. Thank you for listening. I do appreciate it.
First Posted 2/15/2013