Fluconazole (trade name 'diflucan') is an inhibitor of CYP2C19 (IC50=12.3 µM) and CYP3A4 (IC50=13.1 µM) and to a lesser extend CYP2C9 (IC50=30.3 µM) (
https://www.jstage.jst.go.jp/article/bpb/28/9/28_9_1805/_pdf/-char/en)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885031/
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208411lbl.pdf
So the inhbition of CYP450 enzymes is most likely not the cause. Sadly I couldn't find info on which isozyme is responsible for the glucuronidation. It might be possible that it's UGT2B7 and thus taking fluconazole might inhibit the metabolism of naloxone, increasing the bioavailability and causing precipitated withdrawal.
Buprenorphine is metabolized into norbuprenorphine via CYP3A4 and is a potent µ-receptor agonist. So taking fluconazole will most likely decrease the metabolism into norbuprenorphine, but it looks like norbupe has poor CNS penetration due to it being a P-gp substrate (
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464040/) so I'm not sure if this plays a role..
Fluconazole does have some nasty ADRs that are similar to withdrawal so this might play a role as well(wikipedia)
THANK YOU SO MUCH FOR REPLYING AND HELPING ME!! IT MEANS SO MUCH TO NOT FEEL ALONE.
First of all:
Why would suboxone and fluconazole be listed as severe interaction ?
Next:
So, I was thinking. The day before I had a bad reaction..... I did a good bit of fentanyl on top of my 12mg suboxone However--- I have done this quite a few times as idiotic as it may be. Even after waiting 48 hours i still feel like shit taking my sub.
So anyways my thought was this. Apparently diflucan interacts with fentanyl potentiating it and slowing down the metabolism/excretion of fentanyl causing higher levels. Perhaps when I took the diflucan it caused the fent to hangout longer even though technically I should've still had a good amount of bupe (12mg a day for past week/2weeks) on my receptors. Which could explain the precipitated withdrawal that took 10 hours to go away/lessen.
My doctor called and said it could be ciprofloxacin I have for kidney infection.....I think shes wrong because I've been taking it for days with no issue.
I'm just worried that I'll be dealing with precipitated withdrawal symptoms until diflucan leaves my system half life of 30 hours....looking like 5-6+ days. I have to work and take care of my family. It's a very very important week for me as I own a small business and my first clients job started today and continues until Friday
I took 4 mg of sub........but I did grab a bit on fent to put on top so I didnt get sick. I'm so upset right now. I had 3-4 days sober--which isnt much, I know. But it was a start and I was really proud even though I felt horrible. If i didnt have to work it wouldn't be a problem.
I also wonder....I've never been stable on subs
I cant remember the last time I felt good/normal. Years ago. Now everytime I take it even after waiting, scoring on cows, I feel bad and end up doing 12mg sub waiting 1-2hours and doing a bit of fent. I stopped doing that last Thurs/Friday. Just at a loss right now, feeling really down and wishing there was a answer. Maybe I'm sensitive to naloxone ? I'm sure my brain is saying "wtf" everytime I do it. My brain has gotten used to having opiates daily for 10 years.
Thank you for any and all of your help + advice.
What do you think ?
