LIST OF REFERENCES
Interested in the science? Read on.
Caffeine and Luvox— who would have known that there could be a serious interaction issue? The prescribing information for fluvoxamine doesn’t mention the word “caffeine” at all; it only says "Fluvoxamine is a known potent inhibitor of CYP1A2.” (Does that say to you “This will make my cup of coffee last 30-35 hours?" Not to us!!)
A big thanks to the users of CrazyBoards.org, a site that has changed many people’s lives, and contributor “scream_phoenix,” for being the one whose post alerted the author of this page to this issue.
The author wondered: If neither doctors nor patients are aware of this, could studies using fluvoxamine for COVID-19 treatment be ruined by intolerable headaches, jitters, and insomnia-- and it would get blamed on the fluvoxamine, rather than the caffeine?
Sure enough, the issue was confirmed by a quick look at Wikipedia. It’s due to a CYP1A2 interaction (a member of the cytochrome P450 superfamily of enzymes, metabolism pathways for drugs):
Fluvoxamine inhibits the following cytochrome P450 enzymes: […] CYP1A2 (strongly) which metabolizes agomelatine, amitriptyline, caffeine,
This could have serious implications. Since around 90% of people consume caffeine, imagine the number of people having trouble with Luvox and having no idea why!
In fact, the large national COVID-OUT study ended up testing only a half-dose of fluvoxamine -- 50 mg twice a day, instead of 100 mg twice a day -- for exactly that reason (concern about side effects). Not surprisingly, it wasn't as effective as in previous studies!
Some reference papers from a quick search:
Br J Clin Pharmacol. 2005 Nov; 60(5): 486–493.
Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics
Highlights: At 200 mg/day, fluvoxamine prolonged caffeine's elimination half-life (4.9 vs. 56 h). Caffeine produced CNS-stimulating effects compared with placebo. Issues were not seen with a single dose of caffeine but cannot be ruled out with accumulation from daily ingestion.
Fluvoxamine is a Potent Inhibitor of the Metabolism of Caffeine in vitro
Excerpt: The formation of 1,7-dimethylxanthine was virtually abolished by 10 pM of fluvoxamine, indicating that the N3-demethylation of caffeine is almost exclusively catalysed by CYPlA2.
A fluvoxamine-caffeine interaction study
Crossover study; 50 mg for 4 days, then 100 mg for 8 days. Then single dose of caffeine. Half-life of caffeine increased from 5 to 31 hours; various measures of clearance reduced 2-fold to 5-fold. Check out figure 2. And from the conclusion: “…our data clearly point to the the possibility of caffeine intoxication during fluvoxamine treatment. Caffeine intoxication during fluvoxamine treatment could be a disregarded adverse effect leading to discontinuation of the drug."
To top it off, there are genetic differences. Some people are super-sensitive to caffeine to start with, and some people can drink coffee all day.
You probably know or can guess which you are. If you have to stop drinking coffee before noon, you may be a slow metabolizer. If you drink 4 or more cups a day, you may be and "ultra-rapid metabolizer." Somewhere in between? You're probably a regular metabolizer.
Just remember, whatever your normal is, with fluvoxamine it's "times five." Still not sure? Then just be cautious and assume the worst.
Curious to know for sure? If you have 23andMe results and paid for the upgraded "Membership" version, you can get your CYP1A2 caffeine sensitivity status, although the way they report it is a little confusing; or, you can feed your basic 23andMe or Ancestry.com results into XCode Life.
A few more reader-friendly links about genetic differences:
(the beginning of this article is helpful; the end can be skipped)
CYP1A2 Enzyme: Where Caffeine Meets Genetics