Abiraterone, CYP3A4 and interactions with drugs/ supplements

[cbgjr]

There were some recent discussions on this site about the risks of using supplements while taking Zytiga (Abiraterone). I found them very interesting, as I am currently taking some supplements along with Zytiga, so I tried to research this a little bit..

This is from the official Zytiga website:

“CYP3A4 Inducers: Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency.”

My understanding is that “CYP3A4 inducers” increase the activity of this liver enzyme, thus breaking down Zytiga (Abiraterone) at a higher rate so that its bio-availability is reduced. The opposite effect is caused by CYP3A4 inhibitors, and so in that case the availability of Abiraterone is increased.

Of course, neither is really desirable. Higher bio-availability of Abiraterone can increase the bad side effects while lower bio-availability would make it ineffective fighting cancer.

(But worse side effects are probably a lesser evil than lower potency for fighting PCa !)

So what is a “strong CYP3A4 inducer”? I found a list here:

en.wikipedia.org/wiki/CYP3A4

at the end of the article, there is a list of drugs and supplements that can act as inhibitors and inducers.

Interestingly, under “CYP3A4 inhibitors” there is a category for drugs and supplements with “undetermined potency” I guess meaning that this group inhibits CYP3A4 to some degree, but to an unknown level. So they could potentially increase the level of Zytiga in the system, along with a higher risk of side-effects. However this group should not affect the cancer-fighting properties of Zytiga.

Interestingly, Quercetin is listed as both an inhibitor and an inducer in two different studies.

I really would welcome feedback on this. Is my understanding basically correct?

Thanks

CG

[NPfisherman]

Early on, I took a sleep supplement that had valerian root and phenobarbital...my LFT's went up and after removing that and replacing it with melatonin, my LFt's were back to normal...yes....quercetin is in both as an inducer and an inhibitor although questionable potency... Is anybody on Zytiga and quercetin?? Interesting article....thanks for posting....

Fish

[Trecento]

Hi, also find this an interesting question- read a proof of concept and other studies that quercetin could work synergistically with Xtandi to reboot it after resistance to the drug occurred. Seem to remember another article suggesting same for Zytiga but would need to find this again. My husband also taking Zytiga and pred, wish it was Xtandi - reckon he did better on it although his onco said they acted very similarly. Will share what I find - he started the Life Extension vitamin c with quercetin with this morning (his integrative care practitioner is a big fan of vitamin c - not sure myself).

[BruceSF in reply to Trecento]

I think you were interested in this article: ncbi.nlm.nih.gov/pmc/articl... "Quercetin targets hnRNPA1 to overcome enzalutamide resistance in prostate cancer cells"

Basically they show that in vitro research showed that quercetin suppresses a substance that can cause Ar-v7 progression, so it should help keep ABI and enza working