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TOPIC: Caffeine, codeine, noni not good with daclatasvir?

Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6686

  • Phoenix
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Wikipedia page on CYP3A4 (the enzyme that one doesn't want to mess with when taking daclatasvir) lists "Selected inducers, inhibitors and substrates of CYP3A4".

The "substrate" list includes:

Caffeine
Codeine
Testosterone
Cocaine

Should we be worried about "substrates" as well as "inducers and inhibitors"? It seems unlikely that caffeine would be a problem.

The page also notes that bergamottin, the "moderate inhibitor" found in grapefruit, is also found in noni and pomegranate. Beware that "healthy" noni juice!
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6690

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Right, now I'm confused lol. Looked up hep-interactions and there are no contraindications with codeine for Dac - just wondering as I had to take panadeine yesterday as the nerve pain in my arm got so that it was pretty unbearable...anyone have any ideas about this? I know the doc uses this site when prescribing as he ran Gabapetin through it for me when writing up my script...and wikipedia is well, not the University of Liverpool lol


www.hep-druginteractions.org/checker



GT1a since 1988, diagnosed 1990
F0, tx naive
VL 262,000 ALT 40 AST 26 GGT 13 Fibroscan 04/12/15 - 2.9
Started Mesochem sof/dac 12 weeks 01/01/2016
11/02/2016 - 6 weeks UNDETECTED
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Last Edit: 1 year 1 month ago by Hieupham.
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6692

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Substrates of CYP3A4 are the drugs that are metabolised by it. The inhibitors and inducers are the chemicals/drugs that effect the rate of metabolisation and are the ones we want to avoid. The link gives a reasonable explanation.

Daclatasvir is one of the substrates of CYP3A4 as are the others Phoenix listed. Now, two substrates at the same time can effect how efficiently CYP3A4 works if one is monopolising the enzyme but we just need to check the drug interactions chart which should pick those up.

www.straighthealthcare.com/cytochrome-p450-3a4.html
G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17
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SRV12 - 27/07/17 UND!!! :cheer: :silly: :woohoo:
Last Edit: 1 year 7 months ago by Gaj.
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6693

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Hi Phoenix,

Thanks for the tip about pomegranate and noni juice too!

<edit> I was also told that Seville Oranges and marmalade made with them should be avoided during my 2013 trial.
G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17
SVR7 - 22/06/17 UND
SRV12 - 27/07/17 UND!!! :cheer: :silly: :woohoo:
Last Edit: 1 year 7 months ago by Gaj.
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6694

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Hi GAJ & zhuk, thanks for helpful replies. Just to make sure, I'm going to avoid everything on the substrate list - easy for me as I don't drink coffee or tea! You'd have to think that caffeine must be okay, considering that the majority of people on the trials were probably drinking it if not told to stop.

I'm definitely going to steer clear of all citrus fruits - these days there are so many new and tweaked varieties of fruit, it's hard to say I'm going to eat this kind of orange and not that one.
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6702

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Just found another webpage on "Inhibitors of CYP3A4", which lists red wine, garlic, pawpaw and other tropical fruit:

http://www.ganfyd.org/index.php?title=Inhibitors_of_CYP3A4

I'm becoming more and more convinced that the drug interactions info we're relying on is far from complete. I've got two pawpaws ripening on my kitchen bench and usually have a raw garlic clove with my veggies in the evening. Very glad I've discovered this info.

My suggestion is that we Google "CYP3A4" with any food we eat a lot of, just to make sure, especially those that may be non-mainstream in Europe and the US whose foods seem to dominate the lists (e.g. grapefruit is typically listed but not pawpaw which is more common where I live).
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6703

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Good pickup, thanks Pheonix.

I ate a whole lot of pawpaw/tropical fruit yesterday, so it looks like its apples from now on lol
GT1a since 1988, diagnosed 1990
F0, tx naive
VL 262,000 ALT 40 AST 26 GGT 13 Fibroscan 04/12/15 - 2.9
Started Mesochem sof/dac 12 weeks 01/01/2016
11/02/2016 - 6 weeks UNDETECTED
AST 26
ALT 26
Last Edit: 1 year 7 months ago by zhuk.
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6706

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Hi Phoenix,

We need to keep in mind that CYP3A4 is one of our more important enzymes so pretty much anything we ingest is involved.
We are only concerned about potent inhibitors or inducers. So yes, per the cited article Star Fruit, Paw Paw, Pomeganate, Grapefruit are all inadvisable as are things like Echinacea, Ginko, Soy and Grape Seed extracts. Also keep in mind that these are inhibitors so will result in slower metabolisation of Dac. i.e. They will tend to retain Dac in our bodies for longer which could caused too high levels and sides.
OTOH St Johns Wort is an inducer so it causes our body to lose the Dac too quickly and is therefore an even bigger problem as the Dac may get removed before it does its job.
Garlic apparently does both so a bit difficult to determine effect, but would be warned against by BMS if it was potent at either. I would suggest a bit of garlic for flavour won't have any effect but eating cloves of raw garlic, particularly within a few hours of when we take our meds is probably something to avoid.

So basically avoid items listed as potent inhibitors/inducers and for mild ones don't consume in large quantities or at the same time as you take the Dac.
G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17
SVR7 - 22/06/17 UND
SRV12 - 27/07/17 UND!!! :cheer: :silly: :woohoo:
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6707

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Whoops! I just saw the comment about avoiding everything on the substrate list....that may prove a bit difficult as substrates are the things that the enzyme works on such as Dac and many other things we ingest. Just avoid the potent inhibitors/inducers and check for substrate clashes via the drug interaction charts.

PS BMS may not have listed things like Pawpaw because it is not common in U.S./Europe or they may have checked it and found that the inhibiting it does doesn't impact Dac due to the chemical pathways involved. Best to be cautious with things like that but they will have checked many common items and do not see them as an issue. Ginko and Ginseng are listed on the drug interaction charts though.
G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17
SVR7 - 22/06/17 UND
SRV12 - 27/07/17 UND!!! :cheer: :silly: :woohoo:
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6708

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Ah, so eating the pawpaw on my kitchen bench and the miso (soy extract) in my fridge gives me a higher dose of Dac for free! Maybe I should tuck in until I get bad sides! :sick:
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6709

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Yeah I'd already ditched my daily soy protein powder for a whey-isolate based one a few weeks ago. As for the inhibiting-effect, I'm getting a larger dose in any case due to bodyweight ratio - possibly not a good idea to enhance it lol But too early to tell what sx (if any) I'm going to get...watch & wait :)
GT1a since 1988, diagnosed 1990
F0, tx naive
VL 262,000 ALT 40 AST 26 GGT 13 Fibroscan 04/12/15 - 2.9
Started Mesochem sof/dac 12 weeks 01/01/2016
11/02/2016 - 6 weeks UNDETECTED
AST 26
ALT 26
Last Edit: 1 year 7 months ago by zhuk.
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6728

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Well i'm stuffed then as I take my daily meds with coffee every morning, eat some of the listed fuits and love garlic :(
Two time relapser.

SVR 4 achieved 12/16 at last
SVR 12 achieved 22/02/2017 The Bastard has been defeated :):):)

GT 3 - about 28 yrs with HCV
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Caffeine, codeine, noni not good with daclatasvir? 1 year 7 months ago #6740

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You should be fine Paul, coffee is a substrate that has no effect on Dac (phew!) and later research on garlic shows:

"Exposure of hepatocytes to garlic extract may reduce the expression and activity of CYP2C9 with no detectible effects on CYP3A4."

www.ncbi.nlm.nih.gov/pmc/articles/PMC2951329/

Just avoid the top four fruits on that list where possible and definitely don't wash the Dac down with a glass of grapefruit juice. :(
G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17
SVR7 - 22/06/17 UND
SRV12 - 27/07/17 UND!!! :cheer: :silly: :woohoo:
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Caffeine, codeine, noni not good with daclatasvir? 5 months 1 week ago #23891

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hello
i was serching about herbs and CYP3A4
i found that page wich seems interesting
exemple for garlic
Garlic (Allium sativum)
Garlic ( Allium sativum L., Fam. Alliaceae) is used in
modern phytotherapy to treat hypercholesterolaemia and
prevent arteriosclerosis although the clinical evidence is
far from compelling [2, 3] . Garlic preparations include
garlic powder standardized to contain 1.3% alliin and
0.6% allicin, garlic aged extract, which does not contain
allicin but is high in water soluble phytochemicals, such
as diallyl sulphides and garlic oil (i.e. essential oil obtained
from the distillation of the cloves) [4] .
Two garlic preparations, namely garlic oil and garlic
powder, have been evaluated for their potential to affect
CYP enzymes in clinical trials. The results suggest that
garlic oil may selectively inhibit CYP2E1, but not other
CYP isoforms (such as CYP1A2, CYP3A4 or CYP2D6)
and that garlic powder has no effect on CYP3A4 [54–58] .
Recently, it has been shown that a 21-day garlic treatment
(aged garlic extract) induces intestinal expression of
P-glycoprotein without aff
avalaible on web or pdf
Interactions between Herbs and Conventional Drugs: Overview of the Clinical Data
or pdf
www.karger.com/Article/Pdf/334488
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