More on High-Dose Ribavirin

[Califia]

a href=http://www.natap.org/2005/HCV/012505_01.htm>Editorial

LAIKA, you might want to check out the 3rd paragraph of  the Editorial under  "Article Text."    Drs. Lutchman and Ghany comment that  the studies under discussion "showed no difference in the SVR rate in patients with genotypes 2 and 3 infections using ribavirin doses ranging from 800 to 1,200 mg daily. Thus, the issue can be narrowed to optimizing therapy for genotype 1 patients."

Speaking as a SVR-hungry Geno 1, I wonder if it would be the height of idiocy to increase my daily ribavirin dosage from 1000 mg to 1200 mg?  I've been taking the lower amount,  according to the current  weight-based regime. There is a strong possibiliity that I would be subjecting myself to unnecessary toxicity, assuming that I'm predestined to fall into that lucky 50% who make it the first time out.    And then there's amping up the discomfort a bit in order to increase the odds for a good result.   Hmmm.....

What, am I nuts?  Maybe I've been reading Miles too faithfully, or I'm  actually a closet religious penitent who needs to suffer more to experience a closer encounter with the divine.   Should I banish these thoughts entirely?  What do you all think?  (Heck, it's Tuesday and things are a tad slow around here.)

[Laika]

After you say something a few hundred times, you get to be predictable!--just knew you'd say that!  I do pay attention, I just get lost in the differences between geno 1's and geno 2's.

I'll plan on going with the 1000 and see where it takes me.

Thanks a lot,
Laika

[TnHepGuy_]

Nope, doesn't change my mind at all.

I still firmly believe that the most important thing in tx is to go after it strongly, especially early on. Here is a respoinse to 'southernboy' that I just posted above with my line of thought in this area:

"<i>As far as the riba dosing goes, my general line of thinking is that the most important thing in tx, in terms of viral elimination, is to hit it hard and early. This way, if it is 'super-suppressed' early on and dosage reduction is eventually called for, there is a better chance that having lowered the viral quantity quickly, the lesser dose of interferon and/or riba will have a greater opportunity to maintain suppresion and continue onto final elimination. With that in mind, higher doses of each (especially the riba) early on would be called for - with the option of cutting back at a later date in time.</i>"


I believe that this approach is the best way to maximize the current 'standard' of tx, give yourself the best odds therein to achieve SVR and, hopefully only have to go through this torutre but once.


TnHepGuy

[Laika]

Does the recent study showing that higher doses of riba don't appear to increase chances of SVR w/geno 2's change your opinion that you gave previously on riba dosing?  I'm going to re-post it here, since it was sort of anonymous under another thread and others may be interested:

"Your goal going into tx is to do 24 weeks just once - and to defeat this monster virus. With that in mind, ask for and get the highest does you can of riba. If it's a choice between 800 mg and 1,000 mg - go for the 1,000 mg. It's role is most important early on in tx and if your hemoglobin eventually comes back below 10, you can either begin Procrit or cut back your dosage.

You want to give yourself every chance you can. Especially if you are to dedicate 6 months of your life to this.

Here's a paper that points out the importance of riba dosing:

Ribavirin Dosage Significantly Affects Virological Response Rates in HCV Patients Treated with Interferon/Ribavirin

TnHepGuy"

I thought if I slept on this issue for a couple of days, I would have strong feelings one way or the other, but it's still murky.  My main concern with taking the higher dose is giving myself new and possibly permanent medical problems, so if geno 2's receive no benefit in taking the higher dose, then why put my body thru it.

I would really appreciate your thoughts on this.

[Califia]

Really interesting commentary  --  definitely glad I  brought this up.  Yes, Hepguy as usual nailed the central issues.  The following info about  how riba works may be old news to most of us,  but it's a reminder as to how absolutely brand new this research is.   It was only five ago that Shane Crotty and his fellow scientists identified the mechanism by which ribavirin causes "error catastrophe"  in our favorite virus:

<a href=http://www.sciencedaily.com/releases/2000/12/001208073913.htm><b>Antiviral Drug Works By Causing "Genetic Meltdown"</b></a>

It's really a shame that we can't replicate the Swedish experiment by testing for serum saturation.  Without that, admittedly,  it's all sloppy guesswork,  but I'll remain within the parameters of the possible--the amount of riba I have available to me, as well as my physical tolerance.  If  I begin to feel cardiac discomfort, I'll discreetly retreat.  And it looks like I'll be adding creatine testing to the regular CBC's--my nurse shouldn't fuss too much about that, and it should give me a rough idea about what I'm doing to my renal function.   So Rev, sorry to disappoint but I'm leery of going for the truly heroic dosage.   But a moderate upward revision  might not be a bad idea at all.

[DoubleDose]

I have also read that the Viramidine seems to be falling flat when it comes to producing the same anti-viral impact as Ribavirin.  So, in otherwords, it seems the anemia is much less a problem, BUT the drug does not really work!  So I will be willing to bet that it soon hits the same ashcans reserved for amantadine, zadaxin, gamma interferon, and other greatly anticipated BUSTS!

Oh well...did we think this would be easy????

DoubleDose

[cuteus]

i read the same thing, riba had a higher svr rate

[Southernboy]

Hi Tn,

As usual a masterful summation of the problem and possible solutions.  One point that I have been thinking about.  It seems that different people clear riba at different rates.  This would seem to mean that dosage is not as important as plasma concentration.  In other words, 1200mg for one person will result in a higher or lower plasma concentration then 1200mg for another.

In the High Dose Riba study they were looking for a plasma concentration of approx 15mcg/ml, "regardless of dose".  My question would be why we are not routinely checked for plasma concentration and have dosages adjusted to reflect this.  $ perhaps?

Best to all,
Steve

[Docsgold]

Sorry, didn't see your second comment.  I really, really, really wanted to not get a 2 log drop so I could get off this **** at 12 weeks, but undetected, so I guess that fueled the desire to get this over with.  Of course, my thyroid was trying to blow out at that time.  Somehow I trudge on, have good days and crappy days.  Just keep checking in here and that helps me--and now the fact that I finish 4/15/05!!!!!!!!!!!
I hope it gets better for you, or at least that you get those rare 3-4 days out of the month where you feel normal.  Good luck and I will be thinking about ya.
PS  Say a prayer for me that the "spot on my retina" is nothing too serious and that my fasting blood sugar is normal.  LOL, I can't remember when I have had so much fun for 40 weeks.

[Docsgold]

When I found out about this disease and began to research the tx I found it was 1000 or 1200 mg dosage.  You know, I just can't remember if I ever asked him about the dosage.  I may not have heard about weight dosing until I was already on the 1000mg. (I'll be glad to think clearly again).  But as I already commented, it seems everyone's physician or clinic does things a little differently.  I asked about future bx and he said if you are clear at 3 months post, no need.  I will get a 3 mo PCR and then again at 1 year.  Some get one at 4 weeks...well you get the picture.  
I live in Louisiana and see a GI doc who specalizes in hepatology. He did tell me of one remarkable patient, male, 70 yrs, Geno1 who decided after 12 weeks that tx sucked and quit.  Been clear ever since.  I am very pleased with him so far.

[Califia]

Thanks, Mom, I probably needed that!    Because of the low thyroid situation, I've currently achieved a fat and sassy 135, still well within normal weight range,  but you're right--it's probably not enough ballast to handle a dosage for people carrying an additional 30 lbs.  Yup, crazy alright., and that I can't blame on the treatment.  

Wait a minute!  I _can_ blame the treatment.   I'm incredibly anxious about going through all of this por nada.   Chompin' at the bit here, like everyone else.   When I first started, I thought I'd be satisfied with fibrosis reversal.  Now I'm in this gonzo go for broke state of mind...

I know, I know,  calm down and eat my beet greens.  It's all good (?)

HEPGUY:   These studies drive me nuts.  I have a firmer grasp of deconstruction than scientific logic, that's for sure,  but I wonder how these dosing regimes are determined in the first place.  For one thing, why the cutoff at 165 lbs and not 125 lbs?   (I mean, ever seen any toxicity studies on this?)   And if a dosage decrease post-20 weeks doesn't negatively effect (lousy) SVR rates, does it logically follow that an increase, once the body adjusted to the earlier dosage,  also would not affect SVR rates?    I understand that everything is measured according to a cost/benefit ratio,  and that there is a limit to the amount of Procrit  your average insurance company will willingly pay for, but why a 1200 mg upper limit on the riba?   Toxicity is terrible, but so is putting geno 1's through lengthy treatment that is only hit and miss.  

Just some neurotic rhetorical questions for everyone's entertainment....

[honey1616]

Califia,,,,you ask "am I nuts"....hmmmm wondering here..lol
I can definitely tell you are feeling better now and what are you thinking???  That you want to crash and burn again?  If I remember correctly,,,,you were having problems a few months back before the hand came into play with,,,,Chest Pains!  Right?  You are taking 1000 now or at least before past 2 days of 1200...What is your weight?  Is the 1000 within those limits of your weight?  I know you want to clear but seriously,,,I don't want you to do anything you can't handle at this point,,,Does your dr know or is this your dirty little secret? ha   You have been through quite a bit through your tx now and wouldn't it be great just to end it on a good note?  Or are you afraid you are not doing enough to conquer this last round?  Only you can answer these questions and ask yourself if you are putting your health in a bad situation?  If your dr says its ok to up the dose,,,,then a great idea because only he knows your current situation....

Rev,,,2500?  LOL  I was on 1000 and know if I took that much,,,I would need a full time caretaker just to check my pulse on the hour...

[TnHepGuy_]

Yep, good dectective work. That's the one I was thinking of. In fact, here's a more complete look at the same study:

<a href="http://www.natap.org/2004/HCV/041304_02.htm">Treating Non-Responders with Pegasys plus Ribavirin: HALT-C Study</a>

(from the paper):

"<i>...SVR was adversely affected by reducing the dose of ribavirin during the first 20 weeks of therapy....</i>"



Some more stuff:

<a href="http://www.natap.org/2004/HCV/030404_02.htm">Peginterferon-alpha2a (Pegasys) and Ribavirin Combination Therapy in Chronic Hepatitis C A Randomized Study of Treatment Duration and Ribavirin Dose</a>

(from the paper):

"<i>...Patients with HCV genotype 1 achieved the highest sustained virologic response rates when treated for 48 weeks with peginterferon-{alpha}2a and a standard dose of ribavirin. Decreasing the treatment duration, ribavirin dose, or both markedly decreased sustained virologic response rates in this group....</i>"



Be sure to keep a sharp eye on your red counts.


Happy viral-smashing.



TnHepGuy

[lackalustre]

been there done that.  lloyd wright, dr. zhang.     spent a lot of money and didnt get well.  i also worked with a herbalist from canada at one time.    finally did tx.  beat it.

[Tallblonde]

Yep, that's what I figured.  I don't plan on doing treatment for awhile though (lots of good reasons), so I'll continue to do whatever I can to keep me and my little o' liver as healthy as possible.  

Take care,
Susan

[Tallblonde]

Thank you very much.  I'll definitely take Dr. Zhang's website more seriously.  His low-dose sublingual interferon treatment caught my attention.  I wonder if it would be appropriate for someone like me with a scant VL of only 714 IU/mL.  I'd love to think that a few oral doses of interferon would knock this bug out of my system, but that just sounds too easy, doesn't it?

Susan

[Laika]

Thanks for the post.  Now I can go back to wondering, 800 or 1,000?  1,000 or 800?

You are so funny tonight! Can't believe you've boosted your riba dose and it's having this effect...well, not everything is the disease or the meds, before all that there was a person, personality, etc., right?

[Califia]

Uh huh.   :)

[DH Bill]

If you remember I was on 1400 mg for the first 6 months of tx until I changed provider and the new one would only approve 1200 cause that was all the charts would approve copegus.

I think it made me crazy and f#$*&d up but I'm undetectable at 6 mo. post tx???????? BTW 1-b

[TnHepGuy_]

Why the dosing numbers? Same as: why 48 weeks and not 52, say?

Alot of it appears to be educated (or lack thereof) guesswork, plus the use of regiments they are familiar with (like the 12 week increments), plus very limited amount of study work done to determine differing doses and differing regimes, plus the desire for simple and neat boxes to fit "things" (read: patients) into. And once all of this becomes the "standard", there is great resistance from doctors, insurers, etc to deviate from the now "norm".

I believe two of the biggest factors that cause this on the doctoring level of medical care are: 1.) fear of lawsuits (i.e. - "There is the chance that this is gonna come back and hit me in the wallet, BIGTIME!!!") and pure, unadultered laziness - whether born out of lack of knowledge, overwork, fear of change - you-name-it.

As far as toxicity studies, they are out there from the Phase I, II, and III trials that were done involving riba as part of combo. But I think the one on the super-dosing of the 10 patients is a pretty good indicator of what toxicity-to-the-max is all about. Hell, they had one person taking 4,000 mg!!! You'd think that this patient wouldn't have one functioning red cell left, wouldn't sleep one minute during all of tx, would be one solid skin eruption, would have so much anxiety he/she wouldn't need quarters for the motel vibrating bed and could kiil others just by being in their general vacinity. But 8 out of the 10 finsihed all 48 weeks. And the other two dropped out for non-riba related causes.

As far as the body adjusting to an earlier dosage level, I personally don't think the body ever truly 'adjusts' to any dosage level in the cases of riba and interferon. For example, my Hg level 'settled out' at about 11 for the majority of my tx. Then in the last 6 weeks it tanked to 9.8. If the 'body adjustment theory' were true on riba, I should have held strong forever at 11.

The bottom-line question is: do you think that this dosage increase to 1,200 will really be doing anything to up your SVR chances, especially at this stage of the game? I would say do it as long as you safely can. You are also thinking/hoping/trying to extend your tx. If you are actully successful at meeting that goal, then your time on the increased riba dosage will (logically) be extended along with it.

Perhaps one way to look at this is: you took 4 weeks beyond the the standard week #12 to reach serum clearance. That in-and-of-itself would push the "riba-becomes-less-important-at-week-20" date out to week #24 for you. But I think that may very well be understating it in your case. I believe that most geno 1 patients who show clear at week #12 actually don't become clear that particular week (or the day before testing). They become clear within the weeks preceeding that, thereby adding more "clearance-time" in their overall tx. Let's say, for example, that the average point-in-time of serum clearance for geno 1's is at week #8 (purely a guess on my part). If so, then the average geno 1 would have a grand total of 40 weeks clear. If we were to take that theoretical number of 8 weeks and apply it to your case, that would be a total of 8 extra weeks for you beyond when you reached clearance (week #16) (ie. - the 4 weeks extra beyond week #12 plus the 4 weeks before week #12 that the average patient reaches clear equals a total of 8 extra weeks in your case), which would put you 8 weeks behind the average geno 1 patient. Also, in that case, the "20-week-riba-importance-date" now is at 28 weeks for you (because in the case of a geno 1 who clears at week #8, they would have 12 more weeks of clear to get to the "20-week-riba-importance-date". In your case, 12 weeks post serum clearance would take you to week #28. (This is all theoretical on my part - not supported by any facts or studies - just some guesswork).

My personal thoughts are that riba is important all the way through - no matter what limited dosing range (i.e. - testing only from levels of 800 mg - 1,200 mg) past studies used. Those numbers were chosen because they were happy with the bang (read: SVR rates) they were getting for the buck, all the time trying not to expose themselves to too many lawsuits. Remember, this disease is considered "non-life threatening". Therefore there is no need (nor desire)for drug companies and the FDA to go out on a limb to test and approve something that pushes the limits of toxicity. Better, simpler and easier to play it safe and avoid the potential for problems by finding a happy medium -  where you get a certain number of SVR's for a limited and lesser range of dosing. I think this recent super-dosing pilot study blows all that completely out of the water. If I ever have to do this all over again - and can find a doctor who would work out-of-the-box - I would go for as large a dose of riba as I could (but hopefully Viramidine would be approved by then).


TnHepGuy

[mbn]

I  know  nothing..

[Califia]

Good memory!  Seems to have come through treatment nicely intact.  You were referring to Schiffman's report from the Halt-C Trial which shows that dose reduction of either pegintereron or riba within the first 20 weeks of tx lowers SVR rates substantially, and that reduction after 20 weeks does not:

<a href=http://www.hivandhepatitis.com/hep_c/news/2004/042404_a.html>Selected Non Responders to Prior Interferon-based Therapy Can Achieve a Sustained Virologic Response (SVR) Following Retreatment with Peginterferon Alfa-2a (Pegasys) and Ribavirin</a>

Well, true confession time.  This is Day 2  on 1200 mg riba and I am feeling especially poisoned today.   Bleaaah!   Not sure I want to keep this up.   DOC'SGOLD,  how the heck do you do it?  

[cuteus]

oh heck!
I miss one day and I miss the "fun"!!

flaming and missing posts, huh?
I never would Have guessed!

[Califia]

TALLBLONDE:   Way back in the early 70s, Dr. Zhang trained the person who's been treating me for many years (Misha Cohen, OMD).  He has an impeccable reputation in the TCM community and beyond.   I do feel that his formulas are way over-priced, however.   But he maintains a practice in Manhattan, and his office overhead must be pretty high.   At any rate, the man is the real thing -- a master herbalist.   And before he decided to go for it financially he spent many years treating low-income and drug-addicted patients.

So slagging off Mr. Wright constitutes flaming?   Mea culpa!

DOC'SGOLD:   Maybe I'm getting a tad obsessed with this weight issue, but it's interesting that your doc has you taking 1000 mg of riba at your  low weight.  Any reason given for this deviation from standard dosing practice?    What medical center are you with?

[Tallblonde]

The Lloyd Wright thread below has mysteriously disappeared!  I posted a question there for you, so I guess I'll start again here.  What, if anything, do you know about Dr. Zhang?  He's highly recommended by Dr. Andrew Weil, but that's all I know about his reputation.  I'm very interested in your opinion about his approach to HCV.

Thanks!
Susan