JIM ,HR or anyone pre-dosing Ribavirin

[St. George]

  I'm thinking of pre-dosing riba for a couple of weeks before starting treatment and was wondering if I should do that or just wait and add the increased extra medication I have in my possesion to my prescribed dosage, which will only be a paltry 1,200 mg.  By the way  I am 6 ft 200lbs and feel that the 1,200 mg's he prescribed may be to low .  What is the weight based formula I shoud be receiving?

[copyman]

do you plan to add anything else like alinia to the mix? since you have already treated and failed what makes you think pre-dosing will work. why put yourself through this again with just the same drugs? can you get into a trial for noresponders with a new drug to add to SOC? just my thoughts on this. i do wish you the best, i'm a firm believer that anybody that has the guts to do it all over again deserves alot of credit.

[Proactive]

Thanks for the explanation....You certainly did a custom tx this time!!! Best of luck with your upcoming pcr.....we're rooting for ya.....;^)

[FlGuy]

46 is Strange. Here is how it came to 46.  With the Peg dosing plan with the doc, I did not want to involve insurance in the double dosing plan just to have them throw a monkey wrench in the whole plan.  I was approved for 48 doses of Peg. My wife works in the med field and scrounged up 2 Pegs, so I had a total of 50.  Since I doubled the Peg the first 4 weeks, I ran out after week 46.  The the liverhead I saw in a consult said   "if clear at 4 do 48,  and if not clear by 4 do 72' .   I thought 46 was a nice number since I was clear at week 2.  Since I am geno 3 and did a grown up dose (1200) of riba this time I felt pretty good about the 46. If I was not clear by week 4 I would have had to do some scrambling.

[jmjm530]

I had my suspicions as well, and again, a shame that he stopped posting. Very bright man.  Maybe if you still have his email, you might tell him that "Jim" and others wish he would return. As to explaning that treatise in "words of one syllable or less" , not sure cando. BTW I think HR took a shot at the resistant quasispecies issue in regards to ribavirin and wasn't overly concerned. If he was, I'd imagine he'd be dead set against pre-dosing ribavirn, which he doesn't appear to be.

-- Jim

[desrt]

I'm thinking along the lines of generating resistant quasispecies outside the normal mechanism that keeps genotypes from changing.

RH
www.virologyj.com/content/2/1/10

RH II
www.virologyj.com/content/2/1/70

RH III
www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt=AbstractPlus&list_uids=17355620

...or just google replicative homeostasis.

You read it and explain it to me in words of one syllable or less.
Earlier this year I was trying to explain papers I&III and mangling it as usual, when I nice gentleman using Dr. Sallie's e-mail as a screen name came on and straightened me out. A couple days later sonic started posting - same vocab, same posting style. But you're right - pure speculation on my part. Maybe if I start butchering his work again, he'll come back ;-)

[jmjm530]

I do miss "sonicbandaid" and his professional contribution, however I think it speculation that he and "Sallie" are the same.

Sonic, as you may remember, was a big fan of ribavirin, as per this thread here:
http://www.medhelp.org/posts/show/98287

I also remember stubling though the "replicative homoeostatis" papers, but don't remember how that particular theory might contradict pre-dosing ribavirin. I'll try and look into it later, but maybe you have a link? Ribavirin has been on the planet a long time as monotherapy for one thing or another, so I don't see any obvious red flags.

-- Jim

[Proactive]

I'm curious how you and your doc decided on 46 weeks of tx? Just seems like an odd number. tia

[desrt]

Before you put any ribavirin in your body with no IFN present, try googling "Replicative Homeostasis", specifically "Replicative Homeostasis I" and "Replicative Homeostasis III" two papers by an Aussie doctor Richard Sallie who used to post here.
I don't entirely understand the concepts myself, but I might be reluctant to expose my virus to an RNA mutagen  without any IFN around.

[FlGuy]

A little recap.  I did pre-dose riba for a week (1200 mg) and stayed at 1200 per week for the duration.  The first 4 weeks I doubled the peg (2 x 180).  I was undetected at week 2 and remained undetected throughout tx.  Did a 3 week post-tx pcr and was still undetected.  The next pcr (a 3 month - post) is coming up on 12/14. So, the jury is still out to some extent.  I weighed about 185 going into tx.  G3a, early cirrhosis.  First tx failed was 24 weeks and 800 riba.  So, tx 2 was kicked up a notch and did 46 weeks, instead of 24.  By the way, you recent post about the infergen at 30 daily sounded scary.

[jmjm530]

Since you've had four prior failed attempts at treatment, I certainly understand your wanting to try something different. But as I understand it, the important thing in a re-treatment strategy, is first identifying as best as possible why prior treatments didn't work. Just to take one example, let's say your hemoglobin never budged during the four prior treaments. In that scenario, upping the riba dosage makes a lot of sense. But on the other hand, if you did have a significant hgb drop, then it might not.

Point is to try and identify what happened prior. Did you respond and relapse? Slow response? No response? Were you compliant? Hopefully, you and your doctor are taking all these different variables into consideration before formulating another treatment plan.

Also, if I had four prior failed treatments, I would seek out the advice of at least two well-known hepatologists before embarking on a fifth try. Logic here that I want to make sure I have the best medical input possible before going down a road I had so much trouble with before.

Wish you all the best,

-- Jim

[nygirl7]

What did your doc say about you doing a 1400 riba instead?  Even me - who was a very slim tall woman took 1200 (shhhh my doc only allowed me to up my riba by one pill but..what he didn't know about ;)    was about to handle the 1200 without any problem.  I ran the drastic anemia only after I was taking 1400 - 1600 a day which was double my weight based and caused me big problems.

There are so many pros and cons to pre-dosing the riba and I think Jim wrapped them up all well enough.  How many weeks have you been OFF treatment now? It seems so shortly again you were just starting on the long haul and already you are starting again with the same dogged determination.

Nobody can say that you aren't one of the most stubborn fighters of all time St. George and personally I cannot WAIT until you are SVR.

[jmjm530]

To clarify, my last paragraph referred to high-dose ribavirin. I think pre-dosing ribavirin is something worthwhile for anyone to discuss with their doctor.

St. George -- If I remember correctly, FLGuy did pre-dose for 2 weeks and was UND by week 2. Only one case, but quite extraordinary response compared to his last treatment. And, yes, I'm pretty sure he's SVR.

[St. George]

Thanks for the info.  I have enough riba currently from my past treatment to give me enough to pre-dose 1,200 mg's for 2 weeks.  i beleive that the fisr 8-12 weeks are when the high serum riba levels count based on my last 72 week treatment when I upped my riba to 2,000 mg's the last 6 moths of treatment only have that strategy produce dismal results.

[St. George]

Digging through old posts I read that you pre-dosed riba but I wasn't able to find any info if you SVR'd or not.   Did you?

[jmjm530]

I haven't been able to find any ribavirin pre-dosing studies, although someone did post here about a year ago which suggested that one such study may exist. If so, it appears to be a carefully guarded secret :)

That said, the concept of pre-dosing ribavirin makes sense to this non-medical professional on a logical basis.

Since it takes 2-4 week for ribavirin to reach maxium serum levels, then in a sense, if we don't pre-dose ribavirin, we are under-dosed for the first 2-4 weeks of treatment.. Or conversly, if we pre-dose ribavirin 2-4 weeks prior to starting treatment, then we will have maximum serum riba concentrations coincidental with our first Peg injection.

If I were theoretically to re-treat with the current drugs, pre-dosing ribavirin would be up there on my list to discuss with my doctor.

And that 'discuss with my doctor" part is very important, because pre-dosing ribavirin may mean among other things that anemia may hit sooner. For that reason more CBCs probably should be planned, and if you have a treatment history to look back on, perhaps earlier intervention with Procrit (epo). In fact, pre-dosing Procrit with the ribavirin might make sense let's say in someone who showed they needed it the first time around.

As to your proper dose, I think you still fall within the 1200 mg range at 200 lbs, although we all metabolize ribavirin differently. If you treated before with a similar dose and didn't have much of a hemoglobin drop, then maybe worthwhile discussing with your doc an increase.

Here's a weight-based study:http://www.hivandhepatitis.com/2005icr/aasld/docs/111805_a.html

In the famous small high dose riba Pilot study they actually based riba dosing on serum riba concentrations and not on weight. The problem here, if one wanted to take such an approach, would be no readily available serum riba testing using HPLC -- high performance liquid chromatography. So you'd either have to send yourself and/or blood to Sweden for analysis.

However, if the concept intrigues you and your doctor, there is a 'dirtier' way to gauge serum riba concentrations and that is by measuring hemoglobin response. The greater the response, the higher the concentrations. One using this approach, might therefore keep gradually bumping up their riba until they reached a let's call it a critical hgb point to be determined by your doctor and no doubt based on your individual reaction. Add Procrit to this equation, and you could add even more ribavirin and keep that same critical point.  

Of course, if you don't test hgb  frequently enough, of if you don't bump up the riba gradually enough, then you could end up in trouble and have to come off the riba entirely. That's what happened to me when I treated and though I could emulate the Swedish study.

For all the reasons, only try something like this under the guidance of a liver specialist (hepatologist) who is willing/able to test you often (as much as 2X week) and make whatever adjustments necessary.

I'm also assuming that someone trying such an agressive approach has a good reason to subject themself to additional risks -- such as significant liver damage and/or prior failed treatments.

-- Jim