riba pre dosing

[cruelworld]

what would be the down side to a two month riba pre dose ramp up to over dose levels for a naive patient? EPO allowed if needed.
riba monotherapy does bring UND (not svr) to 10% of patients.
would you start your "time to UND" at the first INF shot? or would that time frame be diluted (extended) to include ramp up time?

[jmjm530]

LOL. Maybe you could use some riba mono therapy to curb that appetite.

[drofi]

Ok, good arguments.
Which pink bonnet?

[jmjm530]

BTW I pictured you different from your profile image. Not that you don't look smart in your pink bonnet.

[jmjm530]

Wasn't just referring to that study. Ribavirn's been in use for over 30 years. Do you have any studies or papers to support your theory that ribavirin is any safer used with interferon than when used alone? All these drugs are toxic, it's all trade off. Also keep in mind that with ribavirin's long half life (and peg's relatively short half lfe) that you are in effect on ribavirin mono therapy for some time after you stop SOC.

-- Jim

[drofi]

in studies you can do nearly everything, as far as you are able to convince the ethics comitee.
The study had n=19 only and it is not a good argument to write "it has been used for for time now". There are many stories of medical substances, which have been used "for some time". Do you remember the Contergan-story?

[jmjm530]

Drofi: The SPCs say it is not allowed to use Riba as a monotherapy. Why?
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My guess is because riba monotherapy has proven ineffective in terms of SVR. But that's not what we're proposing to use it for.

Here's a riba monotherapy study that administed riba alone FOR SIX MONTHS, not  a few weeks. I assume if riba alone was that dangerous, this trial would not have been run. The trial had to do with dosing riba post treatment in non-responders. It didn't work out, but that's a different story.
http://www.hivandhepatitis.com/hep_c/news/2005/ad/061005_c.html

[jmjm530]

You might want to research this out for yourself, but my understanding is that ribavirin has been used as monotherapy for a number of different reasons for some time now. Doubt if a few weeks or riba without the Peg would pose any additional risk. It's the prolonged use of Peg, that's the problem as I see it. So...if you can use more riba with the net of ending up using less Peg...that would be an excellent tradeoff IMO.

-- Jim

[drofi]

Riba is mutagenic to  the virus and human cells too.
http://tinyurl.com/yo8jh9

I do not have any data how high the risk is. The SPCs say it is not allowed to use Riba as a monotherapy. Why?
Ok, the SPCs tell a lot. If I would follow the SPC exactly, my SOC would have stopped in week 4, when I had a pletelet count of 21.000. I did not stop.

[cruelworld]

that was the contrary opinion i was looking for.
mutagens are a possible worry but i think in truth the opposite is true, it defeats the mutations
isnt the cancer risk extra low?

[drofi]

The idea of predosing is nice. There ist one drawback: Ribavirin is a well known mutagen and even the SPCs write it could cause cancer. Interferon activates natural killer cells, which destroy not only virusinfected cells, but new tumorcells too. This should give SOC a balance of induction and protection of cancer. Hmm, difficult to have a clear opinion.

[copyman]

almost my plan. when i treat i will pre-dose and double peg first 4 weeks, if not unde then i quit and wait for better rx. this of course would be with SOC if i can not get into next vx trial.

[jmjm530]

And finally -- assuming UND at week 4 -- consider doing the short course, stopping at week 24.

[jmjm530]

Meant to say in part "would substiture double-dosing Peg until UND instead of injecting Peg every five days..."

[jmjm530]

I prefer not to give out my treating docs name for a number of reasons, including privacy. However, I consulted with at least two doctors who were willing -- and eager -- to work with me on unorthodox approaches including very high dose ribavirin. Ironically, it's often the bigger name docs willing to do this sort of thing as long as there's reasonable science behind the approach. These are the fellows who run trials and often deviate from the standard 'cookbook'. Doctors like Dr. J. and Dr. D. in NYC, Dr. A. in Boston, Doctor S. in Miami, etc. What your friend wants to do outline a potential strategy and then present it to one more more treatment doctors prior to treating. You'll find out soon enough who will work with you and who won't. The approach you describe is quite reasonable, although I think I would substiture double-dosing Peg until UND with injecting every six weeks. I would also like to see very close to UND by week 4, and as you suggest, UND by week 6. You will therefore want an agreement with your doc to do weekly viral load tests starting at week 1.

Good luck with both your treatments.

-- Jim

[cruelworld]

i have a friend who will start soon (naive) with stage 2 and  2.5 million iu viral load.
typical profile otherwise.
ive recommended they get pre riba concentration up and dose peg every 5 days.
since the urgency is low (stage 2) i recommended quitting at 6 weeks if not UND.
they may have trouble finding a doc to do this. can you guys give your docs name
since they are both acceptable to these stategies (at least in your cases)?

[jmjm530]

On the other hand, if you plan on ramping up the riba to tolerance using weekly cbc's and possibly Procrit, a longer time frame might allow more tweaking of dose and less chance of over doing it.

[jmjm530]

This suggests that "steady dose" of riba concentration could be achieved in 4-weeks, so that might be a good number to start with for pre-dosing.
http://www.medscape.com/viewarticle/416602_2

[FlGuy]

I pre-dosed for a week with the rationale that Jim mentioned in the first comment.  Docs were on board with the concept and willing to see me take the chance.  But, alos double dosed peg for the first four weeks.  Together, to get to und as soon as possbile and to be as und for as many weeks as possible.  I got to und at week 2, have one week left and then see how it turns out.  As a relapser with early cirrhosis. I felt the aggressiveness was worth it.  More than two weeeks of pre-riba seems a little excessive.  But, who knows?

[jmjm530]

desrt: My bad for mixing absorption and half-life issues. Still interested to see any proof that pre-dosing has any meaningful effect. Can't find anything in PubMed or anything by Lindahl.
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Our posts crossed. I couldn't find anything either -- one way or another -- and hopefully that point has been made previously -- that while intuitively intriguing (at least to me) no hard data appears to exist as to its efficacy.

[jmjm530]

desrt: 'd be interested to see any proof that pre-dosing for more than a day is anymore effective...
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If you do some "googling" you will find the Swedish pilot study using high dose ribavirin. In the study, they measured serum ribavirin levels using HPLC (high performance liquid chromatography). It does prove that riba takes a few weeks to build up hgher levels in your system. This does not prove that it helps SVR -- not studies I'm aware of on this -- but it does prove that pre-dosing will result in a higher serum riba level the day of your first peg shot than if you simply followed SOC and took the first riba pill that morning.

-- Jim

[desrt]

My bad for mixing absorption and half-life issues. Still interested to see any proof that pre-dosing has any meaningful effect. Can't find anything in PubMed or anything by Lindahl.

[jmjm530]

Got cut off, begin again....

Not true. Ribavrin does have a "hellaciously long" half-life -- TWELVE DAYS to be exact. The reason you take riba twice a day has nothing to do with it leaving the body but more to do with minimizing side effects such as gastro or that riba 'buzz' when it first enters the system. Ribavrin is also saturable, meaning only so much can be absorbed at any one time, but that only becomes important when dosing over 2000mg/day which is beyond SOC.

-- Jim

[jmjm530]

desrt: Riba moves into and out of your bloodstream in a matter of hours - not days, not weeks, not months. It's why you have to take the stuff twice a day.
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Not true. Ribavrin does have a "hellaciously long" half-life -- TWELVE DAYS

[desrt]

www.dhs.ca.gov/ohb/HESIS/riba.htm