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223152 tn?1346978371

Pre-dosing Ribavirin

I wondered what the thoughts were on pre-dosing ribavirn in conjuntion with triple therapy.  I will be doing the 4-week lead in for Victreslis soon (I hope) and wonder about predoing with ribavirin before the 4-week lead in.  My doctor prescribes to the Victrelis labeling --- that is, 100 IU/mL at week 12 means end of treatment.  That scares me and I want to do whatever I can to make sure I am clear at 12. I figure this is a last chance now that I am stage 3-4.

Searching the archives I found this comment by HR

"The predosing of riba holds good theoretical merit, since the effective concentrations are not reached quickly with riba and also because "riba resistance" is not a likely quality that HCV could easily obtain"

Sounds like win win to me.

What do some of you thinK?
frijole
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Avatar universal
Thanks so much for your post!!  That is some great info that I will be able to reference when I talk with my doctor this fall.
Helpful - 0
979080 tn?1323433639
Actually I had posted that study to willing because it showed that Riba can boost
your platelet count during mono which happend to me.
I predosed , highdosed and extended  tx.
It also showed that HgB decline during mono was not associated with initial virological kinetics.

Here is a study that showed continuous high Riba serum concentration thruout tx (wk4,12,24,36,48) is what improved SVR.

http://jac.oxfordjournals.org/content/early/2011/02/22/jac.dkr034

as willing stated above:

"Pre-dosing doesn't increase the total amount of rbv in circulation - it simply ensures the pump is primed when the ifn hits."

Higher Ribavirin dose is what increases rbv serum concentration and circulation.

b





b
Helpful - 0
223152 tn?1346978371
trish
That is a good thought.  I wonder if the doctor would go for a little pre-dosing.  I may give it a shot.  The data presented does show a slight edge. HOwever the insurance company is the big preventative here.  I am not sure we could get thru their block.
Helpful - 0
Avatar universal
What I meant to add was.....perhaps, just perhaps....presenting that to your doctor will be enough to let him toss you a script for some extra weeks of riba, if you wish to go that way.

Trish
Helpful - 0
Avatar universal
frijole...I caught willing's comment on pre-dosing ribavirin being presented at AASLD 2010 so had to go looking.  Interesting stuff.  The data presented at AASLD refers to it as "ribavirin priming".  

willing - thank you for the pointer and hope your holding pattern is holding.  

http://www.hivandhepatitis.com/2010_conference/aasld/docs/1214_2010_a.html

Pre-treatment with Ribavirin Improves Response to Interferon-based Therapy for Hepatitis C

B. Fueloep and colleagues retrospectively analyzed the effect of ribavirin monotherapy followed by standard combination therapy (pegylated interferon plus ribavirin) on initial decline in HCV viral load and overall treatment outcomes.

Addition of ribavirin reduces the risk of relapse after completing treatment, and therefore increases the likelihood of sustained virological response (SVR) to interferon-based therapy. Ribavirin is a weak inhibitor of the HCV NS5B RNA polymerase in vitro, but its mechanism of action is not fully understood.

This analysis included 93 chronic hepatitis C patients from 5 centers in Germany. Just over half were men and 78% had hard-to-treat HCV genotype 1. Within this group, 43 were treatment-naive, 28 were prior relapsers, and 19 were prior non-responders.

All participants were initially treated with ribavirin monotherapy, at an average dose of 15.2 mg/kg, for an average duration of 39 days. They then added pegylated interferon and continued for the usual standard duration of therapy.

Results

The average decline in HCV RNA during the ribavirin monotherapy period was 0.56 log.
Changes were variable, however, ranging from +1.07 to -1.76 log.
Viral load changes varied according to prior treatment status:

Prior relapsers: mean 0.67 log decline;
Treatment-naive: mean 0.48 log decline;
Prior non-responders: mean 0.28 log decline.
Patients with HCV genotype 3 showed the greatest viral load decline (0.95 log), followed by those with genotype 4 (0.6 log).
Platelet counts increased by an average of 24 mcl (range 9-49 mcl) during ribavirin priming.
ALT levels decreased by a mean 17 IU/mL (range 4-31 IU/mL) during the priming period.
Hemoglobin decline during ribavirin monotherapy -- an indicator of anemia -- was not associated with initial viral kinetics.
6 prior non-responders experienced larger and faster viral load decline after ribavirin priming compared with their previous treatment:

Week 4: 2.0 log after priming vs 1.2 log during first treatment;
Week 12: 3.6 vs 2.0 log, respectively;
Week 24: 6.0 vs 5.4 log, respectively.
At the time of abstract submission, 26 previously treated patients had undergone 6 months of post-treatment follow-up.
Within this group, 12 prior relapsers (44%) and 2 prior non-responders (36%) achieved sustained virological response.
"[R]ibavirin monotherapy induces a mild but significant decline in hepatitis C viremia," the investigators concluded. "The highest HCV RNA log10 decline after ribavirin priming occurs in patients with prior relapse and genotype 3."

Investigator affiliations: Gastroenterology and Hepatology, University Leipzig, Leipzig, Germany; Gastroenterology and Hepatology, Charite, Berlin, Germany; Gastroenterology and Hepatology, J.W. Goethe University, Frankfurt, Germany; Hepatology, IFI Institute for Interdisciplinery Medicine, Hamburg, Germany; Gastroenterology, Marienhospital Hamm, Hamm, Germany.

12/14/10

Reference
B Fueloep, P Rohde, P Buggisch, and others. The antiviral efficacy of ribavirin priming. A follow up of 93 patients treated with ribavirin monotherapy followed by standard combination treatment. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 980.



Helpful - 0
Avatar universal
Is there any way you can get your hands on some
RIBA that has not expired?

You want to give this your best shot if you're going to pre-dose.

I wish you the very best going forward.

Elaine
Helpful - 0
Avatar universal
Most dx.   when expired ..lose some of their potency( not all but most)  others yes can break down and change  completely.. I am going to get in touch with the  drug co. directly and see what they will tell me....proly......" don"t take after the expiry date" or "throw them out"  Thats when I will say  " thx. for your wisdom "  and then stare at the bottle for the next year or so  :)

Will
Helpful - 0
Avatar universal
copyman...interesting you say that . I asked  2 pharmacisists how long my riba  would still be good..and they both said the same thing   .."don"t take it after the expiry date" I said I didn:t know the date because it was not on the bottle....then they said " well throw them out" I said "thxs for all your wisdom"      In other words  ..they had no clue :)
Helpful - 0
Avatar universal
You know kathy i thought we would see alot more issues with insurance not wanting to cover these PI"s right out of the box........ So i was surprised that so many were not having any problems............... Sorry though that they are wanting to pick on you.

Willing, wondering how things are going in your tx, about finished right?
Helpful - 0
Avatar universal
Very interesting thought.
I also doubt a pharmacist will know about the science behind riba. I can't see them doing research on it. Well at least the busy pharm's where I live.
What I can see them doing is telling you not to take expired drugs no matter what.  Scared of malpractice.
Helpful - 0
223152 tn?1346978371
NYGIRL - tell whoever had you post that it is a valid point.  I wonder if the pharmacists would really know.

willing - glad to see you back
"you only need show up and serve your time, to collect  SVR"
just like monopoly, huh?  Hope that is correct.  I really do want to predose  but I really don't have enough to do much good anyway.

A note on inscos and the PIs -- BCBS of Texas will not approve Incevik.  The alternative coverage is not shown to be Victrelis, but rather Pegasys.  (They haven't denied the Victrelis yet, but we will see after the 4-week read.)  There must be other cos because the heppo says he has discussed this on a forum.  THere is just not enough time after the 4th shot and before the first dose of VIC to get the PCR done unless it is a quick test and done early in the week. .  That is why he told me I would get my PCR on Monday, after the Friday INF.  And even then, the insco may drag its feet.  I asked the specialty pharmacy to send the VIC with the first month's meds .  She said they would, but I bet the insco will halt it.

I think the issue BCBS has with Vertex is the monthly cost.  I believe over the entire tx, INC and VIC cost the ins co the same.  However the monthly charge is too high for the BCBS to bear.  So if VIC is $4600 (according to the BCBS website) I guess the INC is about $18-20K a month.
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Avatar universal
Trish nicely sums up the case for pre-dosing : if you don't pre-dose you are not getting full effect from your first couple of  ifn shots. Does this make a difference ? From the limited data on pre-dosing presented at AASLD'10 the effect is measurable but not very big. Pre-dosing doesn't increase the total amount of rbv in circulation - it simply ensures the pump is primed when the ifn hits.

The bigger question is whether to bother with all the various strategies for boosting ifn response (alinia, high-dose rbv, SAMe, predosing rbv, coffee, vit D etc.) in the context of triple. The answer depends largely on your past ifn response. If you are a relapser with past cEVR or close to it it doesn't seem worth bothering. The documented odds with triple (and no ifn turbo-charging)  are so good you only need show up and serve your time, to collect  SVR.

A past null or partial responder on the other hand would  want to do everything they can to boost their ifn response and measure the outcome at lead-in before starting the PI. The PI trials are not a good guide here - their objective was to get the drugs approved not cure difficult patients.

It's unfortunate inscos are basing decisions on  lead-in results but there is some sense to it. If someone RVR'd during 4w of soc why should they pay for a PI that will yield no additional benefit?  The harder question is whether they should pay for a PI among  those with less than a log drop (SVR odds drop to 30-40% with PI)  or less than 0.5 drop (null responders). That's a decision that hopefully sits with the Dr/patient, not the insco.

The Vertex  approach (collect no lead-in data, just take the meds and hope for the best) is simpler for the Dr (no difficult on-tx decisions, no arguments with the insco) and definitely good for the drug co (sell the PI whether it will do any good or not) but not so great for the patient (how much is the PI going to help me?)
Helpful - 0
179856 tn?1333547362
Someone asked to post this to you Kat and Michael you are NEVER last ;)

Someone should advise Kathy to check with a pharmacist and see if
ribavirin breaks down into something harmful when its shelf life has
passed.  Some drugs won't hurt (or help much) if taken after their
expiration date but some will break down into something you probably
should not be taking.  A pharmacist will know.




Helpful - 0
223152 tn?1346978371
mike
you were concurrent --- Honest, your post wasn't there when I started writing.
so you would not predose.

specta
You would predose.

Here is the other concerning factor.  I have looked thru the Victrelis prescribing information and can't see any restrictions on starting Victrelis.  They do say "subjects with less than a .5 log drop in HCV-RNA at week 4 are predicted to have null response."  However, they don't say to discontnue the treatment (I think).   However, according to my doctor the insurance companies want to see the 4-week data before they approve the Victrelis. (so what are they looking for -- if the VL is too low would they say I don't need the VIC or if it was too high they would cry "null responder" and deny the VIC?)  Probably one more reason he would prefer to treat with Incevik.  

Helpful - 0
Avatar universal
I would pre-dose even after experiencing the relentless anemia. In the first four weeks no victrelis and it would be great to bring the virus to it's knees (or close to it) before introducing it. You can back off on the riba or start procrit if HGB starts declining too rapidly, Hopefully you can get to that prized RVR before it hits too hard and give yourself the best shot at SVR

Vic suppresses the bone marrow rather then destroying red blood cells so the decline in hgb (at least from the vic) is generally slow and steady. Of course there is a chance that it could backfire and you seem well aware of that. As Lynda said and you are obviously aware monitor often if you are going to do it.

Good luck with whatever you decide,
Dave
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Avatar universal
I was last.
Mike
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223152 tn?1346978371
Last to first -
FL -They are small, aren't they. How can they hurt?  I would just like to get this show on the road!

copyman - no, there is no clinical data to support pre-dosing.  Yet under old SOC there were a lot of doctors willing to go out on a limb in order to give patients -- and I am talking specifically about hard to treat patients, relapsers, cirrhotics, and so on -- the edge.  With the PIs just coming out in May, none of the doctors are willing to do anything extra. I believe it would prewsent a liability issue.  I am sure, if I ask my doctor he would say no on the pre-dosing.  My doctor was a trial doctor for Telaprevir and Boceprevir.  Thus he has experience with what was in the trial.  However he is only willing to do the labeling protocol.

lynda - point taken.  I would have adequate hgb monitoring.

trish - you spell it out very well.  Your words are my thoughts.  I don't see how it will hurt to try to build that serum level of riba a few days early. I am prepared for anemia and willing has presented some good comparisons to know how much earlier that my happen with Victrelis.  It is a risk I am willing to take.

susan - unfotunately right now, treating is almost the same as doing a trial, except there is no placebo. Good luck with your trial.  Glad they allow rescues

hrspwrguy - good move - the desert to the mountains!  I was married in Fairplay!

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Avatar universal
I wouldn't mess aroundt.
The drug works.
I'd follow the prescribed dosing and get clear.
Mike
Helpful - 0
96938 tn?1189799858
I did it and I'd do it again. But, I just had peg/riba in the medical quiver.  Not sure if predosing riba with Vic lead-in might be counter productive or not.  The age-old question is: riba pills are small, how can they possibly hurt ya?
Helpful - 0
Avatar universal
It is not whether I agree with it not. The fact remains there is no data to back it up. Why chance anemia earlier and jeopardize tx. The PI has data to back it up, and that is virus is eradicated within days after starting. So in my opinion pre-dosing is meaningless. No reward for the risk.
Helpful - 0
Avatar universal
Frijole and others, who are not in a trial, have the pre-dose option, should they make that decision and they can get a doctor on board with it.  Those of us in a trial, there is not that leeway.  The trial starts with the protocol predetermined.  You either accept it, or you don't do the trial.  That's it.  Fortunately in my trial I'm in now, I found out from the beginning that they do allow rescue drugs and I'm glad to hear that.  Susan400
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Avatar universal
hgb ...must be low...can"t spell :)
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Avatar universal
HBG
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Avatar universal

Truth is there is no data on predosing or increasing Riba amt.with a P.I.....very good point lynda...extra vigilance on HGB.
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