Dosage reduction. Cr@p. Impact??

[Trish77]

Well, I finally pushed my luck.  I just got the call.  I've been so obsessed with the damn lymphocytes and whites and it's my reds that got me.  I'm down to 9.6 and they are forcing a ribavirin dosage reduction.  I have to go from 1200mg to 1000mg immediately and indefinitely.  Trial protocol.  Not procrit.  Ribavirin reduction.  My ANC is 1.8 and my lymphocytes are down to .4 .. so no INF reduction because my ANC rebounded enough to offset my lymphocytes.  

Indefinite riba reduction.  I'm very strong about my feelings on the importance of riba.

I don't go for my next blood test until July 4th and they are reducing it until I get the results of that test back  

Today is Week 17.   I was UND by Week 6.

Most of you know I'm on the R1626 trial.   My choice here is to go with the dosage reduction .. or ... not.  Which means dropping the trial.  

I would like to have your feedback on the potential impact of a dosage reduction at this point, for about the two weeks I'm facing right now and potentially longer.  I'm thinking...as long as I can get back to normal after July 4th, I'm good.   Longer than that .. I don't know.

I would appreciate any input, thanks.

The odd thing .. is that I feel pretty good. Not like I'm doing anything overly physical but I'm working fulltime and staying very busy. I'm starting to think I've turned into a tx automaton.  Just keeping on keeping on.

Trish

[mremeet]

In my opinion, I don't think the 1200 to 1000mg riba reduction is that big a deal at this point in the game. You did go UND by week 6 which is very good performance (compared to average SOC response rates), and you have maintained an UND status using a sensitive PCR for several months afterward. My very experienced hepatologist told me that riba reductions weren't the end of the world as long as they happened well after going UND. And that's certaintly what's happened with you. Plus at your weight, it's hardly a real reduction, you're basically on weight based dosage at 1000 anyway. If you're going 48 weeks I think you can get away with it, but then of course it's guesswork considering there's no SVR data on this new polymerase inhibitor that I know of. But we do have a feel for SOC alone and I think you're doing fine. Also, did you consider breaking one of the pills in half and take 1100 a day? Or take 6 pills one day and 5 the other alternating every other day? They may not let you do that, but if you "pleadingly" ask your doctor he might be willing to try it, especially if you tell him you feel little effect from the anemia. It's still a dose reduction and you are close to the threshold, so maybe he'll go along with it; at least until your next blood work comes in.

Good luck finishing it up, wishing for your SVR.

[Trish77]

zazza, thanks for that info.  I'm on pegasys, Roche trial, Roche drugs.  I didn't know there was a difference in requirements for each.  God I love this forum.  I hear you.  I am wrestling with it.  I have no problem with 9.6 but the trial does.  Same with reducing dosage every other day.  It's what they tell me, not what makes sense to me.  That is my dilemma.  Furthermore, barely missing the INF reduction week to week .. I need to sort out my response to that if it comes, particularly in light of a riba reduction.  

Thanks for your input, appreciated.

Trish

[zazza]

I understand it to be that Rebetol (the Schering-Plough ribavirin) is dosed at 1000 mg for 65-85 kilo, and Copegus (the Roche ribavirin) is dosed at 1200 mg for 75 kilos up. So are you on Pegasys and Copegus then, since you have been on 1200 mg ribavirin?

At your weight of 77 kilo, 1200 mg is 15.58 mg per kilo, and 1000 mg is 12.98 mg per kilo. I've heard that between 13-15 mg per kilo is a good amount for geno 1's. So I think you would probably be fine with either dose, but still, if it were me, I would follow Jims and Mikesimon's advice and drop out of the study and stick to 1200 mg if possible.

I have myself done the every other day thing that was suggested above and did drop to a hgb of 9.4, and I had no problems with that. I weighed 75 kg and took 1200 every other day and 1000 every other day.

Best of luck to you in whatever you decide.

Za

[Trish77]

Willy..thanks for the links on 80/80/80.  

I did read the first one, couldn't get to the second one right away and it's now 1am and I'm running out of steam so will save that for another time.

I read some other articles on this and my conclusion on the 80% rule is not that we are safe to take down to 80% of our dosages but that adherence of 80% or higher produces better results for genotype 1's than adherence of less than 80%.  

The following reference states that the concern with the 80/80/80 rule is that people will misinterpret and set a lower threshold for adherence when the actual message is the more adherence the better.  

http://www.hcvadvocate.org/hepatitis/factsheets_pdf/Adherence.pdf

"However, the 80/80/80 rule is controversial
because it has not been studied in well designed
prospective clinical trials. Another concern is that the
80/80/80 rule may be sending the wrong message about
treatment adherence since it sets a lower threshold for
taking medications rather than encouraging people to take
100% of the medications, 100% of the time or as close
to 100% as possible – especially during the first twelve
weeks of therapy."

Thank you .... it has added to my big picture to read this ... which I'm getting much closer to completing.  

Trish

[comeagain]

You know what this is about some dragons wont die that easily.

Look at some warries here, they go out over and over again aginst the dragon.
Some just wount settle with that the dragon might be dead they go out in the swamp
to see for themselfs they demand to have strongest possible doses and demand to extend treatment.

I thought my dragon was dead and  24weeks was enough, now i have him there again
looking all dead but this time I´m gonna sit on that sword for another 24weeks and twist
and turn it around and around untill the motherf...cker finally hopefully is completely
dead .

I thrust you gonna follow your true self.
good luck whatever you decide.

ca

[fretboard]

Unfortunate decision to have to make, especially since it's really gonna matter on how comfortable you are going to be, if you go with the riba reduction.  Obviously you are trying to find out as much as you can, however and this is the hard part.  The only ones who have any information as far as the most recent studies concerning riba reduction and your particular study drug are the staff at your trial center.  Tough decision, indeed.  At the conclusion of this study it says "Treatment of CHC should be tailored to individual patients, especially those with renal dysfunction, and should include agents that treat the side-effects of CHC treatment".  That conclusion doesn't help you much, I know.  I just thought I would give it a try to find something for you and I really didn't have much luck.  Oh pubmed, and that other site Hector uses are about the best and more current sites that I know about.  Good luck with your decision.  God Bless

Martin P, Jensen DM.
University of Miami, Miami, Florida, USA. ***@****

BACKGROUND AND AIM: Current practice guidelines recommend that individuals chronically infected with the hepatitis C virus (HCV) be treated with pegylated interferon plus ribavirin. Ribavirin, however, is associated with serious adverse events (AE), especially anemia. We review its mechanism of action, its importance in treating chronic hepatitis C (CHC) patients, the AE associated with its use, and techniques used to lessen these AE. METHODS: Medline searches were performed using the keywords ribavirin and hepatitis, together with the keywords mechanism, anemia, liver transplant, renal function, pharmacokinetics, and dose reduction. Searches of abstracts of recent Digestive Diseases Week, American Association for the Study of Liver Diseases, and European Association for the Study of Liver Diseases meetings were also performed. RESULTS: Ribavirin may be effective in treating CHC by affecting the virus or the host; for example by inducing viral mutations, blocking cellular enzymes, or affecting the host immune response. Although the pegylated interferons are the primary drugs used to treat CHC, a combination with ribavirin is more effective than pegylated interferon alone. Ribavirin-associated AE may be lessened by ribavirin dose reductions and by maintenance of the hematocrit. CONCLUSIONS: Treatments of ribavirin toxicities, especially anemia, can allow patients to continue full-dose combination therapy with peginterferon and ribavirin, enhancing their probability of attaining a sustained virologic response (SVR). Treatment of CHC should be tailored to individual patients, especially those with renal dysfunction, and should include agents that treat the side-effects of CHC treatment. Monitoring of plasma ribavirin concentrations during treatment may help in the future.

PMID: 18565019 [PubMed - in process]