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.
How would you feel about asking Dr. Dieterich for some advice about your situation now? He might be a good resource...
I'm sorry I don't have much knowledge about riba reduction, but I'm sure the others who do will respond as soon as possible. (I'm thinking that 1000 mg is still A LOT of riba and it might be plenty to keep the virus at bay, but it's just a guess on my part. I've "heard" that riba reduction after UND is "okay" but I don't have studies to cite.)
I'm not familiar with your trial drug. Is it a protease inhibitor? If yes, that might be a consideration in making your decision.
Cr*p is right! What a choice to have to make at this point in tx. You were on such a good roll, handling everything really well !!!
To be clear...I have no trial drug anymore. It stopped at Week 12. It's a polymerase inhibitor. To stop the trial drug at Week 12 instead of Week 24 was a potential dosage reduction. To reduce the riba is another. In MY eyes, anyway. Which will have a hard time being objective at the moment, admittedly.
My weight is 160 give or take. To me, 1200mg was just enough riba. 1000mg is too little.
I don't think it's when you go UND .. .it's how long you've been UND and how far along you are in treatment that matters when the dosage reductions happen. And that, I don't know...if I managed to get far enough along without the dosage reduction.
Btw.....nice to see you, pK. :) I hope you're doing okay..I owe you an email.
Are you talking quit, stop tx or jump out of trial and stick with the tx your way?
I would not stop at this point, can you reduce awhile to get the red's up a bit and than ...shhhh.....take that extra pill anyway? I know that is an 'ethical' thing in a trial, but .....you could tell them afterwards??? At a loss here as you were UND by week 6 and would hate to see you stop, do these weeks for 'nothing'. Trials are tricky as you don't want to change, do extra, not put that data in, etc. Through mine if I took less (on days I thought I was dying, I did a bit less Peg a couple times-NOT a good idea all!!) but I always told them.
Anyhow, I do think it'll be ok with 1000mg, while you'd prefer the 1200mg, it is still a good amount for you.
They have told you all that they can do; their hands are tied so to speak.
Yes, IF you can get your reds back up it may not be a great issue at all. Your chances of success are quite good based on your 6 week PCR results. The basic rules are 80% of the drugs at least 80% of the time. You've scored an early response. That's the best time to have your RBV up. IF you can keep the dose up it will help your odds but with each week that goes by it may make incrementally less difference, particularly if your levels are already at recommended levels.
My understanding is that not all people process the RBV the same; your trough levels might be up there and it may not be an issue. IF they are low however a reduction could be an issue. You may make certain that you take yours with adequate fat to ensure best rate of absorbtion and compliance.
Understand also that if they are making a correct adjustment of your dosing they are recommending a REDUCTION which could prevent a treatment STOPPAGE of TX. Just as they have a level which they are forced to reduce the RBV they also have a score which if the patient hits it (yes, no matter how they feel) the treatment ends until the scores improve. I'm just saying; be careful. ; ) Stopping is worse than a reduction, no?
There could be another solution; the question is; aside from reducing RBV, is there any other methods of improving ones RBC? I believe there are. How is your iron? If you are pre-menopausal your iron may be low anyway. For whatever reason many doctors don't check that out before TX even though it is certainly one thing that can be adjusted before treating. IF your iron is low there are dietary things you can do, and supplemental things as well. I won't go into that here and now since it may not be the issue. Even so...... where do you sit with you iron scores?
Just a little "food for thought" for you. I also wanted to say that I'm pullin for you.
I see no upside in staying in the trial - for you, that is. If you have a doctor who will get you the treatment drugs and any rescue drugs that might become appropriate and order your lab test I would be gone in a heartbeat. That's probably selfish insofar as the trial is concerned but I would want to get well and that would trump the trial. Mike
Based on what I remember as a robust activity and QOL level for someone on treatment, I'd take a guess that if you were a private patient there would be no reduction in ribavirin and that Procrit (epo) might not be necessary. Unfortunately, trials often do things by the numbers per their protocols and have often have little leeway. Some people can do quite well with hgb in the 9's without a dose reduction and without epo. Others, like myself, needed Procrit when their hgb was in the low 11's.
Don't throw the baby out with the bath water quite yet. One minor dose reduction may not make or break this depending upon you RBV trough levels. They can be checked. If they are low, then lowering them further is definately a bad move. If they are UP a relatively minor reduction may not impact them. Worth a look.
Same deal with your iron. Where is it? If you have low iron stores going on Procrit won't help you anyway? Where is your iron? Check that too? IF your iron is low there are pills and there is even iron by IV. Can they do this testing and augmentation if needed? Worth asking.
I agree with Mike S. that you could be at a critical point of the trial. Perhaps discussing your concern with them they might be able to take some proactive steps to answer your questions or provide some testing. That might be better than seeing you walk out on the trial. I think that many of us in "the states" may also have a simplistic idea of how one gets HCV chemotherapy; it may be different in Canada, eh?
Your goal is to avoid interuptions. IF you withdrew from the trial today...... you could face a very large interruption in your treatment. Research and THEN act.
It's slightly off topic..... but are you getting better care with the trial than you might by going to a private physician? Would your new private physician be up to snuff on the ins and outs of your current Roche trial and subsequent low neuts issues? IF you were to withdraw from the trial would some aspects of your current low neuts or other issues that could come up be dealt with better by the trial clinic or a new doctor?
I'm great at complicating things. I'm just saying throughly explore all aspects before jumping. I know your post is an effort to do this.
I DO agree that your primary reason to treat is to get cured. I think I also agree that you are still at a critical point in your TX. Do some research, some shopping and apply a little leverage and charm. ; )
You don't mention your weight - which might shed light on the potential impact of the dose reductin. I dropped 200mg toward the end of my tx, and the HGB rose very quickly in response - but I was on a high dose of procrit at the time. You could try reducing by 200 for a while - then do every oher daya for an effective reduction of 100. I bet that would get you back above 10, asssuming that's the magic number....
Willy: Research and THEN act.
Willy, I haven't decided a thing yet .. if you've noticed anything about me you'll know I'm going to think this to *death*.
Could you give me info on that 80 / 80 rule pls Willy? would be greatly appreciated.
The other thing here is that this ribavirin reduction came out of the blue. I didn't expect that. I've barely been missing the INF reduction week to week. We've been testing weekly and it's been touch and go. By rights, my lymphocytes at .4 this week would have been the INF reduction and my ANC at 1.8 instead of 1.5 saved me from that. If they both drop below the magic numbers at the same time, the INF reduces. How many weeks can I go without them throwing an INF reduction at me too? I need to think that out too because next they could be saying the INF has to go down too. And if that comes, I need to know how I'll respond to that.
I have plenty to consider here. I will reduce my riba by one today to give me time to sort through everything.
and Jerry .... I get that a great deal more than you may think. I'm a pretty serious kinda gal that way. Did not go into the trial lightly, would not leave the trial lightly.
Processing. And trying to work at the same time....TGIF.
I don't mean to pry into the "give or take" but 160lb is 72.7kg. Per the most recent, large-scale, study that found a significant advantage to weight-based rbv dosing, weight-based was "1000mg for patients weighing 65 to 85Kg". See Jacobson'07:
So IMHO it seems that this reduction puts you in line with current weight-based guidelines (I'm kind of surprised they let you do 1200)
Re continuing participation in the trial, there's the can of worms regarding whether Roche is going to go ahead with r1626 given the lymphocyte issue or more aggressively back r7128, which arguably they should have done in the first place - but based on the above there may be no need to open that can.
Even with a reduction in riba to 1000mg/day, with your body weight of 73 kg's your still getting 13.7 mg/kg/day, well above the minimum 10.6 mg/kg/day I've read is to be considered weight based. As to dropping out of the trial or not, heck, you were pulled off the trial drug, so imo your job as a guinea pig has been fulfilled.
80/80 is pretty simplistic but it may be considered in your case if only for a week or two while you research.
Hey, my wording wasn't very precise but the general idea is that in HCV treatment there is some room for adjustments and fudge (maybe even hot fudge) ; ) . 100% compliance is not required. It is a long treatment and many people HAVE to reduce dosages from time to time. The point is that one week of dose reductions (particularly with RBV that has a longer half life than IFN) may not make or break your treatment. I feel better that you are at week 17 and not at week 8 and reducing.
The 80%/80% rule is more like you don't want to really go below those levels as the effectiveness really starts doing a nosedive. I just want to point out that you may have some flexibility given it is a small reduction and that you are at week 17 and not in the very early stages of TX where compliance may be more vital. IF you were to graph your current compliance as of yesterday you would be 100% in compliance, no? That bodes very well for you. In terms of total dosing one week of a small RBV reduction isn't a grand scale change while you decide what's going on.
It's absolutely a personal choice you must make. It's also absolutely one that you need to confer with your doctors on. They may be able to give you some stats on what they think your current chances of SVR are based on comparing to SOC. They don't have past data on how R1626 works on populations but they may also hazard a best guess with this drug as well. There really isn't any data so it would really be a guess. So it goes with my opinion too. I'm just throwing out a few ideas.
I googled "HCV, 80% dosage, 80% of the time" there are quite a few articles which you can read. Some were PDF and so I didn't download them but I'd bet you can find quite a few articles.
Here are a few, you can find more by googling the keywords;
Keep in mind they pertain to SOC; you've been on triple therapy for 12 weeks.
Keep in mind that dose reductions are of less importance in the later stages of TX
A near RVR will have a lot of weight in your decision. It's also one reason that I would also agree that it's important to stay proactive and clear this virus THIS TIME. It sure looks as if it is within your reach.
Yes..... I certainly know you will won't make an impetuous decision. ; )
To state the obvious, nobody can say for sure what the impact of a riba dose reduction will be for you, however it has been fairly well determined that weight-based riba is the way to go, so any dose reductions are not ideal. Having said that, a guy in my trial got reductions in both peg and riba from week 5 right through to the end of his tx and still made SVR.
So maybe ask yourself this. What if you accept dose reductions because of trial protocol rather than clinical necessity and then you have a breakthrough or a relapse? You'll never know if you might have SVR'ed but for those dose reductions. Are you prepared to live with that possible outcome?
Given the last posts by willing and Proactive would it be fair to say that even given the dose reduction you will still be above 100% compliance on your RBV dosage? (maybe you've been doing 120% of what you should have been). Just another way of thinking about it. If so you will still be marching ahead doing 100% of both dosages IFN and RBV w/ regard to weight based dosing. It may not be as bad as was first thought.
In my head .. (maybe it's a woman thing) my 77kg interprets to me as the "160 pounds, give or take" that my female mind thinks I am.
On the scale at the doc's, I am 77kg. That's still within your quoted range.
Willing, your reference only goes so far as to say the weight-based range is 800-1400 mg/day. That is the abstract part at your link. I'm trying to find the extended details that go with that, seems to quote the WIN-R study. I'd like to read what dosage goes with what weight.
Anyone...I would like to know the statistics on SVR rates for Geno 1's re-treating. Will research it, however if someone has them at their fingertips, I'd appreciate it.
Pro..thanks for those numbers..I'll be looking into that closer for better perspective. As for the trial, they've said they still plan to use the numbers regardless, that the 12 weeks is still relevant. Remains to be seen, doesn't it. Guess we'll see the SVR rates based on 12 weeks and go from there.
Willy ... thank you. For everything.
Not deciding anything, just gathering info. Really, I should have thought about this harder in the last number of weeks as I could have gotten an INF reduction at any moment. Maybe that's the optimist side of the optimist-realist in me. So anyway, I'm going to think it all through as that is still on the table week to week so I might as well get 'er all done at once, as far as the thinking it out goes.
A quick thanks to everybody who's been tossing their thoughts into the pot, I am most grateful.
I'll have to set this aside for the moment, as my blue Ninja is an hour away from coming back from her winter sojourn in the back of my buddy's truck, all repaired and ready to ride, thanks to the generosity of the buds in my sportbike group. Jimmer had a kidney transplant and he's just got the biggest heart. Have to make dinner to say thank you.
Jim...I tend to agree. If not on the trial, I wouldn't be getting rescue drugs or dosage reduction at this point regardless of the numbers simply due to my own tolerance. I'm thinking I better not slow down...that's the key. :)
can't trust those things; reminds me of the big "IT LIES" sign on the scale at my Drs office.
Sounds like you've got much better things to attend to, but you should be able to get at the full text by clicking on the "full text ...interscience" icon at the top right of the pubmed page (alternately go to the hepatology journal site and navigate to 2007, vol 46 issue 4).
If that fails (hepatology in the past was not free access) let me know and I can forward the pdf.
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.
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
I thrust you gonna follow your true self.
good luck whatever you decide.
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.
"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.
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.
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.
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.
I would not stop at this point, can you reduce awhile to get the red's up a bit and than ...shhhh.....take that extra pill anyway?
A friend of mine from this forum (who rarely posts) was on a trial as well. She too had to do a riba reduction due to a very low Hemoglobin count. Her trial didn't allow for rescue drugs either. She went against dx's suggestion and continued to take full dose ( I believe she was encouraged to do this on this forum) and the results were not good. She "bottomed out" (her words) and had to do an even lower riba dose reduction. Her Hemoglobin count was in the 8's. She stayed in the 8's all the way to the finish line (even with the dose reduction). She wasn't working and would pass out just sitting at the kitchen table. I was very worried about her condition and mental state that developed (that is all I will say about that)...Not getting enough oxygen can be dangerous that is why it IS a concern.
Sorry I don't know her post tx results yet and/or the impact of dose reduction.
Sounds like you are doing really well thus far except for your Hemo count.
Good luck to you and whatever you choose (stay the course/stray the course/drop the course).
Just another bump in the road...this too shall pass...
I was on pegasys 180 and 1200 riba up to week 20 then reduced the riba to 1000 due to sx's and stayed on that dosage up to week 44 then went back up to 1200 riba for the last 4 weeks of std. soc. My vl was 4.7m and my weight when starting tx was 210lbs and lost 30lbs in the first eight weeks but was UND by week 8 and the sx's started mounting an all out assault and by week 20 decided to reduce the riba. The saving grace was the procrit which had kept the hgb in the low 11's and I too worried about the riba reduction and what might happen at the end of tx but at that point and time I had some very knowledgeable coaches here that provided insightful experience that had eased my worries about the possibility of relapse. I had remained UND through the rest of tx and 2 pcr's, one <5 and the other 5 weeks later UND <2 since stopping std soc and then the taper and I'm going into 5 months post with the Big 6 month coming up. With you being at week 17 and UND to this point and if the 200mg reduction has that much of an effect on you then it was meant to be and there would have been nothing you could have done to change that. If you want to stay in the trial go along with the riba reduction and see what happens on the next blood work after the 4 of July. Best of luck to you in what ever you decide.
Thanks for the info on the Pepysis and Copegus. Next week I'm taking my first shot and have been given 180mg INF (Peg) and 1000mg Copegus. I'm only 56kg and thought they may be 'killing me softly' :-( .. Ha! I was ecstatic to read that the dosage is right. I see my Specialist every second time throughout and my nurse really seems a bit dipsy. I thought I should've been on 800mg Ribavirin but feel safer now - they're probably trying to give me a hammering early on. A naturopath has put me on high dose folic acid but says I must stop taking it as it interferes with interferon (I think it assist red blood cell formation). Best of luck Trish; I notice your biopsy results give you a bit of leeway but I'm impressed by your research - when I did it in 1994 I didn't take too much notice, but then, I felt very healthy and decided to 'give myself to science' once only (now it's twice :-)
Trish, it appears from what everyone is saying that you may be alright right now with the RBC dose reduction. However, were it me, I would be really concerned about the possibility of the INF reduction at ANC < 1.5. Reseach has shown that Hep C patients can withstand a much lower ANC without the possibility of infection. However, trial protocol is normally whatever the dose reduction recommendation is on the package.
"PEGASYS and COPEGUS should be used with caution in patients with baseline neutrophil counts <1500 cells/mm3, with baseline platelet counts <90,000 cells/mm3 or baseline hemoglobin <10 g/dL. PEGASYS therapy should be discontinued, at least temporarily, in patients who develop severe decreases in neutrophil and/or platelet counts (see DOSAGE AND ADMINISTRATION: Dose Modifications"
I think I would try to locate a doctor who would be willing to pick up your treatment with SOC and rescue drugs if needed. Although you say you are fine with HGB <10, I have a hard time believing that it is good for your system.. Remember, your brain needs oxygen and the HGB is just the indicator of how much oxygen is flowing in that blood and to the brain.
The issues that you are dealing with hit home to me as I try to decide to treat in a trial situation. I would want to do right by the researchers, but at the same time, I would have to consider myself primary. For me, there will only be one more shot. My stats are very similar to yours except for the duo genotypes (I am 1a). Is there a worry about drug resistance with r1626? That would be another issue to think about when considering whether to bail from the trial.
I didn't mean to suggest that one could reduce by that much. I wanted to suggest that 100% compliance may not always be possible and that essentially down to as low as 80/80 one might still be in the ballpark. The general sense is that if that rule has some merit....... you still are NOWHERE near that reduction and therefore have some time to reflect on this dosage change. Compute the number of riba you've taken and then compute the number of riba less that your new dosage reduction with account for. The few pills less per week are a small portion of what you've taken; no where near any 80/80. You have some time to think and decide. I think it's possible that with the reduction you'll bounce back up and could continue merrily along the path. It could be just a week or two. Even if it isn't it appears that you may still be above the weight based dosage and therefore perhaps a mute point.
You can still ask to get your RIBA trough levels checked. That is more important than how many pills you take. IF your trough levels are up I wouldn't think there would be any issue in a temp reduction. IF your levels are really high it truely might be a good idea to reduce. IF they are low (which seems unlikely) a reduction might not be a good idea. You can ask about this idea. Maybe it has merit; maybe not.
I still think you may as well get iron checked just in case you are low....it could help and would need to be up if procrit came into the equation. I understand that hemolytic anemia won't be cured by supplemental iron but why not address this IF it's a partial factor?
I'd repeat that I'd want to nail this down on this first treatment since a failure could also spell resistance issues for you in the future if you had to re-treat. What will it take to ensure an SVR?
Man...you guys can sure make a woman work. I put a notepad by my computer and started going through each post and taking notes on the things I felt needed to be considered based on all your comments and got to work.
I'm good. I have my ground. I learned alot while researching this to be satisfied with my decision and I'll want to share what I learned later after I get a bit of downtime, hoping some of it will be useful. I'm a bit of a ragdoll today and need some physical rest. Too tired to type right now and will catch up later.
Thanks from the bottom of my heart to every single one of you who commented and emailed and shared information and took the time to share your perspective. I haven't talked to anyone in my life other than all of you about this. This place is pure gold because of the people who are here. Thanks for being there.
sounds like you've been reseraching...
google link for ya
In my mind, the higher the dose of riba toterated the better the chance of svr...period. But each individual will metabolize differently.
Interesting trial of higher dosage...but it ssemd some concensus is already established from prior data.
"Optimal ribavirin dosages are essential in achieving SVR. The initial evidence supporting higher doses of ribavirin for peginterferon alfa-2b comes from a secondary analysis of the pivotal multicenter trial of peginterferon alfa-2b and ribavirin. Patients receiving more than 10.6 mg/kg/day ribavirin experienced significantly higher SVR rates (48% vs. 38%). A large multicenter trial designed to test standard dose ribavirin (1000-1200 mg/day) versus low-dose ribavirin (800 mg/day) in combination with peginterferon alfa-2a, showed 52% SVR in the standard dose group versus 41% in the low-dose group for genotype 1 infected patients. In the pooled data from two pivotal studies with peginterferon alfa-2a and ribavirin, the probability of achieving an SVR for genotype 1 patients was influenced by the ribavirin dose per kg body weight. A 40-50% increase in the probability of SVR was found for a 12-16 mg/kg dose increase of ribavirin. For peginterferon alfa-2b it was also shown among genotype 1 patients, that weight-based ribavirin (800-1400 mg/day) leads to higher SVR rates compared to fixed dose ribavirin (800 mg/day) (34% vs. 29%). Moreover, ribavirin dosing up to 1400 mg/day was safe and the rate of treatment discontinuation was the same for both treatment groups. In a small pilot study, 10 genotype 1 patients with a high baseline load were treated with peginterferon alfa-2a and individualized high-dose ribavirin in order to achieve a ribavirin target concentration in serum of 15 μmol/l. The mean ribavirin dose of 2540 mg/day (range 1600-3600 mg/day) was high, but resulted in 90% SVR. All patients experienced severe anemia, which was treated with concomitant epoetin beta and blood transfusion.
As mentioned before, the main concern of high-dose ribavirin will be a dose-dependent hemolytic anemia and the addition of epoetin alfa has shown significant increase of haemoglobin during (peg)interferon/ribavirin therapy. Erythropoietin doses from 9,000 to 60,000 IU/week have been used in order keep the highest possible ribavirin doses. A recent trial showed a significant higher SVR rate in genotype 1 patients treated with peginterferon alfa-2b, increased dose ribavirin (15.2 mg/kg/day) and epoetin alfa than in patients treated with peginterferon alfa-2b and standard dose ribavirin (13.3 mg/kg/day) with or without epoetin alfa. Using the standard ribavirin dose, routine use of erythropoietin significantly decreased the frequency of anemia and the mean ribavirin dose reduction. Moreover, with the addition of erythropoietin, a significant higher mean dose could be given to patients in the increased ribavirin dose arm."
and for what it's worth,I'll just toss in..I asked my hep doc point blank...."you must be a very firm believer in higher dose riba, huh?" Answer without hestitation- yes.
(he increased my dosage twice, and a different hep doc in the same gastro/hep dept increased another mh poster's dosage as well--both in response, to slow a slow tx response.
I just wanted to make a comment on breaking Ribavirin into half. In the Danish Copegus insert it states that one should NEVER break them in half or crush them. It says that if you accidentally touch a crushed pill you should thoroughly wash your skin with soap and water.
No...not muddying the waters. That's included in one of the articles I read. I'll actually be printing that out and bringing it with me when I go to my appointment on Friday. I need them to explain to me why they're opting for dosage reduction when rescue drugs seem the more prudent choice.
I'm a firm believer in higher dose riba myself. Nothing I've read in the last day changes my mind a bit about that. To take one less riba each day right now isn't sitting well with me. I know this is my first dosage reduction and it might not go beyond this, it just kills me a bit to use less than full firepower. If I wasn't in the trial, the issues would be different. However, I am in the trial, I evaluated that before I went in and now the fire is a little hot and it just makes you think, that's all.
mremeet, geterdone ... thanks for your input. Seems very sensible borne out of plenty of experience.
Teevee..thanks for taking the time to share that. Your thoughts are appreciated
Kristina...I hadn't heard that about the folic acid interfering with interferon and I'm having a hard time believing that one. I have two hep doctors, one of which prescribes it at 1mg a day, the other at 5mg a day, saying it's 15-20% chance of it helping with low hemoglobin. Any actual data on that? I just read your profile ... I wish you best of luck with your next tround of treatment.
frijole...thanks for your comments. No real resistance issues with R1626 from what I know. I tend to agree that higher hgb is better. I admit I feel like a train running out of steam and it's going to catch up sometime. This is the last week for both of hte courses I've been doing and I swear I'll be slowing down and really looking forward to that. I'm concerned about the INF reduction as well, wondering when my time is going to run out on that and hoping it doesn't.. and I'll be talking to them about that when I go on Friday... I have a number of questions I need answers to, to help me make good decisions ongoing.
Willy ... further reading and I find yes...while the concern is that people will think that reducing to 80% of dosage is acceptable, it's more if one MUST reduce, then within 80% of dosage is tolerable, DEPENDING on when one went UND, what week one is in and which drugs, etc. etc. Most impact is to reduce before Week 12, next before Week 20, more if you are not UND yet and how long you've been UND. Lesser impact to reduce riba up to 7 days after week 12 and before Week 20, more impact if also reducing INF with riba and more impact reducing INF with no riba reduction in that Week 12 - 20. Whew. So .. I have some idea of where I'm at and where it can get to and I'll be glad to get to Week 24.
I'm going to stick with the trial and ride it out pending further information. I want them to tell me how the trial data still applies after pulling it at 12 weeks, etc. I also want them to explain to me why we're not using rescue drugs when it's permitted, so that if an INF reduction comes or this riba reduction continues much longer, I'll know where rescue drugs fit into my picture. Personally, I"m not against using them on my own if I can get them. That doesn't contravene the trial. And I'm thinking on that.
Even if I wasn't sticking with the trial, I can't switch docs and get drugs ordered fast enough to keep things uninterrupted. It doesn't happen that fast here in Canada, that I know of but haven't ruled it out. There are a couple of docs I'd be willing to contact if I thought things warranted it, I've left the door open for that a tiny bit but it's very tiny.
I'm convinced my riba dosage is more appropriate at 1200mg. Not enough evidence out on "true" weight based dosing to settle at 1000mg and plenty of evidence out on the importance of riba in this whole process. Interesting comprehensive article on all of this. I found it very good reading:
From everything I've read, due to being UND early on at the 6 week mark and it being past Week 12 at least when the reduction comes, at Week 17, and the reduction being above that 80% mark Willy mentioned, I can tolerate it for 7 days. I see them on the 7th day. They will extend until the blood test results come back and I don't get them until after that appointment. However. I have a standing order for weekly blood tests and I'm going to go in this week and get my blood test done anyway. I'll just play dumb and say I thought I was supposed to go in. I get them locally. It will be there by Friday and we'll all know whether I need to continue with a dosage reduction or not. They're going to keep it going, so if I have results that show otherwise, I might be able to put a stop to it. I also run the risk of the whites being low enough for them to order an INF reduction, but I'm ready to deal with that.
Will increase my folic acid and add shiitake lentinin to the mix.. pure lentinin if I can get it, or shiitakes...more is not more with them apparently, so I'll be reading up more on that to get the right "dosage" so to speak. They are for helping the white counts. Susan400 has mentioned that in the past and it seems there is data to back that up.
Ongoing, I"ll take this a step at a time. I'm committed to the trial, I'm just going to fight a little harder for them to see me as more than a trial number, get more info and do what I can to get my reds and whites up. I'm almost at Week 24 and then I'll rest easier about these sorts of things. I still wouldn't want dosage reductions, however they'll be less critical by then, in my opinion. So I just want to see what I can do to stay the course all around and get there.
There's fighting my own dragon and there's fighting the dragon period. So I just prefer to stick with the trial and ride it out. I have good markers so far .. and I think I can ride it all the way to SVR here.
I'm sorry for all the fuss when it could improve and stay that way ... I wasn't expecting the dosage reduction on the ribavirin after staving off the INF reduction every week ... it's clear you can't afford to be complacent about these things and you need to know what you'll do if things do tank, whether a little or a lot. So now I know.
Will see how it goes. Thank you much to everybody.
"I'm convinced my riba dosage is more appropriate at 1200mg. Not enough evidence out on "true" weight based dosing to settle at 1000mg and plenty of evidence out on the importance of riba in this whole process. Interesting comprehensive article on all of this. I found it very good reading:
There's "true" weight based dosing that applies dosage graduating upwards with weight categories and then standard weight based dosing that goes with 1000mg for <75kg and 1200mg for <75 kg.
While there's plenty of evidence for weight based dosing vs flat dosing, IMHO not enough studies on the dosages laid out in "true" WBD to bank my dosage on that 1000mg mark and I'll take 1200mg, or higher, thank you very much.
Sorry .. you asked about iron a number of times. I asked the trial co-ord about that and she said they're not monitoring that right now as it's not something they're concerned about. My iron had been on the high side earlier in the trial but not a concerning amount, just a puzzle to her. She said we would discuss it on Friday if iron was something they need to be looking at. I'm reading up a bit on creatinin clearance and I'm looking into those trough levels you keep mentioning. I have the rest of the week til I go to keep reading up and get my information.
I noted Dr. Dieterich's response...that when rescue drugs are available, a dosage reduction is NEVER in order over a rescue drug. So...I'll have some questions for my team.
Thanks for all your input, Willy...I like a man who can make me think. ;-> And thanks for your support. Appreciated.
" I have good markers so far .. and I think I can ride it all the way to SVR here. "
Trish, your markers are good but they are not great. You did not get RVR, so pleeeeeeze don't let up on getting your full dose of drugs and also the rescue drugs that you need. It's reeeeeally important!
We who didn't make it to SVR have had a long time to contemplate such things.
Thanks for your care. I'm not letting up. I'm going after the rescue drugs and I'll be fighting them on dosage reduction. I got Dr. Dieterich's answer to when dosage reduction is preferred over rescue drugs when rescue drugs are available and he said "never!". I'm going to do everything I can to stay the course ... and if I get the sense that they are not doing what's best for me when they CAN be doing what's best for me, THAT is where I'll draw the line on staying in the trial.
Well, the really good news and then the really good news.
I called my trial co-ordinator earlier this week, let her know how I felt..that I was okay with 7 days riba reduction and after that, not and certainly no Peg reduction separately or on top of it. I asked her to let me do the blood test mid week this week as 7 days lands today and results would be back by our appt and then I'd know by today if I could go back to normal dose. She agreed. Thank you. I also let her know I wanted a serious consideration of rescue drugs and where they fit into my picture so that I could avoid future dosage reductions. She agreed to pass my request on to the doctor and arranged for me to consult with him today. What I found out TODAY was that she put me with the doc who is known to be the most aggressive on purpose. Bless her.
So today...my hgb is back above 10 at 10.8. My whites have rebounded even more that my lymphocytes are .4, still below the .5, however my ANC is at 2.4 which is the best it's been in awhile and far from that 1.5 mark, so the combo again has me avoiding the Peg reduction. So I am back on regular dosage all around this week.
The REALLY good news is what came out of the consultation with my doctor. I put my perspective to him that I considered that 7 days riba reduction at this point was tolerable but no more..and that I considered that "as much of the drugs as much of the time" made ALOT of sense to me and that I wanted no further dosage reductions, as much firepower as I could get for as much of the time and if I COULD get it, why wouldn't I. And I asked him finally.. "does that make sense to you?" and I braced myself for rebuttals and other sorts of things...and his answer was simply .. "Yes." Just...yes.
And THEN .. we discussed the rescue drugs. Well, we discussed the epo.
The trial parameters say I MUST have a dosage reduction if my limits drop below a certain amount. So my hep doctor has decided to be proactive with that and keep me OUT of the dosage reduction range by putting me on epo for the duration until my hemoglobin gets above 12. Because I will have no choice but to dose reduce.. then we make sure I don't have to dose reduce. I will do weekly epo, weekly blood tests. So we are being proactive and practicing avoidance of dosage reduction.
I found an article about a study that Dr. Dieterich did supporting the idea of using epo to keep hgb at a level that would avoid ribavirin dosage reductions and it supports this approach.
If I wasn't in the trial, we could do the epo first and wait out the expected 3 week or so response time. Because of the trial parameters, I need to keep it from getting below those levels in the first place.
I am VERY happy. I have a strategy in place to help me avoid dosage reductions, a doctor who listens and is aggressive and uses a proactive approach that is in MY best interests and sits well with what is important to ME in my treatment and will help me both stay in the trial and maintain my dosage to the best of my ability on both counts, both of which are important to me.
Now...my iron is low. So he is putting me on iron at the same time as the epo as he says the epo will be less effective with my iron at that level. That has me curious but I'll take it...and will continue to read more about that. (Nod to Willy)
As for my white levels.. my doc isn't crazy about neupogen, has mixed feelings about it's usefulness and figures the epo will help enough to keep my whites out of reduction range too. I'll cross that bridge IF I get to it. I'm happy with what I've gotten out of today and I'll just enjoy that very much and go with what I've got and continue to ride it out.
So far so good. Thankful for a doc who is willing to think outside of the box and what is good for MY big picture. And thankful for my trial co-ordinator who has put up with me this week, listened to me and let me step through all this and had me see this particular doctor.
Still might end up with the dosage reductions and that is out of anybody's control. However, we're all doing everything we can and that's all I really wanted. I'm at Week 18 today...and moving forward. Starting epo next week.
It sounds like a good plan to me. If any cautions...throw 'em at me.
Thanks again to *everybody* who tossed things into the pot...I took ALL the big and little pieces into account and it helped me think through this whole thing and educated me enough to know what I felt was best for me.
A BIG glass of soda water and lime raised to ALL of you!!
Good to hear, excellent in fact!!! It looks like you are going to make it with no problems.
Just a warning...... since the link that you posted came out there have been new warnings on epogen; black label warnings. The drug is not without it's danger and it is not one that you want overprescribed. It is to be used as little as possible; just enough to keep you off the reduction list. This is a drug where less is more. Just check it out and don't let it be overprescribed or serious and long term problems can develop.
I'm glad that they checked your iron. If they get your iron up I think you anemia could improve and almost certainly they won't need as much epogen.
Great to hear this. It bodes well for your success.
Just do what you think is best for you. If you are comfortable with going outside of your trial for private care and can get the SOC w/rescue drugs, then go that route. If you're not comfortable with that, then follow the trial guidelines and hope and pray for the best. That's my advice for what it's worth!
My current trial allows rescue drugs after you've completed the first 29 days w/the study drug (which I now have) and are on SOC. I told my study nurse on Wed., "I want to do whatever it takes w/all available rescue drugs in order to avoid any dose reductions". "I told her that with my history of being unable to clear that I am emphatically requesting no dose reductions!" That's what I did and fortunately for me, it's within the trial guidelines. I will however have to get those rescue drugs through my private insurance and/or my own pocket. This is all if I'm even allowed to continue on w/the treatment, because it all depends on my results from my labs that were drawn last Wed. on July 2nd. If I'm still dropping a steady pace, she told me that they will recommend that I continue on w/treatment.
Sounds like a really good understanding doctor you talked to, at least he has a compromise plan for you that takes what you wanted in the first place and keeps you at a safer place with the addition of epo. I was wondering how this would end up for you. I knew you weren't gonna feel comfortable with that riba reduction, so I'm really glad you worked so hard at getting what you wanted and making your viewpoint heard. Just so you know, I don't know anything at all about epogen. If you get uncomfortable with that idea, I know you will come up with a back up plan. God Bless
Wonderful news about your meeting! All seems to have fallen into place perfectly for you -- in a *trial* no less... You must have made quite a positive impression on the nurse for her to set you up with thee best doctor! It really does help to do your homework and come into appointments armed with knowledge and a plan -- for your doctor to follow closely :-)
I'm so glad you don't have to reduce the riba any more than you already have -- I know that thought did not at all sit well with you.
You must be feeling pretty relieved -- hope you're having a very nice relaxing weekend!
Willy, thanks for the caution on the black box warnings. I have heard of them and read some and will read some more. Thanks for your encouragement. I'm not sure I'll make it with NO problems through 30 more weeks, however this is certainly a good step forward, isn't it. An interesting approach within the parameters of the trial still and I'm happy.
marcia, thanks for your thoughts. :)
fret, thanks for the vote of confidence my friend and thank you for caring. That means alot.
Susan - with this approach I get to stay in the trial AND stay within trial parameters. I'm very happy with that. I too have to pay for my drugs and that's a bit of a hardship with my son's university expenses at the moment, however I'll take it and work it out. Good luck to you and I'm hopeful for your upcoming results.
pK .. you give me far too much credit...lol :) That goes to the doc. All I knew going in was that I didn't want dosage reductions and why and that I'm allowed rescue drugs. I wasn't sure how to pull it all together and wanted to have the discussion with the doc. I hadn't considered he would give me eprex/procrit before my levels dropped too low. That was his idea and I was surprised and pleased. The nurse put me with the most aggressive doctor because she figured that was a good match for my own wishes and bless her for that. Yes, relieved....and having a very decent weekend so far...hope same for you. :)
Harry here, I was put in the same situation for the last 4 months of my treatment and the end results were still negative. Today I went for my post six month blood test, should get results in early August.
I'm so happy that everything worked out so well. Sounds like you and the nurse and the dr are a perfect fit...
I wanted to tell you that once I had a few shots of procrit my hgb returned to normal and stayed there. I hope the same happens for you.
My dr wanted me to keep taking the procrit but I was worried about the black box warning and quit taking it as soon as possible. If I had to do it over again, I wouldn't have worried about the black box warning so much.
Take care and congratulations on being such a great advocate for your care, especially in a trial!
Really good work 'up there' Trish. Tx, sides, low hgb and your still rolling in the research, studies, making sense of it all and standing firm with your Dr.'s. Very impressed :) I have a hard time making sense of it all without much brain fog left!
I didn't realize you didn't get RVR (just can't keep up here since getting back into the 'real' world, being so busy). Understand your worry on the reduction and standing firm on no more. Glad you got the results you wanted from your last app.
Do take heed on Willys warning, tip. (sure you will, your very studious in all of this) Not being allowed rescue drugs in my tx was almost a relief for me as I was so concerned about them also. (Course being 2b it's less concern in reduction, etc.)
Very nice of your bike group! Be extra careful if your riding thru tx.
Keep up the excellent work and the fight. Rooting for you all the way.
........ In the Danish Copegus insert it states that one should NEVER break them in half or crush them. It says that if you accidentally touch a crushed pill you should thoroughly wash your skin with soap and water....................
I have heard this before, on not getting the Peg on your skin, etc. but the Riba also? I'm curious on this as we are injecting, ingesting these drugs, why the concern about on our skin?
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