Advice? Hepatitis Researcher or anyone

I am having trouble keeping my hgb above 10. I am on the max. dose of the rescue drug aranesp but everytime I go back up to 1000mg of Riba it kills my hgb as of yesterday 8.7. I was wondering if I stayed at 800 to get thru tx, I am on week 29 maybe I could just extend my treatment longer to make up the difference that I am missing with the riba. Has anyone else ever done that?

[Alady1620]

I would suggest you try a different rescue drug before you reduce your dose of Rib.

[HCA]

I am in the same predicament,taking Aranesp 200mcg once per week-a stonking dose.I have previously used epo (procrit).
My HGB on Tuesday was 8.5 having tapered the riba dose down from 1200mg to 600mg daily.
I also take iron on prescription,B12 and Folic acid.
It is clear that the Aranesp is not going to facilitate a full theraputic dose of riba.
However there may be a bright side to all this, my doctor believes that my extreme sensisitivity to riba is causing a build up of riba and that the reduced doses are having the desired mutational effect on the virus.Severe hemolytic anemia can from this standpoint be a positive indicator.
Whether the theory is right or wrong,I am eliminating virus succesfully so far with viral level being only just detectible at six weeks-geno 1a/1b.
As you are on week 29 I presume your RNA is undetectible.Riba's role is most critical in the early stages and it may be that that tapering your dose to maintain a bearable level of HGB will see you through to SVR.
Hope so!!!!!!!!!!!!!!

[jordie47]

I hope you are right. I am also geno 1 undetectable at 12 weeks only PCR the doctor would do. I just had liver enzymes tested all in normal range alt, ast, bilirubin etc. No real sx anymore actually feel pretty good till I go see a doctor!

[jmjm530]

The bad news is that you can't seem to stay at what appears to be your prescribed full dose of riba. The good news is that you appear to be very sensitive to ribavirin and therefore may have adequate serum riba levels for successful treatment per studies by Lindahl and Company in Sweeden --  especially in light of your 12 week non-detectible PCR. How much do you weigh and when were you on 800 mg versus 1000mg? As already suggested, you might ask your doctor about switching over to the shorter acting Procrit (epo) as opposed to the newer drug Aranesp. Some members here reported better results with Procrit and because it's shorter acting I imagine it can be tweaked better.

All the best,

-- Jim

[jordie47]

Thanks for the info. I weigh 126, was on 1000 for weeks  1 thru 6 then went to 800 for weeks 7 thru 18, then 900 for weeks 19 thru 22, then 1000 for 23 thru 29. Have been on rescue drug since week 6.

[jmjm530]

HR,

Most of what I've read -- esp from Sweeden -- suggests the discussed correlation between serum ribavirin levels, anemia, rvr, svr, etc; some citations here: http://diss.kib.ki.se/2005/91-7140-348-5/

However, there is one dissenting paper you might want to comment on; my take being a more narrow and less in-depth study. Paper here: http://tinyurl.com/s9mpf

Also, why do you think that HPLC testing for serum ribavirin levels never caught on in this country with sole emphasis on weight-based dosing and very little discussion of either serum riba levels or even the pharmakinetic formulations based on kidney function discussed by the Sweedish researcher? And have you heard any follow up from their remarkable pilot study on HDR (90% SVR for geno 1'), other than a more recent paper on riba saturation at higher dosing? At one point I heard through the grapevine about the promise of higher riba dose *later* in treatment (against common wisdom) as a successful intervention for slow responders, and wondered if anything out on that?  

Also, there was an interesting much earlier paper by Lindahl that talked specifically about the correlation between ribavirin dosing and anemia but I was only able to locate it at a medical library and not on the web. Possibly you might have it handy.

Lastly, have you heard anything about a ribavirin pre-dosing study that someone posted here around 8 months ago? Conceptually it has always sounded like a very good idea to have serum riba levels maximized when the first peg dose is injected.

Sorry about all the riba questions but after taking over 2,000 of those little blue bandits, it does leave an impression :)

Good to see you back helping out and hope you had a fun, restful vacation and a happy and healthy New Year!

All the best,

Jim
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For those relatively new here, I initially modeled my tx after the Sweedish high-dose ribavirin study and ended up in the ER with anemia after only a few weeks which actually caused me to go off ribavirin completely for close to a week early-on in tx. I've commented before at length, but I'll just briefly add that while a correlation between anemia and serum ribavirin levels and SVR appears to exist; anemia is a very crude barometer to base dosing on for a number of reasons including the 2-3 week lag time between a change in riba dose and change in hemoglobin. In other words, don't try this at home and even under a doctors supervision, caution is advised so that treatment does not have to be suspended or possibly even terminated.

[jmjm530]

According to some weight-based schemes, 800 mg/day is enough for your weight, so I wouldn't worry about your current dose. More important is being able to stay the treatment course which your lowered dose, combined with the rescue drugs seem to be doing. Of course follow your doctor's advice or if uncertain seek another medical opinion.

All the best,

-- Jim

[Hepatitis Researcher]

As jim stated above, the pertinent aspect of your situation is the fact that the strong anemia in fact indicates a high bioavailibility/tissue concentration of the riba, caused by good intestinal absorption, limited metabolism, excretion etc.
Thus it will also have its desired therapeutic effect at a high intensity. It is not the amount of riba that you swallow, but the final concentration in your plasma/tisuues that matters.

[GoofyDad]

My experience was different than what Jim posts. Last few weeks of tx Doc insisted I drop a riba pill to get hgb up (just too long, too low he said, and now I thank him for it) and hgb  responded very quickly. In little over a week I was back to my higher dose and rode that out to the end, as the hgb was heading right back south. After stopping riba, one more procrit and hgb was up 3 grams in about a week if I recall. So jordie, maybe you can kinda fluctuate. Good luck - I know first hand how sressful that can be.

[jmjm530]

Thanks for the response. Something that sounded like a pre-dosing study was anecdotally reported here about a year ago but have not heard anything since.

-- Jim

[jmjm530]

On re-reading it appears that Jordie may be currently on 1000mg/day and considering dropping back to 800mg/day (as he did previously) on his doctor's advice. Again, I see nothing wrong with this given Jordie's weight, hemoglobin levels and 12 week viral load response.

-- Jim

[jmjm530]

I said previously: anemia is a very crude barometer to base dosing on for a number of reasons including the 2-3 week lag time between a change in riba dose and change in hemoglobin.
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Maybe this is the statement you disagreed with? My reference here was to using hemoglobin as a measure in a high dose ribavirin strategy, not to ignore hemoglobin as to normal dosing. I was given this advice by a medical doctor very knowledgeable in how ribavirin works.

-- Jim

[jmjm530]

To reclarify, my clarification (cause I'm starting to confuse myself now :)) the "crude measure" reference was more to using hemoglobin levels as a measure of optimum *serum riba levels* which can more accurately be measured by HPLC testing.

[desrt]

Not only is anemia "a very crude barometer to base dosing on", in some cases it may have no relevance at all. My bloodwork stayed so close to normal range during tx that my doctor asked on more than one occasion if I was taking all my meds. I was, up till wk 19 (1200 mg - wt. 220+ lb) at which point I dropped it to 800 mg based on the NIH 2002 Consensus Report that stated that 1200 was no more effective than 800 for geno 3.
I'm curious about the Lindahl study. The only follow up to tx I saw was a 24 wk post-tx PCR. I'm wondering if all those patients stayed clear and what their long term health issues might be. Also wondering about how the high SVR rate for European strain geno 1 in this study would translate to a larger test group of Western hemisphere geno 1 patients.

[jmjm530]

On one hand it's a "crude barometer" to base an optimal dosing plan on, but on the other it does seem to reflect how well ribavirin is being absorbed in many individuals per Lindahl's work but with one dissenting study I referenced above. In your case, the ribavirin response may not have been as critical since you were not a genotype 1. I also share your curiosity about more recent work and follow-up re Lindahl, as well as the longer term effects on patients of the high doses of ribavirin. My speculation -- and only that -- is that while high doses of ribavirin might have significant physiological effects during the course of treatment, it is the interferon that is most problematic in terms of what many report as long lasting side effects once treatment has stopped. Perhaps the Lindahl group has acknowledged this to one degree or another by increasing ribavirin exposure as opposed to increasing interferon exposure (i.e. extended treatment) in their studies. My guess is that all this may become mute soon if/when the newer drugs like VX-950 start to take center stage -- both in tx and research. Still, it would be nice to know what is currently going on with riba research, if anything.

-- Jim

[GoofyDad]

My comments to jordie were simply to reflect my experience in which I found my hgb to respond quite quickly to a reductions in Riba. It was much differrent that the reaction to procrit. I don't know why. I should also mention that I ran with hgb in the 7's and 8's for a long time, and I'm now complaining about memory and cognitive isuues.

[jmjm530]

Understood. Maybe the lag is longer when increasing riba than decreasing it, or just that experiences differ. The caution I received about titering up and delayed hgb reaction was in regard to increasing riba.

-- Jim

[Hepatitis Researcher]

I am not an expert on advanced riba questions.
But it is clear that many factors will affect the final concentration of riba where it matters; Inside the hepatocyte, where the virus replicates.
Absorption is variable and food dependend, excretion depends on the glomerular filtration rate, cellular uptake depends on genetic factors.
Measuring serum riba levels would be a step forward in this area, but it is not considered important enough to make the effort and justify the cost.
The hemolytic anemia is , in this context, a very coarse "measurement" of ribas serum concentration, with additional variability of course due to individual "hemolytic resistance".
Most antiviral drugs tolerate a substantial variation in concentration without loosing critical effectiveness.
Based on this they introduced the fixed dose riba, to make things easier and more feasable.

The following summarizes some research on the effect of ribas concentration and riba reduction on treatment outcome:

"Neither early virologic response nor SVR was affected adversely by ribavirin reductions when the cumulative ribavirin exposure was greater than 60%. The SVR was reduced significantly (P = .0006) in patients with less than the 60% cumulative ribavirin dose and was associated with prolonged periods of dose reduction, temporary interruptions, or premature cessation of ribavirin. Ribavirin dose reductions had minimal impact on SVR in patients who achieved rapid virologic response, defined as undetectable HCV RNA levels after 4 weeks, even when they received less than the 60% cumulative ribavirin dose. In contrast, SVR was reduced markedly in patients who had ribavirin dose reductions and did not achieve rapid virologic response. CONCLUSIONS: Minor ribavirin dose reductions to manage adverse events do not appear to affect SVR adversely, unless cumulative exposure is less than 60%. Prospective studies, however, are required to establish the impact of ribavirin dose reduction on SVR."

To presaturate with riba before the start of IFN is an interesting idea, but to do the trial would be expensive. Who would pay for such a trial, all the way to SVR percentage?
Could be there such a thing as resistance to ribas overall antiviral effect in concert with IFN? Well riba on its own reduces the Vl somewhat, maybe enough to induce countermeasures by HCV to reduce this response in one of many possible ways. It would violate the well known principles of combotherapy and resistance avoidance.

[jmjm530]

Goofy: My experience was different than what Jim posts.
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Maybe I'm misunderstanding your reference --  but I'm not recommending Jordie to change/up his ribavirin, just to continue his present course of 800mg/day and Procrit until/unless his doctor and labs allow him to change doses. He seems to be doing fine with current dosing strategy.

Maybe you were referring to some other "difference" ?

All the best in the New Year,

-- Jim

[jordie47]

Thank you everyone for your input I am going to the GI doctor tomorrow morning. I am sharing the information with him, not sure if he will listen but am going to try. His office called me and said the doctor said to stop everything and get in here Monday am. I said I will come in Monday am but I am not stopping anything I just want to dose reduce riba back to 800 to get hgb under control. They don't appear to be very happy with me. This is how it's been all along on tx. I probably should have found another doctor in the beginning I was just so freaked out about the hep c I was thinking straight. Appreciate everything.