Altering Tx and use for other posts

[Bill1954]

Hi everyone;

Well, my Tx is in a state of flux right now. In my post

[Bill1954]

Again, thanks for the good words. I received the CBC results from the lab done on 6/10/05.

Baseline Hgb 2/18/05 -              17.4        
1200 mg/ Riba Hgb 5/13/05 -         14.9    
14 days post 1800 mg/Riba 6/10/05 - 13.8

Although the Hgb took a hit of 1.1 g/dL over 14 days, the initial drop at baseline was a very similar non-linear event. So far, it seems as though I might tolerate this dosage. I don

[willing]

Here's a California lab that's been doing work in this area : <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12841954&query_hl=2">RIBAPHARM</a> and one in Wisconsin : <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12062668&query_hl=2">COVANCE</a>. I've written to Yeh at ribapharm but have heard nothing back yet -  however it sounds like the leads you're pursuing are much more promising. That's great news about life holding steady at the new dosage, hang in there. And by the way BobK at Davis is a great resource. He doesn't seem to visit here any more but knows the hcv woods very well.

[Califia]

Just wanted to say howdy and wish you luck with this new regime.  it seems you came on the board just as I was entering a little retirement period, and then when I tried posting a long message to you last week my DSL went down for several frustrating days.   Good intentions, at least.   Btw, one of our former list members is at UC Davis and knows the lay of the land there.  E-me if you'd like to be in touch and I'll hook you up.   Bob's a bright and knowledgeable guy, good to network with.   Take good care, guy.

[Bill1954]

Here is an abstract that may be pertinent to this discussion. This study describes a simple analytical method for the quantification of ribavirin in human serum. Here

[willing]

OK - I'll mail the HPLC test description to a couple of testing labs and post back the responses. I think you may well be right about anemia usually accompanying an effective rbv dosage. According to Figure 2 of their study, a significant Hgb drop (about 20%) kicks in around 5.5 micro-mol/L which is below the mean serum level for std riba dosage. However, I've never seen anyone suggest that of the four candidate mechanisms for rbv's anti-viral effect, any were associated with its hemolytic effect.

[landfill]

I don't know what kidney test he ran if any.  He said I didn't have any kidney disease.  He said that old people have stronger responses to other drugs too because they aren't removed from the blood as fast.

He said that the trials suggested that the chances of SVR were related to the total ribavirin during tx.  He said that a reduction of 20% from the 1200mg/day X 48week total didn't have much effect on the outcome but more than that did.  This was in late 2002 so they may have changed their minds since then.

[willing]

landfill: good to hear from you and many congratulations on getting to SVR in the face of such long odds. By not clearing till 26 your prospects looked even dimmer than Ivette's and yet it worked - and with no more than the standard 48 weeks! It's good to hear from someone else who also thinks caution is advisable with respect to non-standard dosage and/or duration. My own inclination is that one should take no more of the drugs than has been proven to significantly improve response odds. This is an attitude that mostly comes out of my own experience : after finishing my 48 week sentence in 01/03 I lost all interest in whether I had or had not eliminated the virus and became much more concerned with whether I would ever clear the effects of the medicine. Thankfully those effects do seem to be fading with time, but they left me with a very deep appreciation of the impact of mucking with our natural biochemistry.

jmjm: I don't think there's anything in <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14738562&query_hl=1">Lindahl et al 2004</a> that suggests there's a correlation between anemia and rbv's therapeutic response (anti-viral effect). All they're reporting is that anemia is well-correlated with serum level and poorly correlated with weight-based dosage (r**2 of .0021). Since the undesired side-effect (anemia) is so clearly related to serum level, they speculate at the end of the paper that the  therapeutic effect should also be related. I hadn't read any of these papers before this thread started but they make a pretty strong case for the inadequacy of weight-based dosage. If I was contemplating high rbv dosages I think it would be well worth calling around a bit to see exactly how much labs would charge for running the HPLC serum test. I'm no lab. tech., but it looks like something you could run in any undergrad O-chem lab. and it sure would provide a lot of information about what you were putting your body through..

[jmjm530]

<< Hemolytic anemia isn't part of the theraputic effect but an undesired side effect.

Actually, it rubs both ways. Lindahl and company in earlier studies  found a direct therapuetic relationship between the severity of anemia and the plasma concentration of ribavirn in the blood.

In other words, those with severe anemia were most probably closer to what Lindahal surmises to be the correct thereapeutic ribavirin level.

What is undesireable, of course, are the other effects anemia has on the body and the chance that the anemia will interfere with treatment resulting in a reduction or temporary cessastion of ribavirin. Studies show that reduction in ribavirin of more than 20  per cent in the first 12 weeks is associated with a lower chance at SVR. That is why early intervention with a hemo builder like Procrit is so critical.

Did you have any kidney function tests or was your doc just guessing your kidney's weren't 100% ? I'm about your age and my kidney function tests were fine.

My guess is that your ribavirn reduction may have played some role in your late viral response. But your SVR just goes to show that statistics are just that, statistics. On an individual basis, we all have a chance.

Congratulations on your SVR!

[landfill]

Willing, I like your posts.  I just started looking at this board again a couple of weeks ago.

My 48 week tx ended in 8/03 and I'm SVR.  At week 4 my HGB had dropped from 15.8 to 10.3.  The dr said that was too much so he reduced the rbv from 1200mg to 800mg.  At week 6 I started 40,000 IU/week Procrit.  At week 14 he raised the rbv to 1000mg and at week 20 to 1200mg.  I was at 2-log at week 4 but I wasn't undetectable until week 26.  I didn't think my chances were very good but it worked.

When he cut the rbv he said that I probably had an excessive concentration in my blood.  The reason was probably that I was 60 years old.  Old kidneys are less efficient than young ones even when there's no disease.  There isn't a cheap laboratory test for blood rbv.  He said that the research laboratory could measure it but the price would be high and Blue Cross wouldn't pay.

Hemolytic anemia isn't part of the theraputic effect but an undesired side effect.  He said that red blood cells weren't really living cells because they lack the capacity to eliminate unwanted chemicals from their interior.  The rbv accumulates inside and they explode.  They're like little bags of hemoglobin.

I notice that the people here seek out gastroenterologists but the medical schools like Johns Hopkins, where I went, want to treat it in infectious diseases.  The virologists are the guys who are tuned in to viremia and antiviral drugs.  I get a chill when I read posts from people who are trying to get their doses raised.  These are dangerous drugs.

[jmjm530]

<< I don't think there's anything in Lindahl et al 2004 that suggests there's a correlation between anemia and rbv's therapeutic response (anti-viral effect). All they're reporting is that anemia is well-correlated with serum level and poorly correlated with weight-based dosage (r**2 of .0021).

Maybe "correlation" is too strong a word, but if anemia is well-correlated with riba serum level and if riba serum level is significant in SVR, then by extrapolation one could logically conclude that anemia and rbv's therapeutic response are related.

BTW, please let us all know if you find anyone in this country willing/able to do a HPLC test. My guess is that you would have to scour the university research labs but not sure if they would make the test available outside their own studies.

[willing]

Pushing the Treatment Envelope for Chronic
Hepatitis C—Is More Necessarily Better?

Ribavirin is a synthetic purine analogue that has a
broad spectrum of antiviral activity and is approved
for use in combination with interferon for
the treatment of chronic hepatitis C. Clinically, it appears
to act synergistically with interferon to result in a small
increase in end-of-treatment response but more importantly
a doubling of the sustained virological response
(SVR) rate by preventing virological relapse. In vitro, ribavirin
has been shown to act as an immunomodulator, a
competitive inhibitor of inosine monophosphate dehydrogenase,
a direct inhibitor of the viral RNA dependent
RNA polymerase and as a viral mutagen. However, it is
unclear which, if any, of these mechanisms is important
for its antiviral effect in vivo.
The recommended therapy for patients with chronic
hepatitis C is the combination of either peginterferon
alfa-2a or -2b once weekly plus daily ribavirin for 48
weeks.1,2 The recommended dose of ribavirin is dependent
on the preparation of peginterferon used. In the
United States, ribavirin is approved for use with peginterferon
alfa-2b at a fixed dose of 800 mg daily, but in combination
with peginterferon alfa-2a, ribavirin is given in a
dose of 1,000 or 1,200 mg based on whether body weight
is less than or greater than 75 kg, respectively. In Europe,
the approved daily dose is based on weight regardless of
peginterferon preparation: 800 mg for patients below 65
kg; 1,000 mg for those between 65 and 85 kg; and 1,200
mg for patients heavier than 85 kg. The decision in the
United States. to approve a lower, fixed dose of ribavirin
in combination with peginterferon alfa-2b was based on
Food and Drug Administration concerns about the lack
of data on efficacy and more importantly, the safety of
higher doses of ribavirin.3 However, in a secondary analysis
of the peginterferon alfa-2b plus ribavirin registration
trial, body weight was identified as an important predictor
of response and the European regulatory agency chose to
approve weight-based ribavirin.1 The approved regimens
yield similar SVR rates ranging from 54% to 63%.1,2,4 In
an effort to improve SVR rates, investigators have experimented
with different regimens by varying the dose and
duration of therapy. A theme emerging from recent studies
is that therapy should be tailored to different groups of
patients. The current data suggest that patients with genotype
1 should be treated for 48 weeks, whereas those
infected with genotypes 2 and 3 might be treated for a
shorter duration of 24 weeks and perhaps as short as 14 to
16 weeks in patients who achieve an early virological response
(hepatitis C virus RNA negative at treatment week
4).5
A controversial issue in chronic hepatitis C therapy is
the optimal dose of ribavirin to use in combination with
peginterferon and whether higher doses of ribavirin are
more effective. The initial evidence supporting higher
doses of ribavirin was largely indirect and evolved from a
secondary analysis of the large multicenter trial of peginterferon
alfa-2b and ribavirin. A logistic regression analysis
revealed that, if the ribavirin dose was expressed as
mg/kg, patients who received higher doses experienced
the highest SVR rates.1 Using an arbitrary ribavirin dose
cutoff of 10.6 mg/kg, genotype 1 patients who received
the standard dose of peginterferon alfa-2b (1.5
g/kg/wk)
and higher doses of ribavirin (
10.6 mg/kg) were shown
to have higher SVR rates compared with those receiving
lower doses (10.6 mg/kg), 48% versus 38%. Although
suggestive that higher doses of ribavirin were better, these
data should be interpreted with caution because they were
derived from a secondary analysis with the potential for
confounding variables and the small numbers of patients
within subgroups. More compelling data came from a
recent randomized trial of peginterferon alfa-2a and ribavirin
which was specifically designed to assess efficacy of
low-dose versus standard dose ribavirin. The results
clearly showed that for genotype 1 patients treated for 48
weeks the SVR rate was superior in those receiving standard
dose (1,000 to 1,200 mg) compared with those receiving
low-dose ribavirin (800 mg), 52% versus 41%.4
In contrast, both studies showed no difference in the SVR
rate in patients with genotypes 2 and 3 infections using
ribavirin doses ranging from 800 to 1,200 mg daily. Thus,
the issue can be narrowed to optimizing therapy for genotype
1 patients.
In this issue of HEPATOLOGY, Lindahl and coworkers
provide some further data regarding the benefit of higher
doses of ribavirin for genotype 1 patients.6 They conducted
a small pilot study in which they treated 10 patients
with standard doses of peginterferon alfa-2a and
individualized the daily dose of ribavirin to achieve a target
ribavirin concentration in serum of 15
mol/mL. The
primary goal was to evaluate the safety of using higher
doses of ribavirin in patients with genotype 1 and high
viral load (the difficult-to-treat patient profile). To
achieve the targeted serum concentration, patients required
a mean ribavirin dose of 2,540 mg/day (range
1,600-3,600 mg/day), which is more than twice the currently
recommend maximum daily dose. However, in an
intention-to-treat analysis of 10 patients, the SVR rate
was an impressive 90%. Side effects were severe, particularly
hemolysis and anemia. Every patient required erythropoietin,
and two patients required blood transfusion on
two separate occasions.
The results of this study are indeed striking but a note
of caution must be struck. Foremost is the issue of safety.
One of the major limitations to combination therapy is
the high frequency of side effects, some of which may be
serious and life-threatening. In the two large multicenter
registration trials, 10% to 14% of patients required discontinuation
of therapy and 32% to 42% required dose
modification for serious or severe side effects.1,2 Higher
doses of ribavirin would undoubtedly lead to more side
effects. Hemolytic anemia is the major risk associated
with ribavirin, and, if defined as a hemoglobin level less
than 10g/ dL, occurred in 7 of 10 patients. All patients
required hemopoetic growth factor, two required blood
transfusion and four required dose reduction or temporary
discontinuation of the drug to manage side effects.
Furthermore, all patients experienced a reduction in ability
to work, although, quality-of-life was not specifically
assessed. The need for erythropoietin, blood transfusion,
and loss of work are not trivial matters particularly in the
typical patient with hepatitis C who has few if any symptoms
and is largely fully functional. Anemia caused by
ribavirin can induce cardiovascular and cerebrovascular
incidents in susceptible patients. Thus, even with intensive
monitoring this high-dose ribavirin regimen can be
life-threatening. Second, we should recognize that the
study by Lindahl et al. was a small, nonrandomized pilot
one without a control group. Finally, difficult-to-treat
patients such as African Americans, those with significant
comorbidities and patients with cirrhosis, all of whom
have been shown to have lower SVR rates, were not included.
7,8
Another concern in today’s practice environment is the
cost associated with this treatment regimen. A 48-week
course of standard treatment without the need for supplementary
therapy or testing costs approximately 24,000
U.S. dollars.9 The additional cost associated with a highdose
ribavirin regimen would not be insignificant and
include paying for a greater quantity of ribavirin, the need
to monitor ribavirin levels, more frequent laboratory
monitoring, use of erythropoietin, blood transfusion, additional
clinic visits, hospitalizations, and time missed
from work. The obvious question is whether the additional
risks and costs are worth the increase in SVR. For
genotype 2 and 3 patients who already have high SVR
rates with standard peginterferon and low-dose ribavirin,
the incremental benefit of higher ribavirin doses is likely
to be minimal and not worth the added risks and costs.
Similarly, it would be difficult to justify this high-dose
ribavirin regimen for treatment naı¨ve genotype 1 patients
given a SVR rate of 42% to 47% with standard therapy.
Such an approach would unnecessarily expose close to
50% of genotype 1 patients to a potentially more toxic
therapy. For the moment, we would suggest that until
more data and experience are available, this regimen
should not be offered outside the setting of a clinical trial.
Ideally, this approach should be evaluated in a prospective
controlled trial using patients who have failed to respond
to standard therapy.
The finding of Lindahl and colleagues that higher
doses of ribavirin may improve the SVR rate suggests that
a safer ribavirin preparation is required and that ribavirinlike
compounds with better safety profiles may have a role
to play in therapy. Viramidine, a prodrug of ribavirin that
specifically targets the liver, is associated with less hemolysis
than ribavirin, and in preliminary clinical studies,
seems to have similar efficacy.10 Levovirin, the L-enantiomer
of ribavirin, has been disappointing thus far in clinical
trials but higher doses have not been tested.11
The apparent increase in effectiveness of high-dose
ribavirin over standard dose is intriguing from a mechanistic
view. At higher doses, ribavirin may either augment
previously proposed antiviral pathways, act through a
novel mechanism or, perhaps, at higher doses more patients
achieve a critical threshold of intracellular ribavirin
concentration. Unfortunately, the results of Lindahl and
coworkers seem to raise more questions than to provide
answers as to the mechanism of action of ribavirin. Clearly
more research is needed in this area. Future studies should
address the dosing, pharmacokinetics, and mechanism of
action of ribavirin. The rationale for choosing a target
concentration of 15
mol/L appeared to be arbitrary and
not based on good pharmacokinetic and pharmacodynamic
data. Lower plasma concentrations may have been
as effective but it also raises the question as to whether
ribavirin should continue to be administered based on
body weight or dosed to achieve a target serum concentration.
Another possibility is that inter-individual varia-
HEPATOLOGY, Vol. 41, No. 2, 2005 LUTCHMAN AND GHANY 235
tions in the metabolism of ribavirin may account for
differences in clinical efficacy. Thus, patients who are
nonresponders to weight-based therapy may be receiving
subtherapeutic doses of ribavirin. This possibility may to
a certain extent explain the low SVR rates observed in two
trials of peginterferon and ribavirin in human immunodeficiency
virus coinfected patients12,13 and a recent Spanish
Trial of 72 weeks versus 48 weeks of peginterferon
plus ribavirin for patients who fail to achieve virological
clearance at week four.14
In summary, Lindahl et al.’s article is an important
study whose results probably provoke more thought
about ribavirin’s mechanism of action than provide a
practical therapeutic approach for patients with chronic
hepatitis C. At present, this strategy should be reserved for
the setting of controlled clinical trials and not become
part of standard clinical practice.

[willing]

I'll try to post that editorial below; it has some good cautionary comments. The high RBV approach is interesting in a couple of ways. Drs have been quite conservative with RBV rx up to now, even though the 1000/1200 regime for 1s has been proven superior to 800 for some time. The caution seems appropriate given the induced anemia, the proven teratogenicity, the incomplete carcinogenic studies and the still unresolved mechanism of its anti-HCV effect. Increasing the quantity of a naturally-produced protein like ifn seems like an overall safer thing to do than flooding the body with an entirely synthetic molecule which, unlike the proteases, clearly has a  very widespread effect. On the other hand, there's been a steady trickle of evidence showing higher SVR rates with higher RBV dosage and the Lindahl paper is likely to trigger more.

I believe 1800 a day is higher than I've seen anyone report on this board (hopefully I'll be corrected if that's not the case). It may be worth checking with a local university/med-school and see if they're willing to run the serum tests and how much they'd charge. That would at least let you monitor how much of it was in circulation. The claim that serum level is actually more closely related to kidney function than to weight means the weight-based calculation may not be very meaningful. As to whether 15 micro-mol/L, almost twice the mean serum level with standard dosage, is an arbitrary target, their own explanation is helpful:
"The probability of response to treatment has been shown to increase with increasing ribavirin concentrations. Therefore, we chose a target concentration > 15 micro-mol/L, based partly on the data of Jen et al [no one in that study did more than 1200], and partly on our prior studies in which some patients on standard therapy achieved concentrations above 15 micro-mol/L".

[willing]

whoa Bill - you're really heading off the beaten track and charting new ground. The assay used to assess serum riba concentration in the Lindahl study is published in :

Svensson J-O, Bruchfeld A, Schvarcz R, et al. Determination of ribavirin in serum using highly selective solid-phase extraction and high performance liquid chromatography. Ther Drug Monit 2000; 22:215–8.

For some reason I couldn't find a PUBMED cite for this, but that could be ineptness on my part. The protocol involves an HPLC pump and UV detector and seems like it should be within easy reach of any university biomed lab.
If you do a PUBMED search for "+Lindahl +ribavirin" or "+Bruchfeld +ribavirin" it seems these guys have been investigating the pharmacokinetics of riba for a few years now, and have been arguing that basing dosage on weight is a poor way to gauge its impact on the body and that kidney function (specifically GFR) is a better predictor. In fact in their 2/05 Hepatology paper, the fact that they got a 90% SVR rate seems both unexpected and almost secondary to their goal of assessing the dosage required to maintain a steady serum concentration of riba >= 15 micro-mol/L.

The hepatology <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15657958">editorial</a>   that accompanies their article is a bit critical : <i>"The rationale
for choosing a target concentration of 15 micro-mol/L appeared to be arbitrary and not based on good pharmacokinetic and pharmacodynamic data" </i> and concludes <i>"At present this strategy  should be reserved for the setting of controlled clinical trials and not become part of standard clinical practice"</i>. But this is how progress happens... You're a brave guy, Bill, but caution seems advisable.

[Bill1954]

Yeow!!!
I had done a lbs/kilo conversion from Herrmann's 13.75, and came up with 6.25. That might expain some of the error , but still, 6.75?...looks like my 10-key doesn't like riba either. Thanks for pointing that out, jmjm, I'd hate for a bunch of people to see a mistake like that. I'd look like a fool,LOL!

[jmjm530]

Bill,

You're on the correct riba dose based on the Hermann stucy but
I think there's a typo the calculation example you used above.

The Hermann study used a multiplier of 13.75 mg/kg. You stated "6.75 mg/kg."

[cuteus]

You are so fortunate to have this doctor for your provider, you are almost guaranteed success with him in your team.

[jmjm530]

I couldn't access the complete editorial, but the target 15 micro-mol/L ribavirin concentration was not arbitrary, but rather based on riba levels Lindahal and group had already observed was attainable by some subjects on normal ribavirin dosing.

As you stated, this group has been doing ribavirin dosing research for many years and one of their findings is that serum ribavirin levels are based more on kidney function (and other factors, perhaps still unknown) as opposed to body weight. For this reason, serum riba levels can vary considerably in what might seem at first glance to be a homogeneous population.

Whether or not 15 micro-mol/L is the optimum risk/reward dose for SVR has not been established by this study but that was not its intent. As you mentioned, the original intent was to study how well high dose ribavirin could be tolerated.

Logically, future trials should test riba levels lower than 15 micro-mol/L but as of right now there seems little interest in formal high dose riba studies in this country with more sexy therapies like protease inhibitors getting a lot of the attention and funding.

In Bill's case, it looks like he won't be getting any serum riba tests anyway, but even so, everything seems to point that the more riba, the better the chances for SVR. Of course, you have to be able to safely tolerate the treatment. Lindhal tells us that a lot can be tolerated as long as doctors and patients are willing to intervene agressively with Epo and transfusions. Certainly this approach is not for everyone and requires vigilant medical supervision.

[jmjm530]

I weighed 165 when I went from 1200 to 2000 mg of riba/day which may have influenced my anemia. But then again, earlier studies from the same Lindahl group suggest that weight (as opposed to kidney function) is a poor predictor of anemia.  

When you do speak to your doctor, see if you can bug him about getting some Procrit now. I guarantee that if you keep upping the riba, eventually you will. (100% of the Lindahl study group ended up on Procrit.)

The only question in my mind is that if you know you're going to end up on Procrit, why wait and suffer? My pre-treatment baseline hemo of 14.9 dropped to 11.4 in just a few weeks which was enough to put me in the ER. It was back up to 13.6 with two weeks of 40,000 units of Procrit injections. Right now I'm still on Procrit and sitting pretty with a hemo of 14.

My experience and observations are that most docs (including mine) are too slow on the draw with Procrit and only seem to administer it when you're suffering. And that means you gotta suffer another 2-4 weeks. Not good.

In my case, I was on top of the world before the anemia hit and was wondering what all the big fuss with side effects was all about. Within a few days I was reduced to practially an invalid, got really depr3essed, and was literally hanging on to for several weeks just to stay on treatment. Anyone who has been there can tell you that anemia is not fun.

Good luck!

[Bill1954]

Jmjm--Thanks for the timely reply. Yes, this is definitely an experiment. I

[DoubleDose]

I agree with the above comments.  You are on a potentially effective track, but you need to prepare fully for a possible big 'hit' to your hemoglobin.  I used twice weekly doses of Procrit to make it through 18 months of tx, and it was the key to my success.  I was able to keep the Ribavirin at full tilt.  You need to be out in front of any big drop in RBC, and Procrit would help you avoid any big catastrophe.  That said, I will say that several times during my tx, I was in the low 8's on my RBC, before using Procrit, and even during Procrit use near the end of tx, and was still able to function (barely).  So in other words, with where you are now, you still have a good amount of cushion, as far as falling red cell counts.  

I also did a dose of Peg-Intron that was about twice standard, which I really believe helped with the clearance times, and with long term eradication.  If for any reason the Riba strategy does not do the trick, the daily infergen should be highly effective, if you are forced to that strategy.  I would just advise that the 15 mcg. daily is much more effective than the 9mcg. dose.

Please keep us up to date on your progress.  Best wishes for success on this regime!!!!

DoubleDose

[Docsgold]

Wow!  Good luck to you, I cannot imagine that much riba.

[jmjm530]

Bill,

Just want to add that I have heard anecdotally a few cases where the high riba approach has worked mid-treatment in cases like yours using standard doses of Pegasys. So I think your doc is very progressive and potentially on the right track. In fact, 1800 mg/day is on the low end of the Swedish study and your doc may want to consider even higher doses later on if you can tolerate.

But again, the key word is "tolerate". One thing the Swedish study concluded, was that everyone metabolizes riba differently. 1800 mg for you may be very different from 1800 mg for me. And, according to them, this is less dependcent on body weight and more dependent on kidney function.

The elegance of their study is that they dosed every patient differently based initally on a formula (based on kidney function) and later on the actual riba levels as measured in blood plasma. But again, the special riba blood plasma test is not available in this country to my knowledge. If you are serious about going down this route -- and have the resources -- you might want to have your doc contact the Swedish researchers, and see if you can send some blood plasma over there for testing.

[jmjm530]

Bill,

Be VERY careful with the riba increase -- very few doctors/patients in this country have any experience in this area. I'm one of those that has.

In a nutshell.

After reading about the Swedish very high ribavin study, I convinced my doc to increase my riba from 1200mg to 2000 mg/day. Within two weeks I ended up in the ER dehydrated and with anemia.
Had to go off riba for a week and now I'm bsck on normal dose.

If you are going to experiment with high riba doses (and regardless of what your doc says, "experiement" is what you're doing) I strongly suggest that: 1) You increase in weekly increments of 200 mg; 2) monitor your hemoglobin at least weekly; 3) Start Procrit prophylactively.

You also have to keep two very important things in mind. It takes about two weeks for the increase in riba to hit, and when it hits, it can hit real fast. I was fine one day and in the hospital the next. And second, it takes 2-4 weeks for the Procrit to kick in and increase your hemoglobin. So the time to take the Procrit is now, not when you're anemic.

Factor in the above, and you can why a a staged increase is a lot safer. The one thing you don't want to do is have to come off riba and/or need a transfusion. You may be lucky and not have the same sides I did, but why take a chance? If you can tolerate it, you can be up to your 1800/mg a day in only 3 weeks.

Did you ask your doc if he upped anyone else's riba 600mg in one pop and how they are doing? It might be a good question.

Remember, in Sweden, the only place I am aware they have high dose ribavirin in trial, they have a special blood test to measure serum ribavirn levels. In other words, they are not flying "blind" like I was or you are.

I think the high dose ribavirin route definitely has merit for hard to treat populations, especially if you have advanced fibrosis and don't have the time to wait for newer and safer treatments. Just keep in mind that the risks are more sides, and the fact that you may have to be taken off treatment if you cannot tolerate it. Two out of the ten patients in the sweedish study required two blood transfusions each.

That all said, I still may up my riba somewhere down the line to give myself a better chance at SVR (I'm at week 14 now, virus free at week 6) since I'm over 50 and a stage 3/4. But if I do it again, and that's a big IF, LOL, I will probably up my riba only 100 mg a week with weekly hemoglobin tests, and, of course, remain on Procrit.

Good luck!