ribavarin dose with Teleprevir

[pcds]

I just received my med and saw the doc orders 600mg of rbavarin.  When I treated last time I used 1000.  I called the office he's out of town.  Did he make a mistake?  If so now I worry about his being sloppy .  If I hadn't treated before I would be in trouble.  Not a great way to start off with a new doc.

[spectda]

It doesn't matter when you take it, but it is actually more common to take more riba in the morning because for some people riba causes restlessness and therefore sleeplessness.

[hrsepwrguy]

Not everyone I take 600 in the am 400 in the pm I weigh 144

[streamline569]

I weigh 107lbs and I'm almost 5'5 and I'm on 1000 Rba but I was told to take 600 in the am and 400 in the evening. I don't see that it would make a difference when you take it. I do notice everyone is doing it the other way though.

[banarep]

I did 600 a day of riba, but it was after 17 weeks of 1200 and telaprevir.  am now svr

[elpasolady]

Just want to give you all an update.  I finally talked to my Dr. yesterday about my  Riba dose.  She admitted that she dosed my riba on the wrong peg interferon. She thanked me several times for 'catching this'.

What I want to say is , thank YOU !  

Without this forum I would have been taking only 800mg of Riba . We will never know the outcome if I had, but your extensive knowledge and experience has saved me from a potentially dismal outcome.

You guys ROCK!  ( and, as I have great faith, God works in mysterious ways sometimes, for sure)

[flcyclist]

What a great example of the benefits of this forum with the great advice and knowledge base of the members.  Being informed and going prepared with good question for your doctor is so important, since you really have to look out for yourself.    

Kudos to you elpasolady.  Best wishes as you begin trt.

[elpasolady]

WOW.....this has become a great, important, discussion, for sure. Thanks for all the inputs!
After more research, and reading comments from this forum, below is what I decided all the confusion may be about, for me at least, and possibly my Dr.
  
My Dr. told me that she did not have anyone on the Pegasys, only the Peg-intron. If you read below, even though the last sentence confers with what everyone has been saying about 1000 mg, , it's possible that she is used to dosing based on the Peg-Intron approved dose, which you will read, is 800 mg.
  I will find out more when I talk to her later today. I will tell her that I WANT the 1000 mg of Riba which is the approved dose for Pegasys, which is what I will be taking.  
I hope this clears things up a bit. If it weren't for you all, it is possible I would have jeopordized my chance of UND at 4 weeks due to not enough Riba.  Of course we will never know, but like you say, better safe than sorry!!!  

My heartfelt thanks for this entire conversation!


~~~Ribavirin comes in 200 mg tablets or capsules. The approved dose of ribavirin when used with Pegasys is 1,000-1,200 mg (5-6 tablets) daily, split into a morning dose (2-3 tablets) and an evening dose (3 tablets). The actual dose is based on body weight: people who weigh less than 165 lbs. take 1,000 mg daily, and people who weigh 165 lbs. or more take 1,200 mg daily. People with genotype 2 or 3 only need 800 mg daily, split into a morning dose (2 tablets) and an evening dose (2 tablets), regardless of weight.

The approved dose of ribavirin when used with Peg-Intron is 800 mg (4 tablets) daily, split into a morning and an evening dose. However most doctors would prescribe 1,000-1,200 mg, based on body weight, and expect the approved dose to change when more data is available. ~~~

[Proactive]

I don't know as the high doses in the Lindahl study are being suggested here.(not by me anyway)
Here is the full study I believe you are referencing.
http://diss.kib.ki.se/2005/91-7140-348-5/thesis.pdf

[desrt]

"Fatigue 10 Moderate to severe
Pruritus or dermatitis 9 Moderate to severe
Nausea 7 All patients were treated with ondansetron
Aphthous ulcers 3  
Oral candida 2 Responded well to fluconazole
Blurred vision 2  
Diabetes mellitus 1 Started at treatment week 10, insulin dependent
Brown spots 1 Oral cavity
Migraine 1 Severe attack in association with a rapid hemoglobin drop "

[desrt]

From the link posted by flcyclist:

"The side effects were more frequent and serious, in particular potentially life-threatening anemia, than those observed with standard combination treatment."

IFN/riba have never been Rx'd by what *works* but by how much the average patient can *tolerate* without sustaining an unacceptable amount of damage.

[Proactive]

Pre PI data

"A positive linear relationship exists between ribavirin dose and SVR; ribavirin doses greater than 10.6 mg/kg/d have higher SVR rates"
http://depts.washington.edu/hepstudy/hepC/mgmt/anemia/discussion.html

[Proactive]

actually, someone posted "the higher the dose you can tolerate, the better--guided by hgb levels" to be precise.

"overdose of ribavirin although rare can be fatal esp if other conditions are present -

I've never heard of a ribavirin overdose. If memory serves,I did read in the ribavirin fda approval notes where one patient took 50 pills..no overdose.
Interested in your source, a link would be great TIA

[willbb]

I don"t think anyone .(.at least I didn"t read so.)...was advising elapsolady of  taking excessive amounts of RIBA.. the guideline for her at 143 lb  is 1000.. ..I believe the general advice here was to take that vs. the 800 mg her pharmacist suggested to err on the side of best chance for enough vs. possibly too little.

Will

[cheesenrice]

funny thing about anemia and hypothyroid conditions - they are associated with better svr results - these are also reasons for dose reduction and even discontinuation - many svr with dose reductions - so more ribavirin does not always = better - always better to follow established guidelines - overdose of ribavirin although rare can be fatal esp if other conditions are present - i remember talking to someone who high dosed ( very high ) and she was a mess during and many years post tx - ribavirin is known to increase interferons efficacy so it will always be included with every option involving inf - someone posted take all you can handle - not a good idea - maybe take all you can handle within recommended guidelines - also most of what is known about ribavirin comes from studies of people with minimal liver damage

[Willy50]

http://pi.vrtx.com/files/uspi_telaprevir.pdf

----------------------DOSAGE AND ADMINISTRATION-----------------------
• 750 mg taken 3 times a day (7-9 hours apart) with food (not low fat). (2,
12.3, 17.4)
• INCIVEK must be administered with both peginterferon alfa and
ribavirin for all patients for 12 weeks, followed by a response-guided
regimen of either 12 or 36 additional weeks of peginterferon alfa and
ribavirin depending on viral response and prior response status. (2)


• For specific dosage instructions for peginterferon alfa and ribavirin,
refer to their respective prescribing information. (2)  (my emphasis-willy)
=======================================================


http://www.gene.com/gene/products/information/pegasys/pdf/pi.pdf

COPEGUS should be taken with food.
Table 1 PEGASYS and COPEGUS Dosing Recommendations
Hepatitis C virus
Genotype
PEGASYS Dose COPEGUS Dose Duration
Genotypes 1, 4 180 mcg <75 kg = 1000 mg
75 kg = 1200 mg
48 weeks
48 weeks
Genotypes 2, 3 180 mcg 800 mg 24 weeks
Genotypes 2 and 3 showed no increased response to treatment beyond 24 weeks
=================================
You can take a look.  This is what I *think* I see.

You can confer w/ Vertex/Incivek, your doctor and/or pharmacist.  None of us are in a position to recommend anything.  I surely don't know the answer but am interested in hearing the correct answer.  Obviously, we are all interested in making sure people get the proper dosing.......

willy

[Willy50]

This almost begs for a new and separate thread, but..... I'm not sure that I've seen a discussion of the differences between treating a PI with Pegasys vrs Pegintron.

The issue is (forgive me if i am misstating this) each drug will have it's own treating instructions for the use of ribaviren.

I believe that the current state of affairs is that without regard to which form of TX you are taking, you simply follow the SOC treating instructions for that drugs regimen (whether Pegintron or Pegaysys with the allied riba dosing) and then add the PI according to the dosing instructions of that drug.  I don't believe that Telaprevir for instance recommends dosing for either IFN or riba.  That is left to the doctor to prescribe on or off label since they are familiar w/ your case and medical history.

So far as Telaprevir trials go..... I was under the impression that they used almost exclusively Pegasys.

Elpaso...... I *think* the riba dosing will be based upon which drug you or your doctor chooses; Pegasys or Pegintron.  

I also think that most of the performance stats for Telaprevir are primarily based upon the use of Pegasys.  
There was a study in which they were compared when dosed with Telaprevir;

http://www.natap.org/2009/AASLD/AASLD_43.htm
(visit the link for the full article)

The 2 drugs provided similar outcomes but the Pegasys seemed to provide a higher SVR rate in both BID and TID telaprevir dosing.

Willy

[Willy50]

(full prescribing information for Incivek)

http://pi.vrtx.com/files/uspi_telaprevir.pdf

14 CLINICAL STUDIES
14.1 Description of Adult Clinical Studies
The efficacy and safety of INCIVEK in subjects with genotype 1 chronic hepatitis C were evaluated in three adequate and well-controlled clinical trials: two
in treatment-naïve subjects and one in previously treated subjects (relapsers, partial responders, and null responders). Subjects in these studies had
compensated liver disease, detectable HCV-RNA, and liver histopathology consistent with chronic hepatitis C.  

((My emphasis-Willy)  In all three studies, INCIVEK was
administered at a dosage of 750 mg every 8 hours; the peginterferon alfa-2a (Peg-IFN-alfa-2a) dose was 180 μg/week, and the ribavirin (RBV) dose was
1000 mg/day (subjects weighing less than 75 kg) or 1200 mg/day (subjects weighing greater than or equal to 75 kg).

Plasma HCV-RNA values were
measured during the clinical trials using the COBAS® TaqMan® HCV test (version 2.0), for use with the High Pure System. The assay had a lower limit of
quantitation of 25 IU/mL. SVR in all studies was defined as HCV-RNA less than 25 IU/mL at 24 weeks after the planned end of treatment.
---------------------------------------------------------------------------------------
Seems to me that this is the trial design upon which FDA approval was based.  

You would have to ask yourself if they know more or know less than the folks who designed the trials.  I personally agree w/ willing and others that a bit too much in the beginning is preferable to starting with reduced dosing.  Starting with reduced dosing to make it "easier" does not factor in having to retreat because you relapse or break through.  Reducing the riba dosing lower than clinical trials will almost certainly cause a lower SVR rate in groups.  A second headache results when you are possibly saddled w/ PI resistance.

This same prescribing information also conveys that no trials have been done testing the effects of attempting to retreat w/ a PI.  

Willy

[roostermom]

I just started second round of treatment with Incevik, and my Ribo dose is 800. I am 130 alb, 5'4's. The first round I started at 1000, and dropped to 88 lbs in 6 ms. The doc reduced the Ribo to 800. I was a bit surprised at the lower dose of Ribo this time, and wasn't sure if it was the new protocal for the triple treatment of based on past history. I will have to ask them about this. My now 25 year old daughter was in the Telapavir Drug trial (and is CURED) and I am fairly sure she was also only on 800 of Ribo

[Proactive]

Elpasolady, I'm certainly no doctor, but was a late responder(cleared at wk 14). My doc was not happy with my rate of viral decline after 1 month on tx and also saw my hgb levels weren't dropping much on 1200mg of ribavirin ( hgb was @16), so he countered with increasing riba dosing, 1400mg, then 1600mg @ wk 8. You won't find this approach in the books..The point is, here in the US, hgb levels are about the only way to gauge serum levels of riba, so they should be followed closely, IMO..

not giving advise, just my opinion and tx story....and times have changed since then

[flcyclist]

My comment was directed to the desrt's post regarding high dosing riba and the large proportion of study subjects needing transfusions.  

I agree completely with your well stated comments. :)

[elpasolady]

Are you saying that the goal is to make sure you get your hgb down between 10 -11?  If you don't, then you need more Riba?  Did I understand you correctly?
Anyone else concur with this?
thanks

[spectda]

I wasn't suggesting that someone high dose ribavirin. I was suggesting that they take the amount to start with that people used in the trials if they expect the same chance of SVR.

If someone was unsuccessful with a previous tx and had no or little hgb drop they might consider speaking to their doctor about increasing the riba dose this time. Just my two cents!
-Dave

[Proactive]

Telaprevir trial results "The relapse rate was 53 percent for the 24-week regimen that did not include ribavirin (arm three)"

http://investors.vrtx.com/releasedetail.cfm?releaseid=457359

[flcyclist]

All I could find regarding this high dosing with ribovirin by Dr. Lindahl was a small pilot study done in 2005.  There were only 10 people in this pilot study and 2 needed transfusions, both who were receiving doses as high as 4,000 mg daily.  If there is other data, please let us know, otherwise this reference to high dosing and needing transfusions might give people an unnecessary scare.

http://onlinelibrary.wiley.com/doi/10.1002/hep.20563/full

The primary goal of this small pilot study was to determine feasibility and safety of the treatment, and not virological outcome. However, in this difficult-to-treat patient population with genotype 1 and a high viral load, nine of ten patients were cured by standard definitions, which seems to be a better response than that found in studies using standard ribavirin doses.