Ribaviron doses

[granitekonig]

I'm a genotype 3, and I begin treatment in the next week or two. My doctor said that I would be taking the 800mg of Ribaviron because i'm geno 3 and that the typical 1200mg wouldn't be needed.

My question is this; can anyone offer any advice or insight on how this difference in dosages reflect on side effects? More specifically, has anyone had to reduce their dose from 1200mg to 800mg? I'd really like to know of any percieved changes in side effects?

[Proactive]

72 weeks of tx...over 4000 riba pills (1600mg/day)...8 1/2 months post..still undy and all blood test are in the normal range..I'm a firm advocate for the highest riba dose you can tolerate-regardless of genotype...pro

[FlGuy]

Taking a 800 fixed dose of riba is like Kimbo Slice taking orange-flavored children's aspirin after a bout.  Think more about the effectiveness of the treatment and less about the side effects.  Your doc can help manage the side effects.  Go for the grown-up dose approach.

[desrt]

Dose reducing from 1200 to 800 at week 19 allowed me to keep going another 4 weeks.

[jmjm530]

G: Well, interesting...just spoke with my Gastro's assistant. Apparently Insurance companies don't like to see patients starting out with higher dosages because of cost.
--------------
I doubt that's the case.  And in fact have heard more misinformation from doctor's offices on what an insurance company will and will not do. Probably once upon a time someone in the office didn't fill out the requisite paperwork or entered a wrong dx code and the insurance company gave them a hard time, i.e. translation more work for the doctor's office. The most probably scenario is that if the doctor orders 1200 mg and someone is willing to fill out any requistite forms that there will be no problem. You can check this yourself by calling the insurance company. Personally, I was told all sorts of things my first NP would have to "fight" to get from the insurance company. As it turns out, all that was needed was a rx.

-- Jim

[sunqueen]

Geno 3 here. I do 1200 Riba/day. My pills are "machine counted" and filled by the specialty pharmacies that my insurance uses. I found this out when I was short a pill when pre-filling my pill box (they sent me a pill when I called). Also, my large national (US) insurance provider switched their pharmacy contract when I was around the 12 week mark. My Riba tablets changed with the contract. I was getting a pink pill and now I get a white pill. The pharmacist confirmed that they use another supply source.

Also, if the company that supplies your medications offers you a RN case manager, then take it! I got a call every few weeks from mine and she really had some great suggestions for helping with sides. She went away when the contract changed :-(

Press them for weight based dosing!  Good luck to you!  

[comeagain]

Hi granite listen to this my first tx 24 weeks that was done between sept 2006 and februar 2007 my weight was then 200lbs and I´ve got 800mg riba and 100mcg  pegintron I alredy then asked my doc how come that I how weighted 200lbs have the same dosis as a woman with a weight of  135lbs the answer to that was that there are studys made that proves that for geno 2-3  its make no differens period...

when I 10 months  after my first tx asked him how come they now have changed the protocol, he then said the study (ies) that has determen the old protocol was made in south european contries where the populaton are smaller and thinner than the average
world populations people period....

He also added thats why studies performed in the US have lower SVRs nr then studies  performed elsewhere they are fatter.
You got to admit some of those doctors are real "clever" people.!!!

ca

PS I´m now on 1200mg riba and 180mcg pegasys (cant compare that with pegintron though) I´v lost + 26lbs been on that lower weight since week 14 I am now in my last week 48 that is.

PPS My hgb is almost the same this time as last just a little bit lesser the last three months 119 verces 120 good luck!!!!

[kickboxingmom]

Thanks to the wonderful, knowledgable people on here I upped my Interferon to 0.5.I also take 1000 mg. riba a day.I weigh 103, now 104 lbs.I am a beleiver of hit it hard and fast.I don't want to retreat.I am geno 1A.Good luck with your decisions.Sides were worse for first three weeks for me .This week # 4 has been better.Knock on wood.
Tammy

[epiphiny]

Wow, here in NZ they dispense the exact amount you need each month, nothing more nothing less... in my case 4 shots and 168 riba each month.

[justme53]

My first two Rx's for Ribavirin and Peg were rejected because of the higher doses. I guess this is pretty standard. My Dr. then resubmits them. My Ribavirin at 1400 mg. per day has now cleared and still waiting on the Peg. In my case anyway, just another hoop to jump through. So far, so good! Maybe this will hold true in your case too.

Good luck!!

Pam

[nygirl7]

My doc wanted to start me at 800 (would have been weight based and actually fine for me) however I wanted more (i had two geno's and convinced myself I needed it to succeed as it turns out I probably did).

Anyway he upped me to 1000 no problem. NONE from the insurance company at all. The pills come in a giant bottle.........everyone ALWAYS has tons left.  I was able to double dose pretty much all the way through all 72 weeks without any problem at all.

I'm not saying yippeeeeeeeee go nuts but what I am saying is that an insurance company really woudln't have any idea how many a day you were taking that much - they aren't counted out and put into a bottle as far as mine they came in two bottles each month with my shots.

Maybe somebody has a different experience? I don't remember this being discussed before. (Not that I'm saying go against your doctors orders)

I've been over tx for 2 years so maybe some one in the USA has their riba/cope bottles cause I think they come pretty standard already filled up.

All I know is that pretty much everybody I know had tons of riba left at the end because each month you'd get the 4 shots and the two bottles of pills...........so nobody really would know how many a doc prescribed a day!

Go for a higher dose f you can.  Some geno3s have it easy and some do not. Just in case you are not one of the "lucky" (yes ask all the relapsers how "lucky" their geno is) you want to do everything you possibly can to make sure you've done the best you can.

Good luck.

[epiphiny]

I know where you are coming from, here in NZ it is strictly protocol based treatment because of money, I had to FIGHT to get where I am.  

I'm pretty sure you will be able to get around it as well and get what you need.  Hopefully a few more informed folks who understand the US health system will chime in soon...  Or you could start a new thread asking for info?

[granitekonig]

Well, interesting...just spoke with my Gastro's assistant. Apparently Insurance companies don't like to see patients starting out with higher dosages because of cost. WTF?? By the way, I'm American and this is an American health insurance system, so that definitely factors in.

I asked to have the doctor call me back....I want to discuss with him what's best for ME, not saving the insurance company some money so that I may have to end up doing 48 weeks, versus 24.

[epiphiny]

Good decision!!  I'm happy the info helped, all the best :)

[granitekonig]

Thank you epiphiny! That was excellent information. I'm going to ask to start at 1200, at least for as long as I can stand it.

[epiphiny]

Regards the side effects and different doses of Riba:

Yes, there is a world of difference in sides severity depending on the Riba dose you are.  More Riba = more sides (anemia, weakness, breathlessness, fatigue to name a few).

However, the more Riba you can tolerate for your weight the more VIRUS you are going to KILL!!

And that's what you're here for, right?!

[epiphiny]

Genotype 2/3 pts who do not achieve an RVR could receive added benefit if treated for 48wks with a higher dose of RBV (1000/1200mg/d)

Increased SVR Rate with 48 Wks' Treatment and Higher RBV Dose in HCV Genotype 2/3 Pts Without a Rapid Virologic Response (RVR) Treated with Peginterferon Alfa-2a (40KD) (PEGASYS) Plus RBV (COPEGUS)

Reported by Jules Levin
DDW May 20, 2007

Background: ACCELERATE, a large-scale (n=1469) prospective study recently showed that, overall, peginterferon alfa-2a (40KD) plus ribavirin (RBV) for 24wks was superior to 16wks in hepatitis C virus (HCV) genotype 2/3 pts (EASL 2006:A734). In this study, two-thirds of pts achieved a rapid virologic response (RVR; HCV-RNA 80% probability of achieving an SVR with 16wks of therapy, suggesting that this shortened treatment regimen may be a reasonable customized option for RVR pts who cannot tolerate a full course of therapy. Conversely, pts without an RVR had an SVR rate of only 49% with 24wks' treatment, suggesting that these pts may benefit from more intensive treatment regimens. To determine whether an intensified regimen of peginterferon alfa-2a plus RBV may be beneficial in genotype 2/3 pts without an RVR, we retrospectively examined available data from other pivotal clinical studies.

Methods: SVR and relapse rates following peginterferon alfa-2a (PEGASYS) plus RBV (COPEGUS) were analyzed in HCV genotype 2/3 pts who did not achieve RVR in two studies (NV15942, NV15801). In NV15942 (Hadziyannis. Ann Int Med 2004), pts were randomized to 24 or 48wks of peginterferon alfa-2a 180µg/wk plus RBV 800 or 1000/1200mg/d. In NV15801 (Fried. NEJM 2002), pts received 48wks of peginterferon alfa-2a plus RBV 1000/1200mg/d.

Results: RVR was achieved by a high proportion of genotype 2/3 pts (75% and 59% in NV15942 and NV15801). In pts in NV15942 who did not achieve an RVR, the lowest relapse rate and the highest SVR rate (76%) was achieved with 48wks of peginterferon alfa-2a plus RBV 1000/1200mg/d (Table). This compared with 61% for 48wks' peginterferon alfa-2a plus RBV 1000/1200mg/d in NV15801 and 49% for 24wks' peginterferon alfa-2a plus RBV 800mg/d in ACCELERATE.

Conclusions: Genotype 2/3 pts who do not achieve an RVR could receive added benefit if treated for 48wks with a higher dose of RBV (1000/1200mg/d).These results merit further investigation in a prospective controlled study to fully elucidate how treatment customization can benefit pts.

Pts without follow-up data were considered not to have achieved an SVR.

B. Willems1; S. J. Hadziyannis2; T. R. Morgan3; M. Diago4; P. Marcellin5; D. E. Bernstein6; P. J. Pockros7; A. Lin8; M. L. Shiffman9; S. Zeuzem10
1. Hopital Saint-Luc-Centre Hospitalier de l'Universite de Montreal, Montreal, QC, Canada.
2. Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece.
3. Gastroenterology-11, VA Medical Center, Long Beach, CA, USA.
4. Hospital General de Valencia, Valencia, Spain.
5. Hopital Beaujon, Clichy, France.
6. North Shore University Hospital, Manhasset, NY, USA.
7. Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla, CA, USA.
8. Roche, Nutley, NJ, USA.
9. Virginia Commonwealth University Medical Center, Richmond, VA, USA.
10. Department of Internal Medicine, Saarland University Hospital, Homburg/Saar, Germany.

http://www.natap.org/2007/DDW/DDW_01.htm

[epiphiny]

Weight-based Dosing Of Ribavirin Improves Outcomes For Patients With Hepatitis C

ScienceDaily (Oct. 26, 2007) — Patients with hepatitis C treated with combination therapy of pegylated interferon and ribavirin had better outcomes when taking a weight-based dosage of ribavirin compared to a flat dosage. This treatment technique also improved the response rates of African American patients, whose outcomes have lagged behind those of Caucasian patients. These findings are in the October issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD).

Combination therapy of pegylated interferon and ribavirin is the standard of care for patients with chronic hepatitis C, allowing more than half to achieve a sustained viral response. However, previous studies have suggested that a weight-based dose of ribavirin might lead to even better results. To examine this possibility, researchers, led by Ira Jacobson of Cornell University, conducted a large, multi-center, randomized, prospective, open-label study between December 2000 and June 2005.

They enrolled 5,027 patients with hepatitis C from more than 200 centers around the country. All participants were 18 to 70 years old, weighed less than 125 kg, had detectable HCV RNA in their blood, and had never been treated for it. They were randomly assigned to receive interferon and a flat dose of ribavirin (800 mg/day), or interferon and a weight-based dose of ribavirin, which started at 800 mg/day for patients weighing under 65 kg, and increased by 200 mg/day for up to each additional 20 kg of weight up to a maxiumum dose of 1400 mg. Those with HCV genotype 2 or 3, which is more responsive to interferon-based therapy, also tested treatment durations of 24 and 48 weeks. Each patient was followed up for 24 weeks after treatment.

"A sustained viral response was achieved by significantly more patients who received a weight-based dose (44.2 percent) than fixed dose (40.5 percent) ribavirin," the authors report. "Overall, response rates decreased as weight increased when a fixed dose was used but remained unaltered with a weight-based dose." Discontinuation rates and reported adverse events did not differ significantly between the two treatment schemes, and relapse rates were lower for patients who had received weight-based dosing. The researchers also found that 48 weeks of treatment offered no additional benefit compared to 24 weeks for patients with genotypes 2 or 3..

Another group of researchers from the same study, also lead by Jacobson, used the study data to understand the impact of weight-based ribavirin with peginterferon alfa-2b in African American patients with HCV genotype 1. Genotype 1 is the hardest to treat, and it afflicts African Americans disproportionately.

Three hundred eighty seven African American patients with genotype 1 were included in the analysis: of those weighing 65 kg or more, and therefore receiving different doses of ribavirin in each arm, 188 had received flat-dose ribavirin, and 174 had received weight-based dosing. Significantly fewer patients in the flat-dose group (10 percent) attained a sustained virological response, compared to 21 percent in the flat-dose group. Relapse rates were 30 percent and 22 percent, respectively.

"An unexpected finding of our study was the increase in efficacy with an increase in ribavirin dose in heavier patients," the authors report. That is, sustained viral response rates increased as body weight increased, suggesting that "ribavirin distribution may be more complex than realized and body weight may only approximate the marker for size required to dose RBV consistently," the authors say.

In conclusion, weight-based dosing of ribavirin offered a significant advantage in efficacy of treatment for African American patients, however, the rate of sustained viral response in this population remains low. "Further studies are needed to elucidate the fundamental basis for the impaired responsiveness in this population," they say.

In an accompanying editorial, Steven-Huy Han, MD and Jason Smith, PharmD of Los Angeles, report that this study adds significantly to our understanding of interferon therapy in African American patients. It will change the approach to ribavirin dosing and will benefit a difficult-to-treat population.

They suggest that the larger question of whether true weight-based dosing of ribavirin is superior to the currently approved standard dosing schemes still awaits head-to-head studies to answer. "At the minimum," they conclude, "the traditional notion that ribavirin dosage should be fixed has now been sidelined by the idea that we should tailor ribavirin dosing to our patients."

Article: "Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients: A Randomized Trial." Jacobson, Ira; Brown, Robert; Freilich, Bradley; Afdhal, Nezam; Kwo, Paul; Santoro, John; Becker, Scott; Wakil, Ed; Pound, David; Godofsky, Eliot; Strauss, Robert; Bernstein, David; Flamm, Steven; Pauley, Mary Pat; Griffel, Louis; Brass, Clifford A. Hepatology; October 2007; (DOI: 10.1002/hep.21932).
Adapted from materials provided by John Wiley & Sons, Inc., via EurekAlert!, a service of AAAS.

http://www.sciencedaily.com/releases/2007/10/071001160641.htm

[epiphiny]

I'm a G3a also and the first time I was treated I was only on 800mg Riba daily.  I am 6' tall woman with a weight of about 164lbs, and at the time of my last treatment I was even lighter than that.

I was a Non Responder to the first round of tx, and suffered virtually no riba sx other than itching.  I had no anemia/low Hb that shows your body is responding to the Riba.

This is my 2nd TX and I am now on 1200mgs Riba daily plus the same amount of IFN as before.

This time I AM responding, UND at 4 weeks, currently at 29 weeks.

My Hb dropped so fast in the first 4 weeks that I had to take a 3 week dose reduction down 1000mg per day and I had a viral rebound at week 8.  Went to back to 1200 and was UND again at week 12.  So reductions are NOT ideal

Getting the right does of Riba is ESSENTIAL!  Especially in the beginning where you need to hit the virus hard and get to UND asap.

My advice is you really fight for this!  This is your life, your body, your health.  And you don't want to be coming back to do it again, like me, this time for 48 weeks.  Btw, there is also benefit in extending treatment out to 48 weeks for G3s, depending on you when you go UND.  In other words, the later you go UND, the longer you treat.

The key is to go hard and aggressive at the beginning, especially when you are still of vim, vigor and enthusiasm.  There are many posts here on the site from people who feel they are being under dosed and have not gone UND and they are G3s, the easy ones to treat.  Yeah right, don't believe that hype!

Anyway, I'll post a couple of studies for you to read and the links to them so you can print them out for you Doc.

Epi.

[Marcia2202]

Personally I believe that your doctor seems to be from the old fashioned school. I would collect some newer studies and show them to him. They strongly advise doing weight based treatment for all genotypes now. I am geno 3 and weigh 54.5 kg (around 120lbs). I am on 800mg.

I hope comeagain will chime in to tell you his story about being under dosed on his first treatment.

As to the difference of sides, I don't think that you can really compare it to anyone else. I think one can only compare it to oneself. Some people react stronger on a low dose compared to someone on a higher dose.

As to reductions, I have not experienced any so far.

All the best,

marcia