Medication reduction already

[PJ1966]

I just started treatment and had to go into lab yesterday to get blood redrawn due to a bilirubin spike after one week.  Common according to my doc but he wanted to make sure.  Sure enough the RBC is starting to go low.  He had to reduce my dosage due to low RBC (3.45), hgb 10.3, hct 30.3, RDW 14.5%.  Bilirubin went retest came down to 1.9.  It's getting better since it went up to 4 after one week of tx.  I'm on triple tx and started with 1200 mg daily riba, but doc cancelled my evening dose yesterday so only took 600 mg yesterday.  Today he has me on 300 mg (1/2 pill) until I get my 200 mg pills in the mail which he'll have me take 2 per day.  I'm only on day 16.  My viral load was:
12/5/2011 344933
7/13/2012 371829
7/30/2012 259914  (start of tx)
9/5/2012   284 (one week on tx)
He's hoping I was undetected end of week 2 which was Wed.  I won't get the results for one week so we don't know for sure.  I guess the reduction in riba is okay if I was undetected.  If not, not sure what that means, but the doc said he couldn't take the chance of my blood getting too low.
Platelets are good so far at 229.
I just thought I'd give my results as I just started and am already disappointed on having to reduced meds, but understand the blood issue can get out of control quickly and he didn't want that.  This is my second time on tx but first time was in 2005 and only the interferon/riba.  I had to do procrit a lot last tx so I have had low RBC & WBC before.  So far my WBC is okay.  I was a responder but relapsed.  Hoping for the best.
thanks to all for your support and advice.

[jules2551]

Also wondering if you have cardiac disease?  Because according to protocol if your HGB <10 and you have cardiac disease, then they would reduce Riba by 50%.  That was the ONLY reason stated.

Jules

[jules2551]

able 5: Guidelines for Dose Modification and Discontinuation of Peginterferon alfa-2b, Interferon alfa-2b or Peginterferon alfa-2b/Ribasphere Capsules Based on Laboratory Parameters in Adults and Pediatrics


*
    For adult patients with a history of stable cardiac disease receiving peginterferon alfa-2b or interferon alfa-2b in combination with ribavirin, the peginterferon alfa-2b or interferon alfa-2b dose should be reduced by half and the Ribasphere dose by 200 mg/day if a > 2 g/dL decrease in hemoglobin is observed during any 4-week period. Both peginterferon alfa-2b and Ribasphere or interferon alfa-2b and Ribasphere should be permanently discontinued if patients have hemoglobin levels < 12 g/dL after this Ribasphere dose reduction. Pediatric patients who have pre-existing cardiac conditions and experience a hemoglobin decrease ≥ 2 g/dL during any 4-week period during treatment should have weekly evaluations and hematology testing.

**************************************************************************************
†
    1st dose reduction of Ribasphere is by 200 mg/day, except in patients receiving the 1400 mg dose it is by 400 mg/day; 2nd dose reduction of Ribasphere (if needed) is by an additional 200 mg/day.

************************************************************************************
‡
    For patients on Ribasphere/Peginterferon alfa-2b combination therapy: 1st dose reduction of peginterferon alfa-2b is to 1 mcg/kg/week, 2nd dose reduction (if needed) of peginterferon alfa-2b is to 0.5 mcg/kg/week. For patients on Ribasphere/interferon alfa-2b combination therapy, reduce interferon alfa-2b dose by 50%.

http://www.drugs.com/pro/ribasphere.html

*****************************************************************************
PJ...this is the protocol for Ribasphere dosage reduction.  If you go to the link I posted it shows a chart more in laymen terms.  Please read about the 1st dosage reduction that I highlighted above.

Jules

[PJ1966]

Thanks for explaining data.  I didn't understand the information until put more plainly.  I'm very new at all this.  You all are so experienced and knowledgeable.  Appreciate the help to understand issues.

[PJ1966]

thank you for your advice.  I'm waiting for my viral load results for week 2 so hoping for the best.  Should have them Monday or Tuesday.
Thanks for the web link.

[8nickers8]

you don't get what I am saying, but I'll just let it be.

[Asuncion]

I think you should read this article about Ribavirin reduction:

http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates/Using%20HCV%20PIs/Modules/Case%20Vignettes/Pages/Page%207.aspx

Your viral load is responding to treatment, so a reduction on Ribavirin should not be so bad. I also think it was a VERY BIG reduction, but it is better than having to suspend treatment for blood issues. I am not a doctor, and I don´t have all the information on your medical file, so I don´t know why he lower your dose so much. I think you should do what your doctor tells you to, but ask him about other options so you can resume the recommended ribavirin dose as soon as possible.

[pooh55811]

If a person is going to use iron supplements, that person needs to ask the Hepatologist first. Many people with liver problems already have problems with iron metabolism and iron storage so a person does not want to add to an already existing problem.

Adding iron may help if the person is suffering from Iron Deficiency Anemia prior to treatment .If a person can correct Iron Deficiency Anemia prior to Tx, then the Iron Def. Anemia would not compound the Hemolytic Anemia caused by the drugs.  

However, adding iron is not going to alter the course of Hemolytic anemia because the Hemolytic Anemia is not caused by iron deficiency. It is caused by the Hep C Tx  drugs(Ribavirin) which 1) causes the destruction of red blood cells (hemolysis), 2) can down-regulate the number of erythropoietin receptors. Interferon can also contribute to the development of anemia by suppressing bone marrow production of erythrocytes, Finally, patients developing anemia during HCV therapy often have inappropriately poor serum erythropoietin responses, probably related to their underlying liver disease.

[8nickers8]

I do realize that and again, would it be a problem for those on short therapies, let's say the 12 or 24 weeks ones, just to use the iron supplement that I mentioned (it doesn't cause diahrrea or stomach pain) just to keep that level up so the drug makers doing the study do not insist on lowering the riba?  You  see what i mean?  Just curious, would it hurt anything?

[8nickers8]

Great article explaining that treatment, thank you.

[8nickers8]

Thank you.

[pooh55811]

Here is the link to that data:

http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htm

[pooh55811]

"Jeepers, I don't understand all that, does anyone else? "
_____________________________________________

Let me try to explain Can-do's data:

Treatment Outcome for Teleprvir 12 (weeks) plus Peg (Inf) and Riba
Number  in study: 363
Overall SVR 79% (285/363)

Percentage of people in the study who attained: eRVR (early rapid viral response) was 58% (212/363)  (eRVR is UND at week 4)
SVR rate in the 58 % of people who attained eRVR  was 92%

Percentage of people in the study who did not attain eRVR:  42% (151/363)
SVR rate in in the 42 % of people who did not attain eRVR:  60% (90/151)

Outcome for Subjects without SVR
On-treatment virologic failurea 7% (26/363)
Relapseb 4% (11/298)
Otherc 11% (41/363)

Hope that helps.

[pooh55811]

"Does anybody know why, when the hemoglobin drops, the docs don't just put folks on the new iron supplements "
----------------------------------------------------

When we are on treatment (Interferon, Ribavirin, and a Protease Inhibitor) we do not become anemic because we are deficient in iron (Iron Deficiency Anemia). Instead we become anemic because the drugs are causing Hemolytic Anemia.

"Causes of Anemia Associated with HCV Therapy"

"Anemia that develops in a patient receiving HCV therapy often has multiple potential contributing factors, including ribavirin (Rebetol, Copegus), interferon or peginterferon, underlying liver disease caused by HCV infection, and co-morbid conditions, such as HIV infection or chronic renal failure[1]. The anemia associated with ribavirin most often occurs as a dose-dependent hemolytic anemia, typically developing within the first 4 weeks of therapy. With use of higher doses of ribavirin (1000-1200 mg/d), hemoglobin levels frequently decline by 2-3 g/dL, as seen in this case. In addition to causing hemolysis, ribavirin can also down-regulate the number of erythropoietin receptors. Interferon can also contribute to the development of anemia by suppressing bone marrow production of erythrocytes, but this process is generally slower and may account for the continued decline in hemoglobin concentration during the second and third months of treatment, as seen in this case. Finally, patients developing anemia during HCV therapy often have inappropriately poor serum erythropoietin responses, probably related to their underlying liver disease. Because of the mixed nature of HCV treatment-associated anemia, it often is not possible to pinpoint one particular drug as the primary cause of the anemia. "

[8nickers8]

Does anybody know why, when the hemoglobin drops, the docs don't just put folks on the new iron supplements like 21/7  by VitaMed which do not have the terrible side effects that most iron supplements do?  I know that with us, it's dangerous for iron to build up in us but I asked a doctor and was told it takes a LONG time for that to happen and it doesn't hurt anyone to take the iron supplement for 12 or 24 weeks.  The buildup doesn't happen that quickly and once we stop the treatment and stop the iron supplements it goes back to normal.  

[8nickers8]

Jeepers, I don't understand all that, does anyone else?

[pooh55811]

In two of the clinical trials they had  arms that contained no Riba, just Incivek and Interferon. The arms without Riba had significantly lower SVR rates.

Reducing Riba may be the initial step when the Hgb drops below 10, but I don't think I have ever heard of going from 1200 mg to 400 mg in one fell swoop at day 15.  And most people on the forum who had Hgb drops reduced Riba some and used Procrit. Many also had transfusions.

I don't know if you have ever had anemia before. I had hemolytic anemia when I had systemic vasculitis. My Hgb was 9. I was short of breath, severely fatigued, white as a sheet, light headed. I could walk only a few steps at a time and then I had to rest. I also had a faster heart rate. I had episodes where I felt like I would pass out and collapse and had to lie down immediately, even when I was driving, I had to pull over and rest. (I only drove to the doctor's office.) I was so tired I did not want anyone to come over or to call me. It was a major effort to keep my eyes open or to talk.

Last fall when my hemoglobin started to drop, I was severely fatigued, short of breath, could feel every  heartbeat (and the heart rate was about 110 all of the time), had runs of fast heart beats of 180 per minute which lasted several minutes, felt like I would pass out, was light headed, had reeling dizzy spells, had to hang onto the walls when I walked, felt weak. I am only telling you this to let you know that anemia causes these symptoms. Last fall I tried to compensate some by walking slowly and not much, using elevators, getting up very slowly, resting as needed, hanging onto walls, not overdoing, keeping hydrated.

Some of the symptoms may not be due to anemia. Or at least, the other drugs are compounding the symptoms. I was no longer anemic yet I was still extremely fatigued, light headed at times, felt like I would faint or collapse if I did not sit or lie down right away, felt weak, had no energy. Those things were at least partially caused just by ingesting the drugs, even when I was not anemic.

Here is the data from the studies each containing an arm without Ribavirin:

"Ribavirin: A Critical Component in HCV Treatment"

"Early studies of protease inhibitors include studies in which RBV was not coadministered largely because RBV is known to caused hemolytic anemia and gastrointestinal problems. However, when RBV was excluded from these regimens, SVR rates dropped and resistance arose (Figure 1).[8-20] "

"For example, in the phase II PROVE 2 study, treatment-naive patients chronically infected with genotype 1 HCV were randomly assigned to one of 4 treatment arms:

1. T12PR24
2. T12PR12
3. T12P12
4. Standard pegIFN/RBV for 48 weeks[8]

Comparing the T12PR12 and T12P12 arms that were identical apart from the inclusion or exclusion of RBV, SVR rates were 60% in the arm with RBV and 36% in the arm without RBV. Rates of virologic breakthrough were 1% and 24%, respectively. Similarly, in PROVE 3, which was conducted in patients who had failed previous pegIFN/RBV treatment, SVR rates were 2 times lower for patients not receiving RBV in their telaprevir-based regimen: 24% in the T24P24 arm vs 53% in the T24PR48 arm (Capsule Summary).[9] Similarly, relapse rates were 53% and 13%, respectively. Finally, in the SPRINT-1 study of boceprevir for genotype 1, treatment-naive patients, those receiving low-dose RBV achieved an SVR rate of only 36% vs 50% with standard weight-based RBV dosing, each combined with boceprevir and pegIFN (Capsule Summary).[10] Thus, RBV remains a critical component of these new antiviral regimens."

http://www.clinicaloptions.com/Hepatitis/Annual%20Updates/2011%20Annual%20Update/Modules/DAA%20Naive/Pages/Page%204.aspx

[orphanedhawk]

Oops, I got confused by the Sacramento Pharmacy reference. I see you're in So Cal.

Who you really should see for a consult is Dr. Gish, a very renown wonderful hepatologist there at UCSD. He's one of the best in the nation.

http://www.healthgrades.com/physician/dr-robert-gish-y9dtj/address

[orphanedhawk]

I find it hard to understand why your doctor would not use procrit unless you have some other medical issues going on.
The reason we suggest hepatologists is as liver specialists they have more training specific to liver disease.

If you are in the Sacramento area you could see one of the hepatologists who do outreach from CPMC. My hepatologist who I adore works in Sac though I'm not sure which days.
You could see him for a consult and continue with your current doctor if you choose.

http://www.sutterpacific.org/locations/outreach/1315alhambra.html

If  you want to talk to me more about him, send me a pm. I have his email.

Coincidentally, I began seeing him when my GI wanted to pull me off treatment. One of the members here recommended him. I was able to continue without missing one shot.

[frijole]

i see you are a quilter,  me too.  i put a couple of pics of my quilts in my photos.  I did not have energy to quilt when I treated.

[frijole]

I have to agree with most of the posters in thinking your doctor got a little radical on the riba reduction.  What was your starting hgb anyway?  A 2 point drop can be pretty devastating and you may have had a 4 point drop.  The doctor does have you on weekly CBCs, right?  You need to know when you can increase your riba.  

My insurance company approved the procrit okay (with a little glitch) and later they would not approve it until I had reduced riba.  But as soon as the doc told them I reduced they approved without time to have any results from the reduction.  Insurance companies are way behind on this.

I hope you are able to increase the riba soon.

[PJ1966]

I do have fatigue, dizziness and shortness of breadth.  I'm down & resting.  He called Curascript right away, but they didn't mail it today.  I was pissed off & calling my insurance to see why I must deal with them instead of the company that my doctor wanted to use.  He usually deals with Greater Sacramento Pharmacy and swears by them.  Thanks for everyone's comments.  I'll talk to my doc more about this.  He is an internist at UCSD.  This department treats all Hep C patients.  He completed a clinical fellowship in Addiction Medicine and Viral Hepatitis C at Weill Medical College of Cornell University. His clinical research involves Hepatitis C in opiate dependent patients.  I did talk to him about protocol of anemia and he told me upfront the first line is reduction of Riba.  He wants me fully on incivek for full 12 wks.  Thanks for your comments.  I'll talk to him more.  Appreciate your help.

[pooh55811]

A Riba reduction of 1200 mg to 400 mg would scare me to death, especially at day 16. An incremental reduction from 1200 mg to 1000 mg and starting Procrit would be my option if it was me. I would even take a blood transfusion if necessary. My Hgb dropped to 10.2 and I never reduced anything.

I know this is early in your treatment (day 16) and it appears the doctor is nervous about the Hgb drop, but I still think it is a drastic reduction. He does not even know if you are UND yet. Even being UND does not mean the virus is gone. It simply means the test cannot count find it.

Is this doctor a Hepatologist or a GI or a Primary Care Physician. If it was me, I would discuss this with the doc and if he insists on only 400 mg a day, I would find a Hepatologist who tries not to reduce Riba anymore than absolutely necessary and who uses a combination of treatment (including Procrit and blood transfusions) so one can stay on an adequate dose of Riba. (Actually, that is what I did when my Hgb started to get near 10.  

It is true that they concluded that Riba reduction did not impact SVR, but they were not specific about how much it can be reduced, at what point in treatment it can be reduced, and how long  it can stay reduced.

[can-do-man]

Treatment Outcome T12/PR
N = 363
n/N (%) Pbo/PR48
N = 361
n/N (%)
Overall SVR 79% (285/363)
46% (166/361)
eRVR 58% (212/363) 8% (29/361)
SVR in eRVR subjects 92% (195/212) 93% (27/29)
No eRVR 42% (151/363) 92% (332/361)
SVR in no eRVR subjects
60% (90/151) 42% (139/332)
Outcome for Subjects without SVR
On-treatment virologic failurea 7% (26/363) 29% (105/361)
Relapseb 4% (11/298) 24% (53/220)
Otherc 11% (41/363) 10% (37/361)
----------------------------------
As one can see response was... eRVR 58% (212/363) 8% (29/361).
So a doctor is " guessing, hoping" your und at week 2 yet only 58% was at week 4............

  

[working dog]

i wish i was 10hgb at day 16.......week 4 is a big one to get through