question about triple therapy and dosages

[Bill200]

I would be interested in hearing any thoughts or comments on starting a reduced dosage regimen due to low WBC.  Thinking about starting treatment with half-dosages (90 mcg Inf and 200 mg Riba BID) and then a month in if all goes well kicking in the Incivek at half-dosage.  Stage 2.  WBC low due to another drug but that's being adjusted and the hope is the WBC will rebound.

[HectorSF]

CSA = Cyclosporin A is an immunosuppressant used in post liver transplant patients to prevent organ rejection. Warning: Cyclosporin causes drug to drug interactions with INCIVEK. It causes the dosage of cyclosporin to go very high! Here is the warning from the INCIVEK package insert...
"Plasma concentrations of cyclosporine and tacrolimus are markedly increased when co-administered with telaprevir. Significant dose reductions and prolongation of the dosing interval of the immunosuppressant to achieve the desired blood levels should be anticipated. Close monitoring of the immunosuppressant blood levels, and frequent assessments of renal function and immunosuppressant-related side effects are recommended when co-administered with telaprevir.
The use of telaprevir in organ transplant patients has not been studied."

INF+Riba has been used for many years post transplant patience to clear the virus. It is the only treatment known to work although the odds are lower than in normal healthy people. (30%) Adverse Events are the problem post treatment. Anemia and other blood level abnormalities are the issues most problematic in post TP patients.

Depending on how active the hep C virus is most post TP patients are treated after a year of two of recovery. Only a hepatologist who has years of experience treating post transplant patients should attempt this. Done poorly can result in organ rejection or worse. So it will require a consent form. Not something anyone wants to happen!

For more info about hepatitis C treatment in post transplants patients this is a paper when by my  hepatologist who is one of the international leaders in hepatitis and liver transplant...

Liver Transpl. 2008 Oct;14 Suppl 2:S58-66.
Hepatitis C therapy before and after liver transplantation.
Terrault NA. Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA 94143, USA.

http://onlinelibrary.wiley.com/doi/10.1002/lt.21624/full

"4. Posttransplant antiviral therapy in those with evidence of recurrent disease is the mainstay of management. A combination of pegylated interferon and ribavirin is the treatment of choice, and sustained virologic response is achieved with 48 weeks of treatment in approximately 30% of treated patients. Attainment of early loss of hepatitis C virus RNA is highly predictive of sustained virologic response. Histologic improvements are seen in responders. Survival is prolonged among those achieving a sustained virologic response.
5. Posttransplant antiviral therapy is limited by poor tolerability and the frequent need for dose reductions and/or discontinuation. Immunologic complications, including acute rejection, chronic rejection, and autoimmune-like hepatitis, occur in association with therapy, albeit at low rates.
6. Hepatitis C virus-infected liver transplant recipients represent an important patient population in need of new therapeutics options to prevent patient and graft losses due to recurrent hepatitis C virus disease."

Work with your transplant center and a hepatologist on your post TP treatment. They are the only ones that can help you.

Good luck clearing the virus!

hector

[Revalation]

I have a naturally low neuprophil count.
When I started it was 1.8 and after 1st inj.dropped to .04.
I have treated in the past so this came as no surprise.
The doctor ordered the Neupogen when he ordered my meds. It works quickly.Probably will be taking in throughout treatment.

Good Luck

Reva

[Sentinel13]

Hi Bill: I believe you are correct with your comment, "Sounds like it's primarily the INF that's the problem with WBC." I've been on treatment 3 times (duel therapy twice and triple therapy with Incivek once). When I wasn't on the complete treatment, I spent years on only pegylated interferon in an attempt to help reverse liver fibrosis. So, I have 5+ years of blood test data and analysis. For me, INF is the drug that drives down WBCs and platelets while riba and Incivek are the drugs that drive down RBCs/hemoglobin. Cheers, GB

[Peter2012]

After week 12 on the April 5th tests my WBC count was at 1.4 and neutrafills at 6.0.

The nurse said not to worry yet, even though the 1.4 is a low number, because the neutrafills are 6.0 it's okay for now.

However, she said they may need to reduce the peg if it gets much lower. There is a drug I can take to increase the WBC, but it's very expensive here in Canada.

I don't want to reduce the dose (despite other unplesant side effects besides the low WBC count) because I feel it will reduce my chances of SVR.

[Bill200]

Post-transplant - even INF+Riba is not FDA approved so all of it's off-label.  WBC low due to CsA.  Genotype 1B.  Dose-reduced regimen is Doctor's rec due to risks involved.  Haven't begun yet.   But the comments are appreciated. Sounds like it's primarily the INF that's the problem with WBC.  Will discuss with Dr.

[flcyclist]

Bill, has your doctor identified the reason for the WBC count and any chance this can be addressed before beginning tx?  As clearly pointed out above, interferon is usually the cause of low WBC's/ANC during tx, so no reason to dose reduce the other meds.  Starting with 200 mg Riba is such a low amount, you're setting yourself up for problems.

Have you discussed these ideas with your tx doctor yet?  Also, curious what your WBC/ANC is currently.  You do have the option of adding neupogen or antibiotics if your doctor thinks that is the best route.   Good luck to you.

[jules2551]

Hi Bill I agree with all the other comments!  Why in the world would you want to prescribe and diagnose yourself?  I think you should listen to your Hepa Dr and do as they say.  SVR is the ultimate goal for all of us.  I think you are reducing your chances.  

Have a great day!
Jules

[Sentinel13]

Hi Bill: Agree with the above. You may want to review the presentation at the following link. This presenter asserts that peg & riba are necessary to eradicate the portion of the virus that is resistant to the protease inhibitor. I believe this researcher's conclusions are aligned with the above comments. Cheers, GB

http://74.43.177.57/courses/2010/pg/pawlotsky/player.html

[willbb]

Starting a reduced dosage regimen due to low WBC.
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Certainly it would be irresponsible  for anyone here to suggest doing the "less than recommended prescribed dosing " as per the Drug Labeling.
Also..you mention you are thinking of doing this because your WBC are baseline low.?

The Incivek really has noy no bearing on WBC  levels anyway .(below) so what would your reasoning be to want to half dose.starting a reduced dosage regimen due to low WBC.?


White Blood Cells: Treatment with peginterferon alfa is associated with decreases in mean values for total white blood cell, absolute neutrophil, and absolute lymphocyte count. More Incivek-treated subjects had decreases in lymphocyte counts to 499/mm3 or less (15% compared to 5%). Decreases in total white cell counts to 1,499/mm3 or less were comparable (8% compared to 5%). The incidence of decreases in absolute neutrophil counts to 749/mm3 or less was 15% in subjects treated with peginterferon alfa and ribavirin alone compared to 12% among those treated with Incivek combination treatment.

Riba does not have much effect on WBC either so why would you want to reduce that also?.

There doesn't seem to be much logic to the idea ,,not to mention the risk of an unsuccessful therapy..

Will

[can-do-man]

As hrsepwrguy said dose reducing Incivek must never be done at anytime . Dose reducing Riba and Inf should only be donce ONCE a person becomes und. Trials starting out using a reduced dose did not work out to well........ I would be surprised and worried if any doctor would agree to starting treatment this way....... Best to you.

[stormy456]

I'm fairly certain that no doctor will support this modified regimen.  You can definitely not reduce the dosage of Incivek (see hrsepwrguy post)  From what I understand, people have SVR'd with reduced riba and IFN once the virus has gone UND, but did not begin tx with reduced dosages.  My husband's dr. reduced his riba about 5 weeks into tx, and it has remained reduced throughout his 20 weeks of tx, and will remain so.  

[Dee1956]

Are you on tx now?  What did your doctor say about this change?
It would help if you provide more information, Geno type, status of tx, etc

[hrsepwrguy]

Dose Reduction
To prevent treatment failure, the dose of INCIVEK must not be reduced or interrupted. Refer to the respective prescribing information for dose modification of peginterferon alfa and ribavirin [see Warnings and Precautions (5.7)].

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