Granulocyte Stimulating Colony Factor Criteria for Use for Hepatitis C Treatment-Related Neutropenia VHA Pharmacy Benefits Management Strategic Healthcare Group and Medical Advisory Panel Prepared by: K. Tortorice, PharmD BCPS , H. Yee Pharm D BCPS, E. Bi

This shows the dosing information for neupogen while on hcv tx. According to this information the neupogen should be stopped or taken less often if the anc is over 1000. Mine was at 6500 after five injections, and my doc tells me to keep taking the neupogen.


Granulocyte Stimulating Colony Factor Criteria for Use
for Hepatitis C Treatment-Related Neutropenia
VHA Pharmacy Benefits Management Strategic Healthcare Group and Medical Advisory Panel
Prepared by: K. Tortorice, PharmD BCPS , H. Yee Pharm D BCPS, E. Bini MD, M. Chapko PhD, T.
Chiao Pharm D, M. Goetz MD, E. Hansen NP, S Ho MD, G. Ioannou MD; R. Miller MD, E. Morrison
MD; H. Mun Pharm D, R. Reddy MD, S. Wongcharatrawee MD, T. Wright MD, J. Dominitz MD


Stimulating Colony Factor Criteria for Use
for Hepatitis C Treatment-Related Anemia
March 2006 1
Updated versions may be found at http://www.vapbm.org or http://vaww.pbm.med.va.gov
Granulocyte Stimulating Colony Factor Criteria for Use
for Hepatitis C Treatment-Related Neutropenia
VHA Pharmacy Benefits Management Strategic Healthcare Group and Medical Advisory Panel
Prepared by: K. Tortorice, PharmD BCPS , H. Yee Pharm D BCPS, E. Bini MD, M. Chapko PhD, T.
Chiao Pharm D, M. Goetz MD, E. Hansen NP, S Ho MD, G. Ioannou MD; R. Miller MD, E. Morrison
MD; H. Mun Pharm D, R. Reddy MD, S. Wongcharatrawee MD, T. Wright MD, J. Dominitz MD
The following recommendations are based on current medical evidence and expert opinion from clinicians. The content of
the document is dynamic and will be revised as new clinical data becomes available. The purpose of this document is to
assist practitioners in clinical decision-making, to standardize and improve the quality of patient care, and to promote costeffective
drug prescribing. The clinician should utilize this guidance and interpret it in the clinical context of the individual
patient. Additional information can be found at www.pbm.va.gov and http://vaww.pbm.va.gov
.
Introduction
Hepatitis C virus (HCV) infection is estimated to affect several million Americans and over 170 million
people worldwide. Standard treatment for chronic HCV involves an interferon-based preparation and
ribavirin for 24 to 48 weeks. Sustained virologic response (SVR), defined as having undetectable virus at 6
months post-treatment, occurs in 54% to 56% of overall patients treated with peginterferon alfa and
ribavirin. Moderate neutropenia is a common adverse effect of hepatitis C antiviral therapy with
peginterferon alfa causing bone marrow suppression, resulting in absolute neutrophil counts (ANC) of
<750/mm3 in approximately 20% of those treated. Peginterferon alfa doses of <60% of target dose appears
to reduce SVR. Conceptually, granulocyte colony stimulating factor use may overcome treatment-related
neutropenia, maintain higher interferon doses and potentially reduce infection in high-risk patients, though
clinical studies to recommend its use are lacking.
Patient Selection
Before using a granulocyte colony stimulating factor:
 Peginterferon dose has been reduced
o Peginterferon alfa 2a reduction from 180mcg/week to 135mcg/week
o Peginterferon alfa 2b reduction from 1.5mcg/kg/week to 1.0mcg/kg/week
AND
 Persistent severe neutropenia despite at least 2 weeks of reduced dose peginterferon along with:
o ANC <250/mm3, OR
o ANC 500/mm3)
 Maintain therapeutic dose of interferon-based preparation (generally, dose reductions of up to 40%
do not appear to compromise SVR)
 Reduced risk of infection and hospitalization
Dosing and Monitoring (Refer to algorithm below)
 Filgrastim 300 mcg sq once or twice a week.
Granulocyte Stimulating Colony Factor Criteria for Use
for Hepatitis C Treatment-Related Anemia
March 2006 2
Updated versions may be found at http://www.vapbm.org or http://vaww.pbm.med.va.gov
 Titrate filgrastim dose to achieve ANC 500-1000/mm3.
 Check nadir ANC just prior to the next dose to evaluate response every 1-2 weeks until stable
 If ANC shows no increase or continues to decrease after at least 1 week of filgrastim, then further
reduce or discontinue peginterferon and titrate filgrastim as above.
o Investigate other potential cause for neutropenia (e.g. myelodysplasia)
 If ANC >1000/mm3, stop filgrastim.
Safety Issues
The most common adverse effects associated with filgrastim include bone pain and generalized
musculoskeletal pain. Other adverse effects infrequently observed and possibly related to filgrastim use
include injection site reaction, rash, hepatomegaly, and arthralgia.
Allergic reactions occurring on initial or subsequent treatment have been rarely reported (<1 in 4,000
patients), generally occurring within the first 30 minutes of administration. These have been generally
characterized by systemic symptoms involving at least 2 body systems, most often skin (rash, urticaria,
facial edema), respiratory (wheezing, dyspnea), and cardiovascular (hypotension, tachycardia). Symptom
resolution occurred in most cases after administration of antihistamines, steroids, bronchodilators, and/or
epinephrine.
Rare fatal cases of splenic rupture have been reported following administration of filgrastim in both healthy
volunteers and patients. Patients reporting left upper abdominal and/or shoulder tip pain should be
evaluated for an enlarged spleen or splenic rupture.
Cytopenias resulting from an antibody response to exogenous growth factors have been reported on rare
occasions in patients treated with recombinant growth factors. Patients receiving filgrastim should be
closely monitored for a paradoxical decrease in ANC and treatment should be discontinued in patients with
evidence of neutralizing antibodies to filgrastim.
Severe sickle cell crisis resulting in death has been associated with filgrastim in patients with sickle cell
disease. Risks and benefits of filgrastim use in patients with sickle cell disease must be carefully
considered.
Since filgrastim single-dose vials and prefilled syringes do not contain preservatives, the vial or prefilled
syringe should only be used once and any unused portion should be discarded.
References
1. Alter MJ, Kruszon-Moran D, Nainan OV, McQuillan GM, Gao F, Moyer LA et al. The
prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J
Med. 1999; 341:556-62.
2. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared
with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized
trial. Lancet 2001; 358:958-65.
3. Fried MW, Shiffman ML, Reddy R, et al. Peginterferon alfa-2a plus ribavirin for chronic
hepatitis C virus infection. N Engl J Med 2002; 347:975-82.
4. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon alpha-2a and ribavirin
combination therapy in chronic hepatitis C: a randomized study of treatment duration and
ribavirin dose. Ann Intern Med 2004; 140:346-55.
5. Sulkowski M, Wasserman R, Hassanein T, et al. Changes in hemoglobin during interferon alpha-
2b plus ribavirin combination therapy for chronic hepatitis C infection. J Viral Hepat
2004;11:243-50.
6. McHutchison JG, Manns M, Patel K, et al. Adherence to combination therapy enhances sustained

[spectda]

The main points:

Titrate filgrastim dose to achieve ANC 500-1000/mm3.
 Check nadir ANC just prior to the next dose to evaluate response every 1-2 weeks until stable
 If ANC shows no increase or continues to decrease after at least 1 week of filgrastim, then further
reduce or discontinue peginterferon and titrate filgrastim as above.
o Investigate other potential cause for neutropenia (e.g. myelodysplasia)
 If ANC >1000/mm3, stop filgrastim.

[frijole]

Well, I can't say I like these recommendations at all.  First, the recommendation is to reduce the interferon for 2 weeks.  Pegasys - 180 to 135;  PegIntron - 1.5mgs/kg to 1.0

Only then if that doesn't work does it recommend Neupogen.  

Furthermore, if I am reading this right, the suggested ANC start to reduce interferon is at 750.  Personally I don't think interferon should be reduced OR Neupogen should be started until ANC is under 500.

Stopping the Neupogen when your ANC reaches 1000 is smart.  I think rarely does the Neup bring the ANC all that high, and it doesn't stay there that long

I didn't see where it recommended the increase in interferon again - did you?

Personally to you, Dave, I cannot imagine why they are continuing Neupogen if your ANC is 6500.  Are you sure?   How is it shown on your bloodwork?  Mine was always shown as K/mL --- so my .6 would equal 600 in ANC/mm3 (I think).My pretreatment ANC was only 2.8 (2800) so I cannot imagine you being 6500 during treatment.

frijole

[spectda]

Hi Kathy-
I have not seen my cbc. I haven't been back to the trial site and won't be there until monday. I asked last week to insure the 6500 number was my anc, they said that was correct and to continue the neup.
Dave

[Bill1954]

Dave, there are two ways of expressing neutrofils; as a percentage (%) and as neutrofils absolute (1000/uL, or k/uL). I wonder if there is a misunderstanding here if you haven’t personally seen the labs?

For instance, in week 12 of my second treatment, my neutrofils value was 40% (L), with a reference range given as 45-75%.

The same week of treatment, by neutrofils absolute value was 1.40 k/uL (L), with a reference range given as 1.500 – 7.800 k/uL.

Does any of this help? I haven’t gone back to look at your individual results yet to compare…

--Bill

[spectda]

I got those results from a new nurse, my main nurse was not in at the time. I asked her to insure it was the anc and to tell me the past results. Since she read the past results as 280 and 710, I assume the 6500 was correct. I sent my regular nurse a note to find out for sure.
- Dave

[frijole]

Hi Dave    Hi Bill

DAve, I think  Bill is thinking like me.  We have apples and oranges here.  Do you have any bloodwork?  Do you have anything that showed your pretreatment ANC?  Me thinks someone is reading your bloodwork to you wrong.  I bet you are at 650, not 6500 -- but .....

Bill - did you notice in the text about they refer to the ANC as xxxx/mm3?  Do you know what the mm3 is?  I never learned my metric system very well, but the 3 really confuses me.

Sure glad it is Friday.

frijole

[spectda]

The nurse said I was a big over achiever, she said wow, you are at 6500. when I was at 710 the considered me too low to increase my inf still.

[frijole]

But Dave....

..considered me too low to increase my inf still. .

ARe they giving you the PegIntron or the Pegasys?  In either case isn't it a case of taking the lesser amount from the prefilled syringe and squirting the rest on the ground, so to speak?

I really don't think you should do any more Neupogen and I do think you should take standard dose inf -- just my opinion.

frijole

[spectda]

Hi Kathy- I don't want to take any drugs I don't need, and I don't want to dose reduce, but I am committed to the trial and the team has gotten me to this point. I take pegintron in a redipen.

take care,

dave