Let's talk about Erythropoiesis Stimulating Agents

[ZpackSux]

I think they are dangerous... thrombogenic and tumor stimulating..

discuss.

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[All4MyDaughter]

Polycythemia and increased blood viscosity.

 

[ZpackSux]

but what about anemia? Needs treatment...

 

[WVUPharm2007]

**** that, anemia is more urgent. What good is preventing a tumor from killing you in a few years if you suffocate. Like all drugs, you should take everything on a patient to patient basis.

 

[ZpackSux]

**** that, anemia is more urgent. What good is preventing a tumor from killing you in a few years if you suffocate. Like all drugs, you should take everything on a patient to patient basis.

Oh..really?..

Ok...what do you consider anemia..when do you treat and when do you hold treatment?

 

[WVUPharm2007]

I'll have to refer you to the hemotologist, sir....

Honestly, I'd have to think about it and have studies. Which I don't have.

 

[ZpackSux]

I'll have to refer you to the hemotologist, sir....

Honestly, I'd have to think about it and have studies. Which I don't have.

weak!

 

[UFGatorRx]

I think they are dangerous... thrombogenic and tumor stimulating..

discuss.

blue cheese is tasty!

 

[ForcedEntry]

but what about anemia? Needs treatment...

Stem cells

 

[twester]

The data about efficacy of erythropoeiten stimulating agents (ESA) is conflicted. It appeared in Phase III trials, that ESAs enhanced survivability amongst cancer patients with anemia, but recent studies show a decrease in both tumor management and survivability.

If it's obvious that the cancer treatment being utilized will lead to anemia, the choice is either transfusion or ESAs. Transfusion has inherent risks associated with infectious disease (a disaster for a patient receiving chemotherapy) or incompatabilities. ESAs seem to bypass that risk.

The FDA has issued recommendations that are listed at:

http://www.fda.gov/cder/drug/InfoSheets/HCP/RHE2007HCP.pdf

In the short term, cost of therapy is an issue. The cost of therapy is roughly $1600 per week in addition to the monitoring necessary to ensure that erythrocyte levels are within a range to prevent thrombolytic events.

I think it all boils down to risk versus benefit and the compentency and willingness of prescribers to manage erythrocyte levels in the patients they treat. Oh, and let's keep studying whether it helps cancer patients or not.

 

[WVUPharm2007]

weak!

You's weak, gimme some studies showing the rate of secondary neoplasia and I'll thought process it for ya.

 

[All4MyDaughter]

Blood doping for performance enhancement.

 

[ZpackSux]

The data about efficacy of erythropoeiten stimulating agents (ESA) is conflicted. It appeared in Phase III trials, that ESAs enhanced survivability amongst cancer patients with anemia, but recent studies show a decrease in both tumor management and survivability.

If it's obvious that the cancer treatment being utilized will lead to anemia, the choice is either transfusion or ESAs. Transfusion has inherent risks associated with infectious disease (a disaster for a patient receiving chemotherapy) or incompatabilities. ESAs seem to bypass that risk.

The FDA has issued recommendations that are listed at:

http://www.fda.gov/cder/drug/InfoSheets/HCP/RHE2007HCP.pdf

In the short term, cost of therapy is an issue. The cost of therapy is roughly $1600 per week in addition to the monitoring necessary to ensure that erythrocyte levels are within a range to prevent thrombolytic events.

I think it all boils down to risk versus benefit and the compentency and willingness of prescribers to manage erythrocyte levels in the patients they treat. Oh, and let's keep studying whether it helps cancer patients or not.

Very good. I think you meant Thromboembolic instead of thrombolytic.

I don't think it's a risk versus benefit issue with ESA. There is no doubt about it. It's beneficial. But to what point?

What prompted the FDA's warning? What about the tumor management? What kind of effect are we talking about? What about iron store?

Is anemia only associated with Cancer patients? What about the Chronic Kidney Disease patients?

Actually, the ESA weekly cost isn't that high...it's about $60 to $100 per 10,000 units of Epogen/Procrit... so if patient is receiving 40,000 units weekly, then it's approximately $240 per week.

Am I the only one who sees a tremendous opportunity in management of erythropoiesis for pharmacists?

 

[ZpackSux]

blue cheese is tasty!

No it's not.

 

[All4MyDaughter]

No it's not.

I enjoy buffalo wings with some blue cheese dressing.

 

[twester]

Very good. I think you meant Thromboembolic instead of thrombolytic.

Thank you. Yes, that's what I meant.

I don't think it's a risk versus benefit issue with ESA. There is no doubt about it. It's beneficial. But to what point?

ESA treatment is only beneficial to the point that the anemia is caused by a deficiency of erythocytes. It has no efficacy in the management of iron-deficiency anemia.

What prompted the FDA's warning? What about the tumor management? What kind of effect are we talking about? What about iron store?

The FDA warning was prompted by studies that showed an increased risk of side effects and death following the use of ESAs. However, the studies all involved off-label use or dosing of ESAs.

It appears that, in patients with head-and-neck cancer who were receiving radiation therapy, tumor management was decreased in patients receiving Aranesp. The study was initiated by the Danish Head and Neck Cancer Study Group and was corroberated in a study by Henke et al.

Patients with non-small cell lung cancer had higher mortality with ESA therapy. It appears that life-span was reduced by about one-half. These patients also continued to need transfusions. So erythrocyte levels were not managed by ESA alone. (Question: does this have something to do with the nature of the cancer?)

Iron replacement is required in order to complete the functionality of Hb. IV iron replacement therapy may increase patient response to ESA therapy over oral iron supplement. More study is required. (Bokemeyer et al)

Is anemia only associated with Cancer patients? What about the Chronic Kidney Disease patients?

Nope.

Since destruction of renal tissue also causes a diminished production of EPO, patients with renal failure can also benefit from ESA therapy. Again, erythrocyte levels must be monitored and iron intake must be increased. Use as directed, please.

Am I the only one who sees a tremendous opportunity in management of erythropoiesis for pharmacists?

I see what you're saying, but what's the size of the market? Are you seeing EPO clinics? Isn't this something that would be managed by an oncology pharmacist or a pharmacist in a renal clinic?

 

[ZpackSux]

ESA treatment is only beneficial to the point that the anemia is caused by a deficiency of erythocytes. It has no efficacy in the management of iron-deficiency anemia.

So, if renal or cancer patient is anemic and Serum Ferritin and TSat is low..should we hold ESA treatment?

The FDA warning was prompted by studies that showed an increased risk of side effects and death following the use of ESAs. However, the studies all involved off-label use or dosing of ESAs.

It appears that, in patients with head-and-neck cancer who were receiving radiation therapy, tumor management was decreased in patients receiving Aranesp. The study was initiated by the Danish Head and Neck Cancer Study Group and was corroberated in a study by Henke et al.

Patients with non-small cell lung cancer had higher mortality with ESA therapy. It appears that life-span was reduced by about one-half. These patients also continued to need transfusions. So erythrocyte levels were not managed by ESA alone. (Question: does this have something to do with the nature of the cancer?)

What off label use? There have been many many studies with ESA use on cancer patients. Tumor cells have a high level of ESA receptors which proliferates tumor progression..some think.

Iron replacement is required in order to complete the functionality of Hb. IV iron replacement therapy may increase patient response to ESA therapy over oral iron supplement. More study is required. (Bokemeyer et al)

Of course... Oral iron absoption is poor at best even in healthy adults.

Since destruction of renal tissue also causes a diminished production of EPO, patients with renal failure can also benefit from ESA therapy. Again, erythrocyte levels must be monitored and iron intake must be increased. Use as directed, please.

Ok... have you seen the direction lately? And do you think anyone is able to follow the direction?

I see what you're saying, but what's the size of the market? Are you seeing EPO clinics? Isn't this something that would be managed by an oncology pharmacist or a pharmacist in a renal clinic?

The market? I cant tell you this. Erythropoietic is in the top 5 pharmaceutical spend for majority of hospitals in the US. For some hospitals, it's the top spend. The renal market is huge...most dialysis patients in the US are on ESA.

The issue is...length of stay is usally less than 7 days for most of these patients when hospitalized. But look at the latest PI for Procrit, Epogen, and Aranesp..and pay close attention to the dosing guideline.

It's hairier than the Heparin titration.

You are so close.... Google CHOIR trial.. and National Cancer Institute statement.

 

[sdn1977]

Very good. I think you meant Thromboembolic instead of thrombolytic.

I don't think it's a risk versus benefit issue with ESA. There is no doubt about it. It's beneficial. But to what point?

What prompted the FDA's warning? What about the tumor management? What kind of effect are we talking about? What about iron store?

Is anemia only associated with Cancer patients? What about the Chronic Kidney Disease patients?

Actually, the ESA weekly cost isn't that high...it's about $60 to $100 per 10,000 units of Epogen/Procrit... so if patient is receiving 40,000 units weekly, then it's approximately $240 per week.

Am I the only one who sees a tremendous opportunity in management of erythropoiesis for pharmacists?

I'm coming a little late to this party...I've been wine tasting on the central coast.....ever been on that road between Cambria & Paso Robles?? Its beautiful at this time of year & there are about 8 new wineries (actually, not new - just open now to the public)

Anyway....yeah - I think you're the only one seeing this as an opportunity. Why? because in Dec, the House Ways & Means Committee held a hearing on patient safety & quality issues with regard to ESRD. Long story short - the GAO is looking to change the reimbursement of CMS to a bundled, fixed rate for a defined episode of care. Currently, all dialysis pts are Medicare eligilble & reimbursement is based on dialysis & separately billable drugs to Part B. Epogen is the single largest drug expenditure in Part B each year. Even when it is not indicated for ERSD, but for oncology, the reimbursement is by a prior auth & they use the same guidelines.

By going to a fixed, bundled rate (similar to a DRG).....CMS can define closely the parameter by which it chooses to pay. By establishing a marker - lets say 39% on when to initiate monitoring (or 36% or 33%) they can then restrict expenditures by making the clinicians choose their patients wisely.

Lets take that ERSD pt who is 39 yo - may have failed a kidney transplant, may be a poor tissue match - this pt may benefit from tx with Epogen or the like even with the increased incidence of heart issues & risk of cancer because this pt may not live long enough to run that risk & also has a family to interact with. (You can substitute cancer for ERSD if you want here...)

On the other end.....the 84 yo ERSD who by age & comorbidities alone is not a transplant choice & is not living a very active life. Altho this pt may "feel" better with Epogen, we may not choose to tx him because his life is not that active.

We make these choices every day. Often a diuretic is not indicated & actually may be a relative contraindication for CHF.....but we give it to the pt anyway because they "feel" better a bit dry & it may not change the actual disease outcome too much.

But...for that pt who is a "new" cancer or dialysis pt....young, active, has good opportunity for remission &/or transplant....yeah - there is a real question if this is indicated & honestly....altho I see it in the hospital setting - it just doesn't get approved by private insurance for outpt use (particularly cancer). So....the reimbursement is limiting opportunity here.

Choices - difficult choices. But - not ones I think pharmacists are too involved in now or in the future - at least in the outpt setting because this is a Medicare reimburseable Part B drug - not normally reimbursed by private insurance (usually held as an outlier). This, I think, will be determined by oncologists & nephrologists & CMS - not by us. However, there are always those pharmacists who are involved at the public policy level - certainly those folks will have a say in this as well......

Oh - bought some very nice Syrah, a coastal Chardonnay & Zinfandel & saw some great pictures of the Rolling Stones & the Sea Lion pups were on the beach (great for kids!!) .

 

[ZpackSux]

I'm coming a little late to this party...I've been wine tasting on the central coast.....ever been on that road between Cambria & Paso Robles?? Its beautiful at this time of year & there are about 8 new wineries (actually, not new - just open now to the public)

Anyway....yeah - I think you're the only one seeing this as an opportunity. Why? because in Dec, the House Ways & Means Committee held a hearing on patient safety & quality issues with regard to ESRD. Long story short - the GAO is looking to change the reimbursement of CMS to a bundled, fixed rate for a defined episode of care. Currently, all dialysis pts are Medicare eligilble & reimbursement is based on dialysis & separately billable drugs to Part B. Epogen is the single largest drug expenditure in Part B each year. Even when it is not indicated for ERSD, but for oncology, the reimbursement is by a prior auth & they use the same guidelines.

By going to a fixed, bundled rate (similar to a DRG).....CMS can define closely the parameter by which it chooses to pay. By establishing a marker - lets say 39% on when to initiate monitoring (or 36% or 33%) they can then restrict expenditures by making the clinicians choose their patients wisely.

Lets take that ERSD pt who is 39 yo - may have failed a kidney transplant, may be a poor tissue match - this pt may benefit from tx with Epogen or the like even with the increased incidence of heart issues & risk of cancer because this pt may not live long enough to run that risk & also has a family to interact with. (You can substitute cancer for ERSD if you want here...)

On the other end.....the 84 yo ERSD who by age & comorbidities alone is not a transplant choice & is not living a very active life. Altho this pt may "feel" better with Epogen, we may not choose to tx him because his life is not that active.

We make these choices every day. Often a diuretic is not indicated & actually may be a relative contraindication for CHF.....but we give it to the pt anyway because they "feel" better a bit dry & it may not change the actual disease outcome too much.

But...for that pt who is a "new" cancer or dialysis pt....young, active, has good opportunity for remission &/or transplant....yeah - there is a real question if this is indicated & honestly....altho I see it in the hospital setting - it just doesn't get approved by private insurance for outpt use (particularly cancer). So....the reimbursement is limiting opportunity here.

Choices - difficult choices. But - not ones I think pharmacists are too involved in now or in the future - at least in the outpt setting because this is a Medicare reimburseable Part B drug - not normally reimbursed by private insurance (usually held as an outlier). This, I think, will be determined by oncologists & nephrologists & CMS - not by us. However, there are always those pharmacists who are involved at the public policy level - certainly those folks will have a say in this as well......

Oh - bought some very nice Syrah, a coastal Chardonnay & Zinfandel & saw some great pictures of the Rolling Stones & the Sea Lion pups were on the beach (great for kids!!) .

I love the central coast...that's where I proposed to my wife..on top of a cliff..and if she was to say no..I would have pushed her off the cliff.

If I would have gotten a job in central coast or San Diego right out of school..when real estate was still reasonable, I may have stayed in CA...who knows.

With ESA...as the reimbursement scenario looms, don't you think more appropriate use will eventually decrease the utilization and provide cost savings to hospitals and outpatient clinics? Here is a brief description of dosing guideline.

Renal:

1. Maintain the lowest HGB level sufficient to avoid the need for RBC transfusion and not to exceed 12g/dL.
2. Increase in dose should not be made more frequently than once a month
3. If HGB is increasing and approaching 12g/dL, reduce dose by 25%
4. If HGB is still increasing, discontinue until the HGB starts to decrease then restart at 25% below the previous dose.
5. If HGB increases by more than 1g/dL, decrease dose by 25%
6. If HGB increase is less than 1g/dL over 4 weeks, increase dose by 25%


Oncology:

1. Starting weekly Aranesp dosing: 2.25mcg/kg SC
2. Starting once every 3 weeks Aranesp dosing: 500mcg SC
3. If the rate of HGB increase is more than 1 g/dL per 2 weeks or HGB > 11g/dL, reduce dose by 40%
4. If HGB > 12g/dL, discontinue until HGB is below 11g/dL then reinitiate at a dose 40% below previous dose.
5. for weekly administration, if HGB increase in less than 1g/dL after 6 weeks, dose of Aranesp should be increased up to 4.5mcg/kg


Now tell me... who's going to monitor and adjust dosing?

The bottom line is, the National Cancer Institute announced increased mortality with ESA when HGB is above 12. The CHOIR trial was cut short when they noticed HCG above 13 increased adverse outcome.

And how often do we see blanket orders of Epo 40,000 now before discharge...or Epo 20,000 QOD.. when patients have low iron store or HGB is above 12?

I believe this is an area where pharmacist monitoring of dosing and patient status is very lacking in many institutions.

 

[sdn1977]

I love the central coast...that's where I proposed to my wife..on top of a cliff..and if she was to say no..I would have pushed her off the cliff.

If I would have gotten a job in central coast or San Diego right out of school..when real estate was still reasonable, I may have stayed in CA...who knows.

With ESA...as the reimbursement scenario looms, don't you think more appropriate use will eventually decrease the utilization and provide cost savings to hospitals and outpatient clinics? Here is a brief description of dosing guideline.

Renal:

1. Maintain the lowest HGB level sufficient to avoid the need for RBC transfusion and not to exceed 12g/dL.
2. Increase in dose should not be made more frequently than once a month
3. If HGB is increasing and approaching 12g/dL, reduce dose by 25%
4. If HGB is still increasing, discontinue until the HGB starts to decrease then restart at 25% below the previous dose.
5. If HGB increases by more than 1g/dL, decrease dose by 25%
6. If HGB increase is less than 1g/dL over 4 weeks, increase dose by 25%


Oncology:

1. Starting weekly Aranesp dosing: 2.25mcg/kg SC
2. Starting once every 3 weeks Aranesp dosing: 500mcg SC
3. If the rate of HGB increase is more than 1 g/dL per 2 weeks or HGB > 11g/dL, reduce dose by 40%
4. If HGB > 12g/dL, discontinue until HGB is below 11g/dL then reinitiate at a dose 40% below previous dose.
5. for weekly administration, if HGB increase in less than 1g/dL after 6 weeks, dose of Aranesp should be increased up to 4.5mcg/kg


Now tell me... who's going to monitor and adjust dosing?

The bottom line is, the National Cancer Institute announced increased mortality with ESA when HGB is above 12. The CHOIR trial was cut short when they noticed HCG above 13 increased adverse outcome.

And how often do we see blanket orders of Epo 40,000 now before discharge...or Epo 20,000 QOD.. when patients have low iron store or HGB is above 12?

I believe this is an area where pharmacist monitoring of dosing and patient status is very lacking in many institutions.

Oh I just knew you were the romantic type - NOT (splash) !

Yeah, yeah - I see your point. Certainly, I'm not sure why institutionally more hospitals don't get this under control (mine included ) since its included in the DRG & just bumps costs tremendously. With this data from both the NCI & CHOIR trial, it will give more emphasis on P&T to develop dosing parameters - like heparin for example.

But...in the outpt setting - once that pt goes home...the drug & dosing is outside of the ambulatory pharmacist's realm. Most of them are given in the dialysis center or outpt infusion center & it gets billed & reimbursed under Part B. Now with the bundling of services coming...it will be even less likely to dispened/administered outside of a dialysis or infusion setting so the motivation for keeping the dose/pt selection optimal will be either 1)the owner of the dialysis/infusion center &/or pts physician will want to do what is "right" therapeutically for the pt or 2) greed will get the better of them & they will reduce "costs" so maximize reimbursement.

So - yes...within the inpt setting we absolutely should be writing these protocols & getting them approved by P&T. Just think if the usage was cut by 1/3 what that would do to the budget? Outpt - not so much...very few pharmacists are actually in these settings outside of the VA or Kaiser. Even in the large clinics where I am, nurses compound & give IV antineoplastics so they also give the erythropoietics, sadly .

 

[ZpackSux]

Remember the popularity of coumadin clinics?

Why not ESA clinic in dialysis center where either RN or pharmacist with access to monthly lab values can titrate dosing and also administer IV-iron per protocol?

Lawyers are starting to target these drugs with FDA warnings... trasylol lawyer.. vioxx lawyer... and now there are Aranesp lawyers..

A pharmacist who dispense ESA when pt's HGB is above 12 is no doubt a target of these lawyers in light of the FDA's new warning.

 

[sdn1977]

Remember the popularity of coumadin clinics?

Why not ESA clinic in dialysis center where either RN or pharmacist with access to monthly lab values can titrate dosing and also administer IV-iron per protocol?

Lawyers are starting to target these drugs with FDA warnings... trasylol lawyer.. vioxx lawyer... and now there are Aranesp lawyers..

A pharmacist who dispense ESA when pt's HGB is above 12 is no doubt a target of these lawyers in light of the FDA's new warning.

Oh yeah - I remember coumadin clinics (can we say BOREDOM!)

But - think about reimbursement. Currently, there are no mechanisms for paying a pharmacist - lets just say conservatively - $160K/yr (based on 1 pharmacist/yr - salary $120K + benefits). An ESA clinic has to make that much money plus profit to justify. All they need to do now is to change their protocols - particularly when they're primarly txing Medicare pts - low reimbursement in the best of circumstances! A nurse with a well-written protocol can do this - just like they do with heparin (after we write the protocols ).

For those non-Medicare pts - its already being limited by the PA process. It gets stopped by insurance & requires a review with justification - probably a pharmacist running protocol standards.

At this point - I can't see the $$s & sense to staff an outpt facility with a pharmacist to do this and iron protocols, which are pretty standard nowdays. But thats just me.

Can you find a way to justify this - do you have these free standing facilities which can justify a pharmacist? If its just a simple "cookbook" protocol, why not just have the parameters & have nursing follow it - just like they do with dialysis or chemo???

 

[ZpackSux]

A lot of the hospitals I consult on have outpatient chemo clinics where medications are dispensed from the pharmacy through 340B program. Pharmacists are already on staff.

For those independent dialysis clinics...it's not the question of can they afford to...the better question is can they afford not to when we're realizing the dangers of ESA therapy.

I almost feel like most of the pharmacists are oblivious to the FDA's warning on ESA..for the safety of patients and also financial impact through better utilization and prevention of potential lawsuits.

If I was a malpractice attorney....I would have a field day looking at labs and MARs... and with electronic record of who dispensed the meds...man.

 

[sdn1977]

A lot of the hospitals I consult on have outpatient chemo clinics where medications are dispensed from the pharmacy through 340B program. Pharmacists are already on staff.

For those independent dialysis clinics...it's not the question of can they afford to...the better question is can they afford not to when we're realizing the dangers of ESA therapy.

I almost feel like most of the pharmacists are oblivious to the FDA's warning on ESA..for the safety of patients and also financial impact through better utilization and prevention of potential lawsuits.

If I was a malpractice attorney....I would have a field day looking at labs and MARs... and with electronic record of who dispensed the meds...man.

Aaah - but very little of this tx is taken to the outpt setting. What is given as an inpt can be justified - initial bone marrow suppression secondary to radiation, surgical rbc depeletion, exposure to bone marrow suppressant drugs in the acute setting - whatever.....so that 1 or 2 doses of epogen, altho a budget buster for you (which indeed should be corrected now) is a bit more difficult to justify in the outpt setting & I would have to say, rarely happens.

If you do have hospitals in your system with chemo clinics...then they should indeed already have pharmacist surveillance in place - just to justify the chemo itself! It would be an easy transition to allow or disallow any erypoietin just by not entering the order since it wouldn't comply with parameters therefore not allowing pyxis entry for the nurses.

Unfortunately, I've never been in that position. Just to remind....the tipping point for me to quit my hospital job of long standing was when I was told I didn't have time to review the labs on the chemo pts I was to sign off their chemo drugs for. Ha! NOT! If I don't see a wbc & rbc that fall within the parameters set by the orders - the drug doesn't go - easy!!! This should be just as easy for those pharmacists - why aren't they doing it?

But...for the bulk of the outpt free-standing dialysis centers & physician based chemo infusion centers....no, I don't see pharmacists getting involved. Sorry...

 

[ZpackSux]

So I presented it to about 20 DOPs... I love it when they have no clue what I'm talking about....

 

[sdn1977]

I warned you !

Did they offer any argument or were they just dumbstruck?

 

[ZpackSux]

I warned you !

Did they offer any argument or were they just dumbstruck?

One director...fairly sharp guy...who used to be a regional clinical manager for a consulting company said... "we brought it up at the P&T and the nephrologists insisted we shoot for Hgb of 13..."

I said...well...did you present "CHOIR" trial..which was cut short? Did you tell them about the Aranesp Attorneys? Did you tell them about the FDA's blackbox warning...and Amgen's new PI?

Sure...Kidney foundation hasn't changed their recommendation yet...but it will change this year...

The rest of the DOPs are hoping their clinical managers will take care of it...whom I inserviced last week.