FDA Urges Reduced Doses for Anemia Drugs

[nygirl7]

FRIDAY, June 24 (HealthDay News) -- Doctors should use the anemia drugs Procrit, Epogen and Aranesp more cautiously in patients with chronic kidney disease, U.S. health officials said Friday.


The new warning comes in response to data showing that patients on these drugs face a higher risk of cardiovascular problems such as heart attack, heart failure, stroke, blood clots and death, the U.S. Food and Drug Administration said.

"FDA is recommending new, more conservative dosing recommendations for erythropoiesis-stimulating agents [ESAs] for patients with *****chronic kidney disease*****," Dr. Robert C. Kane, acting deputy director for safety in the division of hematology products, said during a news conference Friday.

These recommendations are being added to the drug label's black box warning and sections of the package inserts, he said.

This is not the first time health risks have been linked to these anemia drugs. They have also been tied to increased tumor growth in cancer patients and may cause some patients to die sooner. Also, cancer patients have an increased risk of blood clots, heart attack, heart failure and stroke, according to the FDA.

Procrit, Epogen and Aranesp are synthetic versions of a human protein known as erythropoietin that prods bone marrow to produce red blood cells. The drugs are typically used to treat anemia in cancer patients and to reduce the need for frequent blood transfusions. Anemia also occurs in patients with chronic kidney disease. Anemia results from the body's inability to produce enough red blood cells, which contain the hemoglobin needed to carry oxygen to the cells.

Currently, labels on these drugs say ESAs should be used to achieve and maintain hemoglobin levels within 10 to 12 grams per deciliter of blood in patients with chronic kidney disease. These target levels will no longer be given on the label, the agency added.

Hemoglobin levels greater than 11 grams per deciliter of blood increases the risk of stroke, heart attack, heart failure and blood clots and haven't been proven to provide any additional benefit to patients, according to the FDA.

The new label says that for patients with chronic kidney disease not on dialysis, ESA therapy can be started when the hemoglobin level is less than 10 grams per deciliter. However, the goal of treatment should not be to increase hemoglobin levels to 10 or more grams per deciliter. Treatment needs to be individualized for each patient, the FDA said.

For patients on dialysis, ESA therapy can start when the hemoglobin level is less than 10 grams per deciliter. But, if the hemoglobin level approaches or goes over 11 grams per deciliter, the dose of the drug should be lowered or therapy stopped, the agency said.

Doctors should prescribe the lowest possible dose needed to reduce the need for transfusions, the agency added.

Patients taking these drugs should read the information in the medication guide included with these drugs. They should also have frequent blood tests, which help doctors keep hemoglobin at safe levels.

If patients have concerns about these drugs, they should consult with their doctor, the FDA said.

Amgen Inc., the maker of all three drugs, said in a news release that it backs the FDA action.

"Amgen supports the modified ESA prescribing information as it informs physicians of important safety information," Dr. Roger M. Perlmutter, Amgen's executive vice president of research and development, said in the news release. "The revised label also provides physicians with more individualized treatment guidance by distinguishing between patients undergoing dialysis as compared with those who are not on dialysis."

The U.S. Centers for Disease Control and Prevention estimates that more than 20 million Americans aged 20 and older suffer from chronic kidney disease.

More information

To learn more about ESAs, visit the U.S. Food and Drug Administration.

[spectda]

I don't know if feeling better was the right word for it :), just that I was having trouble distinguishing between low and really low. The big drops in hgb were definitely more devastating.

Glad to hear the info helps. We learn a lot from each other.
-Dave

[coeric]

gosh you guys are great, thanks for the wonderful responses.  and for
sharing your experiences of anemia.   i hope the board member i was referring to is able to read your responses.

Trish - the board member is in the telaprevir q12h vs q8h telaprevir trial, if i am not mistaken.  i think her hemoglobin started out around 15 and then went to 8.5 at 5 weeks.  the coordinators dose reduced and ordered epos.  it sounds like the coordinators are getting after the anemia.

Dave- thanks so much for the physiology citation. it is interesting that you started feeling better in the middle of treatment as the hemoglobin continued to drop.

maybe it's a little like the frog that gets placed in the boiling water and the frog jumps out immediately.  however you slowing bring the water temperature to boiling point -  

i wonder if there is anyway to prepare for the effects of anemia, other than making sure the couch is comfortable.
eric

[spectda]

I read that information somewhere in the middle of treatment after it felt as if my hgb had improved but had actually gotten worse. I was wondering why I was able to tolerate those levels. My guess was that those mechanisms are a response to the lack of oxygen getting to our bodies after a period of time rather then what caused the anemia.

Of course as you mentioned we also self adjust our activity level and mine was minimal. There were times besides the inability to exert myself in any way or catch my breath that I felt like I was having a surreal floating experience like perpetual hyperventilation.
-Dave

[Trish77]

Dave - chronic anemia different than our hemolytic anemia of course but wondering if the same compensation mechanisms exist for both.  You think?  Interesting info.

[Trish77]

coeric - is the triple therapy your board member friend taking on a trial or independent of a trial?  Wondering what the response of the treatment team has been, to reduce dosage, introduce procrit ... or?  Thanks.  I hope she manages okay and that treatment is successful.

Trish

[Trish77]

Hector - very difficult situation, to say the least.  Your treatment team is skillful and they will have a perspective on this information, I'm sure.  Aside from that, your faculties are remarkable under such circumstances and your ongoing contributions to others admirable - and invaluable.  I hope you know that you have our support also as you face your own challenges and we stand with you, Hector.  

Trish

[spectda]

http://www.wadsworth.org/labcert/blood_tissue/redblood.htm
"RBC transfusions are given to improve oxygen delivery. It is prudent to transfuse only in the presence of compelling clinical indications in individual patients. No universal trigger has been established for red cell transfusions that is deemed appropriate for all patients. In most healthy patients, oxygen delivery is thought to be adequate even at a hemoglobin of 7 g/dL. Many adaptive, physiological changes occur as a result of anemia, such as increase in cardiac output, and altered blood viscosity, and coronary and cerebral blood flow. Some patients, such as the elderly, those who are already anemic, and those with underlying cardiac and pulmonary disease, may not be able to respond in this manner, and therefore tolerate anemia poorly; they may need to be transfused at higher hemoglobin concentrations."

[spectda]

There is no doubt in my mind that the quick drops as you mentioned are much more difficult to adapt to then a gradual decline.

I had a somewhat gradual drop in hg from 15 at tx start to 7 when I had to stop tx. In between I had some sudden drops that were much more difficult adapt to. I spent many months in the 8s and high 7s and I did get somewhat used to it although I was not working and spent many months unable to do much except lie down. I thought that perhaps my body compensated in a similar way that a person with chronic anemia does.
-Dave

http://www.wadsworth.org/labcert/blood_tissue/redblood.htm
III. CHRONIC ANEMIA

Patients presenting with a chronic anemia will have developed compensatory mechanisms, such as increased blood flow due to lowered viscosity and increased release of oxygen due to higher levels of 2,3-DPG. This may allow time for careful observation and a trial of erythropoietin or other therapy. In patients who do not respond, transfusion may be necessary.

[Trish77]

I think it would be only natural for a sudden drop in hemoglobin to make a sudden noticeable difference.  There's no adjustment period.  You lose that much more oxygen in your blood and it's a significant adjustment.  The end result is the same - you need to figure out how to manage with an hgb of 8.5.  However, if you've been making those subtle adjustments all along and monitoring your hgb, you're paying much more attention to your body's responses to energy exertion and you're responding more appropriately, I would think.  I'd assume that's different than the being hit by a mack truck feeling of a quicker drop.  My hgb dropped quickly over the first 4 weeks - not to 8.5 but simply from 13.4 to 10.3.  I ran 10K the first weekend of treatment.  I sure wasn't running 10K or at all by the 4th week and I had to make some sudden adjustments.  

Aside from that, an hgb of 8.5 is significantly low and a helluva drop even not knowing what she started with and almost in transfusion territory.  

[coeric]

do you think the speed at which hemoglobin drops makes a difference in how we feel?  we recently had a board member who had a hemoglobin drop to 8.5 in 5 weeks with triple therapy and found it brutal.  i am wondering if  it took 5 months for it to drop to 8.5, perhaps she would have had an easier time.   i wonder if our bodies somehow compensate?
eric

[Trish77]

It's good information and should also be viewed in context, that while some of the information is for anyone taking procrit, the focus of this piece is on people with kidney disease.  Requirements for persons on HCV treatment are unique from cancer treatment and other diseases and use of procrit and other helper drugs should be viewed within that context.  Key factors in success are adherence to dosages, early response and completing treatment.  Within that context and in context of HCV and it's own set of risks such as harm to the liver, etc, use of helper drugs like procrit and how they're administered may differ from treatment for other illnesses.  

frijole - I could see a doc giving you procrit if you drop below 11 - IF you are one of those persons who does not do well with hemoglobin in that range.  Everybody is different.  What drops one person to their knees might make far less of an impact on another person.  In the context of adherence and ensuring you can complete your treatment, as long as procrit administration was within the guidelines - seems to still be a cutoff of 12 for those who do NOT have kidney disease? -  and reasonable for a person with HCV, you might have a doc who administers below 11.  My doc did for those reasons.  I was managing okay but facing dosage reductions so we used the procrit to maintain adherence.  I was on procrit with hgb of 10.x for that reason after the first time it dipped below 10.  Something to discuss with your treatment team for sure.

[spectda]

Thanks for posting this Deb-
After my hgb took a dive and my doc ordered reduced riba and procrit he insisted that he would not increase my riba unless I was close to 12 hgb. I argued that it should not be above 11.

Since it never rose above the 9s again it really didn't matter, but this was in an anemia trial for vic where as Willing mentioned Merck provided the procrit. This crap ain"t candy and should be taken seriously.


Hector-
I hope you get your new liver soon. I can't imagine how difficult this has been for you and you still spend time providing excellent information to people and reminding them that avoiding treatment can lead to something much more serious.

-Dave

[frijole]

ny
Good post.  Sounds like when (if) I treat no doctor will rx Procrit until HGB is under 10.  I guess I was a real baby first time around, begging for it when HGB dropped below 11.  

hector
I am sorry this is bad news for you.  ARe you on a transplant list?
frijole

[HectorSF]

Thanks for the posting NYGIRL. Although I had heard the meds were contraindicated in patients with kidney disease and cardio issues...I did not know about "They have also been tied to increased tumor growth in cancer patients and may cause some patients to die sooner. Also, cancer patients have an increased risk of blood clots, heart attack, heart failure and stroke, according to the FDA."

If that applies to liver cancer, and I don't see why it wouldn't, then I can see now that my planned treatment with DAAs despite decompensated cirrhosis is not going to happen now that I have liver cancer. I would need helper drugs and possibly transfusions to stay on treatment for any prolonged treatment. The only way I could see that I would be be treated would be just before transplant to make my viral load undetectable so I would have a good chance of not developing HCV in my new liver.

It seems like things just get more and more complex. Which is why I try to encourage other to try treatment so they don't progress to decompensated cirrhosis and ESLD and possibly liver cancer. Options get less and less quite quickly.

Cheers!
Hector

[willing]

good update thanks, The warnings seem  restricted to using epo to push HgB past 11 among patients with chronic kidney disease but it's a good reminder that, like most tx drugs, you don't want to take more than you have to . I believe the Merck submission included a comment to the effect that epo may have been used too liberally and inconsistently in the vic trials, possibly because it was a freebie.  

I'm hoping to avoid epo before 9.5 and would rather drop rbv from high-dose to standard WIN-R dose (but no lower).