(for veterinary information only)

BRAND NAME: EPOGEN, PROCRIT, AND EPREX

AVAILABLE IN    
1 cc INJECTION VIALS

BACKGROUND

Erythropoietin is the hormone responsible for inducing red blood cell production by the body’s bone marrow. Erythropoietin is primarily produced by the kidney when a drop in blood oxygen is perceived, though 10-15% of the total erythropoietin produced comes from the liver. A dose of erythropoietin lasts about a day but its effect is seen approximately 5 days later when the red cell proliferation it has induced is mature enough for release into the circulation.

Erythropoietin is a protein and its amino acid sequence was first mapped out in 1983.  By 1985, human erythropoietin was being manufactured using recombinant DNA technology. Binding of erythopoietin with sugars (called “glycosylation”)  slows the frequency of clearance from the body thus allowing for some improvement on the natural form of erythropoietin. Glycosylated erythropoietin comes in 3 forms: “alpha” (the most commonly used type in veterinary medicine), “beta” (of similar clinical efficacy to alpha), and Darbepoetin (which is particularly heavily glycosylated and lasts the longest).

While human recombinant erythopoietin works in dogs and cats, it is not the same protein and antibodies eventually develop in response to its exposure. At the present time, the amino acid sequence of the canine and feline versions of erythropoietin are known but commercial products are not available.

In animals, erythropoietin has one major use: the treatment of anemia due to chronic renal disease. Since most erythropoietin is produced by the kidney it should make sense that a damaged kidney cannot product normal amounts of erythropoietin and anemia results. For this use erythropoietin injections are very effective and easy to administer by owners at home. Resolution of anemia leads to better appetite, more energy and higher life quality.

It is tempting to use erythropoeitin for any anemia to which the bone marrow is not adequately responding. Results are mixed with this practice as in most such cases, there are healthy kidneys producing large amounts of erythropoietin already  in response the anemia. For these cases, lack of marrow stimulation is not the problem; the problem is that the marrow cannot respond.

HOW THIS MEDICATION IS USED

Erythropoietin is given by subcutaneous injection initially three times a week in conjunction with an oral iron supplement.  The red cell count is measured weekly at first and the dose is modified accordingly. Many patients can be maintained on weekly injections. It takes roughly one month to stabilize the red blood cell count and monitoring need not be as frequent at this point.

The most common method of monitoring is via a test called a “packed cell volume” or “hematocrit” as these tests are readily run in the hospital without sending samples to an outside laboratory. The value obtained reflects the percentage of blood volume taken up by red blood cells. Normal for dogs is approximately 35-60% (depending on age and gender). Normal for cats is 29-50%.

Because of the potential for antibody production against human origin erythropoietin, is important to withhold use until it is truly warranted rather than beginning it at the first sign of anemia.

It is important to note that there is actually quite a bit more to anemia in kidney patients than lack of erythropoietin. Multiple issues are at work:

• The build-up of renal toxins is very ulcerating to the GI tract and bleeding may result.
   
• Red blood cells do not have normal life spans in the presence of high levels of circulating renal toxins.
   
• Many renal toxins directly suppress the bone marrow’s ability to produce red blood cells.
   
• Poor production of erythropoietin by the kidney.

The point is that erythropoietin use is part of a bigger therapy picture.

SIDE EFFECTS

The main adverse event to be concerned about is antibody production. Antibodies are generated in response to an alien protein in the body. The problem is that antibodies that are generated not just against the alien erythropoietin but also against the patient’s natural erythorpoietin. This means that simply discontinuing the human product is not adequate to stop the reaction. Regular monitoring to check for a sudden drop in red cell count, is crucial as this is the sign that a problem is incipient and the product can be stopped while there is still time.

In one study 2 out of 3 dogs treated for more than 90 days with human erythropoietin and 5 out of 7 cats treated for more than 180 days with human erythropoietin developed refractory anemia due to anti-erythropoietin antibodies.

After discontinuing erythropoietin, antibodies wane over 2-12 months and the red cell count returns to its pre-treatment level. Blood transfusions may be needed to keep the patient alive during this time.

Some patients on erythopoietin develop high blood pressure.  It is thought that this occurs when the red cell count gets too high and the blood becomes abnormally viscous. Blood pressure medications can be used to control this and the erythropoietin dose can be modified to reduce the red cell count.

INTERACTIONS WITH OTHER DRUGS

It is very important to administer an iron supplement in conjunction with the erythropoietin injections so that the bone marrow will have all the necessary “supplies” with which to make red blood cells. A multivitamin with iron is typically used as this will also provide the B vitamins needed in red cell production as well.

CONCERNS AND CAUTIONS

Proper injection technique is important. Be sure you understand how to give the injections and use the needles necessary. An injection into your pet’s fur is not helpful.

The bottle of erythropoietin must be refrigerated at all times.