Epogen Side Effects

Generic Name: epoetin alfa

Note: This page contains information about the side effects of epoetin alfa. Some of the dosage forms included on this document may not apply to the brand name Epogen.

Not all side effects for Epogen may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to epoetin alfa: injection solution

In addition to its needed effects, some unwanted effects may be caused by epoetin alfa (the active ingredient contained in Epogen). In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking epoetin alfa:

More common
  • Chest pain
  • fever
  • headache
  • increased blood pressure
  • shortness of breath
  • swelling of the face, fingers, ankles, feet, or lower legs
  • weight gain
Less common
  • Anxiety
  • blurred vision
  • change in skin color
  • change in vision
  • convulsions (seizures)
  • cough
  • dizziness or lightheadedness
  • double vision
  • fainting
  • fast heartbeat
  • migraine headache
  • nausea
  • pain or discomfort in the arms, jaw, back, or neck
  • pain, tenderness, or swelling of the foot or leg
  • pains in the chest, groin, or legs, especially calves of the legs
  • pale skin
  • partial or complete loss of vision in the eye
  • severe headaches of sudden onset
  • skin rash or hives
  • slurred speech
  • sore throat
  • sudden and severe inability to speak
  • sudden loss of coordination
  • sudden vision changes
  • sweating
  • temporary blindness
  • tenderness, pain, swelling, warmth, or skin discoloration at the injection site
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • vision problems
  • vomiting
  • weakness in the arm or leg on one side of the body, sudden and severe

Some of the side effects that can occur with epoetin alfa may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Abdominal or stomach pain and swelling
  • bone or joint pain, muscle aches, chills, shivering, or sweating
  • constipation
  • diarrhea
  • dizziness
  • general feeling of tiredness or weakness
  • heartburn or belching, acid or sour stomach
  • inability to sleep
  • itching or stinging at the injection site
  • loss of strength or energy
  • muscle pain or weakness
  • skin pain
  • stomach discomfort, upset, or pain
  • weight loss

For Healthcare Professionals

Applies to epoetin alfa: injectable solution

Immunologic

Immunologic side effects including neutralizing antibodies to erythropoietin, in association with pure red cell aplasia (PRCA) or severe anemia (with or without cytopenias) have been reported.[Ref]

General

Epoetin alfa generally has been well tolerated. A flu-like syndrome has been reported in 5% of patients receiving intravenous injections of epoetin alfa (the active ingredient contained in Epogen) This syndrome includes low-grade fever, arthralgias, myalgias, and flank pain. These symptoms may be managed by subcutaneous administration or a slower rate of intravenous administration. Many patients receiving epoetin alfa have serious underlying conditions and it is sometimes difficult to discern true drug toxicity from disease activity.

The most frequently reported adverse effects observed in patients on dialysis were hypertension, headache, tachycardia, nausea and vomiting, clotted vascular access, shortness of breath, hyperkalemia, and diarrhea. In zidovudine treated HIV patients, the incidence of epoetin alfa side effects were not statistically significant from those in the placebo group and were consistent with disease progression. Diarrhea and edema occurred at a statistically significant greater incidence (compared to placebo) in cancer patients on chemotherapy.[Ref]

Cardiovascular

The development or exacerbation of hypertension in patients with chronic renal failure is of concern. Epoetin alfa (the active ingredient contained in Epogen) associated hypertension does not appear to depend on preexisting hypertension and one study suggests a relationship between new onset hypertension and an hematocrit of less than 20%. The mechanism for development of hypertension has not been established, but may be due to increased blood viscosity as red cell production increases or increased peripheral resistance as the anemia is corrected. Therapeutic endpoints should be approached slowly and preexisting hypertension should be controlled prior to initiating therapy.[Ref]

Cardiovascular side effects have been reported the most frequently. These have included hypertension, myocardial infarction, and tachycardia. Up to 35% of patients with hypertension due to chronic renal failure may require additional antihypertensive medication or an adjustment of an existing regimen.

Deep vein thrombosis has been reported in at least one patient receiving 20,000 units three times a week.

Increased mortality has been observed in cardiac patients (ischemic heart disease or congestive heart failure) on hemodialysis with a target hematocrit of 42% compared to similar patients with a target hematocrit of 30% (mortality rate 35% and 29%, respectively). The incidence of nonfatal myocardial infarctions, vascular access thrombosis, and all other thrombotic events was also increased in patients randomized to the higher target hematocrit. Maintenance of hematocrit levels between 30% and 36% is recommended.

A significant increase in thrombosis and mortality has been associated with the use of epoetin alfa (compared to placebo) in patients without renal failure undergoing coronary bypass surgery. In patients receiving epoetin who are at risk for thrombosis, the risk versus benefit of therapy should be individually evaluated.[Ref]

Hematologic

Iron stores are readily incorporated into new red blood cells as hemoglobin is produced during the acute phase of drug therapy. Iron deficiency diminishes the therapeutic effect of the drug. Iron replacement is necessary in nearly all patients treated with epoetin alfa (the active ingredient contained in Epogen) and iron status should be evaluated prior to initiating therapy and at regular intervals. A transferrin saturation of less than 20% or a serum ferritin level of less than 100 mcg/L suggests inadequate iron stores and a need for iron replacement therapy.[Ref]

Hematologic side effects have included incidences of vascular access thrombosis. All other thrombotic events were increased in cardiac patients randomized to a target hematocrit (HCT) of 42% compared to a target HCT of 30%. Maintenance of HCT levels between 30% and 36% is recommended.

A significant increase in thrombosis and mortality has been associated with the use of epoetin alfa (compared to placebo) in patients without renal failure undergoing coronary bypass surgery. In patients requiring epoetin who are at risk for thrombosis, the risk versus benefit of therapy should be individually evaluated.

Iron deficiency has occurred in most patients due to incorporation of iron into newly synthesized red blood cells. Supplemental iron may be necessary.

Arteriovenous shunt clotting may occur in hemodialysis patients due to increased blood viscosity and decreased bleeding time, however, the incidence does not appear to be greater than in hemodialysis patients not receiving epoetin alfa. Clotting within the dialyzer has resulted in a 25% increase in heparin anticoagulation requirements during hemodialysis.[Ref]

Nervous system

Seizures have occurred primarily in the first three months of therapy and may have been associated with a increase in hematocrit or blood pressure. Neurologic monitoring and evaluation during epoetin alfa (the active ingredient contained in Epogen) therapy is recommended in patients with a history of seizure activity. Therapeutic endpoints should be approached slowly to minimize seizure risks.[Ref]

Nervous system side effects have included headache (15%) and seizures (to 5%).[Ref]

Psychiatric

Psychiatric side effects have rarely included hallucinations among the dialysis patients treated with epoetin alfa (the active ingredient contained in Epogen) [Ref]

Oncologic

Erythropoietin receptors have been found to be present on the surface of some malignant cell lines and tumor biopsy specimens. However, there is insufficient data to establish whether use of epoetin products have an adverse effect on time to tumor progression or progression-free survival.[Ref]

Oncologic side effects, particularly with myeloid tumors, may occur due to epoetin alfa's growth factor activity.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea, vomiting, and diarrhea, but these have not occurred at an incidence significantly greater than reported in placebo groups amongst patients with chronic renal failure and HIV-infected patients treated with zidovudine. Diarrhea occurred at a statistically significant greater incidence (compared to placebo) in cancer patients on chemotherapy.[Ref]

Dermatologic

Dermatologic side effects have rarely included mild and transient skin rashes and urticaria.[Ref]

Local

Local side effects of epoetin alfa (the active ingredient contained in Epogen) have included pain at the injection site.[Ref]

References

1. Casadevall N, Dupuy E, Molho-Sabatier P, Tobelem G, Varet B, Mayeux P "Brief report: autoantibodies against erythropoietin in a patient with pure red-cell aplasia." N Engl J Med 334 (1996): 630-3

2. "Product Information. Procrit (epoetin alfa)." Ortho Biotech Inc, Raritan, NJ.

3. Bunn HF "Drug-induced autoimmune red-cell aplasia." N Engl J Med 346 (2002): 522-3

4. Gershon SK, Luksenburg H, Cote TR, Braun MM "Pure red-cell aplasia and recombinant erythropoietin." N Engl J Med 346 (2002): 1584-6; discussion 1584-6

5. "Product Information. Epogen (epoetin alfa)." Amgen, Thousand Oaks, CA.

6. Casadevall N, Nataf J, Viron B, et al. "Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin." N Engl J Med 346 (2002): 469-75

7. Muirhead N, Bargman J, Burgess E, Jindal KK, Levin A, Nolin L, Parfrey P "Evidence-based recommendations for the clinical use of recombinant human erythropoietin." Am J Kidney Dis 26 Suppl (1995): s1-24

8. Kokot F, Wiecek A "Arterial hypertension in uraemic patients treated with erythropoietin." Nephron 71 (1995): 127-32

9. Gimenez LF, Scheel PJ "Clinical application of recombinant erythropoietin in renal dialysis patients." Hematol Oncol Clin North Am 8 (1994): 913

10. Eschbach JW, Abdulhadi MH, Browne JK, Delano BG, Downing MR, Egrie JC, Evans RW, Friedman EA, Graber SE, Haley NR, et al "Recombinant human erythropoietin in anemic patients with end-stage renal disease. Results of a phase III multicenter clinical trial." Ann Intern Med 111 (1989): 992-1000

11. Singbartl G "Adverse events of erythropoietin in long-term and in acute short-term treatment." Clin Investig 72 (1994): s36-43

12. Touam M, Oliva JP, Zingraff J, Drueke T "Does intravenous erythropoietin lead to an immediate, transient increase in arterial blood pressure in dialysis patients?" Nephron 67 (1994): 240-1

13. Raine AE "Hypertension, blood viscosity, and cardiovascular morbidity in renal failure: implications of erythropoietin therapy." Lancet 1 (1988): 97-100

14. Flaharty KK, Grimm AM, Vlasses PH "Epoetin: human recombinant erythropoietin." Clin Pharm 8 (1989): 769-82

15. Buckner FS, Eschbach JW, Haley NR, Davidson RC, Adamson JW "Hypertension following erythropoietin therapy in anemic hemodialysis patients." Am J Hypertens 3 (1990): 947-55

16. Eschbach JW, Aquiling T, Haley NR, Fan MH, Blagg CR "The long-term effects of recombinant human erythropoietin on the cardiovascular system." Clin Nephrol 38 (1992): s98-103

17. Bennett WM "Side effects of erythropoietin therapy." Am J Kidney Dis 18 (1991): 84-6

18. Navarro JF, Teruel JL, Marcen R, Ortuno J "Improvement of erythropoietin-induced hypertension in hemodialysis patients changing the administration route." Scand J Urol Nephrol 29 (1995): 11-4

19. Faris PM, Ritter MA, Abels RI "The effects of recombinant human erythropoietin on perioperative transfusion requirements in patients having a major orthopaedic operation." J Bone Joint Surg Am 78 (1996): 62-72

20. Beccari M "Seizures in dialysis patients treated with recombinant erythropoietin - review of the literature and guidelines for prevention." Int J Artif Organs 17 (1994): 5-13

21. Besarab A, Bolton WK, Browne WK, et al. "The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin." N Engl J Med 339 (1998): 584-90

22. Jones MA, Kingswood JC, Dallyn PE, Andrew M, Cheetham A, Burwood R, Sharpstone P "Changes in diurnal blood pressure variation and red cell and plasma volumes in patients with renal failure who develop erythropoietin-induced hypertension." Clin Nephrol 44 (1995): 193-200

23. Lutz B, Tillman K, Santos M, Morvant C, Webb S "Life threatening venous thrombosis associated with high dose epoetin alfa therapy for HIV-related anemia." Int Conf AIDS 9 (1993): 463

24. Humphries JE "Anemia of renal failure: use of erythropoietin." Med Clin North Am 76 (1992): 711-25

25. Clyne N, Lins LE, Egberg N "Long-term effects of erythropoietin treatment on the coagulation system during standardized hemodialysis." Clin Nephrol 43 (1995): 260-7

26. Wirtz JJ, van Esser JW, Hamulyak K, Leunissen KM, van Hooff JP "The effects of recombinant human erythropoietin on hemostasis and fibrinolysis in hemodialysis patients." Clin Nephrol 38 (1992): 277-82

27. Laupacis A, Feagan B, Wong C "Effectiveness of perioperative recombinant human erythropoietin in elective hip replacement." Lancet 342 (1993): 378

28. Canaud B, Polito-Bouloux C, Garred LJ, Rivory JP, Donnadieu P, Taib J, Florence P, Mion C "Recombinant human erythropoietin: 18 months' experience in hemodialysis patients." Am J Kidney Dis 15 (1990): 169-75

29. Van Wyck DB "Iron management during recombinant human erythropoietin therapy." Am J Kidney Dis 14 (1989): 9-13

30. Rutherford CJ, Schneider TJ, Dempsey H, Kirn DH, Brugnara C, Goldberg MA "Efficacy of different dosing regimens for recombinant human erythropoietin in a simulated perisurgical setting - the importance of iron availability in optimizing response." Am J Med 96 (1994): 139-45

31. Temple RM, Eadington DW, Swainson CP, Winney R "Seizure related to erythropoietin treatment in patients undergoing dialysis." BMJ 300 (1990): 46

32. Vey SN, Ringoir S "The subcutaneous administration route of epoetin: advantages, pain at the injection site and patient acceptance." Int J Artif Organs 16 (1993): 1-3

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