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Clinical Efficacy and Safety

Since Venofer® (iron sucrose injection, USP) was first approved in Switzerland in 1950, a large body of evidence in the form of study reports and publications has been produced that demonstrates the safety and efficacy of intravenous iron sucrose.  The clinical evaluation of Venofer® is based on results from more than 100 studies1-123 involving more than 7,000 subjects.  More than 5,000 patients were treated with Venofer® in these studies. The results demonstrate that Venofer® is effective therapy for the treatment of iron deficiency anemia, alone and in combination with erythropoietin in a variety of patient populations.  The incidence of serious adverse reactions is low. Clinical trials submitted to the US Food and Drug Administration support the safety and efficacy of Venofer® (1,496 patients).9-11,21,22,90,121,122,123  Based on use in an estimated 4.6 million patients that received Venofer® worldwide between 1992 and August 2005, only 108 hypersensitivity reactions have been reported, including serious or life threatening reactions.124  Venofer® is well tolerated in the vast majority of patients, including those with a history of hypersensitivity reactions to iron dextran and other parenteral iron preparations.  Venofer® is easy to administer either as a slow injection or as an infusion.  A test dose is not required, although a test dose was used in two trials of Venofer® in HDD-CKD patients at the physician's discretion.

 

Review of Selected Clinical Trials in Chronic Kidney Disease 

Study A - Hemodialysis Patients (Charytan et al,10 Van Wyck et al.87)
Study A was a multicenter, open-label, historically controlled study in 101 hemodialysis patients (77 patients with Venofer® (iron sucrose injection, USP) treatment and 24 in the historical control group) with iron deficiency anemia. Eligibility for Venofer® treatment included patients undergoing chronic hemodialysis 3 times weekly, receiving erythropoietin, hemoglobin concentration greater than 8.0 and less than 11.0 g/dL for at least 2 consecutive weeks, transferrin saturation <20%, and serum ferritin <300 ng/mL. The erythropoietin dose was to be held constant throughout the study. The protocol did not require administration of a test dose; however, some patients received a test dose at the physician’s discretion. Exclusion criteria included significant underlying disease, asthma, active inflammatory disease, or serious bacterial or viral infection. Venofer® 5 mL (one vial) containing 100 mg of elemental iron was administered through the dialysis line at each dialysis session either as a slow injection or a saline-diluted slow infusion for a total of 10 dialysis sessions with a cumulative dose of 1,000 mg elemental iron. A maximum of 3 vials of Venofer® was administered per week. No additional iron preparations were allowed until after the day 57 evaluation. The mean change in hemoglobin from baseline to day 24 (end of treatment), day 36, and day 57 was assessed.

  • Four of the 77 patients (5%) had 6 adverse events believed to be related to Venofer®, including diarrhea (2 patients), abdominal pain, nausea, constipation, and taste perversion
  • No hypersensitivity reactions were seen, including in any of 10 patients who had shown previous intolerance/allergy to iron dextran injection, USP


The historical control population consisted of 24 patients similar to patients treated with Venofer® (iron sucrose injection, USP) who were off intravenous iron for at least 2 weeks and who had received erythropoietin therapy with hematocrit averaging 31% to 36% for at least 2 months prior to study entry.87 Patient age and serum ferritin level were similar between treatment and historical control patients. The mean baseline hemoglobin and hematocrit were higher, and the erythropoietin dose was lower in the historical control population than in the Venofer®-treated population.

  • Patients in the Venofer®-treated population showed a statistically significantly greater increase in hemoglobin and hematocrit than did patients in the historical control population
    —At the 2-week follow-up, patients in the Venofer®-treated population showed a significantly (p<.01) greater increase in hemoglobin (1.3 g/dL) and hematocrit (3.6%) than did patients in the historical control population (Hb, -0.6 g/dL; Hct, -1.2%)
    —At the 5-week follow-up, Venofer®-treated patients showed a significantly (p<.05) greater increase in hemoglobin (1.2 g/dL) than did patients in the historical control group (-0.1 g/dL)
    —At the end of treatment, patients in the Venofer®-treated population showed a significantly (p<.01) greater increase in hemoglobin (1.0 g/dL) and hematocrit (3.1%) than did patients in the historical control group (Hb, 0 g/dL; Hct, -0.3%)
  • Serum ferritin increased significantly (p=.0001) at endpoint of study from baseline in the Venofer®-treated population (165.3 ng/mL) compared with the historical control population (-27.6 ng/mL). Transferrin saturation also increased significantly (p=.0016) at endpoint of study from baseline in the Venofer®-treated population (8.8%) compared with the historical control population (-5.1%)


The authors concluded that doses of 100 mg Venofer® (iron sucrose injection, USP) given IV in 10 consecutive dialysis sessions for a total dose of 1,000 mg were effective and safe in hemodialysis patients with iron deficiency anemia receiving supplemental erythropoietin therapy and can be administered without a test dose

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Study B - Hemodialysis Patients (Van Wyck et al11)
The safety and efficacy of Venofer® (iron sucrose injection, USP) in hemodialysis patients who had experienced intolerance to iron dextran were also examined in a single-arm, 2-period, open-label, multicenter study by Van Wyck et al. Sixteen patients with Hb <11 g/dL and a history of mild reactions and 7 patients with a history of severe anaphylactoid reactions to iron dextran were included. Following an observation period, patients received 100 mg Venofer® either by intravenous injection or infusion for 10 consecutive dialysis sessions over 3 to 4 weeks. A test dose was not required; however, some patients received a test dose at the physician’s discretion. Since the study was primarily a safety study, efficacy assessments were limited to changes from baseline to day 24 (end of treatment evaluation).

  • There were no hypersensitivity reactions, no serious adverse drug reactions, and no patients discontinued from the study due to adverse drug reactions
  • Three mild adverse events considered related or possibly related to iron sucrose were reported in 2 patients:
    —Taste perversion (metallic taste, 1 patient twice)
    —Pruritus (1 patient)
  • Mean hemoglobin increased from 10.4 g/dL to 11.5 g/dL at day 24 (p<.05, increase of 11.0%)
  • Mean hematocrit increased from 32.8% to 36.4% at day 24 (p<.05, increase of 11.0%)
  • MCV, MCHC, serum iron, TSAT, and serum ferritin also increased significantly, and total iron binding capacity (TIBC) decreased significantly


The authors concluded that Venofer® is safe and effective in the management of anemia in hemodialysis patients receiving supplemental erythropoietin sensitive to iron dextran and can be administered without a test dose by IV push or infusion.

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Study C - Hemodialysis Patients (Van Zyl-Smit et al9)
A study of the safety and efficacy of Venofer® (iron sucrose injection, USP) or the combination of Venofer® and erythropoietin was performed in an open, single-arm, 2-period, multicenter study by Van Zyl-Smit et al in South Africa. One hundred thirty-one patients were enrolled. All suffered from hemodialysis-associated anemia, were undergoing maintenance hemodialysis (2 to 3 sessions per week), had an Hb <10.0 g/dL, serum transferrin saturation <20%, and serum ferritin < 200 ng/mL. A first dose of 50 mg of Venofer® was administered at the first hemodialysis session, followed by doses of 100 mg of iron during dialysis 3 times weekly until an individually calculated dose, based upon baseline hemoglobin and body weight, was administered. Patients were then followed for an additional 4 weeks, in a no-treatment observation period.

The modified intent-to-treat population consisted of 130 patients. Mean hematologic and iron parameters at baseline and following treatment with Venofer® (iron sucrose injection, USP) are given below:

  • Mean hemoglobin increased from 7.2 g/dL to 9.0 g/dL at observation week 2 and 9.2 g/dL at observation week 4 (p<.0001, maximum increase of 28%)
  • Mean hematocrit increased from 22.5% to 27.9% at observation week 2 and 28.5% at observation week 4 (p<.0001, maximum increase of 27%)
  • Mean serum ferritin increased from 65.1 ng/mL to 512.7 ng/mL at observation week 2 and 440.2 ng/mL at observation week 4 (p<.0001, maximum increase of 687%)
  • Mean serum transferrin saturation increased from 11.4% to 27.7% at observation week 2 and 27.6% at observation week 4 (p<.0001, maximum increase of 143%)


Adverse events (>1%) that were reported to be possibly related to Venofer® were hypotension (13%), nausea (3%), increased liver function test (2%), pneumonia (2%), and vomiting (2%). Hypotension was also associated with hemodialysis itself and occurred with similar frequency during the treatment period and during the observation period when no iron was given.

The authors concluded that Venofer® was safe and effective in the treatment of patients with hemodialysis-associated anemia.

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Study D - Non-Dialysis Dependent CKD Patients (Van Wyck et al121 )
The safety and efficacy of Venofer® in non-dialysis dependent CKD patients was examined in a randomized, open-label multicenter, active-controlled study by Van Wyck et al. 182 patients were treated with oral iron (n= 91) or Venofer® (n=91) with or without an erythropoietin.  Erythropoietin therapy was stable for 8 weeks prior to randomization.  Patients with an average baseline Hg < 11g/dL, TSAT  < 25%, ferritin < 300  ng/mL were randomized to receive an erythropoietin and either oral iron (325 mg ferrous sulfate TID for 56 days) or Venofer® (200 mg IV over 2-5 minutes 5 times within 14 days or 500 mg in 250 mL 0.9% NaCl as an IV infusion over 3.5-4 hours on Day 1 and Day 14).  Sixty-one patients received 280 doses of 200 mg iron sucrose and 30 patients received 58 doses of iron sucrose 500 mg.

  • A statistically greater proportion of Venofer® treated patients (44.3%) compared to oral iron patients (28%) had a clinically significant response as defined as an increase in hemoglobin > 1 g/dL at any time during the study.  (p=0.03)
  • The mean increase in hemoglobin at Day 42 was greater in the Venofer® treated patients (0.7g/dL) compared to oral iron patients (0.4 g/dL) (p=0.0298)
  • A greater proportion of Venofer® treated patients (39.2%) compared to oral iron patients (1.2%) had a clinically significant response defined as an increase in hemoglobin > 0.75 g/dL, and ferritin >160 ng/mL at any time during the study (p<0.0001)
  • Patients in the oral iron group, but not the Venofer® group, showed a significant rise in serum creatinine at study day 56 (0.2 mg/dL, p<0.0013)
  • Non-compliance was more common in the oral iron treatment group.
  • No serious adverse drug events were seen in patients administered Venofer® 200 mg IV over 2-5 minutes, but drug related hypotension, including one event considered serious, occurred in 2 females weighing less than 65 kg after 500 mg doses were given over 4 hours.
  • Among non-serious ADEs reported, GI complaints were seen most frequently in both treatment groups, but the nature of the GI complaints differed between groups.  Transient taste disturbance was the most prominent GI complaint associated with Venofer® administration. Constipation, diarrhea, nausea, vomiting, and dyspepsia were associated with oral iron therapy.  Headache, myalgia, and hypotension were also associated with Venofer® administration.


The authors concluded that Venofer ®  administration of 1,000 mg in divided doses is superior to oral iron therapy in the management of NDD-CKD patients with anemia and low iron indices.  Venofer® is safe, well tolerated, and more effective than oral iron treatment.

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Study E - Peritoneal Dialysis Dependent - Chronic Kidney Disease Patients (Singh et al 1, 123 )
The safety and efficacy of Venofer ® (iron sucrose injection, USP) in  peritoneal dialysis dependent CKD patients receiving an erythropoietin was examined in a multicenter, randomized, controlled trial by Singh et al.  121 patients were treated with an erythropoietiin and Venofer® (n= 75) or an erythropoietin alone without iron supplementation.  Erythropoietic therapy was unchanged for 8 weeks prior to randomization and during the study period.  Patients with Hg < 11.5 g/dl, TSAT <25%, and ferritin <500 ng/mL were randomized to receive either no iron (n=46) or Venofer ® (300 mg diluted in 250 mL of 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg diluted in 250 mL of 0.9% NaCl over 2.5 hours on Day 29) (n= 75).

  • Patients in the Venofer®/erythropoietin group had a greater mean hemoglobin change from baseline to the highest hemoglobin value (1.3 g/dL) (p<0.01)  
  • A greater proportion of patients treated with Venofer ®/erythropoietin (59.1%) had an increase in hemoglobin of ≥1 g/dL at any time during the study compared to patients who received erythropoietin alone (33.3%) (p<0.05)
  • There were no serious treatment-related adverse events after Venofer ® administration at either dose level.  8 patients experienced at least 1 non-serious adverse event thought to be related to study drug with GI complaints seen most frequently


The authors concluded that Venofer ®  is an effective adjunct to erythropoietic therapy in anemic patients with PDD-CKD.  Administration of 1,000 mg of Venofer®  in 3 divided doses as 2 infusions of 300 mg over 1.5 hours 14 days apart, followed 14 days later by 400 mg over 2.5 hours, is well tolerated and provides a practical approach to correcting iron deficiency anemia and replenishing iron stores.

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Postmarketing Safety Study 1 - Hemodialysis Patients21
Six hundred sixty-five (665) chronic hemodialysis patients on an erythropoietin were treated with Venofer® (iron sucrose injection, USP) doses of 100 mg at each dialysis session for up to 10 consecutive sessions for their iron deficiency or on a weekly basis for 10 weeks for maintenance of iron stores. A total of 8583 doses of iron were administered. Eighty (80) patients with previous intolerance to other IV iron products (63 iron dextran, 5 ferric gluconate, 12 both) were included. There were no drug-related deaths, serious adverse drug reactions, or withdrawals due to serious adverse reactions. There were 2 nonserious adverse reactions reported (constipation 1, pruritus 1). Prior history of IV intolerance did not affect adverse drug reaction rates.  Only serious and non-serious events considered by the investigators to be drug related were collected.

Postmarketing Safety Study 2 -  Hemodialysis Patients22
Three hundred eighty-six (386) chronic hemodialysis patients on an erythropoietin were exposed to a single dose of Venofer® 100 mg IV by slow injection over 2 minutes or 200 mg IV by slow injection over 5 minutes [200 mg dose not FDA approved for this indication].  No study drug-related serious adverse events (SAEs) were reported.  Three patients experienced unrelated SAEs during the study.  Two patients experienced adverse events that led to premature discontinuation from the study. No anaphylactic reactions were observed during the study. History of iron intolerance had no impact on the occurrence of adverse events.  Only 1 patient with a history of iron intolerance reported a transient taste disturbance.



Adverse Event by Dose Group1
The frequency of adverse events associated with the use of Venofer®has been documented in 6 randomized clinical trials involving 231 hemodialysis dependent, 139 non-dialysis dependent, and 75 peritoneal dialysis dependent - chronic kidney disease patients.

Drug Related Adverse Events Reported in >2% of Patients by Dose Group

 

HDD-CKD

NDD-CKD

PDD-CKD

Adverse Events
 (Preferred Term)

100 mg
 (N=231)
 %

200 mg
 (N=109)
 %

500 mg
 (N=30)
 %

300 mg for 2 doses
 followed by 400 mg
 for 1 dose
 (N=75)
 %

Subjects with any adverse event

 14.7

 23.9

  20.0

 10.7

 Gastrointestinal Disorders
     Diarrhea NOS*
     Dysgeusia
     Nausea


0.9
0.9
1.7


0
7.3
2.8


0
3.3
0


2.7
0
1.3

  General Disorders and  
  Administration Site
  Conditions
     Infusion site burning
     Injection site pain
     Peripheral edema





0
0
0

 


3.7
2.8
1.8

 


0
0
 6.7 

 


0
0
 0 

 Nervous Systems Disorders
     Dizziness
     Headache


 0
 0


 2.8
 2.8


 6.7
 0


 0
 0

 Vascular Disorders
     Hypotension NOS


5.2


0


6.7


0




IMPORTANT SAFETY INFORMATION
Venofer® (iron sucrose injection, USP) is contraindicated in patients with evidence of iron overload, in patients with known hypersensitivity to Venofer® or any of its inactive components, and in patients with anemia not caused by iron deficiency.  Hypersensitivity reactions have been reported with IV iron products.  Hypotension has been reported frequently in hemodialysis dependent-CKD patients receiving IV iron, and has also been reported in non-dialysis dependent and peritoneal dialysis dependent-CKD patients receiving IV iron.  Hypotension following administration of Venofer® may be related to rate of administration and total dose delivered.

In multi-dose efficacy studies in hemodialysis dependent-CKD patients (N=231), the most frequent adverse events (>5%), whether or not related to Venofer® administration, were hypotension, cramps/leg cramps, nausea, headache, graft complications, vomiting, dizziness, hypertension, chest pain and diarrhea.  In post-marketing safety studies in hemodialysis dependent-CKD patients (N=1051), the most frequent adverse events reported (>1%) were congestive heart failure, sepsis and taste perversion.  In multi-dose efficacy studies in non-dialysis dependent-CKD patients (N=91), the most frequent adverse events (≥5%) whether or not related to Venofer® administration, were taste disturbance, peripheral edema, diarrhea, constipation, nausea, dizziness, and hypertension.  In the study of peritoneal dialysis dependent-CKD patients (N=75), the most frequent adverse events, whether or not related to Venofer® , reported by ≥5% of these patients were diarrhea, peritoneal infection, vomiting, hypertension, pharyngitis, peripheral edema and nausea.
    
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References

  1. Danielson BG. Oral and intravenous iron supplementation in renal anemic patients on EPO treatment. Clinical study report, 1993a and data on file. American Regent, Inc., Shirley, NY.
  2. Danielson BG. Supplementation with IV iron sucrose complex in patients with renal anemia. Clinical study report, 1993b and data on file. American Regent, Inc., Shirley, NY.
  3. Al-Momen AK, Huraib SO, Mitwalli AH, et al. Intravenous iron saccharate in hemodialysis patients receiving r-HuEPO. Saudi J Kidney Dis Transplant. 1994; 5:168-172.
  4. Nyvad O, Danielson H, Madsen S. Intravenous iron-sucrose complex to reduce epoetin demand in dialysis patients. Lancet. 1994; 344:1305-1306.
  5. Silverberg DS, Blum M, Agbaria Z, Peer G, Kaplan E, Iaina A. Intravenous ferric saccharate as an iron supplement in dialysis patients. Nephron. 1996;72:413-417
  6. Macdougall IC, Chandler G, Armstrong A, Breen C, Harchowal J, Cavill I. Characterization of iron availability from three different IV iron preparations in dialysis patients. Clinical study report, 1999. Abstract from the 30th Annual Meeting and Scientific Exposition of the American Society of Nephrology. November 2-5, 1997, San Antonio, Texas.
  7. Al-Wakeel JS, Malik GH, Al-Mohaya S, et al. Intravenous iron supplementation in patients treated with erythropoietin. Indian J Nephrol. 1997; 7:91-96.
  8. Tarng D-C, Huang TP, Chen TW. Mathematical approach for estimating iron needs in hemodialysis patients on erythropoietin therapy. Am J Nephrol. 1997; 17:158-164.
  9. Van Zyl-Smit R, Moosa MR, Potgieter CD, Viljoen HG, Naicker S. A multicentre study to investigate the tolerance, safety and efficacy of intravenous iron sucrose in hemodialysis patients with anemia. Clinical study report, 1997 and data on file. American Regent, Inc., Shirley, NY. Abstract in Kidney Int. 1999;55:2130.
  10. Charytan C, Levin N, Al-Saloum M, et al. Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial. Clinical study report, 1999. Am J Kidney Dis. 2001;37(2):300-307.
  11. Van Wyck DB, Cavallo G, Spinowitz BS, et al. Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial. Am J Kidney Dis. 2000;36:88-97.
  12. Kosch M, Bahner U, Bettger H, Matzkies F, Teschner M, Schaefer RM. A randomized, controlled, parallel-group trial on efficacy and safety of iron sucrose Venofer® vs. iron gluconate (Ferrlecit®) in hemodialysis patients treated with rHuEpo. Nephrol Dial Transplant. 2001; 16:1239-1244.
  13. Jones CH, Richardson D, Ayers S, Newstead CG, Will EJ, Davison AM. Percentage hypochromic red cells and the response to intravenous iron therapy in anemic hemodialysis patients. Nephrol Dial Transplant. 1998; 13:2873-2876.
  14. Macdougall IC, Chandler G, Elston O, Harchowal J. Beneficial effects of adopting an aggressive intravenous iron policy in a hemodialysis unit. Am J Kidney Dis. 1999; 34:S40-S48.
  15. Wakefield RM, Haynes PG, Lee MA, Brocklebank JT, Fitzpatrick MM. Intravenous iron saccharate therapy in paediatric end stage renal failure patients. Abstract from the IIIrd Spring Meeting of the Royal College of Paediatrics and Child Health. April 12-15, 1999.
  16. Andrade LJ, Garica MI, Acuna GD, Fogliati MM, Martinez RD, Loredo JP, et al. I.V. iron saccharate, five years experience [A0301]. Abstract from the Annual Meeting and Scientific Exposition of the American Society of Nephrology. October 11-16, 2000.
  17. Richardson D, Bartlett C, Will EJ. Optimizing erythropoietin therapy in hemodialysis patients. Am J Kidney Dis. 2001;38(1):109-117
  18. Baskin E, Besbas S, Ozdemir S, Topaglu R, Ogzen S, Bakkaloglu A, et al. Effect of intravenous iron saccharate in hemodialyzed children. Abstract from the XXXVI Congress of the European Renal Association/European Dialysis and Transplant Association. September 5-8, 1999, Madrid, Spain.
  19. Morgan H, Gautam M, Geary D. Maintenance intravenous iron therapy in pediatric hemodialysis patients. Pediatr Nephrol. 2001; 16:779-783.
  20. Chandler G, Harchowal J, Macdougall IC. Intravenous iron sucrose: establishing a safe dose. Am J Kidney Dis. 2001;38(5):988-991.
  21. Aronoff GR, Bennett WM, Blumenthal S, Charytan C, Pennell JP, Reed J, et al. Iron sucrose in hemodialysis patients: Safety and Efficacy of iron replacement and maintenance therapy. Kidney Int. 2004; 66:1193-1198.
  22. Rothstein M, Carvello A, Charytan C, Collins D. A randomized study to assess the safety and tolerability of 200 and 100 mg of Venofer® administered to hemodialysis patients. Data on file. American Regent, Inc., Shirley, NY [IVEN01015].
  23. McKane W, Green C, Farrington K. Porphyria cutanea tarda precipitated by intravenous iron in a hemodialysis patient. Nephrol Dial Transplant. 2001:1936-1938.
  24. Tarif N, Mitwalli AH, Al-Wakeel JS, Aisha HA, Memon A, Sulaimani F, et al. Safety of intravenous ferrous saccharate administration in hemodialysis patients. A2136 Abstract from the Annual Meeting and Scientific Exposition of the American Society of Nephrology. 2001.
  25. Jamil B, Hussain HH, Nasir H, Kumar H, Naqvi SAJ. Parenteral iron sucrose supplementation in iron repleted hemodialysis patients receiving erythropoietin. A1711 Abstract from the Annual Meeting and Scientific Exposition of the American Society of Nephrology. 2001.
  26. Sikole A, Spasovski G, Zafirov D, Polenakovic M. Epoetin omega for the treatment of anemia in maintenance hemodialysis patients. Clin Nephrol. 2002;57:237-245.
  27. Domrongkitchaiporn S, Jirakranont B, Atamasnkul K, Ungkanont A, Bunyaratvej A. Indices of iron status in continuous ambulatory peritoneal dialysis patients. Am J Kidney Dis. 1999; 34:29-35.
  28.  Richardson D, Bartlett C, Jolly H, Will EJ. Intravenous iron for CAPD populations: proactive or reactive strategies? Nephrol Dial Transplant. 2001;16:115-119.
  29. Prakash S, Walek A, Dimkovic N, Bargman J, Vas S, Oreopolos D. Experience with a large dose (500 mg) of intravenous iron dextran and iron saccharate in peritoneal dialysis patients. Periton Dial Inter. 2001; 21:290-295.
  30. Scarpioni R, Gandolfi S, Cristinelli L. Long-term endovenous iron sucrose in anemic peritoneal dialysis patients on erythropoietin [rHuEPO] treatment do not increase peritonitis complicances: a 48 month study. A1868 Abstract from the Annual Meeting and Scientific Exposition of the American Society of Nephrology. 2001.
  31. Monk AJ, Chandler G, Macdougall IC. Intravenous iron sucrose can be safely administered as a 2 minute bolus injection. Brit Renal Symp. June 2002.
  32. Dittrich E, Schillinger M, Sunder-Plassmann G, Horl WH, Vychytil A. Efficacy of a low dose intravenous iron sucrose regimen in peritoneal dialysis patients. Periton Dial Int. 2002; 22:60-66.
  33. Aggarwal HK, Tziviskou E, Bellizzi V, Khandewal M, Moupas L, Bargman JM, et al. Prolonged administration over six hours of large doses of intravenous iron saccharate [500 mg] prevents severe adverse reactions in peritoneal dialysis patients. Periton Dial Int. 2002; 22:636-637.
  34. Silverberg DS, Iaina A, Peer G, et al. Intravenous iron supplementation for the treatment of the anemia of moderate to severe chronic renal failure patients not receiving dialysis. Am J Kidney Dis. 1996; 27:234-238.
  35. Silverberg DS, Blum M, Agbaria Z, et al. The quick correction of anemia in predialysis chronic renal failure with intravenous iron alone or in combination with erythropoietin. Clin Nephrol. 2001; 55:212-219.
  36. Chandler G, Elston O, Davis CM, Williams K, MacDougall IC. Can higher doses of IV iron be given as a bolus injection? A1366 Abstract from the Annual Meeting and Scientific Exposition of the American Society of Nephrology. 2000.
  37. Ursea N, Garneata L. Intravenous iron supplementation for the treatment of anemia in predialysis chronic renal failure patients. Nephrol Dial Transplant. 15: abstract, 2000.
  38. Stoves J, Inglis H, Newstead CG. A randomized study of oral vs. intravenous iron supplementation in patients with progressive renal insufficiency treated with erythropoietin. Nephrol Dial Transplant. 2001; 16:967-974.
  39. Aaronson ML, Cornell LD. Tolerability of high dose [500 mg] intravenous iron sucrose in pre-dialysis patients receiving either erythropoietin or darbepoetin. SU-PO841 Abstract from the Annual Meeting and Scientific Exposition of the American Society of Nephrology. 2002.
  40. Fassa L, Campos D. Injectable iron in hypochromic anemias in pregnancy. Rev Ginecol Obstet. 1970; 127:402-406.
  41. Chamate E. Treatment of iron deficiency in pregnancy and in the immediate puerperium, and of other ferropenic conditions with saccharated iron administered intravenously in fractionated doses. XIV Internat Cong Hemat. San Paolo Brazil, 1972.
  42. Al-Momen AK, Al-Meshari A, Al-Nuaim L, Saddique A, Abotalib Z, Khashogji T, et al. Intravenous iron sucrose in the treatment of iron deficiency anemia during pregnancy. Europ J Obstet Gynecol Reprod Biol. 1996; 69:121-124.
  43. Lebrecht A, Haberlin F, Eberhard J. Postpartum anemia: Intravenous iron supplementation renders therapy with r-HuEPO redundant. Geburtsh u Frauenheilk. 1995; 55:167-170.
  44. Zimmerman R, Breymann C, Richter C, Huch R, Huch A. r-HuEPO treatment of postpartum anemia. J Perinat Med. 1995; 23:111-117.
  45. Breymann C, Major A, Richter C, Huch R, Huch A. Recombinant human erythropoietin and parenteral iron in the treatment of pregnancy anemia: a pilot study. J Perinat Med. 1995; 23:89-98.
  46. Polatti F, Mandelli B. Treatment with intravenous Fe of hypochromic anemia in pregnancy (translation) Trattamento con Fe per via endovenosa dell'ameina ipocromica gravidica. Bollettino della Societa Medico-Chirurgica di Pavia. 1983; 97(1-2):13-16.
  47. Gravier A, Descargues G, Marpeau L. How to avoid post-partum transfusions: benefit of intravenous iron supplementation. J Gynecol Obstet Reprod. 1999; 28:77-78.
  48. Breymann C, Richter C, Huttner C, Huch R, Huch A. Effectiveness of recombinant erythropoietin and iron sucrose vs. iron therapy only, in patients with post-partum anemia and blunted erythropoiesis. Europ J Clin Invest. 2000; 30:154-161.
  49. Krafft A, Breymann C, Huch R, Huch A. Intravenous iron sucrose in two pregnant women with inflammatory bowel disease and severe iron deficiency anemia. Acta Obstet Gynecol Scand. 2000; 79:720-722.
  50. Delaporte-Cerceau S, Boulay G, Saint Blanquat L, Simon L, Hamza J. Intravenous iron therapy for correction of severe post-partum anemia. Obstet Anaesthesia meeting abstracts A505 April 2000.
  51. Ahmed K, Sadiq I, Yousef AW. Injectable iron therapy: Intramuscular vs. intravenous therapy. Biomedica. 2000; 16:44-47.
  52. Frappier J, Delaporte-Cerceau S, deVaumas C, et al. Prise en charge des anemies severes du post-partum interet du fer saccharose intraveneux. Abstract 41st Congress Nat Anesthes. Reanimat 1999 September 23-26.
  53. Breymann C, Vesca E, Huch R, Huch A. Efficacy and safety of intravenously administered iron sucrose with and without adjuvant recombinant human erythropoietin for the treatment of resistant iron-deficiency anemia during pregnancy. Amer J Obstet Gyneco. 2001; 184:662-667.
  54. Bayoumeu F, Vial F, Zaccabri A, Aguiles O, Laxenaire MC. Anticorps antipublic et grossese: interet du fer intraveneux pour une autofusion avec cryoconservatiob. Ann Fr Anesth Reanim. 2002; 21:27-31.
  55. Chalmanov N. Administration of intravenous iron [Venofer® in postpartum anemia syndrome or "Let's replace a blood transfusion when it's not a life-saver." Akush Ginekol. 2000;39:21-23.
  56. Sifakis S, Angelakis E, Vardaki E, Koumantaki Y, Matalliotakis I, Koumantakis E. Erythropoietin in the treatment of iron deficiency anemia during pregnancy. Gynecol Obstet Invest. 2001; 51:150-156.
  57. Meyer MP, Haworth C, Meyer JH, Commerford A. A comparison of oral and intravenous iron supplementation in preterm infants receiving recombinant erythropoietin. J Pediatr. 1996; 129:258-263.
  58. Martini A, Ravelli A, Di Fuccia G, Rosti V, Cazzola M, Barosi G. Intravenous iron therapy for severe anemia in systemic-onset juvenile chronic arthritis. Lancet. 1994; 344:1052-1054.
  59. Berniére J. Dehullu JP, Gall O, Murat I. Le fer intraveineux dans le traitement des anémies postopératoires dans la chirurgie du rachis de l'enfant et de l'adolescent. Intravenous iron therapy for correction of post-operative anemia following spinal surgery in children. Revue Chir Orthoped. 1998; 8:319-322.
  60. Michaud L, Guimber D, Mention K, Neuville H, Froger H, Gottrand F, et al. Tolerance and efficacy of intravenous iron saccharate for iron deficiency anemia in children and adolescents receiving long-term parenteral nutrition. Clin Nutr. 2002; 21:403-407.
  61. Pollak A, Hayde M, Hayn M, et al. Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants. Pediatrics. 2001; 107:78-85.
  62. Surico G, Muggeo P, Muggeo V, et al. Parenteral iron supplementation for the treatment of iron deficiency anemia in children. Ann Hematol. 2002; 81:154-157.
  63. Atherton DJ, Cox J, Hann I. Intravenous iron [III] hydroxide-sucrose complex for anaemia in epidermolysis bullosa. Brit J Dermatol. 1999; 140:773.
  64.  Delaporte-Cerceau S, Prayssac P, Simon L, Hamza J. Intravenous iron therapy for correction of severe post-operative anemia in children. Ped Anesthes Intensive Care A461, 1-4 April 2000.
  65. Jean N, Fraisse D, Loeb T. Transfusional economy: the interest of iron hydroxide-saccharose in the perioperative stage in pediatrics orthopedia and traumatology. CLSAP, Paris, 1997.
  66. Kapelushnik J, Moser A, Levi JV, Landau D, Pinsk V. Intravenous iron therapy in children. Blood. 2000; 96:6b [A3676].
  67. Jasper A, Adams A, Smith PA, Lewis NJA. Successful strategies for improving outcome and reducing costs in anemia management in chronic renal impairment. Annual Dialysis Conf. February 2001.
  68. Gasché C, Dejaco C, Waldhoer T, Tillinger W, Reinisch W, Fueger GF, et al. Intravenous iron and erythropoietin for anemia associated with Crohn's disease. Ann Intern Med. 1997; 126:782-787.
  69. Gasché C, Dejaco C, Reinisch W, Tillinger W, Waldhoer T, Fueger GF, et al. Sequential treatment of anemia in ulcerative colitis with intravenous iron and erythropoietin. Digestion. 1999; 60(3):262-267.
  70. Bulvik S, Karalnick S, Leibovitz G, Niven M. Intravenous iron gluconate or iron saccharate for patients with malabsorption or oral intolerance. Abstract from the ISH-ASH Combined Hematology Congress July 4-8, 1998, Amsterdam, The Netherlands. Brit J Haematol. 1998; 102(1):40.
  71. Stark P, Luboshitz J, Magen H, Bairey O, Shaklai M. Efficacy and safety of intravenous iron polymaltose (Ferrum Hausmann®) in the treatment of iron deficiency anemia. Blood. 1998; 92:A#3079.
  72. Reffitt DM, Doig LA, Meenan J, Powell JJ, Thompson RPH. Sustained improvement in the quality of life of patients with anemia and inflammatory bowel disease given intravenous iron. Gut. 1999;44:A39.
  73. Gasche C, Waldhoer T, Feichtenschlager T, et al. Prediction of response to iron sucrose in inflammatory bowel disease-associated anemia. Amer J Gastroenterol. 2001; 96:2382-2387.
  74. Mercuriali F, Zanella A, Barosi G, Inghilleri G, Biffi E, Vinci A, et al. Use of erythropoietin to increase the volume of autologous blood donated by orthopedic patients. Transfusion. 1993; 33:55-60.
  75. DePree C, Mermillod B, Hoffmeyer P, Beris P. Recombinant human erythropoietin as adjuvant treatment for autologous blood donation in elective surgery with large blood needs [> or = 5 units]: a randomized study. Transfusion. 1997; 37:708-714.< /SPAN >< /SPAN >< /SPAN >
  76. Weisbach V, Skoda P, Rippel R, Lauer G, Glaser A, Zingsem J, et al. Oral or intravenous iron as an adjuvant to autologous blood donation in elective surgery: a randomized controlled study. Transfusion 1999; 39:465-472.
  77. Rohling RG, Zimmerman AP, Breymann C. Intravenous versus oral iron supplementation for preoperative stimulation of hemoglobin synthesis using recombinant human erythropoietin. J Hematother Stem Cell Res. 2000; 9:497-500.
  78. Kipnis E, Deneux C. Utilisation de fer intra-veneux comme alternative a la transfusion homologue en chirurgie orthopedique. Abstract 72. Third Congres Nat. Securite Transfusionnelle Hemovigilance. September 1999.
  79. Olijhoek G, Megens GN, Musto P, Nogarin L, Gassmann-Mayer C, Vercammen E, et al. Role of oral versus IV iron supplementation in the erythropoietic response to rHuEPO: a randomized, placebo controlled trial. Transfus Med. 2001; 41:957-963.
  80. Walpoth BH, Aregger F, Imboden C, Auckenthaler E, Nydegger U, Carrel T. Safety of preoperative autologous blood donations in cardiac surgery. Infusion Ther. 2002; 29:160-162.
  81. Breymann C, Buhner M, Lex B, Tulusan A. Recombinantes erythropoietin [40 000 E] und eisensaccharatkomplex zur perioperativen anwendung in der gynekologie. Personal communication. February 2003.
  82. Silverberg DS, Wexler D, Blum M, Keren G, Sheps D, et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Amer Coll Cardiol. 2000; 35:1737-1744.
  83. Silverberg DS, Wexler D, Sheps D, et al. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Amer Coll Cardiol. 2001; 37:1775-1780.
  84. Höchli P, Wagenhäuser FJ, Fehr J. Repeated continuous administration of low doses of intravenous iron in anemic patients with active rheumatoid arthritis. Eur J Hematol. 1993; 51:54-55.
  85. Kaltwasser JP, Kessler U, Gottschalk R, Stucki G, Moeller B. Effect of recombinant human erythropoietin and intravenous iron on anemia and disease activity in rheumatoid arthritis. J Rheumatol. 2001; 28:2430-2436.
  86. Montecucco C, Caporali R, Invernizzi R. Iron status in Still's disease. Lancet. 1995; 345:58-59.
  87. Silverberg DS, Blum M, Agbaria V, Deutsch M, Irony D, Schwartz R. The effect of IV iron alone or in combination with low-dose erythropoietin in the rapid correction of anemia of chronic renal failure in the predialysis period. Clinical Nephrology. 2001; 55(3):212-219.
  88. Blaustein DA et al Intolerance to 1 gram iron sucrose infusions in chronic kidney disease patients.  ASN 2003, San Diego Ca.
  89. Blaustein DA et al. The safety and efficacy of an accelerated iron sucrose dosing regimen in patients with chronic kidney diseases. Kidney Int. 2003; 64 (supp 87): s72-s77.
  90. Charytan, C., Qunibi, W., Bailie, G. Comparison of Intravenous Iron Sucrose to Oral Iron in the Treatment of Anemic Patients with Chronic Kidney Disease Not on Dialysis Nephron Clinical Practice. 2005; Vol.100, c55-c62.
  91. Fesyuk AF et al. Use of Venofer fro correction of iron deficiency in patients with programmed haemodialysis. Nephrology Terapevticheskiy. 2003; 8:59-61.
  92. Hollands et al. Safety and efficacy of high dose iron sucrose infusion in hospitalized CKD patients. ASN 2003, San Diego Ca.
  93. Kosmadakis  N et al. Perioperative erythropoietin administration in patients with gastrointestinal tract cancer. Annals of Surgery 2003; 237(3):417-421.
  94. Moniem et al. Tolerability and efficacy of parenteral iron therapy in haemodialysis patients. Abstract ASN 2003, San Diego Ca.
  95. Seronie-Vivien S et al Epoetin alfa and iron sucrose to treat severe anemia in a patient with chronic radiation enteropathy. Medical Oncology. 2003; 20(3):301-306.
  96. Khalid AM et al. a prospective randomized open-label study comparing the efficacy and safety of intraperitoneal iron versus intravenous iron in peritoneal dialysis patients.  Am J Nephrol. 2004; 24:61-146.
  97. Bodemar G. Treatent of anaemia in inflammatory bowel disease with iron sucrose. Scandinavian Journal of Gastroenterology.  2004; 39(5):454-458. 
  98. Agarwal R et al. Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease. Kidney Int. 2004; 65:2279-2289.
  99. Monnerat et al. Early administration of haemaglobin-adapted doses of erythropoietin with intravenous iron for the prevention of chemotherapy induced anaemia. European Journal of Cancer Supplements. 2003; 1(5):s284.
  100. Cavdar C et al. The effect of intravenous iron treatment on oxidant stress and erythrocyte deformability in hemodialysis patients. Scandinavian Journal of Urology and Nephrology. 2003; 37:77-82.
  101. Oliviera A et al. Improvement of preoperative autologous donation (PAD) with recombinant human erythropoietin and intravenous iron. Abstract from NATA 4th Annual Symposium 2003, London UK.
  102. Sharbova-Slavova M et al. Treatment of perioperative anemia with erythropoietin beta and monitoring the therapeutic effect. Abstract from NATA 4th Annual Symposium 2003, London UK.
  103. Cuenca J et al. Parenteral iron useful in the management of trochanteric hip fracture. Abstract from NATA 4th Annual Symposium 2003, London UK.
  104. Olivera A et al. Intravenous iron in different pathologies. Abstract from NATA 4th Annual Symposium 2003, London UK.
  105. Wali A et al. Comparative study- Efficacy, safety and compliance of intravenous iron sucrose and intramuscular iron sorbitol in iron deficiency anaemia of pregnancy. Journal of the Pakistan Medical Association 2002; 52:392-5.
  106. Tabassum R et al. Place of intravenous iron sucrose for the treatment of iron deficiency anemias during pregnancy. Medical Channel. 9(1):55-56.
  107. Chuang CL et al Early prediction of response to intravenous iron supplementation by reticulocyte hemoglobin content and high-flourescence reticulocyte count in hemodialysis. Nephrol Dial Transplant. 2003; 18:370-377.
  108. Furuland H et al. A randomized controlled trial of hemoglobin normalization with epoetin alfa in predialysis and dialysis patients. Nephrol Dial Transplant.  2003; 18:353-361.
  109. Schroder et al. A study for the evaluation of safety and tolerability of intravenous high-dose iron sucrose in patients with iron deficiency anemia due to gastrointestinal bleeding. Z Gastroenterol.  2004; 42:663-667.
  110. Borawski et al. Endothelial injury markers with high-dose intravenous iron therapy in renal failure. Clin Appl Thrombosis/Hemostatis. 2004; 10(4):403-406.
  111. Tiranathangul K et al. Oxidative stress from rapid vs. slow intravenous iron replacement in haemodialysis patients. Nephrology. 2004; 9:217-222.
  112. Abello V et al. Intravenous saccharate iron for the treatment of ferropenic anemia in adults that cannot tolerate oral iron intake. Acta Medica Colombiana.  2004; 29(4):322-327.
  113. Schwenk MH, Blaustein DA et al. Rapid high-dose intravenous iron sucrose therapy in 2 Jehovah's Witness patients with severe anaemia, iron deficiency and chronic kidney disease. Clinical Nephrology.  2004; 62(2):116-120.
  114. Sengoelge G et al Dose-dependent effect of parenteral iron therapy on bleomycin-detectable iron in immune apheresis patients. Kidney Int. 2004; 66:295-302.
  115. Pyatibratov VB et al. Human recombinant erythropoietin and iron therapy in the treatment of patients with chronic renal failure at chronic haemodialysis. Voprosy gematologii/onkologii/immunopatologii v pediatrii. 2004; 3(1):74-77.
  116. Cuenca J et al. Patients with pertrochanteric hip fracture may benefit from preoperative intravenous iron therapy: a pilot study. Transfusion. 2004; 44:1447-1452.
  117. Cuenca Espierrez et al. Safety and usefulness of parenteral iron in the management of anaemia due to hip fracture in the elderly. Med Clin (Barc). 2004; 123(8):281-285.
  118. Abdel-Razeq H et al. Parenteral ferric hydroxide saccharate therapy for iron deficiency anemia: safety and efficacy. Blood. 2004; 104(11): abs #3681.
  119. Erichsen K et al. Oral versus intravenous iron therapy in patients with inflammatory bowel disease. Gut. 2004; 53(Supp V):A220.
  120. Biesenbach G et al. Erythropoietin requirement in patients with type 2 diabetes mellitus on maintenance haemodialysis therapy. Wein Klin Wochenschr. 2004; 116(24):844-848.
  121. Van Wyck et al. A randomized controlled trial comparing IV iron sucrose to oral iron in anemic patients with non-dialysis dependent CKD. Kidney Int. 2005;68:2846-2856
  122. Van Wyck DB. The natural history of iron deficiency in patients with dialysis-associated anemia: Analysis of the first 10 weeks without iron and comparison to LU98001. Clinical study report, 2000 and data on file: American Regent, Inc., Shirley, NY.
  123. Singh H, Reed J, Noble S.  Effect of iron therapy in peritoneal dialysis patients receiving erythropoiesis stimulating agents for anemia:  a randomized, controlled trial (in press).
  124. Data on file. American Regent, Inc., Shirley, NY.

 
   

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