Year : 2003 | Volume
: 14 | Issue : 2 | Page : 129--133
Intravenous Iron Saccharate Complex: Guidelines for its use in the Management of Anemia of Renal Disease
Clinical Pharmacist, Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia
Clinical Pharmacist, Riyadh Armed Forces Hospital, P.O. Box 7897, Riyadh 11159
|How to cite this article:|
Zolezzi M. Intravenous Iron Saccharate Complex: Guidelines for its use in the Management of Anemia of Renal Disease.Saudi J Kidney Dis Transpl 2003;14:129-133
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Zolezzi M. Intravenous Iron Saccharate Complex: Guidelines for its use in the Management of Anemia of Renal Disease. Saudi J Kidney Dis Transpl [serial online] 2003 [cited 2020 Dec 1 ];14:129-133
Available from: https://www.sjkdt.org/text.asp?2003/14/2/129/33021
Anemia has remained a major factor limiting the quality of life of patients with chronic kidney disease (CKD). Despite the success of dialysis, iron deficiency anemia continues to be a challenge in these patients. Many of them cannot tolerate oral iron therapy, are unable to adequately absorb dietary iron, or have chronic continuing blood loss inherent to the dialysis procedures and to the frequent blood tests required.  Consequently, intravenous (i.v.) iron has become the most suitable alternative in these patients. Because it has been available for a long time, iron dextran is still the highest used i.v. iron formulation used worldwide.
Despite the effectiveness of i.v. iron dextran, its use is associated with undesirable adverse effects. Although these reactions were generally mild and self-limiting, up to 3% of patients can experience more severe reactions, including life-threatening anaphylaxis. , It has been postulated that administering i.v. iron dextran at a rate not exceeding 50 mg/ min can lessen the incidence of arthralgias, myalgias and hypotension. However, there are no strong data to indicate that these side effects are related to the rate of infusion of iron dextran.  A test dose of 25 mg is recommended to minimize the risk of complications, although anaphylactoid reactions are not dose-related and may occur with the test dose. , Several possible mechanisms have been proposed, most of which attribute the dextran component to be severe reactions seen in i.v. iron dextran. , Thus, theoretically, i.v. iron products free of dextran may decrease or avoid these severe reactions and even deaths.
Iron saccharate complex (ISC) (Ferosac®, manufactured by SPIMACO, Saudi Pharmaceutical Industries & Medical Appliances Corporation, Saudi Arabia) is one of two i.v. products which were produced in an effort to reduce or avoid the adverse events related to i.v. iron dextran. The ISC formula does not contain dextran and has demonstrated a low incidence of adverse effects. ,, The side effects most frequently reported with this preparation include diarrhea, abdominal pain, nausea, constipation, and a transient minty taste.  Interestingly, patients with a documented history of sensitivity reactions to iron dextran did not experience a hypersensitivity reaction upon administration of ISC.  Although this product has been available for many years in Saudi Arabia, it was not licensed for use in the United States until late 2000. The properties of ISC compared to iron dextran are presented in [Table 1].
Guidelines for the repletion of iron stores in patients CKD:
The publication of the National Kidney Foundation's Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Practice Guidelines in 1997 represented the first comprehensive effort to give evidence-based guidance to clinical care teams in dialysis facilities in the United States.  These guidelines have been widely adopted in the United States and in other countries around the world. With the evolution of DOQI into K/DOQI (Kidney Diseases Outcomes Quality Initiative), the anemia management guidelines have been updated to reflect new information;  however, the guidelines for iron therapy did not reflect the newly available i.v. iron preparation in the United States, namely the ISC.
In order to accommodate the K/DOQI guidelines for iron therapy into our practice, the following recommendations may be followed. These adapted guidelines are intended to reflect the appropriate use of i.v. ISC which is readily available in Saudi Arabia.
Assessment of iron status
Iron status should be monitored by the percent transferrin saturation (TSAT) and the serum ferritin. ,
Target iron level
Patients with chronic kidney disease should have sufficient iron to achieve and maintain hemoglobin (Hgb) and hematocrit (Hct) levels of 110 to 120 g/L and 33 to 36% respectively. To achieve and maintain this target Hgb/Hct, sufficient iron should be administered to maintain a TSAT of > 20% and a serum ferritin level of > 100 ng/mL. ,
Repletion of iron stores
A trial of oral iron is acceptable in the hemodialysis patient, but is unlikely to maintain the TSAT >20%, serum ferritin >100 ng/mL, and Hgb/Hct respectively at 110 to 120 g/L and 33 to 36%. To achieve and maintain these levels of Hgb and Hct, most hemodialysis patients will require i.v. iron on regular basis. Oral iron is not generally indicated for the CKD patient who requires maintenance doses of i.v. iron. ,
Calculation of dose
Parenteral iron should be initiated at calculated doses based on the lowest dose required to restore Hgb levels and iron indices to appropriate levels. Total iron doses are calculated according to the patient's body-weight and total iron deficit as follows: 
Total iron deficiency in mg =
[Body weight (kg) x (normal Hgb-actual Hgb in g/L)] x 0.24 + depot iron
For weights of 35 kg or higher: Normal Hgb = 150 g/L, depot iron = 500 mg
For weights of 34 kg or lower: Normal Hgb = 130 g/L, depot iron = 15 mg/kg.
Administration of i.v. ISC
Multiple doses are often used for repletion of iron stores when frequent administration of i.v. iron products is not inconvenient for the patient (such as those on regular hemodialysis). The drug may be administered by i.v. push at a rate no faster than 20 mg/minute or by slow i.v. infusion by diluting the product in 100 to 250 ml of 0.9% sodium chloride and administered over 1 to 4 hours. One time total dose replacement of iron stores is a useful way to treat iron deficiency anemia when multiple infusions are not convenient. The ISC has been given in doses up to 500 mg by slow i.v. infusion; doses up to 800 mg have been used in a small number of patients. , Because hypertension is related to the total dose administered as well as the rate of infusion, large doses of iron sucrose are best administrated as a two to four hour infusion. [Table 2] provides the administration guide lines for i.v. ISC.
Monitoring iron status
The maintenance iron status should be monitored by measuring the TSAT and serum ferritin no less than every three months. In patients receiving small doses of iron, such as 100 mg of i.v. ISC, blood samples for estimation of serum iron and ferritin may be drawn seven days after iron administration.  If serum ferritin exceeds 800 ng/ml and/or TSAT is > 50%, i.v. iron should be withheld for up to three months at which time the iron parameters should be re-measured before i.v. iron is resumed.  If serum ferritin goes below 500 ng/ml, i.v. iron should be re-started at 50 mg per week. 
Adverse drug reactions to i.v. ISC and recommendations
Rare, potentially fatal sensitivity reactions, including anaphylactic shock, loss of consciousness, collapse, hypotension, dyspnea and seizures, have been reported with i.v. ISC therapy. ,, Although, fatal hypersensitivity reactions have not been reported in clinical studies using i.v. ISC, clinicians should be vigilant when administering this medication.  Hypotension associated with i.v. administration of ISC may be minimized by adhering to recommended total doses and rates of administration as presented in [Table 2].  Certain patients are at increased risk of developing adverse effects to parenteral iron. Patients with rheumatoid arthritis and other inflammatory conditions may be at particular risk for delayed reactions and anaphylaxis. This may be prevented or minimized by administration of non-steroidal drugs and intravenous methylprednisolone. ,,
Use of ISC in special patient populations
Pregnancy and lactation
ISC is presently classified by the FDA as pregnancy category B. Because it is currently unknown whether i.v. ISC is distributed in milk, caution is advised if the drug is administered in nursing women. 
The daily maximum doses of i.v. ISC must be established according to the patient's weight: Children up to 5 kg = 1.25 ml (1/4 ampoule), and children between 5-10 kg 2.5 ml (1/2 ampoule). 
It is recommended to initiate therapy at a relatively low dosage for patients 65 years of age and older, primarily because these patients are at an increased risk of hepatic, renal, and cardiac dysfunction and of concomitant disease and/or other drug therapies. 
Use with Erythropoietin
ISC is commonly used in combination with erythropoietin (EPO) in patients with CKD. It is well established that the use of i.v. iron significantly decreases the dose requirements of EPO (27 to 75% reductions have been reported), leading to substantial cost savings. , Regular weekly doses of 100 mg i.v. ISC for one year resulted in an average increase in Hgb from 96 to 107 g/l in 116 dialysis patients. Over the same period of time, the average EPO doses decreased from 13,277 units/week to 8976 units/week. Monthly costs of i.v. iron during the study totalled approximately $6400 for all 116 patients enrolled in the study. However, the reduced use of EPO resulted in an average cost savings of $240 per patient per month. The annual cost savings from decreased use of EPO was over $300,000, easily outweighing the increased cost of iron of $38,600. [16,]
Based on the improved safety profile, the use of i.v. ISC in the management of anemia associated with renal disease will continue to grow worldwide and as more reports on its efficacy, safety and cost-effectiveness become available, the use of iron dextran will probably be phased out. ISC may be administered as multiple i.v. infusions or as a bolus dose for the repletion of iron stores. Regular doses of i.v. iron in conjunction with EPO can be cost-effective in patients with chronic continuing blood loss. It is hoped that the new K/DOQI guidelines will soon be updated to reflect the benefits of i.v. ISC which is relatively new in the US market.
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