BOXED WARNING
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THE PARENTERAL USE OF COMPLEXES OF IRON AND CARBOHYDRATES HAS RESULTED IN ANAPHYLACTIC-TYPE REACTIONS. DEATHS ASSOCIATED WITH SUCH ADMINISTRATION HAVE BEEN REPORTED. THEREFORE, INFeD SHOULD BE USED ONLY IN THOSE PATIENTS IN WHOM THE INDICATIONS HAVE BEEN CLEARLY ESTABLISHED AND LABORATORY INVESTIGATIONS CONFIRM AN IRON DEFICIENT STATE NOT AMENABLE TO ORAL IRON THERAPY. BECAUSE FATAL ANAPHYLACTIC REACTIONS HAVE BEEN REPORTED AFTER ADMINISTRATION OF IRON DEXTRAN INJECTION, THE DRUG SHOULD BE GIVEN ONLY WHEN RESUSCITATION TECHNIQUES AND TREATMENT OF ANAPHYLACTIC AND ANAPHYLACTOID SHOCK ARE READILY AVAILABLE. |
INDICATIONS AND USAGE
Intravenous or intramuscular injections of iron dextran are indicated for treatment of patients with documented iron deficiency in
whom oral administration is unsatisfactory or impossible.
CONTRAINDICATIONS
Hypersensitivity to the product. All anemias not associated with iron deficiency.
WARNINGS
See WARNING ABOVE.
A risk of carcinogenesis may attend the intramuscular injection of iron-carbohydrate complexes. Such complexes have been found under experimental conditions to produce sarcoma when large doses or small doses injected repeatedly at the same site were given to rats, mice, and rabbits, and possibly in hamsters. The long latent period between the injection of a potential carcinogen and the appearance of a tumor makes it impossible to measure accurately the risk in man. There have, however, been several reports in the literature describing tumors at the injection site in humans who had previously received intramuscular injections of iron-carbohydrate complexes.
Large intravenous doses, such as used with total dose infusions (TDI), have been associated with an increased incidence of adverse effects. The adverse effects frequently are delayed (1-2 days) reactions typified by one or more of the following symptoms: arthralgia, backache, chills, dizziness, moderate to high fever, headache, malaise, myalgia, nausea, and vomiting. The onset is usually 24-48 hours after administration and symptoms generally subside within 3-4 days. These symptoms have also been reported following intramuscular injection and generally subside within 3-7 days. The etiology of these reactions is not known. The potential for a delayed reaction must be considered when estimating the risk/benefit of treatment. The maximum daily dose should not exceed 2 mL undiluted iron dextran. This preparation should be used with extreme care in patients with serious impairment of liver function. It should not be used during the acute phase of infectious kidney disease. Adverse reactions experienced following administration of INFeD may exacerbate cardiovascular complications in patients with preexisting cardiovascular disease.
Pregnancy
Pregnancy Category C: Iron dextran has been shown to be teratogenic and embryocidal in mice, rats, rabbits, dogs, and monkeys when given in doses of about 3 times the maximum human dose. No consistent adverse fetal effects were observed in mice, rats, rabbits, dogs and monkeys at doses of 50 mg iron/kg or less. Fetal and maternal toxicity has been reported in monkeys at a total intravenous dose of 90 mg iron/kg over a 14 day period. Similar effects were observed in mice and rats on administration of a single dose of 125 mg iron/kg. Fetal abnormalities in rats and dogs were observed at doses of 250 mg iron/kg and higher. The animals used in these tests were not iron deficient. There are no adequate and well-controlled studies in pregnant women. INFeD should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Placental Transfer
Various animal studies and studies in pregnant humans have demonstrated inconclusive results with respect to the placental transfer ofiron dextran as iron dextran. It appears that some iron does reach the fetus, but the form in which it crosses the placenta is not clear. Nursing Mothers Caution should be exercised when INFeD is administered to a nursing woman. Traces of unmetabolized iron dextran are excreted in human milk.
Pediatric Use
Not recommended for use in infants under 4 months of age (See DOSAGE AND ADMINISTRATION).
Oral iron should be discontinued prior to administration of INFeD.
Dosage
I. Iron Deficiency Anemia:
Periodic hematologic determination (hemoglobin and hematocrit) is a simple and accurate technique for monitoring hematological response, and should be used as a guide in therapy. It should be recognized that iron storage may lag behind the appearance of normal blood morphology. Serum iron, total iron binding capacity (TIBC) and percent saturation of transferrin are other important tests for detecting and monitoring the iron deficient state. After administration of iron dextran complex, evidence of a therapeutic response can be seen in a few days as an increase in the reticulocyte count. Although serum ferritin is usually a good guide to body iron stores, the correlation of body iron stores and serum ferritin may not be valid in patients on chronic renal dialysis who are also receiving iron dextran complex. Although there are significant variations in body build and weight distribution among males and females, the accompanying table and formula represent a convenient means for estimating the total iron required. This total iron requirement reflects the amount of iron needed to restore hemoglobin concentration to normal or near normal levels plus an additional allowance to provide adequate replenishment of iron stores in most individuals with moderately or severely reduced levels of hemoglobin. It should be remembered that iron deficiency anemia will not appear until essentially all iron stores have been depleted. Therapy, thus, should aim at not only replenishment of hemoglobin iron but iron stores as well.
Factors contributing to the formula are shown below.
DOSAGE AND ADMINISTRATION
| mg blood iron |
|
mL blood |
|
g hemoglobin |
|
mg iron |
| ————— |
= |
————— |
x |
————— |
x |
————— |
| lb body weight |
|
lb body weight |
|
mL blood |
|
g hemoglobin |
a) Blood volume.......................... 65 mL/kg of body weight
b) Normal hemoglobin (males and females)
over 15 kg (33 lbs)................... 14.8 g/dl
15 kg (33 lbs) or less............... 12.0 g/dl
c) Iron content of hemoglobin ....................0.34%
d) Hemoglobin deficit
e) Weight
Based on the above factors, individuals with normal hemoglobin levels will have approximately 33 mg of blood iron per kilogram of body
weight (15 mg/lb).
Note: The table and accompanying formula are applicable for dosage determinations only in patients with iron deficiency anemia;
they are not to be used for dosage determinations in patients requiring
iron replacement for blood loss.
TOTAL INFeD® REQUIREMENT FOR HEMOGLOBIN RESTORATION AND IRON STORES REPLACEMENT*
| PATIENT |
Milliliter Requirement of INFeD
Based On Observed
|
| LEAN BODY |
Hemoglobin of |
| WEIGHT |
|
|
|
|
|
|
|
|
| 3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
| kg |
lb |
(g/dl) |
(g/dl) |
(g/dl) |
(g/dl) |
(g/dl) |
(g/dl) |
(g/dl) |
(g/dl) |
| *Table values were calculated
based on a normal adult hemoglobin of 14.8 g/dl for weights greater than
15 kg (33 lbs) and a hemoglobin of 12.0 g/dl for weights less than or
equal to 15 kg (33 lbs). |
| 5 |
11 |
3 |
3 |
3 |
3 |
2 |
2 |
2 |
2 |
| 10 |
22 |
7 |
6 |
6 |
5 |
5 |
4 |
4 |
3 |
| 15 |
33 |
10 |
9 |
9 |
8 |
7 |
7 |
6 |
5 |
| 20 |
44 |
16 |
15 |
14 |
13 |
12 |
11 |
10 |
9 |
| 25 |
55 |
20 |
18 |
17 |
16 |
15 |
14 |
13 |
12 |
| 30 |
66 |
23 |
22 |
21 |
19 |
18 |
17 |
15 |
14 |
| 35 |
77 |
27 |
26 |
24 |
23 |
21 |
20 |
18 |
17 |
| 40 |
88 |
31 |
29 |
28 |
26 |
24 |
22 |
21 |
19 |
| 45 |
99 |
35 |
33 |
31 |
29 |
27 |
25 |
23 |
21 |
| 50 |
110 |
39 |
37 |
35 |
32 |
30 |
28 |
26 |
24 |
| 55 |
121 |
43 |
41 |
38 |
36 |
33 |
31 |
28 |
26 |
| 60 |
132 |
47 |
44 |
42 |
39 |
36 |
34 |
31 |
28 |
| 65 |
143 |
51 |
48 |
45 |
42 |
39 |
36 |
34 |
31 |
| 70 |
154 |
55 |
52 |
49 |
45 |
42 |
39 |
36 |
33 |
| 75 |
165 |
59 |
55 |
52 |
49 |
45 |
42 |
39 |
35 |
| 80 |
176 |
63 |
59 |
55 |
52 |
48 |
45 |
41 |
38 |
| 85 |
187 |
66 |
63 |
59 |
55 |
51 |
48 |
44 |
40 |
| 90 |
198 |
70 |
66 |
62 |
58 |
54 |
50 |
46 |
42 |
| 95 |
209 |
74 |
70 |
66 |
62 |
57 |
53 |
49 |
45 |
| 100 |
220 |
78 |
74 |
69 |
65 |
60 |
56 |
52 |
47 |
| 105 |
231 |
82 |
77 |
73 |
68 |
63 |
59 |
54 |
50 |
| 110 |
242 |
86 |
81 |
76 |
71 |
67 |
62 |
57 |
52 |
| 115 |
253 |
90 |
85 |
80 |
75 |
70 |
64 |
59 |
54 |
| 120 |
264 |
94 |
88 |
83 |
78 |
73 |
67 |
62 |
57 |
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Adults and Children over 15 kg (33 lbs):
Alternatively the total dose may be calculated:
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Dose (mL)
= 0.0442 (Desired Hb - Observed Hb) x LBW + (0.26 x LBW)
Based on:
Desired Hb = the target Hb in g/dl.
Observed Hb = the patient’s current hemoglobin in g/dl.
LBW = Lean body weight in kg. A patient’s lean body weight (or actual body weight if less than lean body
weight) should be utilized when determining dosage.
For males: LBW = 50 kg + 2.3 kg for each inch of patient’s height over 5 feet
For females: LBW = 45.5 kg + 2.3 kg for each inch of patient’s height over 5 feet
To calculate a patient’s weight in kg when lbs are known:
patient’s weight in pounds = weight in kilograms/2.2
|
| Children 5 - 15 kg (11 - 33 lbs): See Dosage Table. |
INFeD should not normally be given in the first four months of
life. (See PRECAUTIONS: Pediatric Use)
Alternatively the total dose may be calculated:
Dose (mL) = 0.0442 (Desired Hb - Observed Hb) x W + (0.26 x W)
Based on: Desired Hb = the target Hb in g/dl. (Normal Hb for Children 15 kg or less is 12 g/dl)
W = Weight in kg.
To calculate a patient’s weight in kg when lbs are known:
patient’s weight in pounds = weight in kilograms/2.2 |
II. Iron Replacement for Blood Loss: Some individuals sustain blood losses on an intermittent or repetitive basis. Such blood losses may occur periodically in patients with hemorrhagic diatheses (familial telangiectasia; hemophilia; gastrointestinal bleeding) and on a repetitive basis from procedures such as renal hemodialysis. Iron therapy in these patients should be directed toward replacement of the equivalent amount of iron represented in the blood loss. The table and formula described under I. Iron Deficiency Anemia are not applicable for simple iron replacement values. Quantitative estimates of the individual’s periodic blood loss and hematocrit during the bleeding episode provide a convenient method for the calculation of the required iron dose. The formula shown below is based on the approximation that 1 mL of normocytic, normochromic red cells contains 1 mg of elemental iron:
Replacement iron (in mg) = Blood loss (in mL) x hematocrit
Example: Blood loss of 500 mL with 20% hematocrit
Replacement Iron = 500 x 0.20 = 100 mg
INFeD dose = 100 mg/50 = 2 mL
Administration: The total amount of INFeD required for the treatment of iron deficiency anemia or iron replacement for blood loss is determined from the table or appropriate formula (See Dosage).
I. Intravenous Injection - PRIOR TO RECEIVING THEIR FIRST INFeD THERAPEUTIC DOSE, ALL PATIENTS SHOULD BE GIVEN AN INTRAVENOUS TEST DOSE OF 0.5 mL. (See PRECAUTIONS: General.) THE TEST DOSE SHOULD BE ADMINISTERED AT A GRADUAL RATE OVER AT LEAST 30 SECONDS. Although anaphylactic reactions known to occur following INFeD administration are usually evident within a few minutes, or sooner, it is recommended that a period of an hour or longer elapse before the remainder of the initial therapeutic dose is given. Individual doses of 2 mL or less may be given on a daily basis until the calculated total amount required has been reached. INFeD is given undiluted at a slow gradual rate not to exceed 50 mg (1 mL) per minute.
2. Intramuscular Injection - PRIOR TO RECEIVING THEIR FIRST INFeD THERAPEUTIC DOSE, ALL PATIENTS SHOULD BE GIVEN AN INTRAMUSCULAR TEST DOSE OF 0.5 mL. (See PRECAUTIONS: General.) The test dose should be administered in the same recommended test site and by the same technique as described in the last paragraph of this section. Although anaphylactic reactions known to occur following INFeD administration are usually evident within a few minutes or sooner, it is recommended that at least an hour or longer elapse before the remainder of the initial therapeutic dose is given. If no adverse reactions are observed, INFeD can be given according to the following schedule until the calculated total amount required has been reached. Each day’s dose should ordinarily not exceed 0.5 mL (25 mg of iron) for infants under 5 kg (11 lbs); 1.0 mL (50 mg of iron) for children under 10 kg (22 lbs); and 2.0 mL (100 mg of iron) for other patients. INFeD should be injected only into the muscle mass of the upper outer quadrant of the buttock - never into the arm or other exposed areas - and should be injected deeply, with a 2-inch or 3-inch 19 or 20 gauge needle. If the patient is standing, he/she should be bearing his/her weight on the leg opposite the injection site, or if in bed, he/she should be in the lateral position with injection site uppermost. To avoid injection or leakage into the subcutaneous tissue, a Z-track technique (displacement of the skin laterally prior to injection) is recommended.
NOTE: Do not mix INFeD with other medications or add to parenteral nutrition solutions for intravenous infusion. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit.
HOW SUPPLIED: INFeD® (Iron Dextran Injection USP) containing 50 mg of elemental iron per mL, is available in 2 mL single dose amber vials (for intramuscular or intravenous use) in cartons of 10 (NDC 52544-931-02). Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Rx Only
REFERENCES:
1. Hatton RC, Portales IT, Finlay A, Ross EA. Removal of Iron Dextran
by Hemodialysis: An In Vitro Study. Am J Kid Dis. 1995;
26(2):327-330.
2. Manuel MA, Stewart WK, St. Clair Neill GD, Hutchinson F. Loss
of Iron-Dextran through Cuprophane Membrane of a Disposable
Coil Dialyser. Nephron. 1972;9:94-98.
Literature revised: March 2006
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A test dose of 25 mg diluted in 50 ml normal saline and
infused over 5 minutes should be
given. Infusion should then be stopped for 1 hour. If there is no
reaction after 1 hour continue. Fatal anaphylactic reactions are
possible. Epinephrine should be immediately available.
Total amount of iron dextran required in ml (Total dose infusion):=
0.0442 (14.8 - observed Hgb) x ibw + (0.26 x ibw).
Parenterally administered iron does not give a
faster response compared to oral administration, therefore, the rate of
recovery from anemia should be the same. Reticulocyte count will
increase in 3-4 days and peak in 7-10 days. Hemoglobin may increase at a
rate of 1.5-2.2 g/dl/week for the first 2 weeks, followed by 0.7 to 1.6
g/dl/week until normal hemoglobin levels are achieved. Parenteral iron
treatment should be administered only when iron deficiency is not
correctable with oral treatment. Note: Iron dextran is cleared by
the reticuloendothelial system. Smaller doses (50-500mg) are
cleared within 3 days, however, larger doses(>500mg) are cleared at a
constant rate of 10-20mg/hr and are associated with increased plasma
concentration of iron dextran for as long as 3 weeks.
Iron replacement for blood loss: Dose (mg)= Blood loss (ml) x
Hematocrit %. Total mg of iron/50 = dose in ml.
Reactions to IV administration include: fever, chills, backache,
myalgia, dizziness, syncope,rash and anaphylaxis-immediate or
delayed.
Total dose infusion: the overall consensus regarding IV
administration of iron dextran is that total dose infusion is the
preferred method. If severe reactions develop, multiple bolus injections
over several days may be required. Average total body
content of iron in adult male: 4 grams (70% in Hgb, 25% in storage).
The first changes seen with treatment is an
increase in reticulocytes (4-6 days initially, peak: 9-12 days)
Hemoglobin will rise slowly--it should rise by 2 g/dl after 3 weeks. The
plasma iron will gradually increase, and the initially elevated TIBC
will return to normal in about one month. Blood levels return to normal
in about 4-6 months (ferritin levels will return to normal). Laboratory:
Transferrin: delivers iron to bone marrow and storage sites. Circulating
transferrin is normally only about 30% saturated with iron. The
remaining 70% in unbound and represents the TIBC. Iron is stored as
either ferritin or hemosiderin within macrocytes (reticuloendothelial
system). Normal RBC survival time: 120 days.
In iron deficiency anemia (microcytic-hypochromic=decreased
Hemoglobin), iron stores are depleted prior to anemia; therefore, the
earliest change observed is usually decreased ferritin. Hemoglobin:
Normal (female): 12-16 g/dL ; Male 14-18 g/dL. Hematocrit: Normal
(female): 35-40% ; (Male): 42-52%. A low Hematocrit indicates a
decrease in number or size of RBC or increase in plasma volume. RBC
count: 4.5 to 6 million/ml (4 to 5.5 female). MCV(mean corpuscular
volume): indicates microcytic, normocytic or macrocytic
morphology. MCH(mean corpuscular hemoglobin): Average weight of
Hgb in RBC. Decreased in microcytosis and hypochromia(low hgb). MCH
alone cannot distinguish between the two. MCHC(mean corpuscular
hemoglobin conc.): (Nml: 31-36%): weight of Hemoglobin/volume of cells.
Independent of cell size and, therefore, is more useful than MCH in
distinguishing between microcytosis and hypochromia. A low MCHC always
indicates hypochromia, as a microcyte with a normal Hemoglobin
concentration will have a low MCH but a normal MCHC. Red cell
distribution width (RDW): Normal: 11.4 - 14.5% Indicates how much the
RBC's vary in size. Elevated in anemia's resulting from nutritional
deficiencies (iron,folic acid, B12). Serum iron concentration:
concentration of iron bound to transferrin. Unfortunately, the serum
level of many patients with iron deficiency anemia remains within the
lower limits of normal. There is a 20-30% diurnal variation in serum
iron levels--it is best to draw levels in the morning. Total iron
binding capacity (TIBC): indirect measurement of serum transferrin.
Unlike the serum iron level, the TIBC is remarkably constant. The
finding of a low serum iron and a high TIBC indicates iron deficiency
anemia. Serum ferritin: the concentration of ferritin (storage iron) in
the serum is proportional to total iron stores. Low ferritin levels are
virtually diagnostic of iron deficiency anemia as they are decreased
only in iron deficiency anemia. Liver disease causes an elevation in
serum ferritin; thus ferritin should not be used for diagnostic purposes
in patients with even mild hepatic pathology.
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1. Auerbach M, Witt D, Toler W, Fierstein M, Lerner RG, Ballard H.
Clinical use of the total dose intravenous infusion of iron dextran.
J Lab Clin Med. 1988 May;111(5):566-70.
2. Bhowmik D, Modi G, Ray D, Gupta S, Agarwal SK, Tiwari SC, Dash SC.
Total dose iron infusion: safety and efficacy in predialysis patients. Ren Fail. 2000 Jan;22(1):39-43.
3. Burns DL, Mascioli EA, Bistrian BR. Parenteral iron dextran therapy: a review.
Nutrition. 1995 Mar-Apr;11(2):163-8.
4. Case G. Maintaining iron balance with total-dose infusion of intravenous iron
dextran. ANNA J. 1998 Feb;25(1):65-8.
5. Hanson DB, Hendeles L. Guide to total dose intravenous iron dextran therapy.
Am J Hosp Pharm. 1974 Jun;31(6):592-5.
6. Jacobs P, Dommisse J. The plasma ferritin level as a reliable index of body iron stores following intravenous iron
dextran.
J Med. 1982;13(4):309-21.
7. Koda-Kimble MA, Applied Therapeutics for Clinical Pharmacists, 2nd ed, edited by
Koda-Kimble et al, Applied Therapeutics, Inc., San Francisco 1978.
8. Kumpf VJ. Parenteral iron supplementation. Nutr Clin
Pract. 1996 Aug;11(4):139-46.
9. Kumpf VJ, Holland EG. Parenteral iron dextran therapy. DICP. 1990 Feb;24(2):162-6.
10. Low CL, Bailie GR, Eisele G. Sensitivity and specificity of transferrin saturation and serum ferritin as markers of iron status after intravenous iron dextran in hemodialysis patients.
Ren Fail. 1997 Nov;19(6):781-8.
11. Sloand JA, Shelly MA, Erenstone AL, Schiff MJ, Talley TE, Dhakal MP.
Safety and efficacy of total dose iron dextran administration in patients on home renal replacement therapies.
Perit Dial Int. 1998 Sep-Oct;18(5):522-7.
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