PARENTERAL IRON DEXTRAN THERAPY
`
`Vanessa J. Kumpf and Eileen G. Holland
`
`ABSTRACT: Parenteral iron therapy is indicated in patients with iron(cid:173)
`deficiency anemia associated with conditions that interfere with the
`ingestion or absorption of oral iron. Replacement doses of iron
`required to replenish iron stores are based on body weight and the
`observed hemoglobin value. Methods of administering iron dextran
`are reviewed, including intramuscular and intravenous injections of
`the undiluted drug, intravenous infusion of a diluted preparation, and
`as an addition to parenteral nutrition solutions. The overall incidence
`of adverse reactions associated with the parenteral administration of
`iron is low, but the potential for an anaphylactic reaction requires that
`an initial test dose be given followed by careful patient observation.
`D1CP Ann Pharmacother 1990;24:162-6.
`
`IN GENERAL. CHRONIC BLOOD LOSS is the most common
`cause of iron deficiency and, more specifically, gastroin(cid:173)
`testinal blood loss is the most common cause of iron-defi(cid:173)
`ciency anemia. Therapy for iron-deficiency anemia in(cid:173)
`cludes treatment of its underlying cause and restoration of
`normal hemoglobin concentrations and iron stores. In the
`acute setting blood transfusion may be indicated to
`promptly supply oxygen to tissues; however, the mainstay
`of treatment is iron replacement accomplished by the oral,
`intravenous, or intramuscular routes. Although the oral
`route is preferred, situations exist in which the parenteral
`route is indicated. This article will review the use of paren(cid:173)
`teral iron therapy, including guidelines for dose and admin(cid:173)
`istration, adverse effects, and its use in parenteral nutrition
`solutions.
`
`Indicauons
`Indications for the administration of iron via the paren(cid:173)
`teral route are limited (Table I).1-4 Candidates for paren(cid:173)
`teral
`iron therapy are those patients who have iron-defi(cid:173)
`ciency anemia associated with the inability either to
`adequately absorb or tolerate the oral intake of iron. Non(cid:173)
`compliance with oral iron dosage regimens may also be an
`indication for parenteral iron therapy.
`In addition, there are less obvious conditions that war(cid:173)
`rant parenteral iron therapy. Hemodialysis, which chron(cid:173)
`ically results in significant blood loss, may necessitate the
`use of parenteral iron therapy to restore the hemoglobin
`level. A high intake of antacids or other substances that bind
`to iron and inhibit its absorption may also warrant the use of
`
`parenteral iron." Another indication for parenteral iron
`may be in the patient with significant blood loss who
`refuses blood transfusions and in whom oral iron adminis(cid:173)
`tration is not possible. S
`
`Product Information
`
`Iron dextran injection is commercially available as a ster(cid:173)
`ile solution of iron dextran complex containing 5% iron and
`20% dextran. It contains 50 mg/mL of elemental iron, most
`of which is present in the ferric state. Iron dextran is a
`stable, clear brown solution available in 2- and 5-mL
`ampuls and a lO-mL multiple-dose vial. Because of its
`phenol content, the multiple-dose vial should only be used
`for intramuscular administration.s In the blood, iron dex(cid:173)
`tran is a highly stable complex from which elemental iron is
`slowly released to the carrier protein, transferrin.
`
`Intravenous vs. Intramuscular Route
`
`Once it is decided to replace the iron stores parenterally,
`it must be determined whether to give the iron via the
`intramuscular or intravenous route. Iron dextran was orig(cid:173)
`inally intended for im use; however, there are several disad(cid:173)
`vantages to giving it by small, repetitive im doses. The
`dose that can be administered im is limited to 2 mL (100
`mg) per injection. Therefore, up to 20 injections may be
`needed for a single course of therapy." Not uncommonly,
`patients experience considerable discomfort secondary to
`the multiple injections. Multiple im injections may also be
`a problem in the malnourished patient with limited muscle
`mass. Other risks include bleeding, staining of the skin,
`formation of sterile abscesses, tissue necrosis or atrophy,
`and sarcoma formation.?" The Z-track technique of im
`injection, in which the subcutaneous tissue over the injec(cid:173)
`tion site is firmly pushed aside before inserting the needle,
`may minimize skin staining.
`In view of the numerous problems associated with im
`administration, the iv route is generally preferred whenever
`possible. Methods of iv administration include multiple
`slow injections of 2 mL (100 mg) of the undiluted solution
`or as an infusion of a diluted preparation, referred to as total
`dose infusion. Table 2 compares the three methods of iron
`dextran administration.
`
`VANESSA J. KUMPF, Pharm.D.. is a Clinical Pharmacist, Nutritional Support,
`Department of Pharmacy, Christ Hospital and Medical Center, 4440 W. 95th St., Oak
`Lawn. IL 60453; and EILEEN G. HOLLAND, Pharm.D., is a Clinical Pharmacy
`Resident-Fellow. Department of Family Medicine, University of Georgia and Medical
`College of Georgia. Reprints: Vanessa J. Kumpf, Pharm.D.
`
`Total Dose Infusion
`
`Although the use of total dose infusion (TDI) to adminis(cid:173)
`ter iron dextran was first introduced in 1963 and is fre-
`
`162
`
`• D1CP. The Annals of Pharmacotherapy
`
`•
`
`1990 February, Volume 24
`
`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1054 - Page 1
`
`

`

`quently used in clinical practice today, it is not currently a
`method approved by the Food and Drug Administration for
`giving iron dextran. Initial reports on the use of this tech(cid:173)
`nique to administer iron dextran were encouraging. 10,11
`However, a study published in 1965 by Clay et al. reported
`seven severe reactions following the iv infusion of iron
`dextran in 150 pregnant or postnatal patients. Severe reac(cid:173)
`tions were identified as those requiring resuscitative treat(cid:173)
`ment. In all seven cases the reaction occurred within
`minutes of starting the infusion, the women were in the
`third trimester of pregnancy, and all recovered from the
`incident with no ill effects. Although no cause to explain
`this unexpectedly high incidence of reactions was identi(cid:173)
`fied, the authors felt this form of treatment could no longer
`be justified. U Numerous letters to the editor followed the
`publication of the study questioning the results. U-1S Rea(cid:173)
`sons attempting to explain why the results of this study
`differed from the experiences of others included: (I) possi(cid:173)
`ble differences in technique; (2) the group of patients stud(cid:173)
`ied; (3) underlying folic acid deficiency which may have
`been present resulting in enhanced susceptibility to a reac(cid:173)
`tion; and (4) the use of dextrose 5% injection as the diluent
`instead of NaCI 0.9%.
`Subsequent studies have been conducted to support the
`safety and efficacy of the TDI technique of iron dextran
`administration.V'P-" Halpin et al. studied six children
`with inflammatory bowel disease and iron deficiency ane(cid:173)
`mia. The children received a single dose of iron dextran
`275-840 mg in 200 mL of NaCI 0.9% over two hours. All
`patients demonstrated a satisfactory hemoglobin response
`(average increase in hemoglobin was 3.5 g/dl.) with no
`observed adverse reactions."
`Benito and Guerrero compared the response of a single
`iv infusion to multiple im injections of iron dextran in 27
`malnourished children with iron-deficiency anemia. Eigh(cid:173)
`teen children received a single iv infusion of iron dextran
`and the remaining nine received multiple im injections on a
`daily or every-other-day basis until
`the entire calculated
`dose was administered. Periodic follow-up studies were
`performed in nearly all of the children for three months. A
`rise in mean hemoglobin and hematocrit values was noted
`in each treatment group and one child in each group
`developed an urticarial rash. No other adverse reactions
`were noted."
`Auerbach et al. administered a TDI of iron dextran to 87
`patients with anemia to better define the type and frequency
`of adverse reactions and to determine if the rate of infusion
`or premedication influenced the frequency of adverse
`effects. The results demonstrated that there was no dif(cid:173)
`ference in the frequency of adverse effects associated with
`an infusion at a rate of 2 mg/min compared with 6 mg/min.
`Premedication with aspirin, diphenhydramine, or steroids
`
`Table I. Indications for Parenteral Iron Therapy
`
`Conditions interfering with absorption of oral iron, e.g.:
`short-bowel syndrome
`subtotal gastrectomy
`malabsorption syndrome
`chronic bowel obstruction
`inflammatory bowel disease
`protein calorie malnutrition
`high intake of antacids
`Hemodialysis
`Poor compliance with oral iron regimen
`
`FDA = Foodand Drug Administration; TOI = total dose infusion.
`
`DICP, The Annals of Pharmacotherapy
`
`•
`
`1990 February, Volume 24
`
`•
`
`163
`
`did not appear to influence the frequency.' The prevailing
`conclusion from available studies is that TDI is a safe,
`efficacious, and convenient method of administering iron
`dextran. In addition, TDI is more cost-effective than multi(cid:173)
`ple injections, requiring less time to prepare and administer
`the drug.
`
`Dosage and Administration
`The amount of iron required to restore the hemoglobin
`concentration to normal and to replenish iron stores is based
`on body weight and the observed hemoglobin value. The
`dose is calculated using the following equation:"
`mg iron = 0.3 x wt x (100 - Hgb x 1(0)
`14.8
`where wt = weight in pounds and Hgb = observed hemo(cid:173)
`globin level in g/dL. This equation assumes a normal mean
`hemoglobin of 14.8 g/dL. For children weighing less than
`13.6 kg a normal mean hemoglobin of 12,0 g/dl. is used in
`place of 14.8 in the above equation."
`To determine the iron replacement dose in patients
`actively bleeding, a different equation is used. Estimated
`iron requirements are based on the assumption that I mL of
`normocytic, normochromic erythrocytes contain I mg of
`
`Table 2. Methods of Iron Dextran Administration
`
`INTERMITIENT
`1M
`
`INTERMfITENT
`tV
`
`TO)
`
`administercalcu-
`lated replacement
`dose over 2-6 h
`
`not to exceed 100
`not to exceed 100
`rng (2 rnl.) per
`mg(2mL)per
`injection
`injection
`not to exceed 100
`not to exceed
`100 rng/d
`mg/d
`(manufacturer
`rate: not to exceed
`recommendations) 50 rug/min
`(manufacturer
`recommendations)
`administer
`undiluted
`
`administer
`undiluted
`
`Dose
`
`Diluent
`
`Test dose
`
`250-1000 mL of
`NaCI0.9%
`injection
`25 mg (0.5 rnl.) im 25 mg (0.5 ml.) iv administer
`approximately25
`observe patient
`observe patient
`mg of diluted
`for at least I h
`for at least Ih
`preparationby iv
`infusion over
`5-10 min
`observe patient for
`at least Ih before
`resumingthe
`infusion
`no
`
`yes
`
`iron dextran
`injectioncontain-
`ing phenol should
`not be used for iv
`injection
`
`the use of dextrose
`5% injection in-
`stead of NaCI
`0.9% as thediluent
`is associatedwith a
`higher incidenceof
`localpainand
`phlebitis
`
`yes
`
`FDA
`approved
`Comments inject deeply into
`the upper outer
`quadrant of the
`buttock
`to minimize skin
`staining:
`(I) use the Z·track
`technique
`(2) use a separate
`needle to withdraw
`drug from
`container
`
`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1054 - Page 2
`
`

`

`elemental iron. The dose of iron replacement secondary to
`blood loss is estimated using the following equation:"
`Iron dextran injection (mL) =
`0.02 X blood loss (mL) x Hct
`where Hct = observed hematocrit expressed as a decimal
`fraction.
`Before any patient receives these large replacement
`doses, it is recommended that a test dose be given to deter(cid:173)
`mine the patient's susceptibility to adverse reactions." A
`25-mg test dose may be delivered im/iv with the undiluted
`solution (0.5 mL) or as an iv infusion of a diluted TDI
`delivered over five to ten minutes. After the test dose is
`given, the patient should be observed closely for at least
`one hour. In the absence of untoward reactions, patients
`receiving a TDI may be given the remaining solution over
`the next two to six hours."
`
`AdverseReactions
`The reported incidence of adverse reactions following
`iron dextran administration is low. In one series of 481 iron
`dextran recipients, 26 percent experienced a reaction, but in
`only 5 percent of these (25 patients) did the reaction limit or
`inhibit ordinary activity," It is important to note that the
`incidence of adverse reactions associated with the im route
`is similar to that with the iv route. 1,4 Complications associ(cid:173)
`ated with the administration of iron dextran can be classi(cid:173)
`fied as mild,
`transient reactions; more severe, systemic
`complications; and anaphylactic reactions.
`Mild and transient reactions such as malaise, flushing,
`fever, myalgia, and arthralgia are the most common and
`generally appear within 24 hours of administration. More
`severe systemic reactions include headache, dizziness,
`hypotension, urticaria, diaphoresis, nausea, vomiting, diar(cid:173)
`rhea, delayed arthralgia, generalized pain, and lymphad(cid:173)
`enopathy. These systemic reactions appear related to the
`dose and rapidity of administration.4,20 The reported over(cid:173)
`all incidence of life-threatening anaphylactic reactions,
`occurring primarily during test-dose administration, is
`0.1-0.6 percent. 4Thus, it is recommended that iv diphen(cid:173)
`hydramine (50 mg), epinephrine (0.3-0.5 mL of 1:1000
`solution), methylprednisolone (100 mg), oxygen, and other
`supportive equipment be available at the patient's bedside
`during the test dose. 1.4 Although the incidence of anaphy(cid:173)
`lactic reactions does not appear to differ significantly
`between the im and iv routes of iron administration, an
`anaphylactic reaction following an im injection may
`require prolonged treatment due to slow absorption from
`the injection site.
`Depending on the route of administration, local reac(cid:173)
`tions may be observed at the injection site. Phlebitis, which
`occurs in a small percentage of patients receiving a TDI of
`iron dextran, may be minimized by diluting the iron dextran
`in NaCI 0.9% rather than dextrose 5%.1,2As previously
`mentioned, the im administration of iron may be associated
`with severe pain, formation of sterile or pyogenic intra(cid:173)
`muscular abscesses, tissue staining due to residual iron and
`melanin deposition, sarcoma formation of the buttock, and
`muscle necrosis with ulceration.v"
`An increased susceptibility to bacterial infections has
`been observed in neonates receiving prophylactic iron dex(cid:173)
`tran." It has been suggested that excessive amounts of
`circulating iron may stimulate growth of bacteria in these
`patients. In a similar manner, an increased risk of infection
`
`may also exist for malnourished patients with low serum
`transferrin concentrations. When these patients are given a
`substantial amount of iron, an excessive level of circulating
`free iron may result. Therefore, a blood transfusion may be
`an option to consider in patients with severe protein mal(cid:173)
`nutrition who require treatment for iron-deficiency ane(cid:173)
`mia.f
`Hepatosplenic siderosis, the accumulation of iron in the
`liver and spleen, has been observed in hemodialysis
`patients receiving long-term intravenous iron dextran
`therapy." These patients may exhibit a paradoxical
`depletion of iron in the bone marrow and only small
`increases in hematocrit values. A lack of equilibrium
`between iron taken up by the reticuloendothelial system
`(primarily liver and spleen) and marrow iron may exist in
`these patients. The result is a lack of accessible iron for
`erythropoiesis. Also contributing to the risk of developing
`hepatosplenic siderosis with parenteral iron dextran is that
`this route bypasses the intestinal mechanism for the regula(cid:173)
`tion of iron absorption coupled with a limited ability of the
`body to excrete excessive amounts of iron. 24
`Individuals with a history of allergies, asthma, or active
`inflammatory disease appear to be highly susceptible to the
`adverse effects of iron dextran. Other high-risk patients are
`those with active rheumatoid arthritis or active systemic
`lupus erythematosus. An 80-90 percent risk of developing
`an adverse reaction has been reported in these patient popu(cid:173)
`lations.' Therefore, extreme caution should be observed
`when administering iron dextran to these groups of patients
`and they should all receive the standard test dose. Pre(cid:173)
`medication with methylprednisolone 100 mg iv is also rec(cid:173)
`ommended."
`
`Additionto Total ParenJeral Nutrition
`Total parenteral nutrition (TPN) solutions have been
`used as a vehicle for the administration of iron dextran in
`both maintenances'-" and therapeutic replacement
`doses.Y Iron is not routinely added to TPN solutions and
`is not a component of current injectable multiple trace-ele(cid:173)
`ment preparations. Although protein hydrolysate solution
`contained an amount of iron that appeared to meet daily
`requirements, its use has been replaced with synthetic
`amino acid solutions that contain only negligible amounts
`of iron. 26,:27 Iron supplementation is not required during
`short-term therapy in patients without existing iron defi(cid:173)
`ciency. However, the use of low-dose daily or periodic iron
`supplementation via TPN solutions in patients receiving
`long-term therapy (e.g., two to three months or longer) has
`become common practice to meet estimated requirements.
`Norton et al. prospectively evaluated varying dosages of
`iron dextran (0-25 mg/d) added to TPN solutions in 42
`patients requiring at least 20 days of TPN. Based on serum
`iron concentration response a dose of 12.5 mg/d was deter(cid:173)
`mined most appropriate. However, the addition of iron did
`not affect hemoglobin levels, reticulocyte counts, transfu(cid:173)
`sion requirements, or red blood cell indices. In addition, it
`is unknown whether the increase in measured serum iron
`was transferrin-bound or iron-dextran-bound." Although
`this study failed to document a clear benefit to the use of
`low-dose iron supplementation in these patients, there was
`no evidence of risk associated with its use. No adverse reac(cid:173)
`tions were observed and the incidence of sepsis was not
`increased with increasing doses of iron, based on study cri-
`
`164
`
`• DICP, The Annals of Pharmacotherapy
`
`•
`
`1990 February, Volume 24
`
`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1054 - Page 3
`
`

`

`teria. In fact, no allergic or systemic reactions have been
`reported to date in any patients receiving low-dose iron
`dextran diluted in TPN solutions.
`In opposition to the routine practice of parenteral iron
`administration in the long-term TPN patient is a current
`report addressing trace-element metabolism in adults on
`TPN, including long-term home TPN. The report was pre(cid:173)
`pared at the request of the Committee on Clinical Issues in
`Health and Disease of the American Society of Clinical
`Nutrition. It recommends limiting the administration of
`parenteral iron to those TPN patients with well-docu(cid:173)
`mented iron deficiency and established intolerance or
`inability to absorb oral iron." The recommendation was
`based on the potential for the accumulation of iron in the
`liver and spleen and resulting organ damage, which has
`been observed in hemodialysis patients given parenteral
`iron routinely." It was also based on the theoretical risk of
`infection associated with parenteral iron administration, as
`previously discussed. The report does recognize, however,
`the difficulty in diagnosing iron deficiency in malnourished
`patients on TPN therapy.
`If the diagnosis of iron deficiency is determined, the use
`of TPN solutions as a vehicle for the administration of an
`iron replacement dose may be considered. The addition of
`repletion doses of iron to TPN solutions was clinically eval(cid:173)
`uated in eight patients with moderate-to-severe anemia who
`refused blood transfusions. Total doses of iron dextran
`ranged from 1.6 to 7 g, with a maximum concentration of
`500 mg/L. In the six patients with acute blood loss, hemo(cid:173)
`globin levels increased from a mean initial value of 5.0
`g/dL (range 2.6-8.4) to a mean value of 10.6 g/dL (range
`7.5-12.8). Final hemoglobin values were measured within
`a range of 7-21 days after completion of the iron dosage
`regimen. In the two patients with chronic anemia, hemo(cid:173)
`globin levels increased from an initial mean value of 3.8
`g/dL to a mean of 10.6 g/dL over a mean treatment period of
`121 days. No adverse reactions were observed in any
`patients. The authors concluded that replacement doses of
`iron dextran via TPN solutions can stimulate hematopoiesis
`and allow rapid and safe repletion of the red blood cell
`mass." From a compatibility and stability standpoint, the
`high concentration of iron dextran (500 mg/L of TPN) used
`in this study has not been evaluated.
`No physiochemical evidence of instability or incom(cid:173)
`patibility is apparent when iron dextran is added to TPN
`solution (lOO mg/L) and stored at room temperature for 18
`hours." Longer periods of storage or higher concentra(cid:173)
`tions in conventional TPN solutions have not been evalu(cid:173)
`ated. A single study evaluating the stability of iron dextran
`in a total nutrient admixture tested a concentration of 50
`mgIL stored at4 °C for 14days. By day 14, light microscopy
`revealed that the lipid particles in the admixture were trans(cid:173)
`formed from a normal spherical shape to an elongated
`shape. The authors recommend a 24-hour room tempera(cid:173)
`ture expiration date when iron dextran is added to a total
`nutrient admixture. 30
`
`Summary
`Therapy with parenteral iron dextran is limited to pa(cid:173)
`tients with documented iron deficiency anemia associated
`with conditions which preclude the use of oral iron therapy.
`Currently, the only FDA-approved method of administer(cid:173)
`ing iron dextran is via multiple intramuscular or intravenous
`
`Parenteral/ron
`
`injections of the undiluted solution. However, in many
`patients it may be more advantageous to provide the calcu(cid:173)
`lated replacement dose either via a total dose infusion or as
`an addition to parenteral nutrition. Regardless of the
`method of administration, patients should first receive a test
`dose of iron dextran to determine susceptibility to an ana(cid:173)
`phylactic reaction.e>
`
`References
`I. FREED N. Intravenous iron replacement: indications and safety. J Am
`OsteopathAssoc 1982;82:115-8.
`2. REED MD, BEKI'INO JS, HALPIN Te. Use of intravenous iron dextran
`injectioninchildrenreceivingtotaI parenteralnutrition.AmJ DisChild
`1981;135:829-31.
`3. AUERBACH M, WIlT D. TOLER W, AERSTEIN M, LERNER RG, BAL(cid:173)
`LARD H. Clinical use of the total dose intravenous infusion of iron
`dextran. J Lab Clin Med 1988;//1:566-70.
`4. HAMSTRA RD.BLO:K MH, SCHOCKET AL. Intravenous iron dextran in
`clinical medicine. MMA 1980;243:1726-31.
`5. DUDRICK SJ, O'OONNELLJJ, RALEIGH DP, MATHENY RG, UNKEL SP.
`Rapid restoration of red blood cell mass in severely anemic surgical
`patients who refuse transfusion. Arch Surg 1985;120:721-7.
`6. MCEVOY GK, ed. American hospitalfonnulary service drug infonnation
`88. Bethesda, MD: American Society of Hospital Pharmacists,
`1989:694-6.
`7. BENITO RP,GUERREROrc. Responseto a singleintravenousdose versus
`multiple intramuscularadministration of iron-dextrancomplex:a com(cid:173)
`parative study. Curr Ther Res 1973;/5:373-82.
`8. GREENBERG G. Sarcoma after intramuscular iron injection. Br Med J
`1976;/:1508-9.
`9. FULLER JD. MCRORIE Tl. Necrotic bilateral buttocks ulcerationsoccur(cid:173)
`ring after multiple intramuscular iron dextran injections. Arch Der(cid:173)
`matoI1988;124:1722-3.
`10. BASU SK. Rapid administrationof irondextran in late pregnancy. Lancet
`1963;/:1430.
`II. LANE RS. Intravenous infusion of iron-dextran complex for iron-defi(cid:173)
`ciency anemia. Lancet 1964;/:852-4.
`12. CLAY B. ROSENBERG B, SAMPSON N. SAMUELS SI. Reactions to total
`dose intravenousinfusion of iron dextran (Imferon). Br Med J 1965;
`1:29-31.
`13. GOLDTHORP Wo, SPENCER D, DAWSON DW. Reactions to intravenous
`iron dextran (letter). Br Med J 1965;1:316.
`14. LANE RS.SCOIT JM. Reactions to intravenousiron dextran (letter). Br
`Med J 1965;1:449.
`15. MANSON tw. Reactions to intravenous iron dextran (letter). Br Med J
`1965;1:794.
`16. VARDE KN. Treatment of 300 cases of iron deficiency of pregnancy by
`total dose infusion of iron-dextran complex. J Obstet Gynaecol Br
`Commonw 1964;71:919-22.
`17. HALPIN rc, BERTINO JS, ROTHSTEIN Fe, KURCYZNSKI EM, REEDMD.
`Iron-deficiency anemiain childhoodinflammatoryboweldisease:treat(cid:173)
`ment with intravenousiron-dextran.JPEN 1982;6:9-11.
`18. HANSON DB, HENDELES L. Guide to totaldose intravenousirondextran.
`Am J Hosp Pharm 1974;3/:592-5.
`19. BOLINGER AM. KORMAN NR. Iron deficiency anemia. In: Young LY,
`Koda-KimbleMA. eds. Appliedtherapeutics:theclinicaluseof drugs.
`Vancouver. WA: Applied Therapeutics. 1988:1052-60.
`20. POIITER KA,BLACKBURN GL, BISTRIAN BR. Safety of iron dextran in
`totaI parenteralnutrition:a case report. JAm CollNutr 1988;7:107-10.
`21. BECROFT DMO, DIX MR, FARMER K. Intramuscular iron-dextran and
`susceptibilityof neonates to bacterial infections.Arch Dis Child 1977;
`52:778-81.
`22. BOTHE A. BENarn P,BIS1RIAN BR, BLACKBURN GL. Use of iron with
`total parenteral nutrition (letter). N Engl J Med 1975;293:1133.
`23. AU M, FAYEMI AD, RIGOLOSI R, et al. Hemosiderosis in hemodialysis
`patients: an autopsy study of 50 cases. MMA 1980;244:343-5.
`24. SOLOMONS MW. Iron. In: BaurngartnerTG. ed. Clinicalguide to paren(cid:173)
`teral micronutrition.Melrose Park, IL: EducationalPublications,Ltd.,
`1984:103-14.
`25. NORTON JA, PETERSML, WESLEY R. MAHER MM, BRENNAN MF. Iron
`supplementation of total parenteral nutrition: a prospective study.
`JPEN 1983;7:457-61.
`
`DlCP, The Annals of Pharmacotherapy
`
`•
`
`1990 February, Volume 24
`
`•
`
`165
`
`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1054 - Page 4
`
`

`

`26. SAYERS MH. JOHNSON DK. SCHUMANN LA.et aI. Supplementation of
`total parenteral nutrition solutions with ferrous citrate. JPEN 1983;
`7:117-20.
`27. PHILLIPS GD. GARNYS VP. Trace element balance in adults receiving
`parenteral nutrition: preliminary data. J PEN 1981;5: 11-4.
`28. FLEMING CR.Trace element metabolism in adult patients requiring total
`parenteral nutrition. Am J Clin Nutr 1989;49:573-9.
`29. WAN KK. TSALLAS G. Dilute iron dextran formulation for addition to
`parenteral nutrient solutions. Am J Hosp Pharm 1980;37:206-10.
`30. MCCORMICK DC. KNUTSEN CV. WELLS PA. KAMINSKI MY. Physical
`stability of a tri-substrate admixture. Nutr Support Serv 1987;
`7:18,27-8.
`
`EXTRACTO
`EI tratamiento con hierro parenteral esta indicado en pacientes con
`anemia por deficiencia de hierro en los cuales la administraci6n
`oral de hierro esta impedida debido a problemas de absorci6n 0
`intolerancia a este medicamento. Las dosis de reemplazo requeridas
`para lIenar los depositos de hierro se basan en el peso corporal y en
`los valores de hemoglobina obtenidos. En este articulo se revisan
`los rnetodos de administraci6n del complejo de hierro dextrano,
`inc1uyendo su administraci6n por via intramuscular, intravenosa en
`forma de bolo 0 de infusion, y como aditivo de las soluciones
`
`parenterales. La incidencia general de reacciones adversas es baja,
`pero se recomienda administrar una dosis de prueba seguida de la
`observaci6n cercana del paciente, debido a la posibilidad de
`desarrollo de una reacci6n anafilactica.
`
`ENCARNACION C. SUAREZ
`
`RESUME
`L'administration du fer par voie parenterale est reservee aux
`malades avec anernie ferriprive ne pouvant ingerer ou absorber des
`quantites suffisantes de fer par voie orale. La quantite totale de fer
`requise pour reconstituer les reserves medullaires est basee sur Ie
`poids du malade et sur Ie degre d'anernie determine par la valeur de
`I'hernoglobine. Les methodes d'administration du fer dextran
`inc1uentl'injection intramusculaire et intraveineuse du produit non(cid:173)
`dilue, I'infusion intraveineuse de la preparation diluee, et I'ajout du
`fer dextran dans les solutions d'alimentation parenterale.
`L'incidence des reactions secondaires associees a I'administration
`parenterale du fer est faible. Cependant, dO a la possibilite de choc
`anaphylactique, il est recornmande d'administrer une dose-test de
`25 mg suivie d'une observation continue du malade pour une
`periode d'au moins une heure avantl'injection de la dose
`therapeutique,
`
`MICHELLE DEPOT
`
`SVCHOTROPIC
`
`RUG
`
`Excellent Reviews of the Fifth Edition:
`from Clinical Pharmacy, 1988
`I would recommend that the Psychotropic Drug Handbook
`be Included In drug Information libraries. The handbook Is
`very InexpensIve, and I have yet to see another that fulfills
`this book's purpose.
`
`Peter G. Dorson, Pharm.D.
`
`from OnContinuing Practice, 1988
`The Psychotropic Drug Handbook Is a concise, well·organ.
`Ized, easily readable and understood text •.. of use to the
`pharmacIst on a hospital ward, as well as In a community
`setting.
`
`Kalyna Bezchtlbnyk·But/er, B.Sc.Phm.
`
`ANDBOOK
`
`Paul J. Perry, Ph.D.
`Bruce Alexander, Pharm.D.
`
`Barry I. Liskow, M.D.
`
`Psychotropic Drug Handbook, 5th Ed., vi + 346 pages , ISBN 0-9606488-5-2
`
`PRICE: $15.00
`
`Send __ copies of PsychotropicDrug Handbook, 5th
`Edition, at $15.00 each postpaid to:
`Name
`Address
`
`_
`
`_
`
`Clty
`
`StatelCountry
`
`_
`
`_
`
`ZIP
`
`please biB O VISA O MC
`O payment enclosed
`O sood prepayment invoice ($3 plus postage wiDbe added lor
`this service)
`SIg.
`_
`Exp. date
`
`~· 1I 1 111 11 1111 111 11
`
`HARVEY WHITNEY BOOKS COMPANY
`P.O. Box 42696, Cincinnati.Ohio 45242 USA
`Telephone 513/793-3555 / FAX 513/793-3600
`
`166 • DICP, The Annals of Pharmacotherapy
`
`e
`
`1990 February, Volume 24
`
`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1054 - Page 5
`
`