HIGH RATE OF SUCCESS IN AN NIH-SPONSORED STUDY

of hypertensive patients- the highest

83% withpercentageNORVASC#{174}- remained(amlodipineon initialbesylate)therapy after 4 years; nearly all patients were on the 5-mg starting dose’

LOW RATE OF DISCONTINUATION

NY J50,oof(n=patients1730) discontinuedin placebo-controlledtherapy duestudiesto adverse effects2

PROVEN SAFETY

No negative inotropic effects at clinical doses in hemodynamic studies2* No clinically significant effect on cardiac conduction or heart rate2

* Similar hemodynamic findings, however, have been observed with agents possessing

significant negative inotropic effects.

5-mg and 10-mg tablets Once-Daily

(amlodipinebesylate)

EFFICACY AND SAFETY THAT’S EASY TO LIVE WITH Brief Summary NORVASC (amtodlpfne besylate) Tablets For Oral Use CONTRAINDICATIONS: NORVASC is conlraindicaled in palients wilh known sensitivity to amlodipine In hypertension WARNINGS: Increased Angina and/or Myocardlal Infarction: Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration and/sr severity of angina or acute myscardiat infarction on starting calcium channel blocker therapy or atthe time of dosage increase The mechanism of this effect has not been elucidated. PRECAUTIONS: General: Since the vasodilation induced by NORVASC is gradual in onset, acute hypvtension has rarely been reported after oral administration of NORVASC. Nonetheless, caution should be evercised when admin- or angina,convenient istering NORVASC as with any other peripheral vasodilator particularly in patients with severe aortic stenosis. Use In Patients wIth CongestIve Heart FaIlure: In general, calcium channel blockers should be used with caution in patients with heart failure. NORVASC (5-10 mg per day) has been studied in a placebo-controlled trial of 1153 patients with NYHA Class Ill or IV heart failure vn stable doses of ACE inhibitor, digoxin. and diuretics. Follow-up was at least 6 months, with a mean of about 14 months. There was no overall adverse effecl on survival or cardiac morbidity/as once-daily dosing defined by life-threatening arrhythmia, acute myscardial infarction, or hospitalization for worsened heart failure). NORVASChas been compared to placebo in four 8-t2 week studies of patients with NYHA Class Il/Ill heart failure, involving a total of 697 patients. In these studies, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or LVEF. Beta-Blocker WIthdrawal: NORVASC is not a beta-blocker and therefore gives no protection against the dangers of abrupt beta-blocker withdrawal, any such withdrawal should be by gradual reduction of the dose of the beta-blocker. #{149}The usual starting dose is 5 mg in hypertension PatIents wIth Hepatic Failure: Since NORVASC is extensively metabolized by the liver and the plasma elimination half- life 1) is 56 hours in patients with impaired hepatic function, caution should be eoercised when administering or angina NORVASCto patients with severe hepatic impairment. Drug InteractIons: In vitro data in human plasma indicate that NORVASC has no effect on the protein binding of drugs tested )digooin, phenytoin, warfarin, and rndsmethacin). Special studies have indicated thatthe co-administration of - In hypertension, small, fragile, or elderly individuals NORVASCwith digosin did not change serum drgooin levels or digoxin renal clearance in normal volunteers; that co- or patients with hepatic insufficiency may be started on administration with cimetidine did not alter the pharmacokinetics of amlodipine; and that co-administration with warfarin did not change the warfarin prothrombin response time. 2.5 mg once daily2 In clinical trials, NORVASC has been safely administered with thiazrde diuretics, beta-blockers, angiotensin converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerin, digooin. warfarin, non-steroidal anti- inflammatory drugs, antibiotics, and oral hypoglycemic drugs. #{149}litration can proceed to 10 mg Drug/Laboratory Teat InteractIons: None known. Carclnogenesls, Mutagenesls, ImpaIrment of Fertllfty: Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of - Most angina patients will require 10 mg carcinogenicity. The highest dose (for mice, similar to, and for rats twice’ the maximum recommended clinical dose of 10 mg on a mg/m2 basis), was close to the maximum tolerated dose for mice but notfor rats Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels. #{149}Can be taken with or without food There was no effecton the fertility of rats treated with amlodipine males for 64 days and females 14 days prior to meting) at doses up to to mg/kg/day 8 times’ the maximum recommended human dose of 10 mg on a mg/m2 basis). Pregnancy Category C: No evidence ofteratogenicity or other embryo/fetal toxicity was found when pregnant rats or #{149}The most common side effects are headache rabbits were treated orally with up to 10 mg/kg amlodipine respectively 8 times* and 23 times the maximum recoin- mended human dose of 10 mg on a mg/m basis) during their respective periods of major organogenesis. However, litter size was significantly decreased by about 50%) and the number of intrauterine deaths was significantly increased about 5-fold) in rats administered 10 mg/kg amlodipine for 14days before mating and throughout mating and and edema gestation Amlodipine has been shown to prolong both the gestation period and the duration of labor in rats atthis dose There are no adequate and well-controlled studies in pregnant women Amlodipine should be used during pregnancy only if the potential benefit luslifies the potential risk to the fetus NursIng Mothers: It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while NORVASC is administered. PedIatrIc Use: Safety and effectiveness of NORVASC in children have not been established. I ADVERSE REACTiONS: NORVASC has been evaluated for safety in mvre than t 1.000 patients in U.S and foreign clinical trials. In general, treatment with NORVASCwas well-tolerated at doses up to 10 mg daily. Most adverse reactions reported during therapy with NORVASC were of mild or moderate severity. In controlled clinical trials directly comparing Utdo} f NORVASC )N =1730) in doses up to tO mg to placebo )N 125O), discontinuation of NORVASC due to adverse reactions was required in only about 1.5% of patients arid was riot significantly different from placebo about t%) The most common side effects are headache and edema The incidence )%) of side effects which occurred in a dose related manner are as follows: edema 1.8% at 2.5 mg, 3.0% at 5.0 mg, and tO.8% at 10.0 mg, compared with 0.6% placebo): JI 3u dizziness 1.1% at 2.5 mg, 3.4% at 5.0 mg, and 3.4% at 10.0 mg, compared with 1.5% placebo): flushing 0.7% at 2.5 mg. 1.4% at 5.0 mg, and 2 6% at 10 0 mg. compared with 0.0% placebo): and palpitation 0.7% at 2.5 mg, t 4% at 5 0 mg, and 4 5% at 10.0 mg, compared with 0.6% placebo). Other adverse experiences which were not clearly dose related butwhrch were reported with an incidence greater c/Ok than t 0% in placebo-controlled clinical trials include the following: headache 7.3%, compared with 7.8% ptacebo); fatigue 4 5%, compared with 2.8% placebv), nausea 2 9%. compared with t.9% placebo): abdominal pain 1.6%, compared with 0.3% placebo); and somnolence 1 4%, compared with 0.6% placebo). For several adverse eoperiences that appear to be drug and dose related, there was a greater incidence in women than men associated with amlodipine treatment as follows edema 5 6% in men, 14 6% in women, compared with a placebo incidence in men of .4% and 5.t% in women): flushing 1.5% in men, 4.5% in women, compared with a placebo incidence of 0.3% in men and 0.9% in women): palpitations 1.4% in men, 3.3% in women, compared with a placebo incidence of 0.9% in men and 0.9% in women): and somnolence 1.3% in men, 1.6% in women, compared with a placebo incidence of 0 8% in men and 0 3% in women). The following events occurred in t% but >0.1% of patients in controlled clinical trials or under conditions of open nce-1Iaily 5-mg and 10-mg tablets trials or marketing experience where a causal relationship is uncertain: they are listed to alert the physician to a possible relationship: cardIovascular: arrhythmia including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, hypotension, peripheral ischemia, syncope, tachycardiu, postural dizziness, postural hypotension: central and perIpheral nervous system: hypoesthesia, paresthesia, tremor, vertigo, gastrointestInal: anorexia, constipation, dyspepsia, dysphagia, diarrhea, flatulence, vomiting, gingival hyperplasia: general: asthexia, back pain, hot flushes, malaise, pain, rigors. weight gain: musculo-skeletat system: arthralgia, arthrosis, muscle cramps,** myalgia: psychIatrIc: sexual dysfunction )male’ and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization: respIratory system: dyspnea.** epistaois, skIn and appendages: prurrtus.’ rash,’ rash erythematous, rash maculopapular: specIal senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus: urInary system: micturition frequency, micturition disorder, nocturia: autonomlc nervous system: dry mouth, sweating increased: metabolIc and nutrItIonal: thirst: hemopoletlc: purpura The following events occurred in O.t% of patients: cardiac failure, pulse irregularity, extrasystoles, skin discoloration, NORVASC#{174}urticaria, skin dryness. alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation. amnesia, gastritis, increased appetite, loose stools, coughing, rhinitis, dysuria, pvlyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia Other reactions occurred sporadically and cannot be distinguished from medications or concurrent disease states (amlodipinebesylate) such as myocardial infarction and angina. NORVASCtherapy has not been associated with clinically significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, serum glucose, totaltriglycerides. total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, creatinine or liver function tests. NORVASC has been used safely in patients with chronic obstructive pulmonary disease, well compensated congestive heart failure, peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles. OVERDOSAGE: Single oral doses of 40 mg/kg and 100 mg/kg in mice and rats, respectively, caused deaths. A single oral dose of 4 mg/kg or higher in dogs caused a marked peripheral vasodilation and hypotension. Oxerdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, eoperience with intentional overdosage of NORVASC is limited. Reports of intentional oxerdosage include a patient who ingested 250 mg and was asymptomatic and was not hospitalized: another 120 mg) was hospitalized, underwent gastric tavage and remained nvrmotensive, the third 105 mg) was hospitalized and had hypotension 90/50 mmHg) which normalized following plasma expansion. A patient who took 70 mg amlodipine and an unknown quantity of benzodiazepine in a suicide attempt, developed shock which was refractory totreatment and died the following day with abnormally high benzodiazepine plasma concentration. A case of accidental drug overdose has been documented in a ig month old male who ingested 30 mg amlodiprne about 2 mg/kg). During the emergency room References presentation, vital signs were stable with no evidence of hypotension, but a heart rate of 180 bpm Ipecac was administered 3 5 hours after ingestion and on subsequent observation overnight) no sequelae were noted 1. Neaton JO, Gnmm RH Jr, Phneas RJ, et al, for the Treatment of Mild Hypertension Study Research Group. It massive overdose should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood Treatment of Mild Hypertension Study: final results. JAMA. 1993;270:713-724. pressure measurements are essential. Should hypotension occur. cardiovascular support including elevation of the 2. Data on file. Pfizer Inc, New York, NY. extremities and the judicious administration offluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors such as phenylephrine), should be considered with attention to circulating volume and urine output. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade As NORVASC is highly protein bound, hemodialysis is not likely to be of benefit * Based on patient weight of 50 kg. These events occurred in less than t% in placebo controlled trials, butthe incidence ofthese side effects was between Labs #{149}NHO #{149}Pratt#{149} 1%and 2% in all multiple dose studies. W U.S. PharmaceuticaIi Group More detailed professional information available on request Revised June 1996 There’s More To EPOGEN#{174}(Epoe alfa) Than Epoetin Alfa.

When you specify EPOGEN#{174}(Epoetin Support Services. Your Amgen Professional alfa), you get more than a product. You also Sales Representative can tell you more about get a comprehensive support system. That’s the ways these programs can satisfy your needs. important, because the depth and quality of There simply is no comparable source of professional support is a significant element professional support. That’s not surprising, in long-term clinical success. because EPOGEN#{174}is a lot more than just a EPOGEN#{174}support encompasses the drug. It’s away of life. Amgen Reimbursement Hotline, the Amgen For more information, please call SAFETY NET#{174}Program, Professional Services, 1-800-77-AMGEN. Professional Education Programs, and Clinical

EPEN Programs available exclusively for dialysis patients and providers. (EPOETINALFA) ©l994Amgen Inc. RECOMBINANT In Adult ialysis Patients...

HELP ERADICATE HEPA Use the only a

4Omcg/m isely

The to Help

RECOMBIVAX HB is contraindicated in the presence of hypersensitivity to yeast or to any component of the vaccine. Patients who develop symptoms suggestive of hypersensitivity after an injection should not receive further injections of the vaccine. RECOMBIVAX HB Dialysis Formulation (40 mcg/mL) is intended only for adult predialysis/dialysis patients. A booster dose or revaccination may be considered if the anti-HBs level is less than 10 mlU/mL 1-.2 months after the third dose. Please read the Brief Summary of the Prescribing Information accompanying this advertisement.

MERCK Copyright © 1997 by Merck & Co., Inc. vaccine avision All rights reserved. 97320713)131 4)-HBV BRIEF SUMMARY Incidence Less Than 1% of Injections BODYASA WHOLE Sweating; achiness; sensation of warmth; lightheadedness; chills; and RECOMBIVAX HB#{174} flushing HEPATITIS B VACCINE (RECOMBINANT) DIGESTIVE SYSTEM Vomiting; abdominal pains/cramps; dyspepsia; and diminished appetite Please read the full Prescribing Information for complete details. RESPIRATORY SYSTEM Rhinitis; influenza; and cough INDICATIONS AND USAGE RECOMBIVAX HB is indicated for vaccination against infection caused by all NERVOUS SYSTEM known subtypes of hepatitis B virus. RECOMBIVAX HB Dialysis Formulation Vertigo/dizziness; and paresthesia is indicated for vaccination of adult predialysis and dialysis patients against INTEGUMENTARY SYSTEM infection caused by all known subtypes of hepatitis B virus. Pruritus; rash (non-specified); angioedema; and urticaria

CONTRAINDICATIONS MUSCULOSKELETAL SYSTEM Arthralgia including monoarticular; myalgia; back pain; neck pain; shoulder pain; Hypersensitivity to yeast or any component of the vaccine. and neck stiffness

WARNINGS HEM/C/LYMPHATIC SYSTEM Patients who develop symptoms suggestive of hypersensitivity after an Lymphadenopathy injection should not receive further injections ofthe vaccine (see CONTRAINDICAT1ONSt PSYCHIATRIC/BEHAVIORAL Because of the long incubation period for hepatitis B, it is possible for Insomnia/disturbed sleep unrecognized infection to be present at the time the vaccine is given. The vaccine may not prevent hepatitis B in such patients. SPECIAL SENSES Earache PRECAUTIONS UROGENITAL SYSTEM General Dysuria As with any percutaneous vaccine, epinephrine should be available for CARDIOVASCULAR SYSTEM immediate use should an anaphylactoid reaction occur. Hypotension Any serious active infection is reason for delaying use of the vaccine except when in the opinion of the physician, withholding the vaccine entails a greater risk. Marketed Experience Caution and appropriate care should be exercised in administering the vaccine The following additional adverse reactions have been reported with use of the to individuals with severely compromised cardiopulmonary status or to others in marketed vaccine. In many instances, the relationship to the vaccine was whom a febrile or systemic reaction could pose a significant risk. unclear. Pregnancy Hypersensitivity Pregnancy Category C: Animal reproduction studies have not been conducted Anaphylaxis and symptoms of immediate hypersensitivity reactions including with the vaccine. It is also not known whether the vaccine can cause fetal harm rash, pruritus, urticaria, edema, angioedema, dyspnea, chest discomfort, bronchial when administered to a pregnant woman or can affect reproduction capacity. The spasm, palpitation, or symptoms consistent with a hypotensive episode have vaccine should be given to a pregnant woman only if clearly needed. been reported within the first few hours after vaccination. An apparent hypersensitivity syndrome (serum-sickness-like) of delayed onset has been reported Nursing Mothers days to weeks after vaccination, including; arthralgia/arthritis (usually transient), feve, It is not known whether the vaccine is excreted in human milk. Because many and dermatologic reactions such as urticaria, erythema multiforme, ecchymoses and drugs are excreted in human milk, caution should be exercised when the vaccine is erythema nodosum (see WARNINGS and PRECAUTiONS). administered to a nursing woman. Digestive System Pediatric Use Elevation of liver enzymes; constipation. RECOMBIVAX HB has been shown to be usually well-tolerated and highly immunogenic in infants and children of all ages. Newborns also respond Nervous System well; maternally transferred antibodies do not interfere with the active immune Guillain-Barr#{233} Syndrome; multiple sclerosis; myelitis including transverse response to the vaccine. See DOSAGE AND ADMINISTRATION in full Prescribing myelitis; peripheral neuropathy including Bell’s Palsy; radiculopathy; herpes Information for recommended pediatric dosage and for recommended dosage for zoster; migraine; muscle weakness; hypesthesia. infants born to HBsAG positive mothers. Integumentary System The safety and effectiveness of RECOMBIVAX HB Dialysis Formulation in chil- Stevens-Johnson Syndrome; petechiae. dren have not been established. Musculoskeletal System Arthritis. ADVERSE REACTIONS Hematologic RECOMBIVAX HB and RECOMBIVAX HB Dialysis Formulation are generally Increased erythrocyte sedimentation rate; thrombocytopenia. well-tolerated. No serious adverse reactions attributable to the vaccine have been reported during the course of clinical trials. No adverse experiences were Immune System reported during clinical trials which could be related to changes in the titers of Lupus-like syndrome. antibodies to yeast. As with any vaccine, there is the possibility that broad use of Psychiatric/Behavioral the vaccine could reveal adverse reactions not observed in clinical trials. Irritability; agitation; somnolence. In a group of studies, 1636 doses of RECOMBIVAX HB were administered to 653 healthy infants and children (up to 10 years of age) who were monitored for 5 days Special Senses after each dose. Injection site reactions (including erythema and swelling) and Optic neuritis; tinnitus; conjunctivitis; visual disturbances. systematic complaints were reported following 8% and 17% of the injections, Cardiovascular System respectively. The most frequently reported systemic adverse reactions Syncope, tachycardia. (>1% injections), in decreasing order of frequency, were irritability, tiredness, fever (>101#{176}Foral equivalent), crying, diarrhea, vomiting, diminished appetite and insomnia. The following adverse reaction has been reported with another Hepatitis B In a group of studies, 3258 doses of RECOMBIVAX HB were administered to Vaccine (Recombinant) but not with RECOMBIVAX HB: keratitis. 1252 healthy adults who were monitored for 5 days after each dose. Injection site and systemic complaints were reported following 17% and 15% of the injections, respectively. The following adverse reactions were reported:

Incidence Equal to or Greater Than 1% of Injections LOCAL REACTION (INJECTION SITE) Injection site reactions consisting principally of soreness, and including pain, ten- derness, pruritus, erythema, ecchymosis, swelling, warmth, and nodule formation. BODYASA WHOLE vat aviDi b The most frequent systemic complaints include fatigue/weakness; headache; 0 riia&co., itic., West Poini PA 19486, USA fever l100#{176}F);and malaise. Syringes of RECOMBIVAX HB are also manufactured by: Evans Medical Ltd. DIGESTIVE SYSTEM Gaskill Road. Speke. Uverpool 24 9GR. England Nausea; and diarrhea RESPIRATORY SYSTEM Issued February 1996 7462214 Pharyngitis; and upper respiratory infection J6254-1296 PRINTED IN U.S.A. CONTAINS 50% RECYCLED MATERIAL#{174} Chromagen Forte Liquid-Iron Gelcaps

I Contains 151 mg of elemental I Reduces the need for and risks iron-the most elemental iron associated with IV iron5 available in an oral hematinic today #{149}Delivers liquid iron to the site of I Supplies the essential amount of optimal absorption for iron for successful Epogen#{174}t enhanced GI tolerability and therapy24 excellent patient compliance

Recommend the most wklelyprescrthed

formulated to meet the needs of those who Q D neediron most. The strength of liquid iron in a soft gelcap

Pleasesee full prescribing information adjacent 10 this ad. ‘Based on a nationwide survey of nephrologists.Data on file, SavageLaboratories. F.pogen lepoelin alfa) is a registeredtrademark of Amgen Inc. © 1997 Savage 9sud on IMSNational PrescriptionAudit, December1996. hypochromic anemia associated with pregnancy, chronic or acute blood loss, dietary restriction, metabolic disease and post-surgical convalescence.

CONTRAINDICATIONS Hemochromatosis and hemosiderosis are contraindications to iron therapy. Folic h 0r acid is contraindicafed in patients with pernicious anemia (see PRECAUTIONS). SIDE EFFECTS Average capsule doses in sensitive individuals or excessive dosage may cause nau- 00 sea, skin rash, vomiting, diarrhea, precordia) pain. or flushing of the face and ex- tremities.

PRECAUTIONS Folic acid should not be prescribed until the diagnosis of pernicious anemia has been eliminated, since it can alleviate the hematologic manifestations, while al- lowing neurological damage to continue undetected.14

DOSAGE AND ADMINISTRATION CHROMAGEN#{174} IPITI Usual adult dose is 1 soft gelatin capsule daily. HOW SUPPLIED SOFT GELATIN CAPSULES Capsules: NDC 0281 -0262-53, Bottle of 100 NDC 0281-0262-56, Bottle of 500

DESCRIPTION CAUTION: Federal law prohibits dispensing without prescription. CONTENTS: Each brown soft ge)atin capsu)e contains: ferrous fumarate USP, 460 BIBLIOGRAPHY mg (151 mg e)ementa) iron), ascorbic acid USP. 60 mg, fo)ic acid USP. 1 mg, 1Berk, MS. and Novich, MA.: ‘Treatment of Iron Deficiency Anemia With Ferrous cyanocoba)amin USP, 10 mcg. Fumarate,” Am. J. Obst. & Gynec., 203-206, 1962. 2Shapleigh, J.B., and Mont- DISCUSSION: The amount of e)ementa) iron and the absorption of the iron com- gomery. A.:Am. Pract. & Dig. Treat. 10-461, 1959. 3Brise, H. And Ha))berg, L.: “Ef- ponents of commercia) iron preparations vary wide)y. It is further established that fect of Ascorbic Acid on Iron Absorption,’ Acta. Med. Scand.1 71:376, 51-58, 1962. certain “accessory components’ may be included to enhance absorption and uti- 4New Drugs, p. 309, AMA, Chicago, 1966. #{176}Mazur,A., Green, S. and Carleton, A,: )ization of iron. Chromagen#{174}Forte Capsules are formulated to provide the essential ‘Mechanism of Plasma Iron Incorporation into Hepatic Ferritin,” J. Bio. Chem. 3:595- factors for a complete, versatile hematinic. 603, 1960. #{176}GreenbergS.M., Tucker, A. E.. Mathues, H and J.D.: Iron Absorption and Metabolism, I. Interrelationship of Ascorbic Acid and Vitamin E,” J. Nutrition ACTIONS 63:19-31 , 1957. 7Moore, CV. and Dubach, R. “Observations on the Absorption of HIGH ELEMENTAL IRON CONTENT: Ferrous fumarate, used in Chromagen#{174} Iron from Foods Tagged with Radioiron” Trans. Assoc. Amer. Physic. 64:245, 1951. Forte Capsules. is an organic iron complex which has the highest elemental iron 8Steinkamp, R. Dubach, R. And Moore, CV. : Studies in Iron Transportation and content of any hematinic salt -33%. This compares with 20% for ferrous sulfate Metabolism,’Arch. Int. Med. 95:181, 1955. 9Gorten, M. K. And Bradley. J. E.: “The (heptahydrate) and 13% for ferrous gluconate.12 Chromagen#{174}Forte contains 151 Treatment of Nutritional Anemia in Infancy and Childhood with Oral Iron and Ascor- mg of elemental iron. bic Acid,’ J. Pediatrics, 45:1 , 1954. 10Mazur, A.: “Role of Ascorbic Acid in the In- MORE COMPLETE ABSORPTION: It has been repeatedly shown that ascorbic corporation of Plasma Iron into Ferritin,” Ann. N.Y. Acad. Sci, 92:223-229, 1961. acid, when given in sufficient amounts. can increase the absorption of ferrous iron 11Cox, E.V. et a).: “The Anemia of Scurvy,’ Amer. J. Med. 42:220-227, 1967. from the gastrointestinal 6 7 8 9 The absorption-promoting effect is mainly 12McEvoy, G.K., Ed.: AHFS Drug Information, p. 2667-2669, Am. Soc. Hosp. due to the reducing action of ascorbic acid within the gastrointestinal lumen, which Pharm., Bethesda, 1996. 13Berenbaum, MC. et a).: Blood, 15:540, 1960. 14Drug helps to prevent or delay the formation of insoluble or less dissociated ferric com- Information for the Health Care Professional, p.1365-1368, U. S. Pharmacopeial pounds. Conven., Rockville, 1995. #{176}FrankenDG, Boers GH, Blom HJ, Trijbels JM. Effect of various regimens of vitamin B6 and folic acid on mild hyerhomocysteinemia in vas- PROMOTES MOVEMENT OF PLASMA IRON: Ascorbic acid also plays an impor- cular patients. J Inherit Metab Dis 1994; 17:159-62. 1 Brattstrom L, Israelsson B, tant role in the movement of plasma iron to storage depots in the tissues.#{176}The ac- Norrving B, et a). Impaired homocysteine metabolism in early-onset cerebral and tion, which leads to the transport of plasma iron to ferritin. presumably involves its peripheral occlusive disease - effects of pyridoxine and folic acid treatment. Ather- reducing effect, converting transferrin iron from the ferric to the ferrous state.#{176}There osclerosis 1990: 81: 2004-6. 1Kang S. Wong PWK. Norusis M. Homocysteinemia is also evidence that ascorbic acid improves iron utilization, presumably as a fur- due to folate deficiency. Metabolism 1987: 36: 458-62. 1tAlIen RH, Stabler SP, Say- ther result of its reducing action,6 9 and some evidence that it may have a direct ef- age DG, Lindernbaum J. Diagnosis of cobalamin deficiency. IL usefulness of serum fect upon erythropoiesis. Ascorbic acid is further alleged to enhance the conversion methylmalonic acid and total homocysteine concentrations. AM J Hematol 1990; 34: of folic acid to a more physiologically active form, folinic acid, which would make it 90-98. 19Dekker GA, de Vries JI, Doelitzsch PM, Huijgens PC, von Blomberg BM. even more important in the treatment of anemia since it would aid in the utilization Jakobs, C. van Geijn HP. 1985. Underlying disorder associated with severe early- of dietary folic acid.11 onset preeclampsia. Am. J. Obstet Gynecol. 173: 1042-1048. 20MiIIs JL, McPartlin EXCELLENT ORAL TOLERATION: Ferrous fumarate is used in Chromagen#{174} JM, Kirke PN, Lee YJ, Conley MA, Weir DG, Scott JM. 1995. Homocysteine me- Forte Capsules because it is less likely to cause the gastric disturbances so often tabolism in pregnancies complicated by neural-tube defects. Lancet. 345: 149-151. associated with oral iron therapy. Ferrous tumarate has a low ionization constant 21Steegers-Theunissen AP, Boers GH, Blom HJ, Nijhuis JG, Thomas CM, Borm GF, and high solubility in the entire pH range of the gastrointestinal tract. It does not Eskes TK. 1995. Neural tube defects and elevated homocysteine levels in amniotic precipitate proteins or have the astringency of more ionizable forms of iron, and fluid. Am. J. Obstet Gynecol. 172: 1436-1441 . 22Landgren F. Israelsson B. Lindgren does not interfere with proteolytic or diastatic activities of the digestive system. Be- A, Hultberg B, Andersson A, Brattstrom L. 1995. Plasma homocysteine in acute my- cause of excellent oral toleration, Chromagen#{174}Forte Capsules can usually be ad- ocardial infarction: Homocysteine-lowering effect of folic acid. J Intern Med. 237: ministered between meals when iron absorption is maximal. 381-388. 23Mayer EL, Jacobsen DW, Aobinson K. 1996. Homocysteine and Coro- nary Atherosclerosis. J. Am. CoIl. Cardiol. 27: 517-27. FOLIC ACID SUPPLEMENTATION: The use of supplemental folic acid may be in- dicated in patients with increased requirements for this vitamin, such as iron def i- REFERENCES ciency anemia. Folic acid administration may reduce the risk of neural tube defects 1. Drug Facts and Comparisons . 1993 Facts and Comparisons. St. Louis, Mo; in the developing fetus.’2 Folic acid has also been shown to reduce circulating ho- 208-236. 2. Dunea G. Swagel MA, Bodiwala U, et a), Intradialytic oral iron therapy. mocysteine levels in the blood.56 Folate as 5-methy)tetrahydrofo)ate and B2 as IntJArtifOrgans. 1994;17:261-264. 3. Kirlin LF. Case management of the anemic methylcobalamin are involved in the remethylation reaction of homocysteine to me- patient epoetin alfa-focus on iron supplementation. ANNA Journel. 1993; 20:678- thionine.#{176}Elevated homocysteine plasma levels are associated with increased 681 . 4. Wingard AL, Parker AA, Ismail N. et a). Efficacy of oral iron therapy in pa- risk of preec)ampsia, neural tubb detects, myocardial infarction and artherosc)ero- tients receiving recombinant human erythropoietin. Am J Kidney Dis. 1995:25:433- sis 1923 439. 5. Data on file, Savage Laboratories. TOXICITY: Ferrous fumarate was found to be the least toxic of three popular oral Manufactured for: iron salts, with an oral LD50of 630 mg/kg. In the same report, the LD50 of ferrous v) SAVAGE LABORATORIES’ a division ofAltana Inc. gluconate was reported to be 320 mg/kg and ferrous sulfate 230 mg/kg.1 13 MELVILLE, NEW YORK 11747 INDICATIONS by: R.P. Scherer Corporation. St. Petersburg. Florida 33702 For the treatment of all anemias responsive to oral iron therapy, such as @1 996 Savage Laboratories 1F70259 Al 0/96

CALCIJEX#{174} CALCITRIOL tNJECTION 1 mcg end 2 mcg/mL

BRIEF SUMMARY INDICATIONS AND USAGE Calcijen#{174}(calcitriol inlection) is indicated in the management of hypocalcemia in patients undergoing chronic renal dialysis. It has been shown to significantly reduce elevated parathyroid hormone levels. Reduction of PTH has been shown to result in an improvement in renal osteudystrophy CONTRA INDICA TIONS Catcilen#{174}(caicitriol injection) should not be given to patients with hypercalcemia or evidence of vitamin 0 toxicity. WARNINGS Since calcitriol is the most potent metabolite of vitamin 0 available, vitamin D and its derivatives should be withheld during treatment. A non-aluminum phusphate.binding compound should be used to control serum phosphorus levels in patients undergoing dialysis. Overdosage of any form of vitamin 0 is dangerous Isee also OvERDO5AGE). Progressive hypercalcemia due to overdosage of vitamin 0 and its metabolites may be so severe as to require emergency attention. Chronic hypercalcemia can lead to generalized vascular calcification, nephrocalcinosis and other soft-tissue calcification. announces the formation The serum calcium times phosphate Ca n P1 product should nut be allowed to exceed 70. Radiographic evaluation of suspect anatomical regions may be useful in the early detection of this condition. PRECAUTIONS 1. General Excessive dosage of Calcijen#{174}Icalcitriol injection) induces hypercalcemia and in some instances hypercalciuria; therefore, early in treatment during dosage adjustment, serum calcium and phosphorus should be determined at least twice weekly. Should hypercalcemia develop, the drug should be discontinued of the immediately. Catcijex should be given cautiously to patients on digitalis, because hypercalcemia in such patients may precipitate cardiac arrhythmias. 2. Information for the Patient The patient and his or her parents should be informed about adherence to instructions about diet and calcium supplementation and avoidance of the use of unapproved non-prescription drugs, including magnesium- containing antacids. Patients should also be carefully informed about the symptoms of hypercalcemia see NATIONAL RENAL ADVERSE REACTIONS). 3. Essential Laboratory Tests Serum calcium, phosphorus, magnesium and alkaline phosphatase and 24-hour urinary calcium and phosphorus should be determined periodically. During the initial phase of the medication, serum calcium and phosphorus should be determined more frequently twice weekly). Adynamic bone disease may develop if PTH levels are suppressed to abnormal levels. If biopsy is not being done for other diagnostic) reasons, PTH levels may be used to indicate the rate of bone turnover. If PTH levels CREDENTIALING fall below recommended target range )t.5 to 3 times the upper limit of normal), in patients treated with Calcijex, the Calcijen dose should be reduced or therapy discontinued. Discontinuation of Calcijer therapy may result in rebound effect, therefore, appropriate titration downward to a maintenance dose is recommended. 4. Drug Interactions Magnesium-containing antacid and Ca)cileu should not be used concomitantly, because such use may lead to the development of hypermagnesemia. 5. Carcinogenesis. Mutagenasis. Impairment at Fertility Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Calcijex CENTER )calcitriol injection). There was no evidence of mutagenicity as studied by the Ames Method. No significant effects of calcitriol on fertility were reported using oral calcitriol. 6. Use in Pregnancy: Pregnancy catego C: Calcitriol given orally has been reported to be teratogenic in rabbits when given in doses 4 and 15 times the dose recommended for human use. All t5 fetuses in 3 liners at these doses showed external and skeletal abnormalities. However, none of the a non-profit service for other 23 liners 156 fetuses) showed significant abnorma)ities compared with controls. Teratology studies in rats showed no evidence of teratogenic potential. There are no adequate and well- controlled studies in pregnant women. Calciteo should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. promoting quality, cost-effective 7. Nursing Mothers It is not known whether this drug is eucreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from calcitriol, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the management ofrenal disease. drug to the mother. 0. Pediatric Use Safety and efficacy of Calcijen in pediatric patients have not been established. AD VERSE REACTIONS Adverse effects of Calcijen#{174})calcitriol injection) are, in general, similar to those encountered with excessive vitamin 0 intake. The early and late signs and symptoms of vitamin 0 intoxication associated with hypercalcemia include: 1. Early The NRCC is guided by a Scientific Weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain and metallic taste. 2. Late Advisory Board that includes leaders in Polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis Icalcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated SOOT and SGPT, ectopic calcification, hypertension, cardiac arrhythmias and, rarely, overt psychosis. Occasional mild pain on injection has been observed. all facets of the renal care field. OVEROOSAGE Administration of Calcilex#{174})calcitrio) injection) to patients in excess of their requirements can cause hypercalcemia, hypercalciuria and hyperphosphatemia. High intake of calcium and phosphate concomitant with Through its comprehensive Calcijex nay lead to similar abnormalities. t. Treatment of Hypercatcemia and Overdosage in Patients on Hemodiatysis Genera) treatment of hypercalcemia greater than 1 mg/dL above the upper limit of normal range) consists of credentialing process, the NRCC immediate discontinuation of Calcijeu therapy, institution of a low calcium diet and withdrawal of calcium supplements. Serum calcium levels should be determined daily until normocalcemia ensues. Hypercalcemia usually resolves in two to seven days. When serum calcium levels have returned to within normal limits, Calcijex therapy may be reinstituted at a dose 0.5 mcg less than prior therapy. Serum calcium levels should be obtained promotes measurable improvements at least twice week)y after all dosage changes. Persistent or markedly elevated serum calcium levels may be corrected by dialysis against a calcium-free dialysate. in patient outcomes. 2. Treatment of Accidental Overdosage of Calcitniol Iniectian The treatment of acute accidental overdosage of Calciieu should consist of general supportive measures. Serial serum electrolyte determinations especially calcium), rate of urinary calcium excretion and assessment of electrocardiographic abnormalities due lx hypercalcemia should be obtained. Such monitoring is critical in patients receiving digitalis. Discontinuation uf supplemental calcium and low calcium diet are also indicated in accidental overdosage. Due to the relatively shun duration of the pharmacological action of calcitriol, further measures are probably unnecessary. Should, however, persistent and markedly elevated serum calcium levels occur, there are o variety of therapeutic alternatives which may be considered, depending on the patients’ underlying condition. These include the uue of drugs such as phosphates and corticosteroids as we)) as measures to induce an appropriate forced diuresis. The use of peritoneal dialysis against a calcium-free dialysate has also been reported. HOWSUPPLIED National Renal Credentialing Center Calcijex#{174})calcitriol Injection) 5 supplied in t mL ampuls containing t mcg List No. 1200) and 2 mcg List No. t2tO). Protect from tight. 393 Walnut Street Store at control)ed room temperature 5’ to 30’C 59’ to B6’F). Pasadena, CA 91188 Caution: Federal USA) law pruhibits dispensing without prescription. it2Abbott 997 Reference 06-9656-R8-Rev. Jun., 997 Phone: (626) 405-3277 1 Llach F, Hervas J, Cerezo 5: The importance of dosing intravenous calcitriol in dialysis patients with severe hyperparathyroidism. Am J Kidney Din 26)5):845-05t, 995. 2 DressIer R, Laut J, Lynn R, Ginsberg N: Long-term high dose intravenous calcitriol therapy in end-stage renal disease patients with severe secondary hyperparathyroidism. Clin Nephrol 43)31:324-331, 1995. 3 Cannella 0, Bonuicci E, Rolla 0, Bal)anti P. Moriero E, DeGrandi R, Augeri C, Claudiani F, DiMaix 5: Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol. Kid 1nt46:tt24-t132, 1994. Family of Renal Vitamins

THE STANDARD OF CA.RE IN VITAMIN REPLACEMENT THERAPY FOR RENAL PATIENTS

I renaL failure patients, renal specific vitamin replacement is essen- tiai. The Nephro-Vite#{174} family of renal vitamins is formulated to meet the spe- cial n#{252}cronutrient replacement needs of renal failure patients. NepKro-Vite#{174} provides complete B and C vitamin replacement therapy, with increased amounts of folic acid and B6. It also includes Bi, B2, B12, biotin, pantothemc acid and macrn.

Providing Leadership in the Nutritional and Pharmaceutical Management of Kidney Disease

R&D Laboratories, Inc. 4640 Admiralty Way, Suite 710, Marina del Rey, CA 90292

800/338-9066 . 310/305-8053 #{149}FAX 310/305-8103 E-Mail: [email protected] Internet:www.rndlabs.cornlrndlabs Patient and professional education materials and product samples available on request.

See accompanying prescribing information. __ a

Iniily of Renal Vitamins

THE STANDARD OF CARE IN VITAMIN REPLACEMENT THERAPY FOR RENAL PATIENTS

WRITE NpmoVrraRx DO NOT SUBSTITUTE To AssuiYoui Pirs G RENAL Vimiwirt STANDARD OF CARE.

REIMBURSABLE UI 43 STATES, BY .- ,,- MEDICAID, AND BY MOST PRIVATE INSURANCE PLANS.

PRESCRIBING INFORMATION

Nephro-Vite#{174} Rx INDICATIONS: Nephro-Vite#{174} Rx is a vitamin B complex and C supplement for vitamin deficien- cies.l CAUTION: Federal law prohibits dispensing with- out prescription. Williams &Wil1ns PRECAUTION: Folic acid may partially correct the hematological damage due to vitamin Bl2 deficien- cy of pernicious anemia, while the associated neu- rological damage progresses. WARNING: Folic acid alone is improper therapy in Quick Copies. the treatment of pernicious anemia and other megaloblastic aisemiaa where Vitamin B12 is defi- cient. Keep out ofreach of children. ADVERSE REACTION: Allergic sensitization has been reported following both oral and parenteral administration of folic acid. Tellus today DOSAGE: One tablet daily or as prescribed by physician. For patients on hemodialysis, Nephr- Vite#{174}RXshould be taken afr treatment on dialysis days. HOW SUPPLIED: Round, yellow tablet, film coated. NDC #54391-1002-1. Tablets in plastic bottles of Read ittomorrow 100. A child proof safety cap is standard on each 100 tablet bottle as a safeguard against accidental ingestion by children. Store at controlled room temperature l53OnC (5986vF). The moat recent ou can get copies of any article published in any revision of this labeling is July, 1994. Nephro-Vite#{174}+Fe Williams & Wilkins journal. It’s fast - because INDICATIONS: For any patient needing vitamin and iron supplementation for documented iron we’re the primary source, we can fax an article to deficiency. Suitable for persons with end stage renal disease, certain patients undergoing therapy you within 24 hours of when we receive your with erythropoietin or iron deficiency anemia. CAUTION: Federal law prohibits dispensing with- out prescription. request. It costs less - there are no copyright fees PRECAUTION: Folic acid may partially correct the hematological damage due to vitamin B12 deficien- and the cost of faxing is included in the price. cy of pernicious anemia while the associated neu- rological damage progresses. WARNING: Folic acid is improper therapy in the It’s affordable - look at the table below treatment of pernicious anemia and other mega- loblastic anemias where vitamin B12 is deficient. Williams & Wilkins Quick Copies. Tell us today. Keep out ofreach of children. ADVERSE REACTION: Allergic sensitization has been reported following both oral and parenteral React it tomorrow. administration of folic acid. Iron sensitivity to low doses of iron has been reported and high doses result in iron toxicity which is characterized by: transient bloating, flatulence, constipation, and RATES, PER ARTICLE diarrhea. Ingestion of greater than 400 mg per day of elemental iron can result in nausea and vomiting. DOSAGE: One tablet daily between meals or as 1-5 pages $12 16-20 pages $21 prescribed the attending physician. If more than 100 mg elemental iron per day is required, 6-10 pages $15 21-25 pages $24 prescribe an iron supplement. Do not prescribe more than one Nephro-Vitel#{174}+Fe per day. 11-15 pages $18 26+ pages $30 HOW SUPPLIED: Film coated, oval tablets marked RD23. NDC #5439l-2213-6.Plastic bottles of 120 Additional charges for overnight delivery tablets. A child proof safety cap is standard on each 120 tablet bottle as a safeguard against accidental ingestion by children. Store at controlled room tom- perature, l53OvC (5986vF).The most recent revi- sion of this labeling is January, 1994.

1. Kopple Nutrition, diet and the kidney in Shils J: e ME andYoung VR (eds): Modem Nutrition in Williams & Wilkins Health and Disease. Lea & Febiger 1988, 1230-1263. A WAVERLY COMPANY

Providing Leadership in the Nutritional and Pharmaceutical Fa phone, or mailyour order to.#{149} Management ofKldney Disease I$Iu1 \rilliams & riIkins I Quick Copies

R&D Laboratories, Inc. 351 Camden Street Call 1-800-354-9685 T011 FREE) 4640 AdzniraltyWay, Suite 710, Marina del Roy, CA 90292 800/338-9066 . 310/305-8053 . FAX 310/305-8103 Baltimore,MD 21201-2436 Fax1-410-528-4458 E-Mail: rndlabs©aoLcom Internet: www.rnd1abs.com/rnd1abs DDSAD 56189 ‘nE! S E I. - / !

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Reterences: 1. Eschbach JW, Haley NA, Adsmson JW. New insights into tIre treatment of the anemia of chronic renal failure with erythropoietin. Semin Dial. 1990;3)2):1 12121. 2. Van Wyck DO, Stivelman JC, Ruiz J, Kirlin LF, Katz MA, Ogden DA. Iron otatus in patiento receiving erythropoietin for dialyoio-asoociated anemia. Kidney)nf. 1989;35:712-716. 3. Van Wyck DB. Iron management during recombinant human erythropoieoin therapy. Am I Kidney Dis. 19B9;14)2))supp) 1(:9-13 4. Van Wyck DB. Iron deficiency in patiento with dialysis-associated anemia during erythropoietin replacement therapy: strategies for assessment and management. Semis Nephro). 1989;9)1suppl 2):21’24. 5. Prescribing Information for EPOGEN (epoetin aifa). Amgen Inc., Thousand Oaks, Ca. 6. Daugirdas JT, log TS, eds. Handbook ofDialysis. 2nd ed. Boston, Mass: Little, Brown and Cs; 1994:445-457. 7. Wingard AL, Parker RA, Ismail N, Hakim AM. Efficacy of oral iron therapy in patients receiving recombinant human erythropoietin Am JKidneyDis. 1995;25)3)433-439. 8. Fishbane S. Ungureanu V-D, Maesaka JK, et al. A multicenter study of the safety of intravenous iron deolran )IVFe) in hemodialysis patients. AmlKidneyDis. 1996;27)4):A6.

INFsO (IRON DEXTRAN INJECTION, USP) he valid in patients or chronic renal dialysis who are also receiving iron dextran compleo Although there are significant vasations in body build and weight distribution among males and females, the accompanying table I WANIlI #{149}THE PARENTERAL USE OF COMPLEXES OF IRON ANDCARBOHYDRATESHASRESULTED IN ANAPHYLACT1Cj and formula represent a convenient means for estimating thetotal iron required. This total iron requirement reflects the amount I TYPE REACTIONS. DEAThS ASSOCIATED WITh SUCH ADMINISTRAtiON HAVE BEEN REPORTED. ThEREFORE, INFeD of iron needed to restore hemoglobin concentration to normal or near normal levels plus an additional allowance to provide ade’ I SHOULD BE USED ONLY IN ThOSE PATiENTS IN WHOM THE INDICATIONS HAVE BEEN CLEARLY ESTABLISHED AND quate replenishment of iron stores in must individuals with moderately or severely reduced levels of hemoglobin. It should be

I LABORATORYINVESTiGATIONSCONFIRM ANIRONDEFICIENTSTATENOTAMENABLETOORALIRONTHERAPY. shouldrememberedaim atthatnot irononly deficiencyreplenishmentanemiaof hemoglobinwillnot appearironuntilbut essentiallyiron stores allasironwell.stores have beer depleted Therapy, thus, DESCRIPTION: INFeD (iron deotran inlection, USP( is a dark brown, slightly viscous sterile liquid compleo of ferric hydrooide and Factorscontributing to the formula areshown below. dextran for intravenous or inframuscular use. Each mL contains the equivalent of 50 mg of elementaliron (as an iron deotrar complex), approuimately 0 9% sodium chlonde, mg blood iron = mL blood x g hemoglobin o mg iron in water for inlection Sodium hydrooide and/or hydrochloric acid may havebeen usedto adiust pH The pH of fhe solution is lb body weight lb body weight mL blood g hemoglobin between5.2 and 6.5. a) Blood volume 65 mt/kg of body weight The iron dentran compleo has an average apparent molecular weight of 165,000 b( Normal hemoglobin (males and females) TherapeuticClass.Hematinic over 15 kg 133lbs( 14.8 gJdl CLINICALPHARMACOLOGY:General: After intramuscular inlection, iron deotran is absorbed from the injection site into the is kg (33 Ibs) or less 12.0 g/dl capillaries and the lymphatic system. Circulating iron deotran is removedfrom the plasma by cells of the reticuloendothelial c) Iron content of hemoglobin 0 34% tem, which split the complex into its components of iron and deotran.The iron is immediately bound to the availableprotein me- eties to form hemosiderin or ferritin, the physiological forms of iron, or to a lesser eotent to transferrin This iron which is sublect d( Hemoglobin defici to physiological control replenishes hemoglobin and depleted iron stores e( Weight Deotran, a polyglucose, is either metabolized or eocreted. Negligible amounts of iron are lost via the usnary or alimentary path Based on the above factors, individuals with normal hemoglobin levels will have approoimately 33 mg of blood iron per kilogram ways after administration of iron deotran. of body weight 15 mgllb(. The major portion of intramuscular inlections of iron deotran is absorbed within 72 hours, most of fhe remaining iron is ab- Note: the table and accompanying formula are applicable for dosage determinations only in patients wdh iron deficiency anemia. sorbed over the ensuing 3 to 4 weeks they are not to be used for dosage determinations in patients requiring iron replacement for blood loss. Various studies involving intravenously administered 5tFe iron deotran to iron deficient sublects, some of whom had coeoisting TOTAL INFeO DCflhIID5UC5 FOR HEMOGLOBIN RESTORATION AND IRON STORES REPLACEMENT’ diseases, have yielded halflife values ranging from 5 hours to more than 20 hours The 5-hour value was determined for 59Fe Milliliter Requirementot INFeDBasedOn ObservedHemoglnbin of iron deotran from a study that used laboratory methods to separate the circulating 59Feiron deotran from the transferrinbound PATIENT . - #{176}tFeThe 20hour value reflects a half-life determined by measunng total 5tFe,both circulating and bound If should be under 10 stood that these halflife values do not represent clearance of iron from the body Iron is not easily eliminated from the body and LEANBODY WEIGHT accumulation of iron can be tonic. kg lb guI) (g/dl) gui)) )dl) )g/dl) (dl) (gui)) (gui) INDICATIONS AND USAGE: Intravenous or intramuscular in)ections of iron deotran are indicated for treatment of patients with 5 11 documented iron deficiency in whom oral administration is unsatisfactory or impossible. 10 22 CONTRAINOICAT1ONS: HypersensitiviOy to the product All anemias not associated with iron deficiency 15 33 10 WARNINGS: See BOXED WAANING 20 44 16 15 14 13 12 10 A risk of carcinogenesis may attend the intramuscular inlection of ironcarbohydrate compleoes Such compleoes havebeen 25 55 20 18 17 16 15 14 13 12 found under eoperimental conditions to produce sarcoma when large doses or small doses inlected repeatedly at the same site 30 66 23 22 21 19 18 17 15 14 were given to rats, mice, and rabbits, and possibly in hamsters. 35 77 27 26 24 23 21 20 18 17 The long latent period between the inlection of a potential carcinogen and the appearance of a tumor makes it impossible to mea 40 88 31 29 28 26 24 22 21 19 sure accurately the risk in man. There have, however. been several reports in the literature describing tumors at the injection sic 45 99 35 33 31 29 27 25 23 21 in humans who had previously receivedintramuscular inlections of iron-carbohydrate compleses, 50 110 39 37 35 32 30 28 26 24 Large intravenous doses, such as used with total dose infusions (TDI(, have been associated with an increased incidence of 55 121 43 41 38 36 33 31 28 26 adverse effects. The adverse effects frequently are delayed (1-2 days( reactions typified by one or more of the following symp- 60 132 47 44 42 39 36 34 31 28 toms. arthrslgia, backache, chills, dizziness, moderate to high fever, headache, malaise, myalgia, nausea, and vomding. The 65 143 51 48 45 42 39 36 34 31 onset is usually 24-48 hours after administration and symptoms generally subside within 34 days These symptoms have also 70 154 55 52 49 45 42 39 36 33 been reported following intramuscular injection and generally subside within 3-7 days The etiology of these reactions is not 75 165 59 55 52 49 45 42 39 35 known Thepotential for a delayedreaction must be considered when estimating the risk/benefit o(treatment. 80 176 63 59 55 52 48 45 41 38 The maoimum daily dose should not eoceed2 mL undiluted iron deotrar. 85 187 66 63 59 55 51 48 44 40 This preparation should be used with eotreme care in patients with serious impairment of liver function. 90 198 70 66 62 58 54 50 46 42 It should not be used during the acute phaseof infectious kidney disease 95 209 74 70 66 62 57 53 49 45 Adverse reactions experiencedfollowing administration of INFeOmay eoacerbatecardiovascular complications in patients with 100 220 78 74 69 65 60 56 52 47 pre-eoisting cardiovascular disease 105 231 82 77 73 68 63 59 54 50 PRECAUTIONS: General: Unwarranted therapy with parenteral iron will cause eocess storage of iron with the consequenf possi- 110 242 86 81 76 71 67 62 57 52 bildy of eoogenous hemosiderosis Such iron overload is parficularly apt to occur in patients with hemoglobinopathies and other 115 253 90 85 80 75 70 64 59 54 refractory anemiasthat might be erroneously diagnosed as iron deficiency anemias 120 264 94 88 83 78 73 67 62 57 INFeD should be used wdh caution in individuals with histories of significant allergies and/or asthma Anaphylaxis and other hypersensitivity reactions have been reported after uneventful test doses as well as therapeutic doses of Table values were calculated based on a normal adult hemoglobin of 14.8 g/dl for weights greater than 15 kg (33 Ibs) and a iron deotran injection. Therefore, administration of subsequent test doses during therapy should be considered (See DOSAGE hemoglobin of 12.0 gudI for weights less than or equal to 15 kg (33 lbs(. AND ADMINISTAATION Administration ( The total amount of INFeD in mL required to treat the anemia and replenish iron stores may be approoimated as follows. Epinephrine should be immediately available in the event of acute hypersensitivity reactions (Usual aduO dose: 0.5 mL of a AdultsandCh!Idren over 15kg (33!bs):See DosageTable.Alternatively the total dose may be calculated: 1 1000 solution, by subcutaneous or intramuscular inlection.) Note: Patients using betablocking agents may not respond ade Dose )mL( 0.0442 (Desired Hb . Observed Hb( o LBW + (0.26 o LBW( quately to epinephrine. Isoproterenol or similar beta-agonist agents may be required in these patients. Based on: Desired Hb = the target Hb in gldl. Patients with rheumatoid arthntis may have an acute eoacerbation of joint pain and swelling following the administration of INFeD. Observed Hb = the patient’s current hemoglobin in gidI. Aeports in the literature from counfnes outside the United States (in particular, New Zealand( have suggested that the use of intra LBW = Lean body weight in kg. A patients lean body weight or actual body weight if less than lean body weight) should muscular iron deotran in neonates has been associated with an increased incidence of gram-negative sepsis, primarily due toE. CoIi. utilizti when determining dosage. Inlsrmatlsn FsrPatients:Patientsshould be advised of the potential adverse reactions associated with the use of INFeD. For mates: LBW 50 kg + 2.3 kg for each inch of patient’s fieight over 5 feet Drug/Laboratory Test Interactioes: Large doses of iron deotran (5 mL or more) have been reported to give a brown color to For females: LBW 45.5 kg + 2.3 kg for each inch of patient’s height over 5 feet serum from a blood sample drawn 4 hours after administration To calculate a patient’s weight in kg when lbs are known’ patient’s weight in pounds = weight in kilograms The drug may cause falsely elevated values of serum bilirubin and falsely decreased values of serum calcium 22 Serum iron determinations (especially by colorimetric assays) may not be meaningful for 3 weeks following the administration of ChIIdn 5 - 15kg (11 - 331bs): See Dosage Table iron deotran INFeD should not normally be given in the first four months of life (See PRECAUTIONS. Pediatric Use Serum fernfin peaks approoimatefy 7 to 9 days after an intravenous dose of INFeDand slowly returns to baseline afterabeot 3 weeks. Alternatively the total dose may be calculated’ Eoamination of the bone marrow for iron stores may not be meaningful for prolonged periods following iron deotran therapy Dosa )mL) = 0.0442 (Desired Hb . Observed Hb( o W + (0 26 oW) because residual iron deotran may remain in the reticuloendothelial cells Based on: Desired Hb = the target Hb in g/dl. (Normal Hb for Children 15 kg or less is 12 g./dl.( Bone scans involving 99m Tcdiphosphonate have been reported to show a dense, crescentic area of activity in the buoocks, foI W = Weight in kg lowing the contour of the iliac crest, 1 to 6 days after intramuscular inlecti005 of iron deotrar. To calculate a patient’s weight in kg when lbs are known: patient’s weight in pounds = weight in kilograms Bonescans wdh 9gm Tc-labeled bone seeking agents, in the presence of high serum femhn levels orfollowing iron deotran infusions, 22 have been reportedto show reduchon ofbony uptake, marked renalactivity, and eocessive blood poeland softtissue accumulation. Carclnogenesin,Mutaenesis, Impairment OtFertility: See WAANINGS II. ItOn RoplacemenflorBloodLoss:Someindividuals sustain blood losses on an intermittent or repetitive basis. Such blood Pregnancy: Pregnancy CafegorjC: Iron deotranhas beenshown to be teratogenic and embryocidal in mice, rats, rabbits, dogs, losses may occur penodically in patients with hemorrhagic diatheses(familial telangiectasia;hemophilia; gastrointestinal bleed- and monkeys when given in doses of about 3 times the maximum human dose. ing) and on a repetitive basis from procedures such as renal hemodialysis. No consistent adverse fetal effects were observed in mice, ruts, rabbits, dogs and monkeys at doses of 50 mg iron/hg or less. Iron therapy in these patients should be directed toward replacement of the equivalent amount of iron represented in the blood Fetal and maternal tooicity has been reported in monkeys at a total intravenous dose of 90 mg iron/kg over a 14 day period. loss. The table and formula described under I. Iron OellclencyAnernlaare notapplicable for simple iron replacement values. Similar eftects were observed in mice and rats on administration of a single dose of 125 mg iron/bg Fetal abnormalities in rats Quantitative estimates of the individuars periodic blood loss and hematocnt during the bleeding episode provide a convenient and dogs were observed at doses of 250 mg iron/hg and higher The animals used in these tests were not iron deficient. There methOd for the calculation of the required iron dose are no adequate and well-controlled studies in pregnant women. INFeD should be used during pregnancy only if the potential The formula shown below is based on the approsimation that 1 mL of normocytic, normochromic red cells contains 1 mg of ele- benefit lustifies the potential risk to the fetus mental iron: Placental Transfer Various animal studies and studies in pregnant humans have demonstrated inconclusive results with Aeplacement iron (in mg) = Blood loss (in mL( o hematocrit respect to the placental transfer of iron dextran as iron deotran. It appears that some iron does reach the fetus, but the form in Eoample’ Blood loss of 500 mL with 20% hematocrit which it crosses the placenta is not clear Aeplacement Iron = 500 o 0.20 100 mg Nsrsing Mothers:Caution should be eoercised when INFeD is administered to a nursing woman. Traces of unmetabolized iron INFeD dose = 100 mg 2 mL deotran are escreted in human milk. “il” Pediatric Use: Not recommended for use in infants under 4 months of age (See DOSAGE AND ADMINISTRATION.) AdminIstratIon: The total amount of INFeD required for the treatment of iron deficiency anemia or iron replacement for blood ADVERSEREACTIONS:Severe/Fatal: Anaphylactic reactions have been reported with the use of iron deofran injection, on occa loss is determined from the table or appropriate formula. (See Dosaae I sions these reactions have been fatal. Such reactions, which occur most often within the first several minutes of administration, 1. !ntravanous!nJect!on- PRIDA TO RECEIVING THEIR FIRST lNFeb THEAAPEUTIC DOSE, ALL PATIENTS SHOULD BE GIVEN have been generally characterized by sudden onset of respiratory difticufty and/or cardiovascular collapse. See booed WAAN AN INTRAVENOUS TEST DOSE OF 0.5 mL See PAECAUTIONS: General I THE TEST DOSE SHOULD BE ADMINISTERED AT A INGand PAECAUTIONS’General,pertaining to immediate availability of epinephrine.) GRADUALAATEOVERAT LEAST30 SECONDS.Athough anaphylacticreactions known to occur following INFeDadministration Cardiovaacslar:Chest pain, chest tightness, shock, hypotension, hypertension, tachycardia, flushing, arrhythmias (Flushing are usually evident within a few minutes, or sooner, it is recommended that a period of an hour or longer elapse before the and hypotension may occur from too rapid inlections by the intravenous route.) remainder of the initial therapeutic dose is given. Dermatologic: Urticaria. pruritus, purpura, rash. Individual doses of 2 mL or less may be given on a daily basis until the calculated total amount required has been reached INFeD Gastrointestinal: Abdomisal pain, nausea, vomding, diarrhea is given undiluted at a slow gradual rate not to eoceed 50 mg (1 mL( pen minute. Hematotoglc/Iymphatic: Leucocytosis, lymphadenopathy 2. Intramuscularlnject!on#{149}PAIOA TO RECEIVING THEIR FIRST INFeD THERAPEUTIC DOSE, ALL PATIENTS SHOULD BE Msscsloskeletsl/seft linac: Arthrslgis. arthntis (may represent reactivation in patients with quiescent rheumatoid arthritis - GIVEN AN INTRAMUSCULAR TEST DOSE OF 0.5 mL (See PRECAUTIONS: General.) The test dose should be administered in the See PRECAUTIONS: General), myalgia, backache; sterile abscess, atrophy/fibrosis (intramuscular inlection site). brown skin same recommended test ode and bythe same technique as described in the last paragraph of this section. Although anaphylactic and/or underlying tissue discoloration (staining). soreness or pain at or near intramuscular inlection sites: cellulitis, swelling, reactions known to occur following INFeD administration are usually evident within a few minutes or sooner, it is recommended inflammation, local phlebitis at or near intravenous inlection site that at least an hour or longer elapse before the remainder of the initial therapeutic dose is given. Neurolsgic: Convulsions, seizures, syncope. headache, weakness, unresponsiveness, puresthesia, febrile episodes, chills, dizzi If no adverse reactions are observed, INFeD can be given according to the following schedule until the calculated total amount ness, disorientation, numbness. required has been reached Each day’s dose should ordinarily not eoceed 0 5 mL 25 mg of iron) for infants under 5 kg (1 1 Ibs), Respiratory: Respiratory arrest, dyspnea, bronchospasm 1.0 mL (50 mg of iron) for children uoder it kg (22 Ibs); and 2.0 mL (100 mg of iron) for other patients. Urologic: Hematuria. INFeD should be injected only into the muscle mass of fhe upper outer quadrant of the buoock - neverintothe arm or other Oetayed reactIons: Arthralgia, backache,chills, dizziness, fever, headache, malaise, myalgia, nausea, vomding. (See WARNINGS.) eopssed 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 Miscellaneous:Febrile episodes, sweating, shivering. chills, malaise, aftered taste should be bearing his/herweight on the leg opposite the injection site, or if in bed, he/she should be in the lateralposition with OVEROOSAGE: Ovendosage with iron deotran is unlikely to be associated with any acute manifestations Dosages of iron deotran injection site uppermost To avoid inlection or leakage into the subcutaneous tisnue, a Ztrack technique (displacement of the in eocess of the requirements for restoration of hemoglobin and replenishment of iron stores may lead to hemosiderosis. skin laterally priorto inection( is recommended. Periodic monitoring of serum ferrbn levels may be helpful in recognizing a deleterious progressiveaccumulation of iron re NOTE:Do not mio INFeD with other medications or add to parenteral nutrition solutions for intravenous infusion. suIting from impaired uptake of iron from the reticuloendothelial system in concurrent medical conditions such as chronic renal Parenferaldrug products should be inspected visually for parhculate matter and discoloration pnor to administration, whenever failure, Hodgkin’s disease, and rheumatoid arthritis The LD of iron deotran is not less than 500 mg/kg in the mouse. the solution and container permit. DOSAGE ANDADMINISTRATION:Oral iron should be discontinued prior to adminiotration of INFeD HOW SUPPLIED: INFeD’ Iron Dextran Injection, USP) containing 50 mg of elemental iron per mL, io available in 2 mL single Dosage: dose amber vials (for intramuscular or intravenous use) in cartons of 10 (NDC 03643012-47) I. Iron DeflciencyAnemla: Periodic hematologic determination (hemoglobin and hematocrit) is a simple and accurate technique Store at controlled room temperature 15’ - 30’ C (59’ ‘86’ F) for monitoring hematological response, and should be used as a guide in therapy. It should be recognized that iron storage may CAUTiON: Federal law prohibitsdispensingwithtst prescription. lag behind the appearance of normal blood morphology Serum iron, total iron binding capacity (TIBC( and percent saturation of Literature revised: July1995 transferrin are other important tests for detecting and monitoring the iron deficient state Product No ‘1001-02 695310010364’El IF1O reticulocyte count SCHEINPHARMACEUTiCAL,INC. WI/P SCIIEIN After administrafion of iron deotran compleo. evidence of a therapeutic response can be seen in a few days as an increase in the Afthough serum ferritinis usually a good guide to body iron stores, the correlation of body iron stores and serum ferritin may not Florham Park, NJ 07932 USA p H A e M A C C U n I C A INSTRUCTIONS TO AUTHORS

Send manuscripts to the Editor: Copyright Transfer Include one of the two following statements on copyright C. Craig Tisher, M.D. interests signed by all authors: “In consideration of the Amer- J. Am. Soc. Nephrol. ican Society of Nephrology’s taking action in reviewing and Division of Nephrology editing this submission, the author(s) undersigned hereby Box 100224 transfer(s), assign(s) or otherwise convey(s) all copyright own- 1600 SW Archer Road ership to the ASN in the event this work is published by the University of florida ASN.” Gainesville, Florida 32610 Federal Government: “I was an employee of the United States Federal Government when this work was conducted and The Journal of the American Society of Nephrology will prepared for publication; therefore, it is not protected by the publish original manuscripts judged by peers to be of high Copyright Act and there is no copyright of which the owner- quality and relevant to the broad field of nephrology. 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Journal names should be abbreviated Society of Nephrology will receive reprint order forms with the according to the BIOSIS list of serials. page proofs. Reprint order forms must be returned within 48 hours of receipt. Send Reprint Order forms to: Author Reprint 1. Teng-umnuay P, Verlander JW, Yuan W, Tisher CC, Department, Williams & Wilkins, 35 1 West Camden Street, Madsen KM: Identification of distinct populations of inter- Baltimore, MD 2 1201 -2436. Telephone: 1-800-34 1-2258, Fax: calated cells in the mouse collecting duct. J Am Soc Nephrol 4 10-361-80 16, E-mail: [email protected], Internet: 7:260-274, 1996 http://www.wwilkins.comlperiodicals/author-reprints. 2. May RC, Mitch WE: Pathophysiology of uremia. In: The Disclaimer-The statements and opinions contained in the Kidney, 5th ed., edited by Brenner BM, Philadelphia, WB articles of the JOURNAL OF THE AMERICAN SOCIETY Saunders, 1996, pp 2148-2169 OF NEPHROLOGY are solely those of the individual authors 3. Yoo KH, Norwood VF, Chevalier RL: Regulation of and contributors and not of the American Society of Nephrol- angiotensin II AT1 and AT2 receptors in neonatal unilateral ogy or Williams & Wilkins. The appearance of advertisements ureteral obstruction [Abstract]. J Am Soc Nephrol 6:1035, in the Journal is not a warranty, endorsement or approval of the 1995 products or services advertised or of their safety. The Ameri- . Manuscripts on Electronic Diskettes: Authors must sub- can Society of Nephrology and the Publisher disclaim respon- mit electronic diskettes of the final version of their manu- sibility for any injury to persons or property resulting from any scripts along with the printout of the revised manuscript. ideas or products referred to in the articles or advertisements. coagulase-negative staphylococcus

This bacterium can cost a Iife’5

This Blue catheter can S

The hemodialysis patient population has a high incidence of catheter-related bacteremias.2 Overall, central venous catheter-related nosocomial infections occur at a rate of 3% to I2%, with a I0-20% fatality rate.’ Fortunately, there is a catheter that can help minimize this risk and its associated costs in your hospital.

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t. Coroea ML es aLInfections elated to central venous catheters. Mayo Ctin Proc. 990:65:979-986. 2. Duhlberg PJcc al. Subctavian hemodiafysis catheter infections.American Journal of Kidney Diseases. l986;7(5)421-421. 3. EtiiotTSj. tntravaucuiar-device infections.J Med Microbio. 1988;27;t6l-I67. 4. Maki DG et al Clinical trial ofa novel aotiseptic.coated central venous catheter. Presented at 31st Interscience Conference on AnumicrolaalAgents and Chemotberapy.Chicags.Iltineis. October I, 991. 5. Maid DO. Infections due to infusion thera. In: Bennet JV,Brachman PS. edo. Hospital Infections. Boston, Mass: Linde,Brown and Ce: 1992:849.898.

© I996Arrow International. Inc. Improving outcomes through catheter technology.

DEXFERRUM#{174} (IRON DEXTRAN INJECTION, USP)

WARNtNG C.relnogenesis, Mutageeesl., Impairment 01 Fertility: 5cc WARNINGS. THE PARENTERAL USE OF COMPLEXES OF IRON AND CARBOHYDRATES HAS RESULTED IN Pregnancy: Teratogenic Effects, Pregnancy Category C’ iron deotran has been shown to be teratogenic and ANAPHYLACTIC-TYPE REACTIONS. DEATHS ASSOCIATED WITH SUCH ADMINISTRATION HAVE BEEN embryocidal in mice. rats, rabbits, dogs, and monkeys when given in doses of about 3 times the munimum human dose. REPORTED. THEREFORE. DEXFERRUM SHOULD BE USED ONLY IN ThOSE PATiENTS IN WHOM ThE INDICATIONS HAVE BEEN CLEARLY ESTABLISHED AND LABORATORY INVESTIGATIONS CONFIRM AN IRON No consistent adverse fetal effects were observed in mice, rats, rabbits, dogs and monkeys at doses of 50 mg iron/kg DEFiCIENT STATE NOT AMENABLE TO ORAL IRON ThERAPY. or less. Fetal and maternal toxicity has been reported in monkeys at a total intravenous dose of 90 mg iron/kg over a t4 day period Similar effects were observed in mice and rats on administration of a single dose of 125 mg iron/kg. Fetal DESCRIPTION: DEXFERRUM#{174}IiRON DEXTRAN iNJECTiON, U5P) s a dark brvwn, siightiy vjscous sterile hquid cvmpiex abnormalities in rats and dogs were observed at doses of 250 mg iron/kg and higher The animals used in these tests of ternic oxytydroxide and a iow moiecuiar weight dextran denvative for ntr avenvusu ow. Each mL cvnrains 50 mg were not iron deficient There are no adequate and welicontroiled studies in pregnant women DexFerrum should be eiementai aonasan ron deolrarr compier. 5vdum chionde may have been added for tonicfy. Water for niecttorr q.s pH used during pregnancy only if the potential beneht iustifies the potential risk to the fetus. adiusted to 5 2 ‘6.5 *rth hydrochioric and and, 1 necessa ry. sodjum hydroode Otenie, nonpyrogenc Placental Transfer: Various animal studies and studies in pregnant humans have demonstrated inconclusive results Therapeut.c Ciass. Hemaf;no with respect to the placental transfer of iron deotran as iron deotran. it appears that some iron does reach the fetus, but the form in which it crosses the placenta is not cleat INDICATIONS AND USAGE: DeoFerrum s :ndicafed for treatment of pat:ents with documented ron deficiency fl whom orel administrarion is unsatisfactory or impvssibie. Nursing Mothers: Caution should be exercised when DeoFerrum is administered to a nursing woman. Traces of unmetabolized iron deotran are eocreted in human milk CONTRAINDICATIONS: Hypersens:tivity to the product Au anemias not associated with iron deficiency PedIatric Use: Not recommended for use in infants under 4 months of age 15cc DOSAGE AND ADMINISTRATIONI. WARNINGS: 5cc BOXED WARNING A risk of carcinogenesis may attend the intramuscuiar iniection of iron-carbvhydrate cvmpieoes. 5uch complexes have ADVERSE REACTiONS: SeverelFatat: Anaphylactic reactions have been reported with the use of iron deotran iniection; on occasions these reactions have been fatal Ouch reactions, which occur most often within the first several been found under eoperimentai conditions to produce sarcoma when iarge doses or smaii doses iniected repeatedly at minutes of administration, have been generally characterized by sudden onset of respiratory difficulty and/or the same site were given to rats. mice, and rabbits. and possibly in hamsters. cardiovascular collapse. lOon boxed WARNING and PRECAUTIONO: General, pertaining to immediate aoailability of The long latent period between the niection of a pvtentiai carcinogen and the appearance of a tumor makes it impossible epinephnne I to measure accurately the risk in man There have, however, been several reports in the literature describing tumors at CardIovascular: Chest pain, chest tightness. shock. hypvtension, hypertension, tachycardia, flushing, arrf’iyfhmias. the iniection site in humans who had previously received intramuscular iniectlons of iron-carbohydrate compieoes. IFlushing and hypotension may occur from too rapid iniections by the intravenous route,l Large Intravenous doses, such as used with total dose infusions ITOII. have beenass ociated with anincre ased incidence of adverse effects. The adverse effects frequently are delayed lt’2 days) reactions tyyified by one or more ofthe following Dermelologie: Urticaria, pruritus, puryura. rash symptoms: arthraigia, backache, chills, dizziness. moderate to high fever, headache. malaise, myalgia, nausea, and Gastroinleellnel: Abdominal pain, nausea, vomiting, diarrhea vomiting. The onset is usually 2448 hours after administration and symptoms generally subside within 34 days. The Hemetologle/lymphatic: Leucocytosis. lymphadenopathy etiology of these reactions Is not known. The potential for a delayed reaction must be considered when estimating the risk/benefit of treatment. Musculoekeletel/eoft Clssue: Arthraigia. arthritis Imay represent reactivation in patients with quiescent rheumatoid arthritis ‘See PRECAUTIONS Generall, myalgia. backache, sterile abscess, brown skin and/or underlying tissue The maximum daily dose should not eoceed 2 mL undiluted iron deotran. discoloration lstainingl; celluiitis; swelling: inflammation; local phlebitis at or near intravenous iniection site. This preparation should be used with entrem ecarein patients with serious impairment of liver function Nearologle: Convulsions. seizures, syncope, headache, weakness, unresponsiveness, paresthesia, febrile episodes. it should not be used during the acute phase of infectious kidney disease. chills. dizziness, disorientation, numbness. Adverse reactions experienced following administration of DexFerrum may exacerbate cardiovascular complications in Respiratory: Respiratory arrest, dyspnea. brvnchvspasm. patients with pre’existing cardiovascular disease. Urologie: Hematuria. PRECAUTiONS: G.n.r.I: Unwarranted therapy with parenteral iron will cause access storage of iron with the Delayed reactIons: Arthraigia, backache, chills, dizziness, fever, headache, malaise, myalgia, nausea, vomiting 15cc consequent possibility of exogenous hemosiderosis. Ouch iron overload is particularly apt to occur in patients with WARNINGOI. hemogiobinopatf’iies and other refractory anemias that might be erroneously diagnosed as irvn deficiency anemias. Mleeelleneoue: Febrile episodes. sweating, shivering, chills, malaise, altered taste, DeaFerrum should be used with caution in individuals with histories of significant allergies and/or asthma. DOSAGE AND ADMINISTRATION: Oral iron should be discontinued prior to administration of DeaFerrum. Anaphylaois and other hypersensitivity reactions have been reported after uneventful test doses as well as therapeutic doses of iron deatran injection Therefore, administration of subsequent test doses dunng therapy should be considered. Intravenous Injection PRIOR TO RECEIVING THEIR FIRST DEXFERRUM THERAPEUTIC DOSE, ALL PATIENTS SHOULD BE GIVEN AN‘INTRAVENOUS TEST DOSE OF 0.5 mL. 15cc PRECAUTiONS: General.l THE TEST DOSE 15cc DO5AGE AND ADMiNI5TRATiON: Administration I SHOULD BE ADMINISTERED AT A GRADUAL RATE OVER AT LEAST 5 MINUTES Although anaphylactic reactions Epinephrine should be immediately aoailabie in the everrt of acute hypersensitivity reactions. lUsual adult dose 0.5 mL known to occur following DeoFerrum administrati onareusu ally evident within a few minutes. or sooner. it is of a t 1000 solution. by subcutaneous or intramuscular iniection I Nols: Patients using beta.blocking agents may not recommended that a period of an hour or longer elapse before the remainder of the initial therapeutic dose is given respond adequately to epinepftrine isoproterenol or similar beta’agonist agents may be required in these patients. Individual doses of 2 mL or less may be given on a daily basis until the calculated total amount required has been Patients with rheumatoid arthritis may h aveanacu te eaacerbation of joint pain and swelling following the administration reached. DeeFerrum is given undiluted at a slow gr.duaI rate not to exceed 50 mg It mLl per minute. of DenFerrum If no adverse reactions are observed, DeoFerrum can be given according to the following schedule until the calculated InformatIon For PsII#{149}nts: Patients should be advised of the potential adverse reacti onsass ociated with the use of total amount reqaired has been reached Each day’s dose should ordinarily not exceed 0.5 mLl25 mg of ironl for infants DeeFerrum under 5 kg Itt IbsI, t mL 150 mg of ironl for children under 10 kg 122 IbsI, and 2 mL lion mg of ironl or other patients. Drsg/L..bor.tory use Int#{149}racllons: Large doses of iron dextran 15 mL or morel have been repvrted to give a brown NOTE: Do not mix DeeFerruw with other medications or add to parenteral nutrition solutions for intravenous infusion color to serum from a blood sample drawn 4 hours after administration Parenteral drug products should be inspected oisually for particulate maner and discoloration prior to administration, The drug may cause falsely elevated values of serum bilirubin and falsely decreased calues of serum calcium whenever the solution and container permit. Oerum iron determinations lespecially by colorimetric assaysi may not be meaningful for 3 weeks following the HOW SUPPUED: DeoFerrum#{174}llron Deotran infection, USP) containing 50 mg xl elemental iron per mL A available in 2 mL administration of iron deotran. stngle dose vials Ifor intravenous usel in cartons of tO INDC 05t7-v234-1OI and individually packaged INDC O5t7’O234-tl Oerum ferritin peaks approximately 7 to 9 days after anmtravenvu s dose of DeeFerrum and slowly returns to baseline Store at controlled room temperature 15’ . 3o’C 159’ ‘e6’Fl. after about 3 weeks. CAUTiON: Federel law prohibIts dIspensing wIthout prescrIption. Examination of the bone marrow for iron stores may not be meaningful for prolonged periods following iron deotran therapy because residual iron deotran may remain lv the reticuloendotheiiai cells. This is a bnef summary; see product package insert for full prescribing informative. Bone scans with 99m Tc-labeled bone seeking agenfs. in the presence of high serum terrifin levels or following iron BS0234 deotran infusions, have been reported to show reduction of bony uptake, marked renal activity. and eocessioe blood povi Rev. 2/97 and soft tissue accumulation.

AMERICAN REGENT LABORATORIES, INC. SHIRLEY, NY 11967

BC/BE Nephrologist Tojoin 6 physician group in their growing 100% Nephrol- SCOTF &wim ogy practice. Southern city of25OK. All aspects of Nephrol- ogy. Busy work days but home at a reasonable hour. Full Director benefits, generous time off. Excellent Salary leading to partnership. Reply to: JASN Box #1-9, 351 W. Camden Division of Nephrology

Street-SN, Baltimore, MD 2 1201-2436. , . Scott & White Clinic/Texas A&M i\ Uniersitv Health ‘tciencc Center College Nephrology Join two physicians in a well established, busy, private HEALTH of Medicine is seeking candidates for the SCIENCE position of Director of the Division of group practice affiliated with the areas largest hospital and CENTER Nephrology. Excellent clinical skills, the Medical College Hospital in Toledo, Ohio. Excellent (-o//t’uy’ ‘if,I/e’/iiivie leadership ability, and a commitment to blend of all aspects of nephrology. Position due to growth. teaching are all essential. Special interest in clinical Teaching/research responsibilities included ifdesired. Corn- research would be an asset. Salary and academic petitive compensation package offered by group. Toledo appointment are commensurate with qualifications. Scott located on western shore of Lake Eric in NW Ohio. Wide & White is among the nation’s largest integrated health variety of rural/suburban lifestyle with large variety of care organizations. Temple is a city of 50.000 in Central cultural and recreational activities. Contact Sherri Fishchaber Texas; trees and lakes are abundant, the climate is 800-281-7701. Fax CV 419-824-1770. conducive to outdoor activities and recreational activities Nephrologist are plentiful. Austin, the capital ofTexas and home of the To join three nephrologists in a unique, exclusive renal University of Texas is 65 miles to the south while Baylor practice in the North Central Ohio region. Friendly cornrnu- University is 35 miles to the north. Reply with CV and names of three references to: nity/safe family environment. Large multi-site outpatient chronic hernodialysis and peritoneal dialysis. Active inpa- Mike Nichols tient acute dialysis, 100% consultation nephrology practice Director of Physician Recruitment and transplant follow-up. Excellent salary/benefits leading Scott & White Clinic to early partnership. To start 7/98. Send CV to Business 2401 South 31st Street Manager, Kidney Associates, 120 Sturges Avenue, Temple,TX 76508 Mansfield, OH 44903, Phone: (419) 526-1828. Fax: (419) Scott & White is an equal opportunity employer. For more 26- 1223. information about Scott & White. please visit our internet site at: http://www.sw.org

Nephrologist BC/BE to join our well established, expanding two physician practice in central New York. Affiliated with several dialysis VENOUS AND HEMODIALYSIS units. All aspects of nephrology including acute and chronic dialysis. Partnership and excellent income opportunities. Reply to: JASN Box #1-10, 351 W. Camden Street-5N, Baltimore, MD ACCESS Smiositnvi 21201-2436.

Beautiful Sunny Florida February 3-8, 1997 Top Quality Nephrologist needed for hi-tech expanding practice. Clinically challenging patient population. Partnership opportu- Keystone Resort * Keystone, Colorado nity. Great school system, world-class shopping and year-round Sponsored by Indiana University School of Medicine’s recreational activities. Send Resume in confidence to: David Division of Continuing Medical Education and Hamilton, Healthcare Professions Plus, 15495 Eagle Nest Lane, Department of Radiology Suite 130. Miami Lakes, FL 33014. Phone (305) 556-4699, Fax Scott 0. Trerotola, M.D. (305) 364-0085. Course Dfrector

This course is designed for interventional radiologists, nephrologists, vascular surgeons and other health care professionals engaged in the comprehensive care ofpatients with venous and hemodialysis access.

MONTANA Experts from different disciplines will review and discuss current knowl- edge ofthe following topics: overview ofhemodialysis access (includ- Large multispecialty group, N. Rockies University town, ing physical examination and catheter access). PTA offailing hemodi- serving referral base of 250,000, seeks 2nd BC/BE alysis access, European perspective on hemodialysis access interven- nephrologist to replace retiring physician. Join 18 member Lions, surgical revision of thrombosed hemodialysis access, cost and IM department with all subspecialities represented. outcome analysis for hemodialysis access salvage. oncologist’s per- Practice covers 2 dialysis units, CAVH, CAPD, transplant spective on central venous access, alternative access for infusion and hemodialysis catheters, management of infected access sites, cost and follow-up. Unparalleled recreational opportunities in outcomes in central venous access, venous thrombolysis, permanent liveable small city with excellent schools. Excellent and temporary inferior vena cava filters, and transjugular intrahepatic benefit package, competitive guarantee. Opportunity to portosystematic shunts. teach students/residents from U of W\ Med School. For furtherinformation, call the Indiana University School

Reply: D. Ramsey, Administrator, Western Montana / : ofMedicine Division ofContinuing MedicalEducation at Clinic, P0 Box 7609, Missoula, MT 59807. ,/ (317) 274-8353. THE AMERICAN Socun OF NEPHROLOGY

1200 19th Street, N.W., Suite 300, Washington, D.C. 20036-2412 #{149}202/857-1190

Application for Active and Corresponding Membership

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For office use only:

1F)t notte pntered Chrk Cheek nstme Training in Nephrology (Give inclusive datesfor residences, fellowships, other relevant postgraduate education.) Institution Name and Address Position Preceptor(s) Inclusive Dates

List your five most significant publications.

Describe your clinical experiences as a specialist and consultant in kidney disease and related conditions that would provide basis for qualification of membership.

List other societies to which you belong.

Provide names and addresses of three persons from whom leuers of reference may be requested if needed.

Please return your completed application with the first year’s dues (see below) payable to the ASN in U.S. funds.

______$125-ACTIvE MEMBERSHIP for residents of North or Central America. ______$14O-CoRiisPoNDING MEMBERSHIP for those who meet the qualifications for Active Membership, but are not residents of North or Central America. Corresponding Members will receive all Society mailings and member discounts, but do not have the right to vote or hold office.

If you would like to pay by Visa or MasterCard, please list the cardholder’s name, number and expiration date below:

Visa MasterCard

CARDHOLDER’S NAME (PLEASE PRINT OR TYPE) SIGNATURE

CARD NUMBER EXPIRATION DATE