NN&I - July 2010
Renal EconomicsSubscribe to our free eNewsletter at www.nephronline.comJuly 2010 Nephrology News & Issues 27 Drug related adverse events reported by 2% of Venofer ® (iron sucrose injection,USP) treated patients are shown by dose group in Table 4. Table 4.Most Common Adverse Events Related to Study Drug Reported in 2% of Patients by Dose Group (Multidose Safety Population) HDD-CKD PDD-CKD Adverse Events 100 mg 300 mg for 2 doses followed by (Preferred Term) (N=231) 400 mg for 1 dose (N=75) %% Subjects with any adverse event 14.7 10.7 Gastrointestinal Disorders Diarrhea NOS* 0.9 2.7 Dysgeusia 0.9 0 Nausea 1.7 1.3 Vascular Disorders Hypotension NOS 5.2 0 *NOS=Not otherwise specified Adverse Events Observed in Hemodialysis Dependent Chronic Kidney Disease (HDD-CKD) Patients Adverse reactions,whether or not related to Venofer ® administration,reported by >5% of treated patients from a total of 231 patients in the 3 pivotal HDD-CKD Studies were as follows:hypotension (39.4%),muscle cramps (29.4%), nausea (14.7%),headache (12.6%),graft complications (9.5%),vomiting (9.1%),dizziness (6.5%),hypertension (6.5%),chest pain (6.1%),and diarrhea (5.2%). In the first post-marketing safety study,665 chronic hemodialysis patients were treated with Venofer ® doses of 100 mg at each dialysis session for up to 10 consecutive dialysis sessions for their iron deficiency or on a weekly basis for 10 weeks for maintenance of iron stores.In this study,72% of the patients received up to 10 doses,27% received between 11-30 doses,and 1% received 40 to 50 doses of Venofer ® .Serious adverse events and drug-related non-serious adverse events were collected.In the second post-marketing safety study,386 hemodialysis patients were exposed to a single dose of Venofer ® (100 mg IV by slow injection over 2 minutes or 200 mg IV by slow injection over 5 minutes).Adverse events reported by > 1% of 1,051 treated patients were:cardiac failure congestive,sepsis NOS and dysgeusia. Adverse Events Observed in Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) Patients In the pivotal study of 121 treated PDD-CKD patients,75 patients were exposed to Venofer ® .Adverse events,whether or not related to Venofer ® reported by 5% of these patients are as follows:diarrhea,peritoneal infection,vomiting, hypertension,pharyngitis,peripheral edema and nausea. In these 75 patients exposed to Venofer ® ,9 patients experienced serious adverse events as follows:peritoneal infection (2 patients) and 1 patient each with cardiopulmonary arrest,myocardial infarction,upper respiratory infection NOS,anemia,gangrene,hypovolemia and tuberculosis.None of these events were considered drug-related.Two Venofer ® patients experienced a moderate hypersensitivity/allergic reaction (rash or swelling/itching) during the study. The only drug related adverse reaction to Venofer ® administration reported by 2% of patients was diarrhea. Three patients in the Venofer ® study group discontinued study treatment due to adverse events (cardiopulmonary arrest,peritonitis and myocardial infarction,hypertension) which were considered to be not drug-related. Hypersensitivity Reactions: See WARNINGS and PRECAUTIONS. In clinical studies,several patients experienced hypersensitivity reactions presenting with wheezing,dyspnea, hypotension,rashes,or pruritus.Serious episodes of hypotension occurred in 2 patients treated with Venofer ® at a dose of 500 mg. The post-marketing spontaneous reporting system includes reports of patients who experienced serious or life-threatening reactions (anaphylactic shock,loss of consciousness or collapse,bronchospasm with dyspnea,or convulsion) associated with Venofer ® administration. One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S.trials in HDD-CKD patients (studies A,B and the two post marketing studies) had prior other intravenous iron therapy and were reported to be intolerant (defined as precluding further use of that iron product).When these patients were treated with Venofer ® there were no occurrences of adverse events that precluded further use of Venofer ® . OVERDOSAGE Dosages of Venofer ® (iron sucrose injection,USP) in excess of iron needs may lead to accumulation of iron in storage sites leading to hemosiderosis.Periodic monitoring of iron parameters such as serum ferritin and transferrin saturation may assist in recognizing iron accumulation.Venofer ® should not be administered to patients with iron overload and should be discontinued when serum ferritin levels equal or exceed established guidelines [1].Particular caution should be exercised to avoid iron overload where anemia unresponsive to treatment has been incorrectly diagnosed as iron deficiency anemia. Symptoms associated with overdosage or infusing Venofer ® too rapidly included hypotension,dyspnea,headache, vomiting,nausea,dizziness,joint aches,paresthesia,abdominal and muscle pain,edema,and cardiovascular collapse. Most symptoms have been successfully treated with IV fluids,hydrocortisone,and/or antihistamines.Infusing the solution as recommended or at a slower rate may also alleviate symptoms. Preclinical Data: Single IV doses of Venofer ® at 150 mg iron/kg in mice (about 3 times the recommended maximum human dose on a body surface area basis) and 100 mg iron/kg in rats (about 8 times the recommended maximum human dose on a body surface area basis) were lethal. The symptoms of acute toxicity were sedation,hypoactivity,pale eyes,and bleeding in the gastrointestinal tract and lungs. DOSAGE AND ADMINISTRATION The dosage of Venofer ® is expressed in terms of mg of elemental iron.Each mL contains 20 mg of elemental iron. Most CKD patients will require a minimum cumulative repletion dose of 1,000 mg of elemental iron,administered over sequential sessions,to achieve a favorable hemoglobin response and to replenish iron stores (ferritin,TSAT). Hemodialysis patients may continue to require therapy with Venofer ® or other intravenous iron preparations at the lowest dose necessary to maintain target levels of hemoglobin,and laboratory parameters of iron storage within acceptable limits. Administration: Venofer ® must only be administered intravenously either by slow injection or by infusion. Recommended Adult Dosage: Hemodialysis Dependent-Chronic Kidney Disease Patients (HDD-CKD): Venofer ® may be administered undiluted as a 100 mg slow intravenous injection over 2 to 5 minutes or as an infusion of 100 mg,diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes per consecutive hemodialysis session for a total cumulative dose of 1,000 mg. Peritoneal Dialysis Dependent-Chronic Kidney Disease Patients (PDD-CKD): Venofer ® is administered as a total cumulative dose of 1,000 mg in 3 divided doses,given by slow intravenous infusion,within a 28 day period:2 infusions of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later.The Venofer ® dose should be diluted in a maximum of 250 mL of 0.9% NaCl. Rx Only REFERENCE: [1] National Kidney Foundation.K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease,2000. Am J Kidney Dis. 37:S182-S238,(suppl 1) 2001. IN534BS 100987-01 Iss.01/09 © 2008 Fresenius Medical Care Venofer ® is manufactured under license from American Regent,Inc.(Shirley,NY) and Vifor (International) Inc., Switzerland. Venofer ® is a trademark of Vifor (International) Inc.used by permission. Manufactured for & Distributed by: Fresenius Medical Care NA Waltham,MA 02451 1-800-323-5188 FVEN0068 RBE Effi NNI DR 3/8/10 12:31 PM Page 3 ment, combined with the unexpended extreme demand, the reimbursement rate or composite rate was held steady to erode with inflation. The saving grace for the industry back in 1990 was erythropoietin. Erythropoietin was revo-lutionary to patients and replaced the risks that could be associated with the previous anemia treatment, blood trans-fusions. It was also financially revolutionary for dialysis pro-viders with a new untested source of revenue. Because the government, as well as other commercial carriers, did not fully understand the treatment value of Amgen's erythropoi -etin, or EPO, a cap was initially used to evaluate the doses in regards to improvement of hemoglobin levels. Once the government fully understood the benefits of erythropoietin, the cap was raised and the average doses for all patients began to rise. That continued unabated until the CHOIR and CREATE studies, released in 2006, scared everyone over the potential side effects of EPO. Warning labels and revised guidelines followed. In many respects, the red flags about high EPO use from these and other clinical trials accom-plished what the government couldn't do: lower doses and ultimately, Medicare payments. While the studies have helped to bring EPO doses down, Medicare still had other costs it needed to bring under con- trol. Extending Medicare as Secondary Payer, or MSP could initially reduce outlays for dialysis by the government from its present level. While the idea has support among provid-ers (more dialysis care under commercial payers), it does not seem to be politically feasible right now (the last attempt at moving from 30 to 42 months failed under pressure from commercial insurance carriers). But even if Medicare could increase the MSP, it would likely yield very little impact on the total expenditures for dialysis, given that the bulk of the baby boomers have yet to retire and will gradually add to the Program's cost. Other than simply eroding the composite rate through inflation, the only other alternative is to change from a combined partial bundle/fee-for-service system to a dialysis treatment bundle. Will this be the financial windfall the gov-ernment is hoping for? Even if the bundle is held steady, the total number of patients will continue to increase, leading to higher expenditures. Capping individual treatment costs will help, but the program will still expand. It is difficult to ascertain what the real goal of the govern -ment is with this significant policy change. Doses of EPO have already decreased regardless of the upcoming bundle. In a March 2010 report to Congress on assessing the poten-tial impact of the bundle, the General Accounting Office is clear in its focus on erythropoietin and dose and thus, the reasoning behind Medicare's policy change in reimburse -ment structure. The research quality of the report is relative- ly light with limited citations, primarily from previous GAO reports and the reliance on 73 clinicians for other insight. RenalEconomics_13.indd 27 6/16/10 6:43:24 PM
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