Pure Red-Cell Aplasia and Epoetin Therapy

Bennett, Charles L.; Luminari, Stefano; Nissenson, Allen R.; Tallman, Martin S.; Klinge, Stephen A.; McWilliams, N.; McKoy, June M.; Kim, Benjamin; Lyons, E. A.; Trifilio, Steve; Raisch, Dennis W.; Evens, Andrew M.; Kuzel, Timothy M.; Schumock, Glen T.; Belknap, Steven M.; Locatelli, Francesco; Rossert, Jérôme; Casadevall, Nicole

doi:10.1056/nejmoa040528

Cited by 389 publications

(248 citation statements)

References 16 publications

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“…Causal relationships were not widely accepted until epidemiologic studies implicating aspirin, erythropoietin, and gadodiamide with these syndromes were published. [5][6][7] These reports appeared 81, 13, and 17 years, respectively, after the implicated drugs had been introduced into practice.…”

Section: Discussionmentioning

confidence: 99%

“…7 Most patients were male, undergoing hemodialysis, and all had CKD. All had received epoetin subcutaneously; 95 % received the epoetin-alfa formulation with polysorbate 80.…”

Section: Pure Red Cell Aplasiamentioning

confidence: 99%

“…53 Exposure-adjusted PRCA incidence rates with subcutaneous administration of this formulation increased in France, England, and Spain between 1998 and 2001 and in Canada until 2002 to 18 cases per 100,000 epoetin alfa with polysorbate 80 treated CKD patients. 7,50 After regulatory advisories warned against disrupting cold chain storage conditions or administering epoetin alfa with polysorbate 80 subcutaneously, and Teflon-coated rubber stoppers were added to prefilled epoetin alfa syringes, PRCA incidence subsequently decreased by 90 % in France, the United Kingdom, and Spain and by 80 % in Canada. 7,53 …”

Section: Pure Red Cell Aplasiamentioning

confidence: 99%

“…7,50 After regulatory advisories warned against disrupting cold chain storage conditions or administering epoetin alfa with polysorbate 80 subcutaneously, and Teflon-coated rubber stoppers were added to prefilled epoetin alfa syringes, PRCA incidence subsequently decreased by 90 % in France, the United Kingdom, and Spain and by 80 % in Canada. 7,53 …”

Section: Pure Red Cell Aplasiamentioning

confidence: 99%

“…[2][3][4] Unexpected associations with pharmaceuticals were published 29,6, and 4 years later, respectively. [4][5][6][7] Overall, 81, 13, and 17 years elapsed between introduction of the implicated drug into practice and identification of the causal relationships with these three unique sADRs. Responses of clinicians, consumers, regulators, and man-ufacturers led to large decreases in new cases and eventual virtual eradication.…”

Section: Introductionmentioning

confidence: 99%

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Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

et al. 2012

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Identification of serious adverse drug reactions (sADRS) associated with commonly used drugs can elude detection for years. Reye’s syndrome (RS), nephrogenic systemic fibrosis (NSF), and pure red cell aplasia (PRCA) among chronic kidney disease (CKD) patients were recognized in 1951, 2000, and 1998, respectively. Reports associating these syndromes with aspirin, gadodiamide, and epoetin, were published 29, 6, and 4 years later, respectively. We obtained primary information from clinicians who identified causes of these sADRs and reviewed factors contributing to delayed identification of these toxicities. Overall, 3,500 aspirin-associated RS cases in the United States, 1,605 gadolinium-associated NSF cases, and 181 epoetin-associated PRCA cases were reported. Delays in FDA regulation of over-the- counter medications and administration of aspirin to children contributed to development of RS. For NSF, in 1996, the Danish Medicine Agency approved high-dose gadodiamide administration to chronic kidney disease (CKD) patients undergoing MR scans. Overall, 88 % of Danish NSF cases were from two hospitals and 97 % of United States’ NSF cases were from 60 hospitals. These hospitals frequently administered high-doses of gadodiamide to CKD patients. Another factor was the decision to administer linear chelated contrast agents versus lower risk macrocyclic chelated agents. For PRCA, increased use of subcutaneous epoetin formulations to CKD patients, in part due to convenience and cost-savings considerations, and a European regulatory requirement requiring removal of albumin as a stabilizer, led to toxicity. Overall, 81, 13, and 17 years elapsed between drug introduction into practice and identification of a causal relationship for aspirin, erythropoietin, and gadodiamide, respectively. A substantial decline in new cases of these sADRs occurred within two years of identification of the offending drug. Clinicians should be vigilant for sADRs, even for frequently-prescribed pharmaceuticals, particularly in settings where formulation or regulatory changes have occurred, or when over-the-counter, off-label, or pediatric use is common

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Section: Discussionmentioning

confidence: 99%

“…7 Most patients were male, undergoing hemodialysis, and all had CKD. All had received epoetin subcutaneously; 95 % received the epoetin-alfa formulation with polysorbate 80.…”

Section: Pure Red Cell Aplasiamentioning

confidence: 99%

Section: Pure Red Cell Aplasiamentioning

confidence: 99%

Section: Pure Red Cell Aplasiamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

et al. 2012

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Evaluation of Serious Adverse Drug Reactions

Bennett¹,

Nebeker

Yarnold³

et al. 2007

Arch Intern Med

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Background: The Food and Drug Administration (FDA) and pharmaceutical manufacturers conduct most postmarketing pharmaceutical safety investigations. These efforts are frequently based on data mining of databases. In 1998, investigators initiated the Research on Adverse Drug events And Reports (RADAR) project to investigate reports of serious adverse drug reactions (ADRs) and prospectively obtain information on these cases. We compare safety efforts for evaluating serious ADRs conducted by the FDA and pharmaceutical manufacturers vs the RADAR project.

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Potential Risk of Progressive Multifocal Leukoencephalopathy With Natalizumab Therapy

Stüve¹,

Marra²,

Cravens³

et al. 2007

Arch Neurol

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Pure Red-Cell Aplasia and Epoetin Therapy

Abstract: After the peak incidence of Eprex-associated pure red-cell aplasia was reached in 2001, interventions designed in response to drug-monitoring programs worldwide resulted in a reduction of more than 80 percent in the incidence of pure red-cell aplasia due to Eprex.

Cited by 389 publications

References 16 publications

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

Evaluation of Serious Adverse Drug Reactions

Potential Risk of Progressive Multifocal Leukoencephalopathy With Natalizumab Therapy

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