The increased incidence of pure red cell aplasia with an Eprex formulation in uncoated rubber stopper syringes

Boven, Katia; Stryker, Scott; Knight, John; Thomas, Adrian G; Regenmortel, Marc van; Kemeny, David M.; Power, David; Rossert, Jérôme; Casadevall, Nicole

doi:10.1111/j.1523-1755.2005.00340.x

Cited by 210 publications

(117 citation statements)

References 9 publications

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“…Between 1998 and 2000, nearly 200 cases of epoetin-associated PRCA cases were reported (21). Most cases occurred outside the United States and were attributed to the substitution of Tween in place of human serum albumin as a stabilizer for epoetin (22)(23)(24). The interaction of Tween with the uncoated rubber in prefilled syringes seems to cause leachates.…”

Section: Esa-induced Prcamentioning

confidence: 99%

Anemia of Chronic Kidney Disease

Singh¹

2008

Clinical Journal of the American Society of Nephrology

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Section: Esa-induced Prcamentioning

confidence: 99%

Anemia of Chronic Kidney Disease

Singh¹

2008

Clinical Journal of the American Society of Nephrology

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“…Epidemiologic, chemical, and immunologic data supported the hypothesis that leachates from uncoated rubber syringe stoppers caused increased PRCA incidence associated with epoetin alfa with polysorbate 80. 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.…”

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%

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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“…After these were replaced by Teflon 1 -coated stoppers, the incidence of anti-EPO antibodymediated PRCA decreased to very low rates, again. It has been proposed that the PS-80 released leachates from the rubber stoppers, which acted as adjuvants [120]. An alternative hypothesis suggests that the formation of anti-EPO Abs was induced by micelles loaded with aggregated rhEPO in PS-80 [121].…”

Section: Anti-epo Antibody-mediated Prcamentioning

confidence: 99%

Biosimilar epoetins and other “follow‐on” biologics: Update on the European experiences

Jelkmann¹

2010

American J Hematol

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After the patents of biopharmaceuticals have expired, based on specific regulatory approval pathways copied products (“biosimilars” or “follow‐on biologics”) have been launched in the EU. This article summarizes experiences with hematopoietic medicines, namely the epoetins (two biosimilars traded under five different brand names) and the filgrastims (two biosimilars, six brand names). Physicians and pharmacists should be familiar with the legal and pharmacological specialities of biosimilars: The production process can differ from that of the original, clinical indications can be extrapolated, glycoproteins contain varying isoforms, the formulation may differ from the original, and biopharmaceuticals are potentially immunogenic. Only on proof of quality, efficacy and safety, biosimilars are a viable option because of their lower costs. Am. J. Hematol. 2010. © 2010 Wiley‐Liss, Inc.

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The increased incidence of pure red cell aplasia with an Eprex formulation in uncoated rubber stopper syringes

Cited by 210 publications

References 9 publications

Anemia of Chronic Kidney Disease

Anemia of Chronic Kidney Disease

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)

Biosimilar epoetins and other “follow‐on” biologics: Update on the European experiences

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