Heparin pharmacovigilance in Brazil

Junqueira, Daniela Rezende Garcia; Viana, Thércia Guedes; Peixoto, Eliane R. de M.; Barros, Fabiana C.R. de; Carvrvalho, Maria das Graças; Perini, Édson

doi:10.1016/s0104-4230(11)70067-7

Cited by 5 publications

(4 citation statements)

References 12 publications

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“…Although only porcine intestinal heparin is currently used in the United States, bovine lung and intestinal heparins have been used in South America and in the Middle East, and ovine intestinal and porcine lung heparins have been used in Asia. Heparins derived from different organisms and tissues display different physical–chemical properties (i.e., molecular weight properties, disaccharide composition, and antithrombin III pentasaccharide binding sites (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…5 Heparin, while commanding a multibillion dollar worldwide market, has a fragile supply chain that was jeopardized in the past by fears of prion (i.e., bovine spongiform encephalopathy and scrapies) and viral impurities, 6 was briefly interrupted in 2007-2008 during a contamination crisis, 7 and has been adversely impacted by the recent appearance of the porcine epidemic diarrhea virus. 8 Although only porcine intestinal heparin is currently used in the United States, bovine lung and intestinal heparins 9,10 have been used in South America and in the Middle East, and ovine intestinal and porcine lung heparins have been used in Asia. Heparins derived from different organisms and tissues display different physical-chemical properties (i.e., molecular weight properties, disaccharide composition, and antithrombin III pentasaccharide binding sites ( Fig.…”

Section: Introductionmentioning

confidence: 99%

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Stable Isotopic Analysis of Porcine, Bovine, and Ovine Heparins

Jasper

Zhang

Poe³

et al. 2015

Journal of Pharmaceutical Sciences

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The assessment of provenance of heparin is becoming a major concern for the pharmaceutical industry and its regulatory bodies. Batch-specific [carbon (δ13C), nitrogen (δ15N), oxygen (δ18O), sulfur (δ34S), and hydrogen (δD)] stable-isotopic compositions of five different animal-derived heparins were performed. Measurements readily allowed their differentiation into groups and/or subgroups based on their isotopic provenance. Principle component analysis showed that a bivariate plot of δ13C and δ18O is the best single, bivariate plot that results in the maximum discrimination ability when only two stable isotopes are used to describe the variation in the data set. Stable-isotopic analyses revealed that (i) stable-isotope measurements on these highly-sulfated polysaccharide (MW ~15 kDa) natural products (“biologics”) were feasible; (ii) in bivariate plots, the δ13C versus δ18O plot reveals a well-defined relationship for source differentiation of hogs raised in the US from hogs raised in Europe and China; (iii) the δD versus δ18O plot revealed the most well-defined relationship for source differentiation based on the hydrologic-environmental isotopes of water (D/H and 18O/16O), and (iv) the δ15N versus δ18O and δ34S versus δ18O relationships are both very similar, possibly reflecting the food sources used by the different heparin producers.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stable Isotopic Analysis of Porcine, Bovine, and Ovine Heparins

Jasper

Zhang

Poe³

et al. 2015

Journal of Pharmaceutical Sciences

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“…Besides being the market leader, Liquemine™ also was the only brand employed in cardiovascular surgeries that required high doses of UFH (11). Shortly after the Liquemine™ discontinuation, several bleeding incidents during or after cardiovascular surgeries began to be reported in Brazilian hospitals (25, 26). At first, the medical community attributed the incidents to the adulterated HPIs though their reported adverse effect was hypotension but not bleeding (22–24).…”

Section: Time Of Crisismentioning

confidence: 99%

“…Therefore, two UFH products, with distinct pharmacological features, might soon be simultaneously available worldwide (10). However, the concomitant use of HBI and HPI, disregarding their differing anticoagulant activities, can provoke serious medical incidents, such as those experienced in Brazil (25, 26). The pioneer initiative of the BP in publishing novel monographs approaching separately the distinct pharmacological features of HBI and HPI certainly was a pivotal step toward their safe use as interchangeable UFHs; therefore, such a framework should be used as a template for the reformulation of pharmacopeias of other countries willing to introduce HBI.…”

Section: Final Considerationsmentioning

confidence: 99%

Heparins Sourced From Bovine and Porcine Mucosa Gain Exclusive Monographs in the Brazilian Pharmacopeia

et al. 2019

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Most of the unfractionated heparin (UFH) consumed worldwide is manufactured using porcine mucosa as raw material (HPI); however, some countries also employ products sourced from bovine mucosa (HBI) as interchangeable versions of the gold standard HPI. Although accounted as a single UFH, HBI, and HPI have differing anticoagulant activities (~100 and 200 IU mg−1, respectively) because of their compositional dissimilarities. The concomitant use of HBI and HPI in Brazil had already provoked serious bleeding incidents, which led to the withdrawal of HBI products in 2009. In 2010, the Brazilian Pharmacopeia (BP) formed a special committee to develop two complementary monographs approaching HBI and HPI separately, as distinct active pharmaceutical ingredients (APIs). The committee has rapidly agreed on requirements concerning the composition and presence of contaminants based on nuclear magnetic resonance and anion-exchange chromatography. On the other hand, consensus on the anticoagulant activity of HBI was the subject of long and intense discussions. Nevertheless, the committee has ultimately agreed to recommend minimum anti-FIIa activities of 100 IU mg−1 for HBI and 180 IU mg−1 for HPI. Upon the approval by the Brazilian Health Authority (ANVISA), the BP published the new monographs for HPI and HBI APIs in 2016 and 2017, respectively. These pioneer monographs represent a pivotal step toward the safest use of HBI and HPI as interchangeable anticoagulants and serve as a valuable template for the reformulation of pharmacopeias of other countries willing to introduce HBI.

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Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients

Junqueira¹,

Perini

Penholati

et al. 2012

Cochrane Database of Systematic Reviews

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There was a lower incidence of HIT and HIT complicated by VTE in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH. This is consistent with the current clinical use of LMWH over UFH as front-line heparin therapy. However, conclusions are limited by a scarcity of high quality evidence. We did not expect the paucity of RCTs including HIT as an outcome as heparin is one of the most commonly used drugs worldwide and HIT is a life-threatening adverse drug reaction. To address the scarcity of clinically-relevant information on the topic of HIT as a whole, HIT should be included as an outcome in future RCTs of heparin, and HIT as an adverse drug reaction should be considered in clinical recommendations regarding monitoring of the platelet count for HIT.

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Heparin pharmacovigilance in Brazil

Cited by 5 publications

References 12 publications

Stable Isotopic Analysis of Porcine, Bovine, and Ovine Heparins

Stable Isotopic Analysis of Porcine, Bovine, and Ovine Heparins

Heparins Sourced From Bovine and Porcine Mucosa Gain Exclusive Monographs in the Brazilian Pharmacopeia

Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients

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