title: New and generic anticoagulants and biosimilars: safety considerations.
abstract: The recent health care changes and approval of a generic low-molecular-weight heparin (LMWH) by the US Food and Drug Administration (FDA) merit a review of the facts regarding the new and generic anticoagulants. Fatal hypotension from anaphylactoid type reactions following heparin administration was responsible for more than 149 deaths all over the world. Researchers detected a heparin-like semisynthetic contaminant, over-sulfated chondroitin sulfate (OSCS), that appeared to be intentional. Low-molecular-weight heparins are produced using unfractionated heparin and OSCS has been found in various batches of LMWHs. Some newer anticoagulants are claiming to be free from the need to monitor for therapeutic effect and bleeding risk. Therefore, monitoring assays are not being developed and there is no antidote to reverse bleeding. In addition, there are concerns about reproducibility, product variation, and quality. In conclusion, although the generic LMWHs and newer anticoagulants may appear to be effective for qualified indications, their safety remains to be a concern.
authors.affiliation: Vascular Surgery Department, Ealing Hospital and Imperial College London, SW7 2AZ, UK. e.kalodiki@imperial.ac.uk
authors.forename: Evi
authors.initials: E
authors.lastname: Kalodiki
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced / Q000401:mortality; D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects* / Q000819:agonists / Q000627:therapeutic use*; D002809:Chondroitin Sulfates / Q000009:adverse effects / Q000032:analysis / Q000494:pharmacology; D004340:Drug Contamination; D064420:Drug-Related Side Effects and Adverse Reactions; D016568:Drugs, Generic / Q000009:adverse effects* / Q000032:analysis / Q000627:therapeutic use*; D006470:Hemorrhage / Q000188:drug therapy; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects* / Q000032:analysis / Q000627:therapeutic use*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000401:mortality; D008991:Monitoring, Physiologic / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000925:Anticoagulants; D016568:Drugs, Generic; D006495:Heparin, Low-Molecular-Weight; D002809:Chondroitin Sulfates