Adverse events associated with vitamin K1: results of a worldwide postmarketing surveillance programme

Abstract

We compared adverse events associated with a conventional vitamin K(1) preparation, Konakion, with a new mixed micellar formulation, Konakion MM. Data were obtained worldwide from spontaneous reports, clinical trials and postmarketing surveillance. During the period 1974 to July 1995, an estimated 635 million adults and 728 million children were prescribed Konakion or Konakion MM. Of the 404 adverse events in 286 subjects reported, 387 (96%) were associated with Konakion. Konakion MM accounted for 4% (n=17) of the reported adverse events, and 5% of total sales figures. Thirteen of the 17 adverse events (76%) reported for Konakion MM were minor injection site reactions. Overall, 120 of the adverse events were serious, of which 117 (98%) were associated with Konakion. Eighty-five probable anaphylactoid reactions (of which six were fatal) were reported for conventional Konakion, compared with one non-fatal anaphylactoid reaction for Konakion MM. During the last 12 months of postmarketing surveillance, there were 14 serious adverse events reported in an estimated 21 million individuals treated with Konakion, but none in the 13 million who received Konakion MM. These results suggest that the Cremophor EL-solubilized preparations of vitamin K(1) have a higher profile of adverse events, including anaphylactoid reactions, than the newer mixed micellar preparation, Konakion MM.