Five years' clinical use of GnRH antagonists: Evaluation of safety and allergic potential

Three antagonists of gonadotrophin-releasing hormone are currently clinically available. Cetrorelix (Cetrotide®) and ganirelix (Orgalutran®/Antagon®) have been safely used in assisted reproduction since 1999 and 2000 respectively. The structurally similar abarelix (Plenaxis®) has been approved for the therapy of advanced androgen sensitive prostate cancer. However, due to the occurrence of allergic reactions, its use is restricted to only a subgroup of patients. These allergic side effects may not be due to abarelix, as the drug itself does not have a strong histamine liberating potential in vitro, but could be attributed to carboxymethylcellulose (CMC), which only Plenaxis, but not Cetrotide or Orgalutran/Antagon contain. CMC is used to obtain the sustained-release characteristics of Plenaxis. Since 1973, numerous case reports and studies have been published regarding allergic reactions and specific immunoglobulin E antibodies against CMC. Thus, the allergic side effects of Plenaxis could be rather due to CMC than to abarelix.