The article considers problems of evaluation of interchangeability of referent and reproduced medicines inhibitors of calcalcineurin. The analysis of 849 spontaneous reports in the Russian database from 2009 to 2015 containing information about undesirable reactions occurring at replacement of mentioned medicines. The clinical picture of undesirable reactions and their distribution by systemic organ classes is assessed. Various alternatives of replacement are considered. The implemented analysis demonstrated that problems mostly occurred ad replacement of original medicine to reproduced one that required returning to initial therapy. It is established that 20.9% of all entered reports about cases of undesirable reactions at replacement of medicines of cyclosporine and 12.2% of medicines of tacrolimus contained information about problems occurred at replacement of medicine within the framework of one international unlicensed item.