A syringe system for the administration of lyophilized drugs includes a syringe barrel (12) and a stopper (30) and a needle guard (40) each coupled with the syringe barrel (12). A reconstruction plunger (80) is removably coupled with the stopper (30). A diluent (20) is withdrawn from the syringe (10) into a vial (100) containing a lyophilized drug (22), and the diluent and drug are mixed to form a therapeutic agent (24). The reconstitution plunger (80) is then replaced by an administration plunger (120). The length of the reconstitution plunger (80) is greater than the length of the administration plunger (120) in order to prevent activation of the needle guard (40) during reconstitution. Alternatively, a single plunger system may be used in which the plunger (200) can transition from an extended length (Fig.7A) during reconstitution to a shortened length (Fig.7B) during administration. During administration, a radial element (88,94,95,128,214) of the plunger (120) contacts latch members (74) of the needle guard (40), whereupon the guard advances to an extended position covering the needle (130).
