The invention of this application relates generally to intravenous (IV) infusion of drugs to patients, and more particularly to aspects of an IV infusion system comprising an infusate cassette and an infusate container. The present invention provides a drug infusion cassette that incorporates a strong vial spike that may be non-metal, a means for sheathing the spike when it is not in use, an anti-free flow device, and other beneficial features such as an air entrainment lockout mechanism, quality assurance tags, stopcocks made of soft materials and means of securing tubing to the cassette with a minimum of individual parts. The drug cassette can be used with an automated spiking mechanism comprising a motorized vial holder that holds a vial. The spike remains sheathed if the drug cassette is not fully engaged with a mating surface of devices such as a pumping unit or a sedation and analgesia delivery system.