Other nominees for the awards, which are handed out in May during a show broadcast from Los Angeles on the FX Network, include Samuel L. Jackson, Bernie Mac, and Neve Campbell.
Nominated for best theatrical feature film were Changing Lanes, The Divine Secrets of the Ya-Ya Sisterhood, Narc, Salton Sea and Skins.
Jackson, who played a recovering alcoholic opposite Ben Affleck in Changing Lanes, will compete against Judd (Ya-Ya Sisterhood), Kilmer (Salton Sea), Jason Patric (Narc) and Graham Greene (Skins) for best performance in a theatrical feature film.
Irons and Campbell, who co-starred in a Showtime television movie about the final days of American writer F. Scott Fitzgerald, were both nominated for best performance in a television movie or miniseries.
Also up for that award are Summer Phoenix and Nick Stahl, both who starred in Wasted an MTV Networks film about the lives of three small town junkies, and Mia Farrow, who played a mother who discovers her daughter is abusing drugs in The Secret Life of Zoey.
Mac, star of The Bernie Mac Show, was nominated for best performance in a television comedy series along with Camille Windbush, who plays his daughter on the Fox-TV hit. Also up for the award are Anthony Clark (Yes, Dear), Tracee Ellis Ross (Girlfriends) and John Slattery (Ed).
The PRISM awards are presented by the Entertainment Industries Council in partnership with the Robert Wood Johnson Foundation and the National Institute on Drug Abuse/National Institutes of Health, which supports research on the health aspects of drug abuse and addiction.