Three of the infants who developed necrotizing enterocolitis during the trial died. All had been exposed to caffeine. Two were randomized to caffeine, and one placebo patient was rescued with open-label caffeine for uncontrolled apnea.
Few data exist on drug interactions with caffeine in preterm neonates.
Caffeine administered concurrently with ketoprofen reduced the urine volume in 4 healthy volunteers. The clinical significance of this interaction in preterm neonates is not known. Interconversion between caffeine and theophylline has been reported in preterm neonates. The concurrent use of these drugs is not recommended.