Safety profile comparison between extemporaneous and a licensed preparation of caffeine citrate in preterm infants with apnea of prematurity

Abstract

Background: Given the lack of a licensed product (LP), extemporaneous caffeine citrate (ECC) has been used by many hospital pharmacies.

Objectives: Since July 2011, an LP has been available in Germany. We prospectively compared the safety profile of ECC and LP in preterm infants with apnea of prematurity.

Methods: Between April 2010 and April 2013, selected side effects occurring with ECC or LP were documented in 6 German NICUs for infants ≤34 weeks' gestation using a longitudinal study design. The software developed for daily prescriptions in NICU residents requires entries if any of the following symptoms occurred during the last 24 h: tachycardia (resting heart rate >200/min), clinical or encephalographic seizures, gastric residuals, vomiting, or necrotizing enterocolitis (NEC). ECC and LP were administered at identical doses (20 mg/kg/day loading, 5-10 mg/kg/day maintenance) and in similar formulations either orally or intravenously.

Results: 562 infants with 14,590 treatment days on ECC and 538 infants with 12,813 treatment days on LP were evaluated. The mean gestational age was similar (29.20 weeks for ECC vs. 29.14 weeks for LP). No relevant differences were seen concerning tachycardia, gastric residuals, or vomiting, but ECC was associated with a higher risk of NEC (risk ratio: 2.68, 95% CI: 1.01-7.23, p = 0.047) and, albeit not significantly so, seizures (risk ratio: 1.91, 95% CI: 0.53-6.96, p = 0.35).

Conclusion: This survey demonstrates a similar safety profile for both forms of caffeine citrate. The lower NEC and seizure rate seen with the LP is intriguing, but requires confirmation in a controlled study design.