title: The Real-World Routine Use of Caffeine Citrate in Preterm Infants: A European Postauthorization Safety Study.
abstract: BACKGROUND
  Caffeine citrate is the treatment of choice for apnea of prematurity (AOP). Regulatory agencies have requested real-world data on drug utilization and safety, a postauthorization safety study, of a pharmaceutical-grade caffeine citrate, Peyona, to confirm its benefit for preterm infants.
  
  
  OBJECTIVE
  To investigate the clinical use, outcomes, and safety profile of this pharmaceutical-grade caffeine citrate in the routine treatment of preterm infants with a gestational age (GA) <37 weeks.
  
  
  METHODS
  We conducted a multicenter, noninterventional, prospective study in five European countries. Patients eligible for study enrollment were <37-week GA neonates who received treatment with the pharmaceutical-grade caffeine citrate and whose parents had given informed consent.
  
  
  RESULTS
  A total of 506 preterm infants were enrolled from 21 institutions. The pharmaceutical-grade caffeine citrate doses were administered intravenously, orally, or via both routes. The main indication of use was AOP treatment (58%) followed by AOP prophylaxis (37%). Median treatment duration was 21 days. The primary cause of study termination was AOP resolution (n = 407; 80%). Hundred and six patients (21%) required supplemental oxygen on day 28; 48 patients (9.5%) had bronchopulmonary dysplasia at 36 weeks' postmenstrual age. Twenty-three adverse drug reactions were observed in 21 neonates (4.2%); the most frequent was tachycardia (2.3%) and only one (seizures) was considered serious. Thirty-one patients (8.1%) had hepatic or renal functional impairment; the side effects were manageable, and these patients also benefitted from treatment.
  
  
  CONCLUSIONS
  The use of this caffeine citrate is safe for the management of AOP in a real-world setting.
authors.affiliation: Department of Neonatology, Ospedale dei Bambini x2018;V. Buzzi' - ICP, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Lista
authors.forename: Laura
authors.initials: L
authors.lastname: Fabbri
authors.forename: Renáta
authors.initials: R
authors.lastname: Polackova
authors.forename: Ursula
authors.initials: U
authors.lastname: Kiechl-Kohlendorfer
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Papagaroufalis
authors.forename: Pilar
authors.initials: P
authors.lastname: Saenz
authors.forename: Fania
authors.initials: F
authors.lastname: Ferrari
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lasagna
authors.forename: Virgilio P
authors.initials: VP
authors.lastname: Carnielli
mesh_terms: D001049:Apnea / Q000188:drug therapy* / Q000453:epidemiology; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000517:prevention & control; D002110:Caffeine / Q000627:therapeutic use*; D002951:Citrates / Q000627:therapeutic use*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D011358:Product Surveillance, Postmarketing
chemical_list: D002951:Citrates; D002110:Caffeine; C026189:caffeine citrate