Caffeine Citrate

Caffeine citrate oral solution is indicated for the short term treatment of apnea of prematurity in infants between 28 and <33 weeks gestational age.

Caffeine citrate is contraindicated in patients who have demonstrated hypersensitivity to any of its components.

During the double-blind, placebo-controlled clinical trial, six cases of necrotizing enterocolitis developed among the 85 infants studied (caffeine=46, placebo=39), with three cases resulting in death. Five of the six patients with necrotizing enterocolitis were randomized to or had been exposed to caffeine citrate. Reports in the published literature have raised a question regarding the possible association between the use of methylxanthines and development of necrotizing enterocolitis, although a causal relationship between methylxanthine use and necrotizing enterocolitis has not been established.

Therefore, as with all preterm infants, patients being treated with caffeine citrate should be carefully monitored for the development of necrotizing enterocolitis.

Overall, the reported number of adverse events in the double-blind period of the controlled trial was similar for the caffeine citrate and placebo groups. The following table shows adverse events that occurred in the double-blind period of the controlled trial and that were more frequent in caffeine citrate treated patients than placebo. ADVERSE EVENTS THAT OCCURRED MORE FREQUENTLY IN CAFFEINE CITRATE TREATED PATIENTS THAN PLACEBO DURING DOUBLE-BLIND THERAPY Adverse Event (AE) Caffeine Citrate N=46 n (%) Placebo N=39 n (%) BODY AS A WHOLE Accidental Injury Feeding Intolerance Sepsis 1 (2.2) 4 (8.7) 2 (4.3) 0 (0) 2 (5.1) 0 (0) CARDIOVASCULAR SYSTEM Hemorrhage 1 (2.2) 0 (0) DIGESTIVE SYSTEM Necrotizing Enterocolitis Gastritis Gastrointestinal Hemorrhage 2 (4.3) 1 (2.2) 1 (2.2) 1 (2.6) 0 (0) 0 (0) HEMIC AND LYMPHATIC SYSTEM Disseminated Intravascular Coagulation 1 (2.2) 0 (0) METABOLIC AND NUTRITIVE DISORDERS Acidosis Healing Abnormal 1 (2.2) 1 (2.2) 0 (0) 0 (0) NERVOUS SYSTEM Cerebral Hemorrhage 1 (2.2) 0 (0) RESPIRATORY SYSTEM Dsypnea Lung Edema 1 (2.2) 1 (2.2) 0 (0) 0 (0) SKIN AND APPENDAGES Dry Skin Rash Skin Breakdown 1 (2.2) 4 (8.7) 1 (2.2) 0 (0) 3 (7.7) 0 (0) SPECIAL SENSES Retinopathy of Prematurity 1 (2.2) 0 (0) UROGENITAL SYSTEM Kidney Failure 1 (2.2) 0 (0) In addition to the cases above, three cases of necrotizing enterocolitis were diagnosed in patients receiving caffeine citrate during the open-label phase of the study.