Caffeine

Caffeine Citrate Injection is indicated for the treatment of apnea of prematurity.

Caffeine is structurally related to other methylxanthines, theophylline, and theobromine. It is a bronchial smooth muscle relaxant, a CNS stimulant, a cardiac muscle stimulant, and a diuretic. Although the mechanism of action of caffeine in apnea of prematurity is not known, several mechanisms have been hypothesized. These include: stimulation of the respiratory center, increased minute ventilation, decreased threshold to hypercapnia, increased response to hypercapnia, increased skeletal muscle tone, decreased diaphragmatic fatigue, increased metabolic rate, and increased oxygen consumption. Most of these effects have been attributed to antagonism of adenosine receptors, both A 1 and A 2 subtypes, by caffeine, which has been demonstrated in receptor binding assays and observed at concentrations approximating those achieved therapeutically.

Prior to initiation of caffeine citrate, baseline serum levels of caffeine should be measured in infants previously treated with theophylline, since preterm infants metabolize theophylline to caffeine. Likewise, baseline serum levels of caffeine should be measured in infants born to mothers who consumed caffeine prior to delivery, since caffeine readily crosses the placenta. The recommended loading dose and maintenance doses of caffeine citrate follow.

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

Necrotizing Enterocolitis During the double-blind, placebo-controlled clinical trial, 6 cases of necrotizing enterocolitis developed among the 85 infants studied (caffeine=46, placebo=39), with 3 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. In a published randomized, placebo-controlled, clinical trial that studied the use of caffeine citrate in apnea of prematurity in approximately 2000 patients, necrotizing enterocolitis was not more common in caffeine treated patients compared to placebo.

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 1 0. Feeding Intolerance 4 2. Sepsis 2 0. CARDIOVASCULAR SYSTEM Hemorrhage 1 0. DIGESTIVE SYSTEM Necrotizing Enterocolitis 2 1. Gastritis 1 0. Gastrointestinal Hemorrhage 1 0. HEMIC AND LYMPHATIC SYSTEM Disseminated Intravascular Coagulation 1 0. METABOLIC AND NUTRITIVE DISORDERS Acidosis 1 0. Healing Abnormal 1 0.

Store at 20° to 25°C (68° to 77°F).