Caffeine-clarithromycin coadministration and hyperlactatemia in a young infant: a case report

Apnea is a major complication of acute respiratory tract infection in young infants and may lead to the need for ventilatory support. Caffeine is methylxanthine, which is considered the mainstay of pharmacologic treatment for apnea of prematurity. On the basis of neonatal guidelines, caffeine has been used as a respiratory stimulant for the treatment of acute respiratory tract infection-related apnea, despite low evidence of its ability to improve clinical outcomes. Hyperlactatemia has been reported in adults with caffeine poisoning. Clarithromycin acts as an inhibitor of human cytochrome P450 and may impair drug metabolism. However, there are no published data concerning lactic acidosis associated with caffeine-clarithromycin coadministration. We report a case of hyperlactatemia in a young infant born prematurely who presented to the emergency department with acute respiratory tract infection-associated apnea and who required noninvasive ventilatory support. Because respiratory viruses were not detected in the nasopharyngeal aspirates and the chest radiography revealed interstitial opacities, clarithromycin (15mg/kg/day) was started via a nasoduodenal tube. In polysomnography, dysmaturity and immaturity of the central nervous system were evident. Hence, caffeine treatment was initiated at a loading dose of 10mg/kg followed by a maintenance dose of 5mg/kg/day. After treatment initiation, the child experienced ventilatory improvement and apnea control. However, a progressive increase in the serum lactate concentration and high anion gap metabolic acidosis were observed, despite hemodynamic stability. Following discontinuation of both drugs, the serum concentrations of lactate gradually returned to normal values. Thus, clarithromycin-caffeine coadministration may cause a sharp increase in lactate concentrations and should be avoided in young infants with acute respiratory tract infection-associated apnea.