From the FDA Drug Label
After oral administration of 10 mg caffeine base/kg to preterm neonates, the peak plasma level (Cmax) for caffeine ranged from 6 to 10 mg/L
- The peak plasma level of caffeine in neonates ranges from 6 to 10 mg/L after oral administration of 10 mg caffeine base/kg.
- The caffeine level in neonates can be expected to be within this range, but the exact level may vary depending on individual factors. 1
From the Research
Caffeine levels in neonates should be maintained between 5-25 mg/L to effectively treat apnea of prematurity while minimizing potential side effects. The recommended dosing regimen begins with a loading dose of 10-20 mg/kg of caffeine citrate, followed by maintenance doses of 5-10 mg/kg of caffeine citrate given once daily 2. Premature infants metabolize caffeine more slowly than adults due to their immature liver enzymes, resulting in a longer half-life of 40-230 hours compared to 5-6 hours in adults. This extended half-life means steady-state levels are reached after approximately 7-10 days of therapy. Monitoring caffeine levels is not routinely required but may be helpful in cases of inadequate response or suspected toxicity. Side effects at therapeutic levels are generally minimal but can include tachycardia, feeding intolerance, or irritability at higher concentrations. Some key points to consider when managing caffeine levels in neonates include:
- The Caffeine for Apnea of Prematurity (CAP) trial showed that caffeine was safe when used with standard dosing and provided both pulmonary and neurological benefits to preterm infants 2.
- Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age have been investigated, and it was found that therapeutic neonatal caffeine administration has no long-term effects on sleep duration or sleep apnea during childhood 3.
- Neurobehavioral outcomes 11 years after neonatal caffeine therapy for apnea of prematurity have been studied, and it was found that caffeine therapy improved visuomotor, visuoperceptual, and visuospatial abilities at age 11 years 4.
- Economic evaluation of caffeine for apnea of prematurity has shown that caffeine therapy is economically appealing for infants up to 18 to 21 months' corrected age 5. Caffeine therapy is typically continued until the infant reaches 34-35 weeks postmenstrual age or is free from significant apnea episodes for 5-7 days, with gradual weaning rather than abrupt discontinuation recommended.