Theophylline Syrup Dosing in a 1-Year-Old
For a 1-year-old infant, initiate theophylline syrup at a starting dose calculated using the formula: [(0.2 × age in weeks) + 5] mg/kg/day, divided into 4 equal doses administered every 6 hours, with a target serum concentration of 5-10 mcg/mL. 1
Initial Dosing Calculation
For full-term infants aged 26 weeks to 52 weeks (approximately 6-12 months), use the FDA-approved formula: Total daily dose (mg) = [(0.2 × age in weeks) + 5.0] × (kg body weight), divided into 4 equal amounts administered at 6-hour intervals 1
For example, a 1-year-old (52 weeks) weighing 10 kg would receive: [(0.2 × 52) + 5] × 10 = 154 mg/day, or approximately 38.5 mg every 6 hours 1
The Hendeles equation is the preferred dosing method for infants ≤1 year of age, as it resulted in 97.3% of serum concentrations falling within the therapeutic range of 5-15 mg/L in clinical validation studies 2
Target Therapeutic Range
Aim for serum theophylline concentrations of 5-10 mcg/mL in infants, which is lower than the 10-15 mcg/mL target used in older children 1
This lower target minimizes the risk of toxicity while maintaining therapeutic efficacy for respiratory conditions 3
Critical Monitoring Requirements
Measure serum theophylline concentration within 6-12 hours after initiating therapy, as steady-state may not be achieved for 2-3 days in a 6-month-old infant and up to 5 days in younger infants 1
Do not increase the maintenance dose even if the initial serum concentration is <10 mcg/mL before steady-state is achieved 1
Continue monitoring at frequent intervals during acute illness, and every 6 months in rapidly growing children once stable 1
Dose Titration and Adjustments
Final dosage should be adjusted based on measured peak steady-state serum concentrations, not empirically increased 1
The maximum recommended dose in children 1-15 years with risk factors for impaired clearance is 16 mg/kg/day up to 400 mg/day 1
Increase doses only if the previous dosage is well tolerated and at intervals of no less than 3 days to allow serum concentrations to reach new steady state 1
Age-Specific Safety Considerations
Cardiovascular Effects
Neonates and young infants are more sensitive to cardiovascular effects, with tachycardia occurring at plasma concentrations as low as 13 mg/L (13 mcg/mL) 3
Monitor heart rate closely, as tachycardia was present in 47% of pediatric toxicity cases 4
Neurological Risks
Seizures can occur even at concentrations <50 mcg/mL in children, and were documented in previously neurologically normal patients 4
Seizures occurred in 5 of 163 pediatric toxicity cases, with 4 of these 5 having concentrations below 50 mcg/mL 4
Gastrointestinal Effects
Vomiting occurred in 52% of pediatric toxicity cases and is more frequent with higher concentrations 4
Minimal gastrointestinal effects occur at therapeutic doses 3
Common Pitfalls to Avoid
Never calculate doses based on total body weight in obese patients; theophylline distributes poorly into body fat, so use ideal body weight 1
Do not use the Nassif equation, as it resulted in 4% of calculated concentrations >20 mg/L, increasing toxicity risk 2
Avoid using theophylline as first-line therapy for acute asthma exacerbations; inhaled beta-2 agonists alone or with systemic corticosteroids are more effective 1
Never assume absence of symptoms indicates non-toxicity; 29% of children with concentrations of 25-50 mcg/mL were asymptomatic 4
Do not omit serum concentration monitoring; in 105 of 126 cases of chronic toxicity, the cause could not be determined, emphasizing the unpredictability of theophylline pharmacokinetics 4
Factors Affecting Serum Concentrations
Multiple variables alter theophylline metabolism: diet, food intake, febrile illness, age, and concomitant medications 5
Interpatient variability in elimination is substantial, making individualized monitoring essential 6, 2
Clinical Context
Theophylline is primarily indicated for apnea of prematurity in neonates and as adjunctive therapy in asthma when other treatments are insufficient 3
Current guidelines emphasize that systemic corticosteroids and inhaled beta-agonists remain primary treatments, with theophylline serving as adjunctive therapy only 7
For chronic cough in children, old observational studies showed resolution within 2 weeks of oral theophylline therapy, though this is not a primary indication 5