Theophylline Dosing for Asthma and COPD
For oral sustained-release theophylline in adults with moderate-to-severe asthma or COPD, start with 200-400 mg daily (approximately 3-6 mg/kg/day) divided into 2-4 doses, then titrate to achieve a target serum concentration of 5-15 μg/L. 1, 2
Initial Dosing Strategy
Adults and Children >1 Year Without Risk Factors
Starting dose for children <45 kg: 12-14 mg/kg/day up to maximum 300 mg/day, divided every 4-6 hours 3
Starting dose for children >45 kg and adults: 300 mg/day divided every 6-8 hours 3
Titration schedule:
- After 3 days if tolerated, increase to 400 mg/day (or 16 mg/kg/day in children) 3
- After 3 more days if tolerated, increase to 600 mg/day (or 20 mg/kg/day in children) 3
- All doses should be calculated based on ideal body weight, not actual weight, as theophylline distributes poorly into fat 3
High-Risk Patients (Elderly >60 Years, Hepatic Disease, Drug Interactions)
Maximum dose should not exceed 400 mg/day in patients with risk factors for reduced clearance or when serum monitoring is not feasible 3
The incidence of adverse events is significantly higher in patients with hepatic disease (odds ratio 1.81) and arrhythmias (odds ratio 1.88) 4
Target Serum Concentrations
Therapeutic range: 5-15 μg/L (equivalent to 5-15 mg/L) 1, 2
- This range provides bronchodilation while minimizing toxicity risk 1, 2
- Some evidence suggests anti-inflammatory effects may occur at concentrations <10 μg/mL, which may be therapeutically relevant with fewer adverse effects 5
- Toxicity risk increases significantly at levels >15 μg/L 2, 6
Monitoring and Dose Adjustment
Check serum theophylline levels:
- After 3 days of any dose change to guide further adjustment 3
- Every 6 months in rapidly growing children 3
- Yearly in stable adult patients 3
- Every 24 hours in acutely ill patients 3
Dose adjustments based on serum levels: 3
- <9.9 μg/mL: Increase dose by 25% if symptoms not controlled and current dose tolerated
- 10-14.9 μg/mL: Maintain dose if symptoms controlled
- 15-19.9 μg/mL: Consider 10% dose reduction for safety margin
- 20-24.9 μg/mL: Decrease dose by 25% even without adverse effects
- 25-30 μg/mL: Skip next dose and decrease by at least 25%
- >30 μg/mL: Treat as overdose, skip doses, and reduce by at least 50% when resuming
Clinical Positioning
Theophylline should be reserved as add-on therapy when patients fail to achieve adequate control with:
- Inhaled corticosteroids and long-acting β2-agonists for asthma 2
- Initial bronchodilator therapy for COPD 1, 2
The European Respiratory Society guidelines position theophylline as an alternative when long-acting β-agonists are not tolerated 1
Critical Safety Considerations
Common adverse effects include: 2, 7, 4
- Nausea (1.05% incidence in elderly patients)
- Gastroesophageal reflux
- Tachycardia and palpitations
- Headache and tremor
Serious toxicity at supratherapeutic levels includes: 2, 6
- Cardiac arrhythmias
- Seizures (though none reported in large elderly cohort at 400 mg/day) 4
Drug interactions through hepatic cytochrome P450 system can significantly alter theophylline levels and require dose adjustment 7
Contraindications and cautions:
- Avoid in patients with pre-existing arrhythmias 2
- Use caution in hepatic disease 2, 4
- Consider lower doses in elderly patients 3, 4
Practical Implementation
Slow titration minimizes adverse effects: Starting low and increasing gradually reduces caffeine-like side effects from >50% to only 1-2% of patients 8
Sustained-release formulations are preferred as they decrease serum concentration fluctuations and permit longer dosing intervals 3, 8
If adverse effects occur: Instruct patients to discontinue, wait until symptoms resolve, then resume at a lower previously tolerated dose 3