Deriphylline (Theophylline) Dosing for Asthma and COPD
For patients with moderate-to-severe COPD or asthma requiring theophylline, prescribe sustained-release preparations adjusted to achieve a peak serum level of 5–15 μg/L (or mg/L), with doses typically ranging from 200-400 mg daily depending on body weight, smoking status, and hepatic function. 1, 2
Dosing Strategy by Disease Severity
Mild Disease
- Theophylline is NOT recommended as first-line therapy 2
- Short-acting β2-agonists or anticholinergics should be used as needed for symptom relief 2
- Reserve theophylline for patients who fail initial bronchodilator therapy 1
Moderate-to-Severe COPD
- Initiate sustained-release theophylline at 200 mg once or twice daily 3
- Adjust dosing based on ideal body weight and smoking status 3
- Target serum concentration: 5–15 μg/L (some guidelines state 5-15 mg/L, which is equivalent) 1, 2, 4
- In elderly patients (≥65 years), 400 mg/day has been shown safe when properly monitored 5
Alternative to Theophylline
- If theophylline is not tolerated due to side effects, consider long-acting oral or inhaled β2-agonists instead 1, 2
Critical Monitoring Requirements
Serum theophylline levels must be monitored regularly to maintain therapeutic range and avoid toxicity 4, 6
Therapeutic Window
- Target range: 5–15 μg/L (or mg/L) 1, 2, 4
- Toxicity risk increases significantly at levels >15 μg/L 4
- Anti-inflammatory effects may occur at lower concentrations (1-5 mg/L), though a recent high-quality trial showed no benefit for exacerbation prevention at these levels 6, 3
Factors Affecting Drug Levels
- Hepatic metabolism is the primary determinant of blood concentrations 6
- Smoking status increases clearance and may require higher doses 3
- Hepatic disease increases risk of adverse events (odds ratio 1.81) 5
- Cardiac arrhythmias increase risk of adverse events (odds ratio 1.88) 5
Common Pitfalls and Side Effects
Dose-Related Side Effects (at therapeutic levels)
- Nausea (most common: 1.05-10.9% incidence) 4, 5, 3
- Loss of appetite (0.56%) 5
- Headaches (7.9-9.0%) 5, 3
- Palpitations (0.39%) 5
- Gastroesophageal reflux 4
Serious Toxicity (at supratherapeutic levels >15 μg/L)
Drug Interactions
- Multiple drug interactions exist that can increase or decrease theophylline metabolism 6, 7
- Unlike newer PDE4 inhibitors, theophylline requires careful attention to concomitant medications 7
Clinical Positioning in Treatment Algorithm
When to Consider Theophylline
- Severe COPD not controlled by bronchodilator therapy alone 6
- Asthma inadequately controlled on inhaled corticosteroids with or without long-acting β2-agonists 6, 8
- As add-on therapy, not first-line treatment 6, 8
When to Avoid Theophylline
- Patients with hepatic disease (use with extreme caution and closer monitoring) 5
- Patients with pre-existing arrhythmias (higher risk of adverse events) 5
- When adequate response achieved with inhaled therapies alone 2
Important Evidence Caveat
The most recent high-quality randomized trial (2018, JAMA) found that low-dose theophylline (targeting 1-5 mg/L) added to inhaled corticosteroids did NOT reduce COPD exacerbations compared to placebo over one year 3. This challenges earlier preclinical data suggesting anti-inflammatory benefits at low doses. Therefore, if prescribing theophylline, target the traditional therapeutic range of 5-15 μg/L for bronchodilator effects rather than lower doses for purported anti-inflammatory effects.
Practical Dosing Approach
- Start with 200 mg once or twice daily of sustained-release preparation 3
- Adjust based on patient factors: lower dose for elderly, hepatic disease, non-smokers; higher dose may be needed for smokers 5, 3
- Measure serum levels after steady state (typically 3-5 days) 4
- Titrate to achieve 5-15 μg/L 1, 2
- Monitor for side effects at each visit, particularly nausea, palpitations, and headache 4, 5
- Reassess need regularly: discontinue if no objective benefit (FEV1 improvement ≥10% predicted and/or >200 mL) 1, 2