What are the dosing guidelines and potential side effects of Theophylline in patients with Chronic Obstructive Pulmonary Disease (COPD) and asthma?

Theophylline Dosing and Side Effects in COPD and Asthma

For stable patients with COPD, oral slow-release theophylline is recommended at 100-400 mg twice daily to prevent acute exacerbations, but should be used with caution due to its narrow therapeutic window and potential side effects. 1

Dosing Guidelines

COPD

• Theophylline is recommended as an alternative treatment in most European countries when patients continue to have exacerbations despite optimal inhaled therapy 1
• Recommended dosage: 100-400 mg twice daily of slow-release theophylline 1, 2
• Target serum concentration: 8-20 mg/L (measured 3-4 hours after dosing) 2
• Should be used at the lowest effective dose to avoid adverse effects 1

Asthma

• Theophylline should be considered to control chronic cough in stable patients with asthma 1
• Dosing should be individualized based on serum concentration measurements 2
• Anti-inflammatory effects may occur at lower serum concentrations (<10 μg/mL) than required for bronchodilation 3
• Initial dosing:
  • Adults <60 years without risk factors: 300 mg/day divided every 6-8 hours, titrated up to 600 mg/day if tolerated 2
  • Children <45 kg: 12-14 mg/kg/day up to maximum 300 mg/day, titrated up to 20 mg/kg/day if tolerated 2

Side Effects and Monitoring

Common Side Effects

• Mild side effects (serum levels <20 μg/mL): nausea, vomiting, headache, insomnia, diarrhea, irritability, restlessness, fine skeletal muscle tremors 2
• Severe side effects (serum levels >20 μg/mL): persistent vomiting, cardiac arrhythmias, seizures (potentially lethal) 2
• GI side effects are threefold higher with theophylline compared to other bronchodilators 1

High-Risk Populations

• Use with extreme caution in patients with:
  • Active peptic ulcer disease
  • Seizure disorders
  • Cardiac arrhythmias
  • Elderly patients (>60 years)
  • Liver disease (cirrhosis, acute hepatitis)
  • Congestive heart failure
  • Fever ≥102°F for 24+ hours 2

Monitoring Recommendations

• Measure serum theophylline concentrations:
  • Every 6 months for rapidly growing children
  • Yearly for all others
  • Every 24 hours in acutely ill patients 2
• Reduce dose if caffeine-like side effects persist, even at therapeutic concentrations 2
• Monitor for drug interactions that may alter theophylline metabolism 1
• Smoking cessation will increase serum theophylline levels; patients should inform physicians if they stop smoking while taking theophylline 1

Clinical Considerations

Place in Therapy

• In COPD: Use as an add-on therapy when patients continue to have exacerbations despite optimal inhaled therapy 1
• In asthma: Consider after inhaled beta-agonists and inhaled corticosteroids 4
• Theophylline should be weaned gradually rather than stopped abruptly, especially when used long-term 5

Contraindications for Acute Exacerbations

• Theophylline should not be used for treatment of acute exacerbations of chronic bronchitis 1
• An inhaled beta-2 selective agonist, alone or with systemic corticosteroids, is more effective for acute exacerbations 2

Important Pitfalls to Avoid

• Never increase theophylline dose in response to an acute exacerbation of symptoms 2
• Avoid starting with high doses (>300 mg/day in adults or >12 mg/kg/day in children) to prevent transient caffeine-like adverse effects 2
• Do not continue dosage that causes adverse effects; withhold medication until symptoms resolve, then resume at a lower dose 2
• Limit dose increases to about 25% of previous total daily dose to reduce risk of excessive serum concentration 2
• Be vigilant about drug interactions that can increase or decrease theophylline metabolism 2

Theophylline remains a useful medication in respiratory medicine when used appropriately, but requires careful monitoring and dose adjustment to balance efficacy and safety 6, 7.