What is the role of Theophyllin (a methylxanthine) injections in treating asthma or Chronic Obstructive Pulmonary Disease (COPD)?

Theophylline Injections in Asthma and COPD

Intravenous theophylline (aminophylline) should NOT be used for acute exacerbations of chronic bronchitis or COPD, and should only be considered as a last-resort option in acute severe asthma when patients fail to respond to standard nebulized bronchodilators and corticosteroids. 1

Role in Acute Exacerbations

COPD and Chronic Bronchitis

• Theophylline is explicitly NOT recommended for acute exacerbations of chronic bronchitis (Grade D recommendation - no benefit demonstrated). 1
• Intravenous aminophylline (0.5 mg/kg per hour) should only be considered in COPD exacerbations if patients are not responding to nebulized bronchodilators, but there is a paucity of evidence supporting its effectiveness in this situation. 1
• The European Respiratory Society notes that intravenous bronchodilators offer no advantage in most acute exacerbations. 2

Acute Severe Asthma

• Consider aminophylline only if response to standard therapy (nebulized beta-agonists, anticholinergics, and systemic corticosteroids) is inadequate. 2
• Before initiating, check for contraindications and drug interactions through the hepatic cytochrome P450 system. 2, 3
• Serum theophylline levels must be monitored daily with a target range of 5-15 mg/L. 2, 3

Role in Stable Chronic Disease

Stable Chronic Bronchitis/COPD

• Oral theophylline (100-400 mg twice daily of slow-release formulation) should be considered as add-on therapy in stable patients with chronic bronchitis to control chronic cough when optimal inhaled therapy is insufficient (Grade A recommendation). 1, 4
• Use the lowest effective dose to minimize adverse effects, particularly gastrointestinal side effects which are threefold higher than other bronchodilators. 4, 3
• Theophylline decreases dyspnea, air trapping, work of breathing, and improves diaphragmatic contractility in COPD patients. 5

Chronic Asthma

• Theophylline is FDA-approved for treatment of symptoms and reversible airflow obstruction in chronic asthma. 5
• It decreases frequency and severity of symptoms, including nocturnal exacerbations, and reduces "as needed" use of inhaled beta-2 agonists. 5
• Should be reserved as second- or third-line therapy behind inhaled corticosteroids and beta-2 agonists. 6, 7

Critical Monitoring and Safety Considerations

Mandatory Monitoring

• Serum theophylline levels should be monitored regularly with target range 5-15 mg/L (some sources cite 10-20 μg/mL for acute therapy). 2, 3, 8
• Risk of toxicity increases significantly at levels >15 μg/mL. 2
• Daily monitoring is required during intravenous infusion. 1

Common Side Effects

• Nausea, vomiting, gastroesophageal reflux (especially problematic compared to other bronchodilators). 2, 3
• Tachycardia, palpitations, arrhythmias. 2, 3
• Headache and tremor. 2

High-Risk Populations Requiring Extreme Caution

• Active peptic ulcer disease. 4
• Congestive heart failure. 4
• Elderly patients (higher risk of side effects and drug interactions). 1

Life-Threatening Toxicity

• Convulsions and fatal arrhythmias can occur with overdose. 9
• Charcoal hemoperfusion dialysis may be indicated when serum concentrations exceed 60 μg/mL. 8
• Patients on long-term theophylline presenting with nonspecific gastrointestinal or cardiac symptoms should be evaluated for toxicity. 9

Clinical Decision Algorithm

For Acute Exacerbations:

1. Start with nebulized beta-agonists and anticholinergics plus systemic corticosteroids. 1
2. If no response after maximal doses of both nebulized agents, consider IV aminophylline ONLY in asthma (not COPD/chronic bronchitis). 1
3. Monitor serum levels daily if initiated. 1, 2

For Stable Disease:

1. Optimize inhaled corticosteroids and long-acting bronchodilators first. 4, 7
2. Consider oral theophylline as add-on therapy if symptoms persist, particularly for chronic cough in chronic bronchitis. 1, 4
3. Start at lowest effective dose and monitor serum levels. 4, 3
4. Use extreme caution in elderly and those with peptic ulcer disease or heart failure. 4