When is Theophylline recommended for patients with asthma or Chronic Obstructive Pulmonary Disease (COPD)?

From the Guidelines

Theophylline is recommended as a third-line therapy for patients with asthma or COPD when other treatments have failed to provide adequate symptom control. For asthma, it should be considered after inhaled corticosteroids and long-acting bronchodilators have proven insufficient, as stated in the expert panel report 3 (epr-3) guidelines for the diagnosis and management of asthma 1. In COPD, theophylline may be added when symptoms persist despite optimal therapy with inhaled bronchodilators and anti-inflammatory medications. The American College of Chest Physicians and Canadian Thoracic Society guideline suggests treatment with oral slow-release theophylline twice daily to prevent acute exacerbations of COPD 1.

Some key points to consider when prescribing theophylline include:

• Typical dosing starts at 200-300mg daily for adults, often given as extended-release formulations, with adjustments based on serum levels (target range 10-20 μg/mL) 1.
• Theophylline requires careful monitoring due to its narrow therapeutic window and potential for significant drug interactions.
• The medication works by inhibiting phosphodiesterase enzymes, which increases cyclic AMP levels, resulting in bronchodilation and reduced airway inflammation.
• It also has mild anti-inflammatory effects and may improve diaphragmatic contractility.
• However, its use has declined substantially due to the development of safer, more effective inhaled medications with fewer side effects and drug interactions.

According to a review of national guidelines for management of COPD in Europe, theophylline was recommended with reservations by all countries except Italy 1. The diagnosis and management of stable chronic obstructive pulmonary disease guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society suggests that clinicians may administer combination inhaled therapies for symptomatic patients with stable COPD and FEV1 <60% predicted, but the use of theophylline is not preferred as a first-line treatment 1.

In terms of specific patient populations, theophylline may be considered for patients with severe COPD who have failed to respond to other treatments, as well as for those with asthma who have not responded to inhaled corticosteroids and long-acting bronchodilators. However, the decision to use theophylline should be made on a case-by-case basis, taking into account the individual patient's preferences, cost, and adverse effect profile.

Overall, while theophylline can be an effective treatment for patients with asthma or COPD, its use should be carefully considered and monitored due to its potential for significant drug interactions and narrow therapeutic window.

From the FDA Drug Label

Theophylline is indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis. Theophylline is recommended for patients with asthma or Chronic Obstructive Pulmonary Disease (COPD) to treat symptoms and reversible airflow obstruction.

• Key benefits for patients with asthma include:
  • Decrease in frequency and severity of symptoms
  • Decrease in nocturnal exacerbations
  • Reduction in "as needed" use of inhaled beta-2 agonists
• Key benefits for patients with COPD include:
  • Decrease in dyspnea
  • Decrease in air trapping
  • Improvement in contractility of diaphragmatic muscles 2

From the Research

Theophylline Recommendations for Asthma and COPD

Theophylline is an oral methylxanthine bronchodilator recommended as alternate therapy for the treatment of asthma and chronic obstructive pulmonary disease (COPD) 3. The following are key points to consider:

• Theophylline is not generally recommended for the treatment of other respiratory disorders such as obstructive sleep apnea (OSA) or hypoxia 3.
• Most clinical practice guidelines rely on evidence published prior to the year 2000 to make these recommendations 3.
• Theophylline is usually used as an add-on therapy in patients with asthma not well controlled on inhaled corticosteroids with or without long-acting β2-agonists and in patients with COPD with severe disease not controlled by bronchodilator therapy 4.

Patient Selection and Dosage

When selecting patients for theophylline treatment, the following factors should be considered:

• Theophylline is recommended as an additional regimen to inhaled beta-agonists and inhaled corticosteroids for patients whose asthma is not controlled completely 5.
• Dosage must be individualized in order to optimize the treatment based on the measurement of theophylline concentration in serum 5.
• Theophylline has a narrow therapeutic range, and side effects are related to plasma concentrations, including nausea, vomiting, and headaches due to PDE inhibition and at higher concentrations to cardiac arrhythmias and seizures due to adenosine A1-receptor antagonism 4.

Monitoring and Potential Toxicity

It is essential to monitor patients on long-term theophylline treatment for potential toxicity:

• Patients with chronic theophylline overdose often present with nonspecific gastrointestinal symptoms, which can result in misdiagnosis for a variety of gastrointestinal conditions 6.
• Convulsions that may be fatal can occur as a result of a theophylline overdose 6.
• Therapeutic serum levels of theophylline are between 10 to 20 mcg/ml, and most adults achieve these concentrations with daily slow-release oral theophylline preparations 7.