From the Guidelines
Theophylline is primarily used to treat respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), and chronic bronchitis, and is now typically used as a third-line therapy when other treatments prove insufficient. It works as a bronchodilator by relaxing the smooth muscles in the airways, making breathing easier for patients experiencing bronchospasm or airway constriction. The therapeutic range is narrow (10-20 mcg/mL in blood), requiring careful monitoring to avoid toxicity. Theophylline functions by inhibiting phosphodiesterase enzymes and blocking adenosine receptors, which increases cyclic AMP levels in cells, leading to bronchodilation and reduced inflammation.
Some of the key points to consider when using theophylline include:
- Typical dosing for adults ranges from 300-600 mg daily, often divided into multiple doses, though extended-release formulations allow for once or twice daily administration.
- Side effects can include nausea, vomiting, headache, insomnia, and at higher levels, cardiac arrhythmias and seizures.
- Due to these potential side effects and the availability of safer alternatives like inhaled bronchodilators, theophylline is now typically used as a third-line therapy when other treatments prove insufficient, as recommended by the 2023 Canadian Thoracic Society guideline on pharmacotherapy in patients with stable COPD 1.
- Theophylline may have mild anti-inflammatory effects, and can be used as alternative, not preferred, therapy for step 2 care (for mild persistent asthma) or as adjunctive therapy with ICS in patients 5 years of age, as stated in the expert panel report 3 (EPR-3) guidelines for the diagnosis and management of asthma 1.
- The use of theophylline is not recommended for maintenance treatment in COPD, and ICS should only be used in combination with inhaled long-acting bronchodilators, as recommended by the 2023 Canadian Thoracic Society guideline on pharmacotherapy in patients with stable COPD 1.
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 used for the treatment of symptoms and reversible airflow obstruction associated with:
- Chronic asthma
- Chronic lung diseases, such as:
- Emphysema
- Chronic bronchitis 2
From the Research
Theophylline Uses
- Theophylline is an oral methylxanthine bronchodilator recommended as alternate therapy for the treatment of asthma and chronic obstructive pulmonary disease (COPD) 3, 4, 5.
- It is not generally recommended for the treatment of other respiratory disorders such as obstructive sleep apnea (OSA) or hypoxia 3.
- Theophylline is 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.
- Low-dose theophylline may be useful in reversing corticosteroid resistance in COPD and severe asthma 4, 5.
- Theophylline has anti-inflammatory and immunomodulatory effects, which may be beneficial in the treatment of asthma and COPD 4, 6, 5, 7.
Theophylline Administration
- Theophylline is given systemically (orally as slow-release preparations for chronic treatment and intravenously for acute exacerbations of asthma) 4.
- Efficacy is related to blood concentrations, which are determined mainly by hepatic metabolism, which may be increased or decreased in several diseases and by concomitant drug therapy 4.
Theophylline Side Effects
- Side effects are related to plasma concentrations and include nausea, vomiting, and headaches due to PDE inhibition and at higher concentrations to cardiac arrhythmias and seizures due to adenosine A1-receptor antagonism 4.
- Theophylline has a number of adverse drug reactions (ADRs), the most serious of which is its effect on the cardiovascular system, which can cause severe arrhythmias or even cardiac arrest when overdosed 6.