Doxofylline Use in Elderly Patients with COPD or Asthma
Doxofylline can be used in elderly patients with COPD or asthma, but anticholinergics should be considered as first-line therapy due to the declining response to beta-agonists with advancing age and doxofylline's better safety profile compared to theophylline.
Pharmacological Profile of Doxofylline in Elderly Patients
Doxofylline is a methylxanthine derivative that differs from theophylline by containing a dioxalane group at position 7, which gives it distinct pharmacological properties:
- Unlike theophylline, doxofylline does not significantly antagonize adenosine receptors or inhibit phosphodiesterase isoforms 1
- It has comparable efficacy to theophylline but with an improved tolerability profile 1, 2
- Fewer drug-drug interactions compared to theophylline, making it more suitable for elderly patients who often take multiple medications 1
Efficacy Considerations in Elderly Patients
For COPD:
- Doxofylline has been shown to significantly increase FEV1 by 8.20% and 317 ml compared to baseline in COPD patients 2
- It can be considered as an alternative to theophylline when other bronchodilators are insufficient 2
- However, the 2018 GOLD guidelines do not specifically recommend methylxanthines as first-line therapy, noting that theophylline is not recommended unless access to or affordability of bronchodilators is an issue 3
For Asthma:
- Methylxanthines (including doxofylline) are considered alternative, not preferred, therapy for step 2 care in asthma management 3
- They can be used as adjunctive therapy with inhaled corticosteroids 3
Age-Specific Considerations
The British Thoracic Society specifically notes several important considerations for elderly patients:
- With advancing age, the response to beta-agonists declines more rapidly than the response to anticholinergics, making anticholinergic treatment a preferred option for elderly patients 3
- Beta-agonists are especially likely to cause tremor in the elderly, and high doses should be avoided unless necessary 3
- Ischemic heart disease is more prevalent with advancing age, requiring caution with high-dose beta-agonist treatment 3
- Elderly patients may have difficulty using metered-dose inhalers due to cognitive impairment, weak fingers, or poor coordination 3
Safety Profile in Elderly Patients
Doxofylline has demonstrated a better safety profile compared to theophylline:
- Lower incidence of adverse effects compared to theophylline 4
- Most common adverse events include epigastralgia, nausea, dyspepsia, and headache 2
- Neurological adverse events occur more frequently with doxofylline (35%) compared to other bronchodilators like procaterol (5%) 5
- No need for serum concentration monitoring, unlike theophylline 1
Practical Approach to Using Doxofylline in Elderly Patients
First-line options:
When to consider doxofylline:
- As an alternative to theophylline when standard bronchodilator therapy is insufficient
- In patients who cannot use inhaled medications properly despite proper instruction and device selection
- As adjunctive therapy to standard treatment in patients with persistent symptoms
Dosing considerations:
- Start with lower doses in elderly patients and titrate based on response and tolerability
- Monitor for adverse effects, particularly neurological symptoms and gastrointestinal disturbances
Monitoring:
- Regular follow-up to assess efficacy and adverse effects
- Unlike theophylline, routine serum level monitoring is not required
Cautions and Contraindications
- Use with caution in elderly patients with:
Conclusion
While doxofylline can be used in elderly patients with COPD or asthma with a better safety profile than theophylline, it should be considered after first-line therapies (anticholinergics for COPD, inhaled corticosteroids for asthma) have been optimized. The decision to use doxofylline should take into account the patient's comorbidities, ability to use inhaled medications, and risk of adverse effects.