Methylxanthines for Chronic Obstructive Pulmonary Disease (COPD)

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Methylxanthines for Chronic Obstructive Pulmonary Disease (COPD)


Generic NameBrand Name
theophyllineTheolair, Uniphyl

These medicines are available in pill, liquid, or injection form. One medicine may be available in multiple forms. Your doctor will help you decide which type is best for you.

How It Works

The actions of methylxanthines are not completely known.

Theophylline may:

  • Slightly relax the airways in the lungs (bronchodilator).
  • Improve breathing by increasing the strength of the diaphragm (if it is weakened) and by stimulating the breathing control centres in the brain.
  • Make it easier to get mucus out of the lungs.

Why It Is Used

Because of their side effects, methylxanthines are not considered first-choice medicines to treat chronic obstructive pulmonary disease (COPD). They are prescribed most often for people with COPD who:

  • Still have major difficulty breathing despite using both an inhaled beta2-agonist and an inhaled anticholinergic.
  • Have persistent nighttime symptoms.
  • Have frequent, rapid, and sometimes sudden increase in shortness of breath (COPD exacerbation).

How Well It Works

A few studies have noted that, compared to a placebo, theophylline provides a small improvement in lung function as measured by tests (spirometry) in people who have stable COPD.1

In a COPD exacerbation, methylxanthines, compared to a placebo, provide a small improvement in lung function as measured by spirometry.2

In general, research shows that the small improvement in lung function does not justify the severe side effects for most people who have COPD. In most cases, newer and safer medicines have replaced methylxanthines for treatment of people who have COPD.

Side Effects

The side effects of methylxanthines are described as being similar to drinking too much caffeine, and they include:

  • Stomach upset.
  • Heartburn.
  • Trouble sleeping (insomnia).
  • Headache.
  • Nervousness or irritability.
  • Rapid heart rate (tachycardia).
  • Rapid breathing (tachypnea).

People taking the medicine may be able to reduce these side effects by avoiding caffeine.

Serious (toxic) side effects are seen in some people. These side effects include:

  • Nausea and vomiting.
  • Seizures.
  • Low blood sugar.
  • Irregular heartbeat (arrhythmia).

The difference between a dose of theophylline that helps improve symptoms and a dangerous dose (one that causes serious side effects) is small. Theophylline also has significant interactions with other prescribed medicines, which can make it less effective and potentially life-threatening.

Theophylline relaxes the esophagus near the opening into the stomach. This may result in heartburn (acid reflux) if stomach acid moves up into the esophagus. Acid reflux may make airway obstruction worse (making breathing more difficult), particularly in people with asthma. For more information, see the topic Gastroesophageal Reflux Disease (GERD).

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

Other medicines may be a better choice than methylxanthines for treating COPD, because the dose needed to improve symptoms is so close to a dose that causes serious side effects.

Theophylline interacts with many different types of medicines, such as antibiotics, antacids, birth control pills, and those used for seizures. Ask your doctor or pharmacist if a new medicine will affect how much theophylline you take.

Different brands of theophylline get into the bloodstream at different rates. So you always should use the same generic or brand-name medicine.

Because medicines and illnesses can affect how quickly theophylline is cleared from the body, the amount of theophylline in the blood must be measured regularly to be certain it remains at a safe level.

Smoking increases how quickly theophylline is cleared from the body, so a person with COPD who continues to smoke may need larger doses of the medicine.

People taking theophylline should avoid caffeine-containing beverages. These may make theophylline's side effects worse, especially jittery nerves and headaches.

Complete the new medication information form (PDF) (What is a PDF document?) to help you understand this medication.



  1. Kerstjens H, et al. (2008). COPD, search date March 2007. Online version of BMJ Clinical Evidence: http://www.clinical
  2. Barr RG, et al. (2003). Methylxanthines for exacerbations of chronic obstructive pulmonary disease: Meta-analysis of randomised trials. BMJ, 327: 643–648.


By Healthwise Staff
Primary Medical Reviewer Caroline S. Rhoads, MD - Internal Medicine
Primary Medical Reviewer Brian D. O'Brien, MD - Internal Medicine
Specialist Medical Reviewer Ken Y. Yoneda, MD - Pulmonology
Last Revised July 9, 2010

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