Low-Dose Theophylline Not Effective at Reducing COPD ...

Oral theophylline has been used as a bronchodilator to treat chronic obstructive pulmonary disease (COPD) for decades, but it has fallen out of favor due to the side effects that come with the higher doses that are required to achieve any beneficial effect, as well as the advancement of improved drug treatment. However, due to its low expense, theophylline is still used around the world. A recent study sought to determine if adding low-dose theophylline to inhaled corticosteroids for COPD would reduce the number of exacerbations, and found that it did not.

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JAMA published results of a randomized clinical trial that included 1567 participants with COPD treated with inhaled corticosteroids.1 Participants were randomized to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (n = 791) or receive placebo (n = 787).

Of the 1567 participants analyzed, the average age was 68.4 years and 54% (843) were men. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 0.7 with at least 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid.

The addition of theophylline did not significantly reduce the mean number of exacerbations compared with placebo over a 1-year period, the study found.

In total, there were 3430 exacerbations: 1727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) versus 1703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, −0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08).

Serious adverse events in the theophylline and placebo groups included cardiac (2.4% vs 3.4%, respectively), gastrointestinal (2.7% vs 1.3%), and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%).

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline does not recommend the use of theophylline unless other long-term treatment bronchodilators are unavailable or unaffordable. However, GOLD does not dismiss the use of low-dose theophylline, highlighting that the clinical relevance of low-dose theophylline has not been fully established and that clinical evidence, particularly on exacerbations, is limited and contradictory.

By 2020, COPD, which is largely preventable and often stems from smoking, is expected to be the third-leading cause of death.

In an accompanying editorial, 2 physicians called the results “disappointing,” noting that the drug is inexpensive.2 They wrote that interest in theophylline to prevent exacerbations stems from its possible anti-inflammatory properties. However, those findings rely on higher plasma concentrations than those tolerated by patients.

References

1. Devereux G, Cotton S, Fielding S, et al. Effect of theophylline as adjunct to inhaled corticosteroids on exacerbations in patients with COPD. JAMA. 2018;320(15):1548-1559. doi:10.1001/jama.2018.14432

2. Criner GJ, Celli BR Failure of low-dose theophylline to prevent exacerbations in patients with COPD. JAMA. 2018;320(15):1541-1542. doi:10.1001/jama.2018.14295

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1. Why is Theophylline no longer used?

Theophylline is a weak bronchodilator and does not help in reducing lung inflammation. It does little but has very severe side effects. Long-term usage can cause toxicity in the body and affect the central nervous system. Plasma toxicity can occur when plasma concentrations in the serum exceed 20 mg/l. Thus, Theophylline is no longer used as widely as it was in the 1900s.

2. How long does it take for Theophylline to work?

Theophylline acts by opening the lungs’ airways. As a Beta2-agonist, it relaxes muscles and reduces the response to substances that constricts the airways. However, it is only available in a long-acting form. It cannot relieve sudden breathing problems and cannot be taken right away. It takes effect within 1–2 days.

3. Can Theophylline be stopped immediately?

Stopping your Theophylline dosage suddenly may lead to your asthma symptoms returning and may cause a fatal asthma attack. You must taper the Theophylline dosage slowly until a stable therapeutic level is achieved. If you’re taking it with other drugs, reducing it by 50% would help. As a precaution, take Theophylline only as and when your doctor prescribes it.

4. Is Theophylline a bronchodilator?

Yes, Theophylline is a bronchodilator. Bronchodilators relax the muscles in the bronchial tubes (air passages) of the lungs. They increase the airflow in the bronchial tubes, relieving cough, wheezing, troubled breathing, and shortness of breath. Theophylline is a bronchodilator used to control asthma and is taken as a pill.

5. When should you take Theophylline?

Your doctor will prescribe Theophylline only if you have serious lung diseases like COPD or asthma. Theophylline is prescribed with other drugs to limit its usage. Administer Theophylline only under expert medical supervision and exactly as prescribed. Due to its intense side effects, your doctor will constantly monitor your system.

6. Can alcohol be taken occasionally with Theophylline?

Alcohol and tobacco consumption under Theophylline can cause a decrease in plasma concentration levels and reduce its effectiveness. Avoid medications containing caffeine if you’re taking Theophylline. You may also need to limit your intake of caffeine-containing beverages or food like colas, chocolates, coffee, tea, etc. Consult your doctor or medical experts to avoid any severe side effects.

7. Is Theophylline a steroid?

No, Theophylline is not a steroid. It is a xanthine drug known as 1,3-dimethylxanthine. Unlike steroids, it is not a chemical version of the body’s hormones. Theophylline is majorly used to treat lung diseases like chronic obstructive pulmonary disease (COPD) and asthma. It is not as effective in reducing inflammation as steroids.

8. Is Theophylline still prescribed?

Theophylline is one of the most widely used drugs since 1922 to treat lung diseases. It has fallen in and out of favor with doctors. Due to its narrow therapeutic window, when taking Theophylline, your body needs constant supervision by medical experts. However, many doctors still recommend Theophylline as it is inexpensive.

9. When should you take Theophylline?

Your doctor will prescribe Theophylline only if you have serious lung diseases like COPD or asthma. Theophylline is prescribed with other drugs to limit its usage. Administer Theophylline only under expert medical supervision and exactly as prescribed. Due to its intense side effects, your doctor will constantly monitor your system.

10. Is Theophylline still used for COPD?

Theophylline has been used as a bronchodilator for COPD since the 1900s. It is still recommended worldwide due to its low cost. However, today, better drugs and bronchodilators are available which have the same effects. However, Theophylline is still administered at low dosages in combination with other drugs. Your doctor will make the final decision here.

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