Methylxanthines: Uses, common brands, and safety info

Methylxanthines are a class of medications that come from naturally occurring substances such as tea, coffee, and chocolate. This class of medications is known for its effects on improving lung function and symptoms of lung conditions. The respiratory benefits of methylxanthines were noted in 1886 when an English physician experienced an improvement in his own asthma symptoms after consuming a strong cup of coffee. Theophylline is an example of a methylxanthine sometimes prescribed to relieve symptoms of wheezing and shortness of breath in those with asthma or COPD (chronic obstructive pulmonary disease). 

Continue reading to learn more about methylxanthines, their uses, and side effects.

Other methylxanthines

• Uniphyl (theophylline)

• Quibron-T (theophylline)

• Truxophylline (theophylline)

• Theolair (theophylline)

• Theochron (theophylline)

• TheoCap (theophylline)

• Theo-Time (theophylline)

• Theo-Dur (theophylline)

• Phyllocontin (aminophylline)

• Lufyllin (dyphylline)

• Dylix (dyphylline)

• Dilor (dyphylline)

What are methylxanthines?

Methylxanthines are substances derived from the purine base xanthine, a compound naturally produced by plants and animals. Also known as methylated xanthines or xanthine derivatives, methylxanthines include several different compounds, such as caffeine, aminophylline, paraxanthine, pentoxifylline, theobromine, and theophylline. Tea and coffee are natural sources of caffeine, and cacao is a natural source of theobromine. 

Theophylline and aminophylline are FDA-approved methylxanthines that may be prescribed to relieve symptoms of asthma or COPD. Theophylline, known by different brands such as Theo-24 and Theochron, is available as an oral elixir solution, extended-release tablet, and extended-release capsule. Aminophylline, known by brand names like Norphyl and Phyllocontin, is available as an oral solution, immediate-release tablet, extended-release tablet, injection, and suppository. 

Methylxanthines may be prescribed for those with COPD who regularly have nighttime symptoms, exacerbations (sudden, rapid worsening of symptoms), or breathing problems while on treatment with an inhaled beta-2 agonist and anticholinergic medication. 

Methylxanthines are typically not first-line agents because they have a narrow therapeutic window. In other words, the dose needed to provide therapeutic benefits is close to the dose that can cause potential adverse effects. 

How do methylxanthines work?

Clinical trials have shown that theophylline is more effective than a placebo for improving lung function in patients with stable COPD. However, the exact mechanism of action of methylxanthines work is unknown. Low doses of methylxanthines have been shown to have anti-inflammatory and immunomodulatory effects in those with asthma. At high doses, methylxanthines act as effective bronchodilators that help widen the airways. 

Researchers believe there are three main ways in which methylxanthines work:

• Phosphodiesterase inhibitor. Methylxanthines block the phosphodiesterase enzyme (PDE), which results in relaxation of smooth muscle in the lungs, dilation of pulmonary blood vessels, elimination of excess fluid through diuresis, and stimulation of the central nervous system (CNS). Phosphodiesterase inhibitors are known to be helpful in the treatment of chronic respiratory conditions. 

  central nervous system

• Adenosine receptor antagonist. Methylxanthines bind to adenosine receptors in the brain resulting in CNS stimulation, which promotes respiratory drive. Calcium uptake in the diaphragm muscles is also increased, which leads to increased contractility of the lungs.

   

• Histone deacetylase activator. Histone deacetylase is an enzyme that regulates inflammation. Methylxanthines increase the actions and effects of histone deacetylase to help decrease inflammation. In addition, methylxanthines can block another enzyme known as phosphoinositide-3-kinase-delta that is responsible for preventing the activation of histone deacetylase.

Theophylline typically needs to be taken in relatively high doses for maximum respiratory benefits. Because of the potential risk of toxicity and side effects, methylxanthines are not usually recommended as first-line agents for lung conditions. The dose of methylxanthines can vary widely and needs to be individualized on a case-by-case basis depending on the person’s response to the medicine. 

What are methylxanthines used for?

Methylxanthines are commonly used to treat breathing problems. Conditions that may be treated with methylxanthines include:

• Chronic obstructive pulmonary disease (COPD)

• Asthma

Non-FDA approved uses may include:

• Sleep apnea

• Apnea of prematurity

• Apnea of infancy

• Anosmia

Who can take methylxanthines?

Adults

Methylxanthines are primarily prescribed to adults with chronic lung conditions. These medications are generally not given as first-line treatments but may be added when other standard medications are not enough to control symptoms. The addition of a methylxanthine, such as theophylline, is considered when symptoms of asthma or COPD are not controlled with inhalers or other medications.

Maintaining the narrow therapeutic window of methylxanthines can be difficult with an oral tablet. Therefore, IV infusion may be the preferred method of administration in adults since it is easier to monitor levels and provides a more predictable concentration of the drug than oral formulations. 

Intravenous infusion of theophylline or aminophylline during an acute asthma attack can help control symptoms not responding to routine treatment. Methylxanthines require steady blood levels of the drug in order to be effective with the lowest possible risk of side effects, and, to achieve the proper levels in the blood, laboratory monitoring is usually required during treatment.

Children

Theophylline may be used in children for the treatment of asthma or COPD when inhaled glucocorticoids are ineffective or inappropriate, or when other medicines are ineffective. However, it is not preferred as a first-line agent. 

When young children have difficulty using an inhaler, slow-release theophylline capsule beads may be sprinkled on food.

Methylxanthines are used off-label to treat preterm infants with apnea, or a disorder in which breathing is interrupted. Caffeine is the preferred medication for preterm infants with apnea since it has been shown to have fewer side effects and a longer half-life than other methylxanthines in infants. 

Seniors

Seniors may take methylxanthines for the control of chronic breathing problems that do not respond to other treatments. 

Older adults are recommended to start treatment with methylxanthines on a low dose. The usual starting dose may be decreased by about 25% in seniors. Methylxanthines are processed in the liver, and older adults are typically at high risk of reduced liver functioning. Therefore, there’s a higher incidence of toxicity in seniors than in other age groups. Blood levels of the drug should be monitored to avoid side effects. 

Can you take methylxanthines while pregnant or breastfeeding?

Methylxanthines can cross the placenta during pregnancy but the exact effects on the developing fetus are still being studied. Uncontrolled asthma during pregnancy may result in harm to both the mother and unborn baby, so the risk and benefits of treatment should be weighed when deciding if treatment with a methylxanthine is appropriate. Blood levels should be monitored during drug therapy. When given near-term, methylxanthines may inhibit uterine contractions. 

Methylxanthines cross into breast milk. Infants may become irritable and should be observed for increased heart rate (tachycardia) or vomiting. Nursing mothers may consider feeding prior to taking a dose of methylxanthines to decrease the concentration of medication in the breast milk. Breastfeeding is not contraindicated when the mother and baby are monitored appropriately; however, the risks and benefits should be taken into account. 

Are methylxanthines safe?

In general, methylxanthines, when monitored appropriately, are safe. However, certain groups of people are at higher risk of side effects from methylxanthines.

Tell your healthcare provider if any of the following apply to you before taking a methylxanthine:

• Any drug allergies, especially drug allergies to xanthine derivatives

• Use of other medications, including prescription medications, over-the-counter drugs, and herbal supplements

• Currently pregnant or breastfeeding

• History of heart disease or heart problems, particularly heart rhythm problems

• Cystic fibrosis

• Liver problems

• Hyperthyroidism

• Peptic ulcer disease

• Seizure disorder

• Gastrointestinal problems

Black box warnings

There are no black box warnings for methylxanthines.

Methylxanthine recalls

There are currently no methylxanthine recalls.

Are methylxanthines controlled substances?

No, methylxanthines are not controlled substances. 

Methylxanthine restrictions

Theophylline injection should be avoided in anyone with a corn allergy or known hypersensitivity to theophylline.

Due to a risk of toxicity, decreased infusion rates and intensive monitoring may be required in neonates, infants, and the elderly, as well as those that are affected by the following:

• Acute pulmonary edema

• Heart failure

• Cor pulmonale

• Fever

• Liver disease

• Thyroid problems

• Sepsis

• Shock

Common methylxanthines side effects

The most common adverse effects of methylxanthines include:

• Nausea

• Vomiting

• Heartburn

• Insomnia

• Headache

• Irritability

• Restlessness

• Increased volume of urine

• Increased stomach acid secretion

• Tremors

Severe but rare side effects may include:

• Seizures

• Irregular heartbeat (cardiac arrhythmia)

• Rapid heart rate

• Slowed heart rate

• Severe vomiting

• Allergic skin reaction

• Elevated liver enzymes

• Shortness of breath

This list of side effects is not comprehensive. Consult a healthcare provider for a complete list of side effects, warnings, and precautions before starting treatment with a methylxanthine.

How much do methylxanthines cost?

Most methylxanthines are moderately priced. Methylxanthines are available in brand-name and generic formulations. Costs will vary depending on your insurance plan. Without insurance, the price can vary widely depending on the medication and quantity of medication prescribed. However, using a prescription discount card from SingleCare may help reduce the cost of methylxanthines.