Theophylline is a prescription drug with a long history as a treatment for asthma (a chronic inflammation of the airway tissues). As one of the first long-term bronchodilators (medications that widen the airways by relaxing the smooth muscle), it has also been used to treat other respiratory disorders such as bronchitis, emphysema and chronic obstructive pulmonary disease (COPD). In recent years, the medication had fallen out of favor with some physicians because of concerns about the danger of toxicity from having too much of the drug in the bloodstream.

However, new discoveries about the medication's effects on inflammation and immune function related to asthma have renewed interest in theophylline. It may be a useful drug to combine with low-dose inhaled corticosteroids (medications that prevent the inflammation associated with asthma attacks) for asthma management. There also is evidence that the drug has a more powerful anti-inflammatory effect than high-dose inhaled corticosteroids in treating COPD. In addition, new extended-release forms of the medication have made it somewhat easier to ensure that patients have just the right amount of theophylline in their bloodstream at all times.

Despite these improvements, theophylline is a drug that must be used with caution. Illnesses, smoking and other medications can alter the rate at which the drug is cleared from the body. Patients who take theophylline must have their blood checked regularly to ensure that the concentration of the medication in their bloodstream remains at a therapeutic level – enough to be effective, but not so much that it becomes toxic.

Theophylline is a prescription drug that has been used to treat asthma (a chronic inflammation of the airway tissues) for decades. In recent years, concern over side effects associated with the drug has lessened its use. Many physicians turned instead to alternative asthma treatments, such as inhaled beta2-agonists (medications that relax muscles in the air passageways to prevent narrowing and to open the airways) and inhaled corticosteroids (medications that prevent the inflammation associated with asthma attacks). While theophylline is still widely prescribed in poorer countries (due to its affordability), its popularity has decreased in industrialized nations.

However, new discoveries about theophylline have led to renewed interest in the drug as an asthma treatment. For many years, the process by which theophylline affects asthma symptoms was unknown. Recent studies now show that theophylline inhibits the release of histamine, a chemical that plays a key role in triggering an asthma attack. In addition, theophylline appears to suppress airway inflammation, another major cause of asthma symptoms.

Theophylline has a powerful effect on the late-phase allergic reaction of allergic asthma (inflammation of the lung's airways that is caused by an allergic reaction), which is believed to be the key reaction in the development of airway hyperreactivity (an exaggerated constriction of the airways in response to stimuli). This is important, because hyperreactive airways go into spasm from many irritants, including cold air and strong perfumes.

In addition, theophylline relaxes smooth muscles in the airway, allowing more air into the body. Theophylline may also increase the strength of a weakened diaphragm (allowing it to draw more air into the lungs) and stimulate the brain’s breathing control centers. Finally, it may reduce the volume of gas trapped in the lungs. All of these effects help improve the breathing ability of patients with asthma and other lung diseases.

Those who take theophylline must be aware that there is a very small difference between a proper dose of the drug and a toxic overdose. For this reason, many physicians reject using theophylline and instead prescribe newer medications with fewer or less serious potential side effects.

Brands of theophylline currently in use include:

Not all brands of theophylline enter the bloodstream at the same rate. Patients should be sure to take the same brand or generic form, and the same formulation for each treatment. 

Theophylline is available in pill, liquid or injectable form. Each dose should be taken at the same time of day to ensure that the drug remains at a consistent concentration in the bloodstream. The medication should be taken with a full glass of water. Taking the medication with food may decrease the chances of an upset stomach. Some formulations may be sprinkled over soft foods such as applesauce and then consumed. However, other forms of the drug should be taken on an empty stomach, either one hour before eating or two hours after a meal.

It is crucial that patients take exactly the prescribed dose of theophylline. For this reason, those who take the medication in liquid form should not use tableware spoons to measure their doses. A measuring spoon or cup should come with the medication. If not, patients can ask a pharmacist for an effective measure. Theophylline also is available in extended-release pill form, which should not be chewed or crushed.

In rare cases, theophylline may be used in combination with other drugs. For example, theophylline, ephedrine and phenobarbital can be combined to treat symptoms of allergic asthma (inflammation of the lung's airways that is caused by an allergic reaction), asthmatic bronchitis (a respiratory condition characterized by a chronic cough, wheezing and airflow obstruction in people with asthma) and other lung disorders. The combination helps force open the air passages and increases the flow of air through the bronchial tubes, two large air passageways that lead from the windpipe into the lungs. These combinations are rarely used because they usually have too little theophylline to be effective and can be sedating.

Theophylline is used to prevent and treat symptoms of asthma (a chronic inflammation of the airway tissues), bronchitis (an inflammation of the mucous membranes in the bronchial tubes, which connect the windpipe to the lungs), emphysema (a condition in which the air sacs in the lungs are damaged, interfering with the normal exchange of oxygen and carbon dioxide) and chronic obstructive pulmonary disease, or COPD (a chronic, progressive lung condition characterized by coughing, wheezing and shortness of breath). It relaxes and opens the air passages in the lungs, making it easier for a person to breathe.

Because of the dangers of toxicity associated with theophylline overdose, it no longer is the drug of first choice to treat these conditions. However, the drug may be combined with low-dose inhaled corticosteroids (medications that prevent the inflammation associated with asthma attacks) to increase the potency of asthma treatments. It also may be prescribed to treat COPD in situations where patients cannot breathe properly despite using both an inhaled beta2 agonist (medications that relax muscles in the air passageways to prevent narrowing and to open the airways) and an inhaled anticholinergic (medications that smooth muscle contractions and reduce excess mucus in the tubes that transport air to and from the lungs).

The amount of theophylline needed to prevent symptoms varies from patient to patient. Dosage is based on a number of factors, including the patient's:

• Age
• Weight
• Severity of asthma
• Diet
• Additional medications
• Rate of theophylline elimination in the body

In order to determine if a patient is receiving the proper amount, a physician may order a blood test to measure the level of theophylline in the blood. The blood level range for safe, effective levels of theophylline is very narrow. Maintaining the proper level of theophylline is important because too little does not work and too much can be toxic. Therefore, it is extremely important to have the levels monitored by the physician as directed.

Those who take theophylline should be aware that there is a very small difference between a proper dose of the medication and a dangerous, toxic dose. For this reason, extreme caution must be exercised by all patients using theophylline.

Theophylline is usually taken every 6, 8, 12 or 24 hours. Those who miss a dose should take theophylline as soon as they remember unless it is at a time near to the next regularly-scheduled dose. In the latter case, the missed dose should not be made up. Never take a double dose of the medication, as there is a very small difference between the proper dose of theophylline and an overdose that requires medical attention.

Patients who have been prescribed this drug should take it exactly as directed by their physician. They should continue to take it even if they feel well and are not experiencing symptoms. A patient should not stop taking the drug unless advised to do so by their physician. 

Minor side effects associated with theophylline (especially nervousness and headache) can be reduced by avoiding food and drinks high in caffeine (e.g., coffee, tea, cocoa, cola, chocolate). Theophylline and caffeine are chemically related and combined use of these substances can increase side effects. Side effects associated with the medication include:

• Upset stomach and heartburn
• Stomach pain
• Diarrhea
• Restlessness
• Nervousness or irritability
• Headache
• Slight nausea
• Vomiting
• Decreased appetite or weight loss
• Insomnia
• Lightheadedness or dizziness
• Slight tremor or shakiness
• Frequent urination (polyuria)

Other side effects might indicate toxic levels of theophylline in the bloodstream. Patients experiencing any of the following should consult a physician immediately:

• Seizures
• Low blood sugar
• Irregular heartbeat (arrhythmia)
• Rapid heart rate (tachycardia)
• Rapid breathing (tachypnea)
• Severe nausea or vomiting
• A fever of 102 degrees Fahrenheit (39 degrees Celsius) or higher develops and persists for more than 12 hours

In addition, patients experiencing signs and symptoms of an allergic reaction (e.g., skin rash) should consult their physician. Individuals experiencing signs and symptoms of anaphylaxis (a severe allergic reaction involving two or more body systems) should seek immediate medical attention. Without immediate emergency treatment, anaphylaxis can quickly progress to life-threatening anaphylactic shock, which is characterized by difficulty breathing and a dangerous drop in blood pressure. Signs and symptoms of anaphylaxis include:

• Breathing problems
  
• Closing of throat
  
• Hives (pink or white bumps that appear on or beneath the skin)
  
• Swelling of lips, tongue or face

Theophylline interacts with several different types of medications. Therefore, it is important that patients inform their physician and pharmacist about any medications they are taking, including prescriptions, over-the-counter medications, vitamins, supplements and herbal remedies. Patients are encouraged to ask about other drugs that should be avoided when taking theophylline. 

Patients may also benefit from avoiding foods and beverages containing caffeine (e.g., coffee, tea, cocoa, cola, chocolate). Caffeine is known to increase minor side effects associated with theophylline because they are chemically related (especially nervousness, shakiness and headache). Individuals who increase or decrease their caffeine intake while taking theophylline should alert their physician because their medication dosage may need to be adjusted.

Patients who take theophylline must be regularly monitored to ensure the safety of medication levels in the bloodstream. There is a very small difference between a proper dose of the medication and a dangerous, toxic dose. Many drugs and other factors may alter the rate at which theophylline is cleared from the body.

Medications known to increase the levels of theophylline in the bloodstream (thereby potentially triggering a medical emergency) include:

• Cimetidine (used to treat gastrointestinal ulcers)
  
  
• Some antibiotics, including:
• • Ciprofloxacin
  • Clarithromycin
  • Enoxacin
  • Erythromycin
  • Lomefloxacin
  • Norfloxacin
  • Ofloxacin
    
    
• Disulfiram (used to treat chronic alcoholism)
  
  
• Estrogens (used in birth control or hormone replacement medications)
  
  
• Methotrexate (used to treat some cancers and rheumatoid arthritis)
  
  
• Some antiarrhythmics (used to treat abnormal heart rhythms), including:
• • Mexiletine
  • Propafenone
    
    
• Some cox-2 inhibitors (used to treat arthritis)
  
  
• Some antihypertensives (used to treat high blood pressure), including:
• • Propranolol
  • Verapamil
    
    
• Tacrine (used to treat Alzheimer’s disease)
  
  
• Ticlopidine (used to prevent blood clots)

In addition, ingredients contained in certain over-the-counter and prescription cold, allergy and asthma medications may increase the risk for side effects when combined with theophylline. These include:

• Ephedrine
• Epinephrine
• Phenylephrine
• Phenylpropanolamine
• Pseudoephedrine

Other factors known to increase the rate that theophylline is removed from the body (and thus require higher doses of the drug for optimum treatment) include:

• Young age (less than 16)
• Alcohol use
• Smoking (tobacco or marijuana)
• High-protein, low-carbohydrate diets
• Barbecued meat (chemical compounds in grilled meat affect the way the liver processes the medication)

Medications known to decrease the levels of theophylline in the bloodstream (thereby decreasing its effectiveness) include:

• Aminoglutethimide (used to treat tumors and other adrenal disorders)
  
  
• Some anticonvulsants (used to treat seizures and epilepsy), including:
• • Carbamazepine
  • Phenytoin
  • Phenobarbital (also a sedative used to treat anxiety)
  • Isoproterenol (used in the treatment of asthma and other lung diseases)
    
    
• Moricizine (used to treat abnormal heart rhythms)
  
  
• Rifampin (an antibiotic used to treat tuberculosis)
  
  
• Sucralfate (used to treat and prevent ulcers)
  
  
• Allopurinol (used to treat gout)
  
  
• Serotonin uptake inhibitors (SSRIs – used to treat depression and obsessive compulsive disorders), including fluvoxamine
  
  
• Some leukotriene modifiers (used to treat asthma and some allergies), including zileuton

Other factors known to decrease the rate that theophylline is removed from the body and increase the chance of side effects include:

• Advanced age
  
  
• Certain medical conditions, including heart failure, liver disease, pneumonia or viral infection and vaccination
  
  
• High-carbohydrate diets

In addition, taking theophylline in combination with lithium (a drug used to treat bipolar disorder) may decrease the amount of lithium in the bloodstream by increasing the amount of lithium lost through urine output. Increased doses of lithium may be needed when these drugs are used together.

The U.S. Food and Drug Administration has listed theophylline as being category C, which means it is unknown whether or not theophylline is harmful to unborn babies. Those who are pregnant or are considering becoming pregnant should inform their physician. The ability of pregnant women to clear theophylline from the body also decreases in latter months, so a dosage adjustment may be recommended.

Theophylline is passed through breast milk and should not be taken by breastfeeding mothers because of potential risks for nursing infants.

Preparing questions in advance can help patients to have more meaningful discussions with their physicians. Patients may wish to ask their doctors the following theophylline-related questions:

1. Theophylline appears to be a controversial drug. Is it safe for me to take?
   
   
2. What risks do I face by taking theophylline?
   
   
3. What side effects may I develop while using theophylline?
   
   
4. What symptoms indicate an overdose of theophylline? What should I do if I experience these symptoms?
   
   
5. What types of drugs/other substances should I avoid while taking theophylline?
   
   
6. How and when should I use this drug?
   
   
7. What should I do if I miss a dose?
   
   
8. How long will it take for the drug to take effect? How will I know if the drug is working?
   
   
9. How long will I have to take the drug?
   
   
10. Will I require frequent blood tests while taking this drug? If so, how often?
    
    
11. Can I use the drug more often if my symptoms persist?
    
    
12. Can I use the drug less often if I feel better?
    
    
13. Is there a chance the drug will not be effective in relieving my symptoms?