What is Elixophyllin (theophylline)?
Elixophyllin also can be used to treat patients with emphysema and chronic bronchitis when their symptoms are related to reversible airway narrowing. Elixophyllin can be administered together with other bronchodilators, such as albuterol for added bronchodilator effect.
Asthma is a breathing problem caused by narrowing of the airways, the breathing passages that allow air to move in and out of the lungs. Airways can be narrowed due to accumulation of mucus, spasm of the muscles that surround these airways, or swelling of the lining of the airways.
Elixophyllin opens airways by relaxing the smooth muscles in the walls of the airways. Elixophyllin also can be helpful in patients with emphysema and chronic bronchitis when their symptoms are partially related to reversible airway narrowing. Elixophyllin also strengthens right heart function and diaphragm movement.
Common side effects of Elixophyllin include:
Serious side effects of Elixophyllin include:
Drug interactions of Elixophyllin include:
- oral contraceptives,
- fluvoxamine, and
St. John’s wort, rifampin, and carbamazepine decrease levels of Elixophyllin and potentially its effect by increasing its elimination.
Elixophyllin may decrease levels and the effect of carbamazepine by increasing its elimination.
There are no adequate studies of Elixophyllin in pregnant women. Elixophyllin is excreted in breast milk and may cause mild side effects such as irritability in the infant. Consult your doctor before breastfeeding.
What are the important side effects of Elixophyllin (theophylline)?
Common side effects are:
Other important and more serious side effects include seizures and heart arrhythmias. Theophylline should be used cautiously in patients with high blood pressure, peptic ulcer disease, seizure disorders, and serious heart disease, especially heart rhythm problems.
Elixophyllin (theophylline) side effects list for healthcare professionals
Adverse reactions associated with theophylline are generally mild when peak serum theophylline concentrations are < 20 mcg/mL and mainly consist of transient caffeine-like adverse effects such as nausea, vomiting, headache, and insomnia. When peak serum theophylline concentrations exceed 20 mcg/mL, however, theophylline produces a wide range of adverse reactions including persistent vomiting, cardiac arrhythmias, and intractable seizures which can be lethal.
The transient caffeine-like adverse reactions occur in about 50% of patients when theophylline therapy is initiated at doses higher than recommended initial doses (e.g., > 300 mg/day in adults and > 12 mg/kg/day in children beyond > 1 year of age). During the initiation of theophylline therapy, caffeine-like adverse effects may transiently alter patient behavior, especially in school age children, but this response rarely persists.
Initiation of theophylline therapy at a low dose with subsequent slow titration to a predetermined agerelated maximum dose will significantly reduce the frequency of these transient adverse effects (see In a small percentage of patients ( < 3% of children and < 10% of adults) the caffeine-like adverse effects persist during maintenance therapy, even at peak serum theophylline concentrations within the therapeutic range (i.e., 10-20 mcg/mL).
Dosage reduction may alleviate the caffeine-like adverse effects in these patients, however, persistent adverse effects should result in a reevaluation of the need for continued theophylline therapy and the potential therapeutic benefit of alternative treatment.
Other adverse reactions that have been reported at serum theophylline concentrations < 20 mcg/mL include diarrhea, irritability, restlessness, fine skeletal muscle tremors, and transient diuresis. In patients with hypoxia secondary to COPD, multifocal atrial tachycardia and flutter have been reported at serum theophylline concentrations ≥ 15 mcg/mL.
There have been a few isolated reports of seizures at serum theophylline concentrations < 20 mcg/mL in patients with an underlying neurological disease or in elderly patients. The occurrence of seizures in elderly patients with serum theophylline concentrations < 20 mcg/mL may be secondary to decreased protein binding resulting in a larger proportion of the total serum theophylline concentration in the pharmacologically active unbound form.
The clinical characteristics of the seizures reported in patients with serum theophylline concentrations < 20 mcg/mL have generally been milder than seizures associated with excessive serum theophylline concentrations resulting from an overdose (i.e., they have generally been transient, often stopped without anticonvulsant therapy, and did not result in neurological residua).
Table IV: Manifestations of theophylline toxicity.*
|Sign/Symptom||Percentage of patients reported with sign or symptom|
(Large Single Inges tion)
|Chronic Overdos age|
(Multiple Exces sive Doses )
|Other supraventricular tachycardias||2||21||12||14|
|Ventricular premature beats||3||21||10||19|
|Atrial fibrillation or flutter||1||NR**||12||NR**|
|Multifocal atrial tachycardia||0||NR**||2||NR**|
|Ventricular arrhythmias with hemodynamic instability||7||14||40||0|
|*These data are derived from two studies in patients with serum theophylline concentrations > 30 mcg/mL. In the first study (Study #1 - Shanon, Ann Intern Med 1993;119:1161-67), data were prospectively collected from 249 consecutive cases of theophylline toxicity referred to a regional poison center for consultation. In the second study (Study #2 - Sessler, Am J Med 1990;88:567-76), data were retrospectively collected from 116 cases with serum theophylline concentrations > 30 three emergency departments. Differences in the incidence of manifestations of theophylline toxicity between the two studies may reflect sample selection as a result of study design (e.g., in Study #1, 48% of the patients had acute intoxications versus only 10% in Study #2) and different methods of reporting results.|
**NR = Not reported in a comparable manner.
What drugs interact with Elixophyllin (theophylline)?
Theophylline interacts with a wide variety of drugs. The interaction may be pharmacodynamic, i.e., alterations in the therapeutic response to theophylline or another drug or occurrence of adverse effects without a change in serum theophylline concentration. More frequently, however, the interaction is pharmacokinetic, i.e., the rate of theophylline clearance is altered by another drug resulting in increased or decreased serum theophylline concentrations. Theophylline only rarely alters the pharmacokinetics of other drugs.
The drugs listed in Table II have the potential to produce clinically significant pharmacodynamic or pharmacokinetic interactions with theophylline. The information in the “Effect” column of Table II assumes that the interacting drug is being added to a steady-state theophylline regimen.
If theophylline is being initiated in a patient who is already taking a drug that inhibits theophylline clearance (e.g., cimetidine, erythromycin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be smaller. Conversely, if theophylline is being initiated in a patient who is already taking a drug that enhances theophylline clearance (e.g., rifampin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be larger.
Discontinuation of a concomitant drug that increases theophylline clearance will result in accumulation of theophylline to potentially toxic levels, unless the theophylline dose is appropriately reduced. Discontinuation of a concomitant drug that inhibits theophylline clearance will result in decreased serum theophylline concentrations, unless the theophylline dose is appropriately increased.
The drugs listed in Table III have either been documented not to interact with theophylline or do not produce a clinically significant interaction (i.e., < 15% change in theophylline clearance).
The listing of drugs in Table II and III are current as of February 9, 1995. New interactions are continuously being reported for theophylline, especially with new chemical entities. The clinician should not assume that a drug does not interact with theophylline if it is not listed in Table II. Before addition of a newly available drug in a patient receiving theophylline, the package insert of the new drug and/or the medical literature should be consulted to determine if an interaction between the new drug and theophylline has been reported.
Table II: Clinically significant drug interactions with theophylline*.
|Drug||Type of Interaction||Effect**|
|Adenosine||Theophylline blocks adenosine receptors.||Higher doses of adenosine may be required to achieve desired effect.|
|Alcohol||A single large dose of alcohol (3 ml/kg of whiskey) decreases theophylline clearance for up to 24 hours.||30% increase|
|Allopurinol||Decreases theophylline clearance at allopurinol doses ≥ 600 mg/day.||25% increase|
|Amino glutethimide||Increases theophylline clearance by induction of microsomal enzyme activity.||25% decrease|
|Carbamazepine||Similar to aminoglutethimide.||30% decrease|
|Cimetidine||Decreases theophylline clearance by inhibiting cytochrome P450 1A2.||70% increase|
|Ciprofloxacin||Similar to cimetidine.||40% increase|
|Clarithromycin||Similar to erythromycin.||25% increase|
|Diazepam Disulfiram||Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors. Decreases theophylline clearance by inhibiting hydroxylation and demethylation.||Larger diazepam doses may be required to produce desired level of sedation. Discontinuation of theophylline without reduction of diazepam dose may result in respiratory depression. 50% increase|
|Enoxacin||Similar to cimetidine.||300% increase|
|Ephedrine||Synergistic CNS effects||Increased frequency of nausea, nervousness, and insomnia.|
|Erythromycin||Erythromycin metabolite decreases theophylline clearance by inhibiting cytochrome P450 3A3.||35% increase. Erythromycin steady-state serum concentrations decrease by a similar amount.|
|Estrogen||Estrogen containing oral contraceptives decrease theophylline clearance in a dose- dependent fashion. The effect of progesterone on theophylline clearance is unknown.||30% increase|
|Flurazepam||Similar to diazepam.||Similar to diazepam.|
|Fluvoxamine||Similar to cimetidine||Similar to cimetidine|
|Halothane||Halothane sensitizes the myocardium to catecholamines, theophylline increases release of endogenous catecholamines.||Increased risk of ventricular arrhythmias.|
|Interferon, human recombinant alpha-A||Decreases theophylline clearance.||100% increase|
|Isoproterenol (IV)||Increases theophylline clearance.||20% decrease|
|Ketamine||Pharmacologic||May lower theophylline seizure threshold.|
|Lithium||Theophylline increases renal lithium clearance.||Lithium dose required to achieve a therapeutic serum concentration increased an average of 60%.|
|Lorazepam||Similar to diazepam.||Similar to diazepam.|
|Methotrexate (MTX)||Decreases theophylline clearance.||20% increase after low dose MTX, higher dose MTX may have a greater effect.|
|Mexiletine||Similar to disulfiram.||80% increase|
|Midazolam||Similar to diazepam.||Similar to diazepam.|
|Moricizine||Increases theophylline clearance.||25% decrease|
|Pancuronium||Theophylline may antagonize nondepolarizing neuromuscular blocking effects; possibly due to phosphodiesterase inhibition.||Larger dose of pancuronium may be required to achieve neuromuscular blockade.|
|Pentoxifylline||Decreases theophylline clearance.||30% increase|
|Phenobarbital (PB)||Similar to aminoglutethimide.||25% decrease after two weeks of concurrent PB.|
|Phenytoin||Phenytoin increases theophylline clearance by increasing microsomal enzyme activity. Theophylline decreases phenytoin absorption.||Serum theophylline and phenytoin concentrations decrease about 40%.|
|Propafenone||Decreases theophylline clearance and pharmacologic interaction.||40% increase. Beta-2 blocking effect may decrease efficacy of theophylline.|
|Propranolol||Similar to cimetidine and pharmacologic interaction.||100% increase. Beta-2 blocking effect may decrease efficacy of theophylline.|
|Rifampin||Increases theophylline clearance by increasing cytochrome P450 1A2 and 3A3 activity.||20-40% decrease|
|Sulfinpyrazone||Increases theophylline clearance by increasing demethylation and hydroxylation. Decreases renal clearanc of theophylline.||20% decrease e|
|T acrine||Similar to cimetidine, also increases renal clearance of theophylline.||90% increase|
|Thiabendazole||Decreases theophylline clearance.||190% increase|
|T iclo pidine||Decreases theophylline clearance.||60% increase|
|Troleandomycin||iSimilar to erythromycin.||33-100% increase depending on troleandomycin dose.|
|Verapamil||Similar to disulfiram.||20% increase|
|*Refer to product labeling for more information.|
**Average effect on steady state theophylline concentration or other clinical effect for pharmacologic interactions . Individual patients may experience larger changes in serum theophylline concentration than the value listed.
Table III. Drugs that have been documented not to interact with theophylline or drugs that produce no clinically significant interaction with theophylline.*
|albuterol, systemic and inhaled||felodipinefinasteride||nizatidine|
|ampicillin, with or without||isoflurane isoniazid||omeprazole prednisone,|
|sulbactam atenolol||isradipine||prednisolone ranitidine|
|caffeine, dietary ingestion||ketoconazo lelomefloxacin||roxithromycin sorbitol (purgative doses do not inhibit theophylline absorption)|
|co-trimoxazole (trimethoprim and sulfamethoxazole)||medroxyprogesterone|
|*Refer to product labeling for more information.|
The Effect Of Other Drugs On Theophylline Serum Concentration Measurements
Most serum theophylline assays in clinical use are immunoassays which are specific for theophylline. Other xanthines such as caffeine, dyphylline, and pentoxifylline are not detected by these assays. Some drugs (e.g., cefazolin, cephalothin), however, may interfere with certain HPLC techniques. Caffeine and xanthine metabolites in neonates or patients with renal dysfunction may cause the reading from some dry reagent office methods to be higher than the actual serum theophylline concentration.
Elixophyllin (theophylline) is a bronchodilator used to relieve and prevent airway narrowing (bronchospasm) in patients with asthma. Common side effects of Elixophyllin include nausea, vomiting, diarrhea, headaches, irritability, flushing, and palpitations. Serious side effects of Elixophyllin include seizures and heart arrhythmias. There are no adequate studies of Elixophyllin in pregnant women. Elixophyllin is excreted in breast milk and may cause mild side effects such as irritability in the infant. Consult your doctor before breastfeeding.
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Bronchitis is inflammation of the airways in the lung. Acute bronchitis is short in duration (10-20 days) in comparison with chronic bronchitis, which lasts for months to years. Causes of acute bronchitis include viruses and bacteria, which means it can be contagious. Acute bronchitis caused by environmental factors such as pollution or cigarette smoke is not contagious. Common symptoms for acute bronchitis include nasal congestion, cough, headache, sore throat, muscle aches, and fatigue. Acute bronchitis in children also my include runny nose, fever, and chest pain. Treatment for acute bronchitis are OTC pain relievers, cough suppressants (although not recommended in children), and rest. Infrequently antibiotics may be prescribed to treat acute bronchitis.
Second Source article from WebMD
Emphysema is a COPD (chronic obstructive pulmonary disease) that often occurs with other obstructive pulmonary problems and chronic bronchitis. Causes of emphysema include chronic cigarette smoking, exposure to secondhand smoke, air pollution, and in the underdeveloped parts of the world. Symptoms of emphysema include chronic cough, chest discomfort, breathlessness, and wheezing. Treatments include medication and lifestyle changes.
COPD vs. Asthma (Differences and Similarities)
COPD (chronic obstructive pulmonary disease) and asthma both have common symptoms like coughing, wheezing, shortness of breath, and a tight feeling in the chest. COPD is caused by tobacco smoking, while asthma is caused by your inherited genetic makeup and their interactions with the environment. Risk factors for asthma are obesity, exposure to cigarette smoke (even secondhand smoke), and personal history of hay fever. There is no cure for either disease, but symptoms can be managed with medication. A person with asthma has a better prognosis and life expectancy than someone with COPD.
Chronic bronchitis is a cough that occurs daily with production of sputum that lasts for at least 3 months, 2 years in a row. Causes of chronic bronchitis include cigarette smoking, inhaled irritants, and underlying disease processes (such as asthma, or congestive heart failure). Symptoms include cough, shortness of breath, and wheezing. Treatments include bronchodilators and steroids. Complications of chronic bronchitis include COPD and emphysema.
Asthma is a condition in which hyperreactive airways constrict and result in symptoms like wheezing, coughing, and shortness of breath. Causes of asthma include genetics, environmental factors, personal history of allergies, and other factors. Asthma is diagnosed by a physician based on a patient's family history and results from lung function tests and other exams. Inhaled corticosteroids (ICS) and long-acting bronchodilators (LABAs) are used in the treatment of asthma. Generally, the prognosis for a patient with asthma is good. Exposure to allergens found on farms may protect against asthma symptoms.
Asthma: Over the Counter Treatment
Patients who have infrequent, mild bouts of asthma attacks may use over-the-counter (OTC) medications to treat their asthma symptoms. OTC asthma medicines are limited to epinephrine and ephedrine. These OTC drugs are best used with the guidance of a physician, as there may be side effects and the drugs may not be very effective.
COPD vs. Emphysema
COPD (chronic obstructive pulmonary disease) is the term doctors and other healthcare professionals use to describe a group of serious, progressive (worsens over time), chronic lung diseases that include emphysema, chronic bronchitis, and sometimes asthma. The number one cause of COPD or emphysema, is smoking, and smoking is the third leading cause of death in the US.
There are two types of asthma medications: long-term control with anti-inflammatory drugs and quick relief from bronchodilators. Asthma medicines may be inhaled using a metered-dose inhaler or nebulizer or they may be taken orally. People with high blood pressure, diabetes, thyroid disease, or heart disease shouldn't take OTC asthma drugs like Primatene Mist and Bronkaid.
Asthma in Children
Asthma in children manifests with symptoms such as coughing and wheezing. Rates of asthma in children are increasing. Asthma in children is usually diagnosed based on the description of symptoms. Lung function tests may also be used. A variety of medications are used for the treatment of childhood asthma.
What Is Asthma? 19 Complex Facts
There are many unusual symptoms of asthma, including sighing, difficulty sleeping, anxiety, chronic cough, recurrent walking pneumonia, and rapid breathing. These symptoms may vary from individual to individual. These asthma complexities make it difficult to accurately diagnose and treat asthma.
Adult-onset asthma is asthma that is diagnosed in people over 20 years of age. Symptoms include wheezing, coughing, shortness of breath and difficulty breathing. Treatment may involve anti-inflammatory medications or bronchodilators.
Occupational asthma is a type of asthma caused by exposure to a substance in the workplace. Symptoms and signs include wheezing, chest tightness, and shortness of breath. The usual treatment for occupational asthma involves removal from exposure and the use of bronchodilators and inhaled anti-inflammatory medicines.
Exercise-induced asthma is asthma triggered by vigorous exercise. Symptoms include coughing, shortness of breath, chest tightness, wheezing, and fatigue while exercising. Preventing exercise-induced asthma attacks involves using inhaled medicines before exercising, performing warm-up exercises and cooling down afterward, avoiding exercising outdoors when pollen counts are high, restricting exercise when you have a viral infection, and wearing a mask over your nose and mouth when exercising in cold weather.
Emphysema, Chronic Bronchitis, and Colds
If you have a COPD such as emphysema, avoiding chronic bronchitis and colds is important to avoid a more severe respiratory infection such as pneumonia. Avoiding cigarette smoking, practice good hygeine, stay away from crowds, and alerting your healthcare provider if you have a sinus infection or cold or cough that becomes worse. Treatment options depend upon the severity of the emphysema, bronchitis, or cold combination.
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Medications & Supplements
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.