Respbid Disease Interactions

Methylxanthines are known to stimulate peptic acid secretion. Therapy with products containing methylxanthines should be administered with extreme caution in patients with active peptic ulcer disease. Some manufacturers consider their use to be contraindicated under such circumstance.

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The metabolites of theophylline, which are generally undetectable in patients with normal renal function, may accumulate in patients with renal impairment and contribute to the toxicity of theophylline. In addition, the plasma protein binding of theophylline may be significantly decreased in renal impairment, resulting in elevated free drug concentrations and further increasing the risk of toxicity. Therapy with theophyllines should be administered cautiously in patients with impaired renal function. Dosage adjustments and more intensive monitoring of serum theophylline concentrations may be required.

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The use of theophyllines is considered by some manufacturers to be contraindicated in patients with underlying seizure disorders unless they are receiving adequate anticonvulsant therapy. Theophyllines may cause seizures, which have generally been associated with toxic drug levels but have also been reported at therapeutic concentrations in patients with head trauma or cerebral infarct. If theophylline therapy is administered in patients with these or other risk factors for seizures, serum drug levels should be monitored closely and maintained in the low therapeutic range. Intractable seizures and death have been reported during acute theophylline toxicity.

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Methylxanthines increase gastric acidity and may also relax lower esophageal sphincter, which can lead to gastric reflux into the esophagus. Therapy with products containing methylxanthines should be administered cautiously in patients with significant gastroesophageal reflux.

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Theophylline is removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

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Certain conditions have been identified as causes of reduced theophylline clearance. They include age (neonates and infants < 1 year as well as elderly patients > 60 years) and the following concurrent diseases: acute pulmonary edema; decompensated heart failure; cor pulmonale; fever (>= 102 degrees for 24 hours or more, or lesser temperature elevations for longer periods); influenza; untreated or uncontrolled hypothyroidism; liver disease, cirrhosis or acute hepatitis; reduced renal function in infants < 3 months of age; sepsis with multi-organ failure; and shock. Therapy with theophyllines should be administered cautiously in patients presenting with one or more of these risk factors, and the dosage should be appropriately reduced to prevent toxicity. More intensive monitoring of serum theophylline concentrations may be required. Toxicity is most likely to occur when levels exceed 20 mcg/mL. Severe cases, sometimes without previous warning, have led to cardiac arrhythmias, intractable seizures, and death.

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The use of theophyllines is associated with an increase in heart rate which may progress to supraventricular tachycardia or ventricular arrhythmia at high serum drug concentrations. Appearance of cardiac adverse effects is generally an indication of theophylline toxicity, although patients with a history of tachyarrhythmias may be more susceptible to the chronotropic effect of these drugs. Therapy with theophyllines should be administered cautiously in such patients. Caution is also advised in patients with hypertension, hyperthyroidism, angina pectoris, or recent myocardial infarction, since high dosages of the drugs are associated with positive inotropic as well as chronotropic effects. Clinical monitoring of serum drug concentrations is recommended to prevent toxicity.

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