Management of Asthma and Chronic Airflow Limitation (Part 14)

Investigators have reported drug interactions with theophylline with increasing frequency. Indeed, the recently introduced quinolone antibiotics such as norfloxacin and ciprofloxacin have been associated with at least one death attributed to theophylline toxicity. Calcium channel blockers are other commonly used drugs that may have profound effects on theophylline clearance. Common non-life-threatening side effects of theophylline include nausea, heartburn, tremor, headache, anxiety and insomnia, while two life-threatening adverse effects associated with theophylline use are intractable seizures and cardiac arrhythmias. The risk of drug toxicity is increased with increasing patient age and with the presence of underlying fiver or congestive heart failure.
Seizures are frequently associated with high serum drug levels, but there is no correlation between blood levels and seizure activity.- They may occur without other warning signs of toxicity and are often refractory to the usual anticonvulsant therapy. Furthermore, mortality associated with this serious complication has been reported to be as high as 50 percent.
Theophylline can precipitate sinus tachycardia or life-threatening atrial and ventricular ectopic rhythms. As with theophylline-induced seizures, serum theophylline levels may be a poor predictor of serious drug-induced arrhythmias. A variety of factors which have been shown to impair theophylline clearance are summarized in Table 2.

Table 2—Other Factors Impairing Theophylline ClearancelAbsorption




Diet (high carbohydrate-low protein


Food in stomach (children)

Viral infections

Cor pulmonale

Pulmonary edema

Liver disease