Theophylline Toxicity

Although theophylline use is decreasing as other therapies for asthma and emphysema are increasingly being recognized as more efficacious, it still remains one of the five leading causes of drug-induced seizures. Because of a narrow toxic-therapeutic ratio and multiple drug interactions, theophylline toxicity is common. Of those individuals taking theophylline, the incidece of toxicity has been reported to be as high as 20%. Theophylline toxicity can be acute, acute-on-chronic, or chronic. Seizures are more common with chronic toxicity. Seizures associated with theophylline can be prolonged and fatal. Mortality as high as 60% has been reported.

Causes

The causes is not entirely clear.

Symptoms

• GI: anorexia, nausea, vomiting, and abdominal pain
• Tremor
• Anxiety or agitation
• Palpitations
• The symptoms of a serious chronic overdose are frequently subtle and nonspecific and may lead to a missed diagnosis.

Signs

• Agitation, confusion, and tremor are common and frequently precede seizures.
• Seizures may be focal or generalized, are frequently refractory, and portend a very high risk of morbidity and mortality. Seizures can occur without concomitant gastrointestinal or cardiac toxicity.
• Other common signs of toxicity include tachycardia, cardiac arrhythmias, hypotension, and hyperventilation.

Treatment

For patients with any of these conditions, theophylline levels should be kept below 10 mg/liter, or, if possible (in consultation with the internist), some alternatives to theophylline should be found.