Precautions concerning of use of theophylline

Theophylline is commonly prescribed for pediatric patients with asthma, other forms of reactive airway disease, and apnea of prematurity.1-3 This statement is to remind physicians of the necessity to reduce the dosage of theophylline and to monitor the patient's serum concentration to prevent increased risk of toxicity when the drug is administered in the presence of acute febrile illness or in combination with certain medications. The serum concentration of theophylline must be maintained within a relatively narrow range to achieve optimal therapeutic benefit while avoiding toxic side effects. While patients with milder airway disease may benefit from serum concentrations less than 10 mg/L, the greatest likelihood of obtaining maximal bronchodilatation with reasonable safety is achieved with peak serum concentrations between 10 mg/L to 20 mg/L.4-7 Serum concentrations of 6 mg/L to 12 mg/L are recommended when treating patients for apnea.3 Doses required to maintain theophylline concentrations within these ranges vary greatly due to large individual differences in theophylline metabolism.8-14 Undesirable side effects, including headaches, dizziness, nervousness, insomnia, anorexia, nausea, vomiting, and epigastric pain have been associated with serum theophylline concentrations which exceed the recommended therapeutic range.15-19 Concentrations greater than 30 mg/L carry an increased risk of more serious side effects, including hypokalemia, cardiac dysrhythmia, and seizures.18-22 Although seizures are uncommon at concentrations less than 40 mg/L,15,17 there is not a strong correlation between serum concentration and risk of seizures. Seizures have occurred in patients with serum concentrations less than 20 mg/L;17 in contrast, individuals have tolerated serum levels greater than 120 mg/L with no seizure activity.19