What is the appropriate dosage of Deriphylline (theophylline) for an adult patient with asthma or chronic obstructive pulmonary disease (COPD)?

Derphylline (Theophylline) 300 mg Dosing

For adult patients with asthma or COPD, a 300 mg dose of theophylline (Derphylline) is within the appropriate range, but dosing must be titrated to achieve target serum levels of 5-15 μg/mL, with therapeutic monitoring required to prevent toxicity. 1

Target Serum Levels and Monitoring

The European Respiratory Society guidelines establish that therapeutic effects occur at blood levels >5 μg/mL, while side effects increase considerably at levels >15 μg/mL. 1 This narrow therapeutic window necessitates careful dose adjustment.

Monitoring Schedule

• Peak blood levels should be monitored after methylxanthines are begun, every 6-12 months during therapy, after changes in dose or preparation, and with changes in drugs or conditions that affect metabolism. 1
• In acutely ill patients, serum theophylline concentrations should be monitored at frequent intervals, such as every 24 hours. 2

Standard Dosing Approach

Most adults achieve therapeutic concentrations with daily slow-release oral theophylline preparations of 200-400 mg (approximately 10 mg/kg) twice daily. 3 A 300 mg dose falls within this range and represents a reasonable starting or maintenance dose.

Dose Titration Strategy

• Start with a sufficiently low dose and slowly increase in small increments if clinically indicated, with dose increases only made if the previous dosage is well tolerated and at intervals of no less than 3 days to allow serum concentrations to reach steady state. 2
• The median theophylline dose required to achieve therapeutic levels varies fourfold among similar patients (400-1600 mg/day in adults <60 years old). 2

Factors Affecting Dosing Requirements

Conditions That Increase Blood Levels (Require Lower Doses)

Old age, sustained fever, heart and liver failure, and drugs such as cimetidine, ciprofloxacin, and oral contraceptives increase blood levels and prolong half-life. 1

Conditions That Decrease Blood Levels (May Require Higher Doses)

Smoking, alcohol, anticonvulsants, and rifampicin induce liver enzymes and reduce the half-life of methylxanthines. 1

Side Effects and Safety Considerations

Side effects include gastric irritation, nausea, diarrhea, headache, tremor, irritability, sleep disturbance, epileptic seizures, and cardiac arrhythmias. 1

Safety in Elderly Patients

A prospective study of 3,810 elderly patients (≥65 years) treated with sustained-release theophylline 400 mg/day showed that theophylline-related adverse events occurred in only 4.71% of patients, with no convulsions reported. 4 The incidence of adverse events was higher in patients with hepatic disease (odds ratio 1.81) and arrhythmia (odds ratio 1.88). 4

Clinical Positioning

Theophylline has comparable or less bronchodilator effect than β2-agonists or anticholinergic agents, but should be prescribed when these first-line agents are insufficient. 1 If theophylline is not tolerated, consider long-acting oral or inhaled β2-agonists as alternatives. 1

Acute Exacerbations

In patients already taking oral theophyllines who present with acute exacerbations, 68% already have therapeutic levels (>10 μg/mL) and do not require additional intravenous theophylline, which may induce serious toxicity. 3

Body Weight Considerations

Theophylline distributes poorly into body fat; therefore, mg/kg dose should be calculated on the basis of ideal body weight, not actual body weight. 2