Is Deriphylline (theophylline) 150mg twice daily (bd) an adequate dose for an adult with asthma or chronic obstructive pulmonary disease (COPD)?

Deriphylline 150mg BD Dosing Assessment

Deriphylline (theophylline) 150mg twice daily (300mg total daily dose) is generally suboptimal for most adults and requires dose adjustment based on therapeutic drug monitoring to achieve target serum levels of 5-15 μg/mL, as this dose alone is unlikely to achieve therapeutic concentrations in the majority of patients.

Therapeutic Considerations

Target Serum Levels and Monitoring

• Therapeutic effects of theophylline occur at blood levels >5 μg/mL, while side-effects increase considerably at levels >15 μg/mL 1
• 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 interacting drugs or clinical conditions 1
• The typical adult dose required to achieve therapeutic levels is usually 400mg/day or higher, making 300mg/day (150mg BD) likely insufficient for most patients 2

Clinical Role and Efficacy

• Theophylline has comparable or less bronchodilator effect than β2-agonists or anticholinergic agents and should not be considered first-line therapy 1
• The British Thoracic Society guidelines state that theophyllines are of limited value in the routine management of COPD 1
• For stable chronic bronchitis, theophylline should be considered to control chronic cough with careful monitoring for complications 1
• For acute exacerbations of chronic bronchitis, theophylline should NOT be used 1

Factors Affecting Dosing Requirements

Factors that DECREASE theophylline levels (requiring higher doses):

• Smoking 1
• Alcohol consumption 1
• Anticonvulsants 1
• Rifampicin 1

Factors that INCREASE theophylline levels (requiring lower doses):

• Old age 1
• Sustained fever 1
• Heart failure 1
• Liver failure 1
• Cimetidine 1
• Ciprofloxacin 1
• Oral contraceptives 1

Safety Profile

• Side-effects include gastric irritation, nausea, diarrhea, headache, tremor, irritability, sleep disturbance, epileptic seizures, and cardiac arrhythmias 1
• A large prospective study in 3,810 elderly patients (mean age 73.8 years) showed theophylline-related adverse events in only 4.71% of patients at 400mg/day, with no convulsions reported 2
• Higher incidence of adverse events occurs in patients with hepatic disease (odds ratio 1.81) and arrhythmia (odds ratio 1.88) 2

Clinical Algorithm for Theophylline Use

Step 1: Ensure patient has failed or is using optimal doses of β2-agonists and anticholinergic agents first 1

Step 2: If theophylline is indicated, start with slow-release formulations that can produce stable serum concentrations with once or twice-daily dosing 1

Step 3: For most adults without contraindications, initiate at 400mg/day rather than 300mg/day 2

Step 4: Measure peak blood levels after initiation to confirm therapeutic range (5-15 μg/mL) 1

Step 5: Adjust dose based on serum levels, clinical response, and presence of drug interactions or comorbidities 1

Step 6: Monitor levels every 6-12 months during stable therapy 1

Critical Pitfalls to Avoid

• Do not use 150mg BD as a final dose without therapeutic drug monitoring - this dose is likely subtherapeutic for most patients
• Do not use theophylline during acute exacerbations - it provides no benefit and increases risk 1
• Do not prescribe without considering drug interactions - multiple medications significantly alter theophylline metabolism 1
• Do not use as first-line therapy - β2-agonists and anticholinergics are superior 1