What is the recommended dosing for theophylline?

Theophylline Dosing Recommendations

The recommended dosing for theophylline must be individualized based on serum concentration monitoring, with a target therapeutic range of 5-15 mcg/mL at steady state, due to wide interpatient variability in theophylline clearance. 1

Initial Dosing Recommendations

Children

• Children <45 kg:

  • Starting dose: 12-14 mg/kg/day divided every 4-6 hours (maximum 300 mg/day)
  • After 3 days, if tolerated: 16 mg/kg/day (maximum 400 mg/day)
  • After 3 more days, if tolerated: 20 mg/kg/day (maximum 600 mg/day) 2

• Age-specific dosing:

  • Children 1-9 years: 10-36 mg/kg/day (average ~24 mg/kg/day) 2, 3
  • Children 9-16 years: Progressively decreasing dose requirements to ~13 mg/kg/day 3

Adults

• Adults <60 years without risk factors:
  • Starting dose: 300 mg/day divided every 6-8 hours
  • After 3 days, if tolerated: 400 mg/day divided every 6-8 hours
  • After 3 more days, if tolerated: 600 mg/day divided every 6-8 hours 2
  • Typical dose range: 400-1600 mg/day 2

Special Populations

• Patients with risk factors for impaired clearance, elderly (>60 years), or when monitoring is not feasible:
  • Children 1-15 years: Maximum 16 mg/kg/day (not exceeding 400 mg/day)
  • Adults and elderly: Maximum 400 mg/day 2

Monitoring and Dose Adjustment

1. Serum concentration monitoring:

   • Essential due to narrow therapeutic window and wide interpatient variability
   • Target serum concentration: 5-15 mcg/mL 1
   • Timing: At least 48 hours on same dosage to reach steady state 1

2. Monitoring frequency:

   • Acutely ill patients: Every 24 hours
   • Rapidly growing children: Every 6 months
   • All others: Yearly intervals 2

3. Dose adjustments:

   • Make adjustments at intervals of no less than 3 days
   • Base adjustments on serum theophylline concentration measurements
   • Discontinue any dosage causing adverse effects and resume at lower, previously tolerated dose 2

Important Considerations and Cautions

1. Risk factors affecting clearance:

   • Upper respiratory tract infections reduce clearance by approximately 40% 4
   • Other factors: Diet, febrile illness, age, smoking, and drug interactions 1

2. Adverse effects:

   • At therapeutic doses: Insomnia, gastric upset, aggravation of ulcer/reflux, hyperactivity in children, difficulty urinating in elderly men with prostatism 1
   • Dose-related toxicities: Tachycardia, nausea, vomiting, tachyarrhythmias, CNS stimulation, headache, seizures, hyperglycemia, hypokalemia 1

3. Drug interactions:

   • Zileuton inhibits theophylline metabolism, requiring dose monitoring 1
   • Tacrine may interact with theophylline 1

Special Clinical Situations

1. Acute bronchodilation:

   • Inhaled beta-2 selective agonists (with or without systemic corticosteroids) are more effective than theophylline for acute exacerbations 2
   • Theophylline provides no added benefit in acute bronchospasm 2

2. Neonates with perinatal asphyxia:

   • A single dose of theophylline may be given in neonates with severe perinatal asphyxia at high risk of acute kidney injury 1

3. Patients on maintenance theophylline presenting with acute asthma:

   • Check serum levels before administering additional theophylline
   • Most patients (68%) already have therapeutic levels and may not require additional IV theophylline 5

Common Pitfalls to Avoid

1. Failing to monitor serum concentrations - Essential due to 4-fold variation in clearance among similar patients 2

2. Increasing dose too rapidly - Wait at least 3 days between dose increases to allow steady state to be reached 2

3. Ignoring risk factors for reduced clearance - Adjust dosing in patients with concurrent URTI (reduce dose by ~40%) 4

4. Calculating dose based on actual rather than ideal body weight - Theophylline distributes poorly into body fat 2

5. Administering loading doses unnecessarily - For patients already on maintenance therapy presenting with acute symptoms, check levels first 5

By following these recommendations and carefully monitoring serum concentrations, theophylline can be used effectively while minimizing the risk of toxicity.