Aminophylline Dosing in Asthma/COPD with Renal Impairment
In patients with impaired renal function and asthma or COPD, aminophylline should be used with extreme caution at reduced infusion rates not exceeding 17 mg/hr (21 mg/hr as aminophylline) unless serum concentrations can be monitored at 24-hour intervals, as renal dysfunction significantly increases serum theophylline levels and toxicity risk. 1
Initial Loading Dose
For patients NOT on oral theophyllines in the previous 24 hours: Administer 4.6 mg/kg theophylline (5.7 mg/kg as aminophylline) based on ideal body weight over 30 minutes, which produces an average serum concentration of 10 mcg/mL (range 6-16 mcg/mL) 1
For patients already on oral theophyllines: DO NOT give a loading dose without first obtaining a serum theophylline level 2, 3. Calculate the loading dose as: D = (Desired C - Measured C) × 0.5 L/kg, where desired concentration should be conservative at 10 mcg/mL 1
Dosing should be based on ideal body weight, not total body weight, as theophylline distributes poorly into body fat 1, 4
Maintenance Infusion in Renal Impairment
Critical adjustment for renal dysfunction:
Initial infusion rate must not exceed 17 mg/hr theophylline (21 mg/hr as aminophylline) in patients with renal dysfunction, regardless of body weight 1
This is substantially lower than the standard adult dose of 0.4 mg/kg/hr (approximately 28 mg/hr for a 70 kg patient) 1
Five days may be required to reach steady-state in patients with renal impairment, compared to 1-2 days in patients with normal renal function 1
Therapeutic Monitoring Requirements
Serum level monitoring is mandatory in renal impairment:
Obtain first level 30 minutes after loading dose to assess distribution 1
Obtain second level one expected half-life after starting infusion (likely prolonged in renal dysfunction - may be 12-24 hours rather than the standard 8 hours) 1
Monitor at 24-hour intervals thereafter until stable, then continue monitoring every 24 hours 1
Target therapeutic range: 5-15 mcg/mL (some sources use 10-20 mcg/mL, but conservative targeting of 5-15 mcg/mL reduces toxicity risk) 2, 1
Side effects increase considerably at levels >15 mcg/mL 2
Clinical Context and Efficacy Considerations
Aminophylline has limited efficacy and significant toxicity concerns:
Aminophylline provides comparable or less bronchodilation than β2-agonists or anticholinergics 2
In acute asthma, most patients receiving maximal nebulized β-agonists derive no additional benefit from intravenous aminophylline 2
A 2012 Cochrane review found no significant reduction in hospital admissions (OR 0.58; 95% CI 0.30-1.12) and no significant improvement in peak expiratory flow when aminophylline was added to β2-agonists 5
Reserve aminophylline for patients with very severe disease at presentation or those who fail to improve rapidly with oxygen, steroids, and β-agonists alone 2, 3
Adverse Effects (Increased Risk in Renal Impairment)
Toxicity is substantially increased in renal dysfunction:
Renal impairment increases serum levels through reduced clearance 1
Common adverse effects include: gastric irritation, nausea, vomiting, diarrhea, headache, tremor, irritability, sleep disturbance 2
Serious toxicity: epileptic seizures, cardiac arrhythmias 2
In clinical trials, aminophylline caused additional vomiting in 20 per 100 patients and arrhythmias/palpitations in 15 per 100 patients compared to standard care 5
Critical Pitfalls to Avoid
Never give a loading dose to patients on oral theophyllines without checking serum level first - this can cause life-threatening toxicity 2, 3, 1, 6
Do not use standard maintenance infusion rates in renal impairment - the 17 mg/hr maximum is absolute unless intensive monitoring is available 1
Do not assume therapeutic benefit - aminophylline should not be first-line therapy and may provide no additional bronchodilation beyond standard treatments 2, 3, 5
Monitor for drug interactions - cimetidine, ciprofloxacin, and oral contraceptives increase theophylline levels and are particularly dangerous in renal impairment 2, 1