AMINOPHYLLIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMINOPHYLLIN (AMINOPHYLLIN).
Non-selective phosphodiesterase inhibitor, increasing intracellular cAMP and cGMP; adenosine receptor antagonist, causing bronchodilation, CNS stimulation, and positive chronotropic/inotropic effects.
| Metabolism | Hepatic demethylation and oxidation via cytochrome P450 isoenzymes (CYP1A2, CYP3A4, CYP2E1); approximately 10% excreted unchanged in urine. |
| Excretion | Renal excretion of unchanged drug accounts for ~10%, with the remainder eliminated as metabolites (caffeine, 3-methylxanthine, 1-methyluric acid, 1,3-dimethyluric acid) via urine; minimal biliary/fecal elimination (<5%). |
| Half-life | Terminal elimination half-life: 3–12 hours in adults (mean ~6 hours); prolonged in hepatic impairment, heart failure, or COPD (up to 30 hours); shorter in smokers (4–5 hours due to CYP1A2 induction); neonates: 20–40 hours. |
| Protein binding | ~40% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 0.5 L/kg (range 0.3–0.7 L/kg); increased in neonates, cirrhosis, and malnutrition; reflects distribution into total body water. |
| Bioavailability | Oral (immediate-release): 100% (well absorbed); rectal: ~80% (variable); IV: 100%. |
| Onset of Action | IV: 5–15 minutes; rectal: 20–30 minutes; oral immediate-release: 30–60 minutes; oral sustained-release: 1–2 hours. |
| Duration of Action | IV: 4–6 hours; oral immediate-release: 4–6 hours; oral sustained-release: 8–12 hours; rectal: 4–6 hours. |
| Action Class | Theophylline & its derivatives |
| Brand Substitutes | Biofylin 250mg Injection |
Loading dose: 6 mg/kg IV over 30 minutes (if not on theophylline); maintenance: 0.5-0.7 mg/kg/hr IV continuous infusion for adults (non-smoking), higher for smokers (0.7-0.9 mg/kg/hr). Oral: immediate-release 200-400 mg every 6 hours; sustained-release 400-600 mg every 12 hours.
| Dosage form | INJECTABLE |
| Renal impairment | GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: reduce dose by 25% and monitor levels; GFR <10 mL/min: reduce dose by 50% and monitor levels closely. |
| Liver impairment | Child-Pugh A: reduce dose by 50%; Child-Pugh B: reduce dose by 75%; Child-Pugh C: use with extreme caution, reduce dose by 90% or consider alternative. |
| Pediatric use | Loading dose: 5-6 mg/kg IV over 30 minutes (if not on theophylline); maintenance: infants <1 year: 0.4-0.7 mg/kg/hr IV; children 1-9 years: 0.8-1.0 mg/kg/hr IV; children >9 years: 0.6-0.8 mg/kg/hr IV. Oral: immediate-release 5 mg/kg every 6 hours; sustained-release not recommended under 6 years. |
| Geriatric use | Reduce maintenance dose by 50-75% compared to younger adults; monitor serum theophylline levels closely; typical starting maintenance: 0.3-0.5 mg/kg/hr IV; avoid doses >400 mg/day oral. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AMINOPHYLLIN (AMINOPHYLLIN).
| Breastfeeding | Aminophylline is excreted into breast milk; the M/P ratio (milk-to-plasma ratio) is approximately 0.6-0.8. Infant exposure is low (about 1-10% of maternal weight-adjusted dose). Use with caution; monitor infant for irritability and sleep disturbance. Generally considered compatible with breastfeeding. |
| Teratogenic Risk | Aminophylline, a theophylline salt, is not teratogenic in humans. First trimester: No increased risk of major malformations. Second trimester: No specific fetal risks; maternal asthma control benefits outweigh risks. Third trimester: Risk of neonatal apnea, irritability, and tachycardia if maternal levels are high; avoid toxic levels. |
■ FDA Black Box Warning
No specific FDA boxed warning for aminophylline; however, theophylline (its active metabolite) has a narrow therapeutic index and requires serum concentration monitoring to avoid toxicity.
| Serious Effects |
Hypersensitivity to aminophylline, theophylline, or ethylenediamine; active peptic ulcer disease; uncontrolled seizure disorders; severe cardiac arrhythmias (unless patient is undergoing monitored treatment).
| Precautions | Narrow therapeutic index; monitor serum concentrations (target 10-20 mcg/mL); caution in patients with peptic ulcer, hyperthyroidism, seizure disorders, cardiac arrhythmias; use with drugs that affect CYP1A2 (e.g., cimetidine, fluoroquinolones, fluvoxamine) or induce metabolism (e.g., smoking, rifampin, phenytoin). |
| Food/Dietary | High-fat meals can delay absorption of aminophylline. Avoid charred meat and foods containing large amounts of caffeine. Cruciferous vegetables (broccoli, brussels sprouts) may increase metabolism. Maintain consistent dietary intake of protein and carbohydrates as changes can affect theophylline clearance. |
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| Fetal Monitoring | Monitor maternal serum theophylline levels (target 5-15 mcg/mL) to avoid toxicity. Assess maternal pulmonary function and symptoms. Fetal monitoring: Non-stress test or biophysical profile if indicated for maternal condition. In third trimester, monitor for neonatal toxicity signs (tachycardia, irritability, vomiting) post-delivery. |
| Fertility Effects | Aminophylline has no known direct effect on human fertility. There is no evidence of impaired fertility in animal studies at therapeutic doses. No impact on ovulation or spermatogenesis reported. |
| Clinical Pearls | Aminophylline is a bronchodilator composed of theophylline and ethylenediamine. The ethylenediamine component can cause hypersensitivity reactions. Monitor theophylline serum levels (target 10-20 mcg/mL). Use with caution in patients with cardiac arrhythmias, seizures, or peptic ulcer disease. Avoid in patients with porphyria. Cimetidine, ciprofloxacin, and macrolides can increase theophylline levels. Smoking induces metabolism, requiring higher doses. |
| Patient Advice | Take this medication exactly as prescribed, with or without food. · Do not crush or chew extended-release formulations. · Avoid consuming large amounts of caffeine (coffee, tea, chocolate, energy drinks) as it may increase side effects. · Report symptoms such as rapid heart rate, persistent nausea/vomiting, insomnia, or seizures immediately. · Do not stop abruptly without consulting your doctor. · Keep a regular dosing schedule to maintain consistent blood levels. |