AMINOPHYLLINE
Clinical safety rating
cautionComprehensive clinical and safety monograph for AMINOPHYLLINE (AMINOPHYLLINE).
Aminophylline is a bronchodilator and respiratory stimulator that acts as a non-selective phosphodiesterase inhibitor, increasing cyclic AMP levels, and as an adenosine receptor antagonist. It also enhances diaphragmatic contractility and mucociliary clearance.
| Metabolism | Hepatic metabolism via CYP1A2 and xanthine oxidase; demethylation and oxidation yield active metabolites (caffeine and 3-methylxanthine). |
| Excretion | Renal: ~10% unchanged; hepatic metabolism (N-demethylation, oxidation) accounts for >80% of elimination; <1% fecal. |
| Half-life | Adults: 7-9 hours (nonsmokers), 4-5 hours (smokers), 10-20 hours (neonates, hepatic impairment, CHF). |
| Protein binding | Approximately 40-60% bound to albumin in adults; lower in neonates (20-30%) and patients with hepatic disease. |
| Volume of Distribution | 0.3-0.7 L/kg (average 0.45 L/kg); increased in neonates, cirrhosis, and CHF. |
| Bioavailability | Oral: ~100% (well-absorbed); Rectal: ~80-100% (variable); IM: ~100% (avoid due to pain and unpredictable absorption). |
| Onset of Action | IV: 1-2 minutes; Oral immediate-release: 30-60 minutes; Oral sustained-release: 1-2 hours. |
| Duration of Action | IV: 30-60 minutes; Oral immediate-release: 4-6 hours; Oral sustained-release: 8-12 hours. |
| Molecular Weight | 420.43 |
| Action Class | Theophylline & its derivatives |
Loading dose: 5-6 mg/kg IV over 20-30 minutes (if no recent theophylline). Maintenance: 0.4-0.6 mg/kg/hour IV continuous infusion; oral: 300-600 mg/day divided every 6-8 hours.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment required based on GFR; monitor theophylline levels closely in renal impairment. |
| Liver impairment | Child-Pugh A: reduce dose by 25%; Child-Pugh B: reduce dose by 50%; Child-Pugh C: reduce dose by 50-75% or consider alternative. |
| Pediatric use | Oral: 5 mg/kg/dose every 6 hours; IV loading: 5-6 mg/kg; maintenance: 0.5-0.9 mg/kg/hour for ages 6 months-9 years, 0.4-0.5 mg/kg/hour for ages 9-16 years. |
| Geriatric use | Reduce initial dose by 50% (e.g., 0.2-0.3 mg/kg/hour IV) due to decreased clearance; monitor serum theophylline levels and titrate slowly. |
| 1st trimester | Limited data; no major teratogenic risk observed in most studies, but use only if clearly needed. |
| 2nd trimester | Use if benefit outweighs risk; monitor for maternal and fetal tachycardia. |
| 3rd trimester | Use caution; may cause neonatal jitteriness, tachycardia, and vomiting due to caffeine metabolite. |
Clinical note
Comprehensive clinical and safety monograph for AMINOPHYLLINE (AMINOPHYLLINE).
| Placental transfer | Crosses placenta readily; fetal concentrations similar to maternal. |
| Breastfeeding | Excreted in breast milk in low amounts; may cause irritability or poor sleep in infants; weigh benefits against risks. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | Aminophylline is a bronchodilator containing theophylline and ethylenediamine. Theophylline crosses the placenta and fetal serum concentrations approximate maternal levels. In the first trimester, limited data do not indicate a significant increase in major malformations, but the drug should be used only if clearly needed. In the second and third trimesters, theophylline may cause fetal tachycardia, jitteriness, and irritability if maternal levels are high. Near term, accumulation of theophylline in the fetus may lead to neonatal withdrawal (irritability, apnea) and transient tachycardia. Risk is dose-dependent and more pronounced at serum levels >15 mcg/mL. |
| Fetal Monitoring | Monitor maternal serum theophylline levels regularly, aiming for trough levels of 5-15 mcg/mL. Assess maternal heart rate, respiratory rate, and signs of toxicity (nausea, vomiting, palpitations, arrhythmias). Fetal monitoring: nonstress test or biophysical profile if maternal levels are high or if fetal tachycardia or decreased fetal movements occur. Neonatal monitoring: observe for jitteriness, irritability, apnea, and feeding difficulties in the first 24-48 hours after delivery, especially if mother received high doses near term. |
| Fertility Effects | No well-documented adverse effects on human fertility. Animal studies have not shown significant impairment of fertility. However, aminophylline may cause changes in uterine contractility (relaxation of uterine muscle), but this does not affect fertility directly. In women requiring bronchodilators for asthma, uncontrolled asthma can adversely affect fertility and pregnancy outcomes, so adequate treatment is important. |
■ FDA Black Box Warning
No FDA boxed warning exists; however, use caution in patients with acute myocardial injury due to potential arrhythmias.
| Serious Effects |
Hypersensitivity to aminophylline or xanthinesUncontrolled seizure disordersSevere coronary artery diseaseActive peptic ulcer disease
| Precautions | Narrow therapeutic index requiring monitoring of serum theophylline levels; increased seizure risk at high concentrations; arrhythmia risk; caution in heart failure, hepatic impairment, and elderly. |
| Food/Dietary | Avoid high-fat meals which can decrease absorption and lead to variable serum levels. Limit caffeine intake (coffee, tea, cola, chocolate) as it may increase theophylline toxicity and side effects. Charcoal-broiled foods and a high-protein, low-carbohydrate diet may increase clearance of theophylline. Consistently maintain dietary habits to avoid fluctuations in theophylline levels. |
| Clinical Pearls | 1. Aminophylline is a bronchodilator that is a combination of theophylline and ethylenediamine; the ethylenediamine component may cause allergic reactions in sensitive individuals. 2. Monitor serum theophylline levels closely (therapeutic range: 10-20 mcg/mL); toxicity can occur at levels >20 mcg/mL with symptoms including nausea, vomiting, tachycardia, and seizures. 3. Use with caution in patients with severe hypoxemia, and treat with diltiazem or benzodiazepines for seizures if they occur. 4. Aminophylline can cause significant drug interactions, particularly with cimetidine, fluoroquinolones, and macrolide antibiotics which increase theophylline levels. 5. In acute asthma exacerbations, aminophylline is typically reserved for cases not responding to inhaled beta-agonists and corticosteroids due to narrow therapeutic index. |
| Patient Advice | Take this medication exactly as prescribed; do not chew or crush extended-release tablets. · Avoid consuming large amounts of caffeine (coffee, tea, chocolate, cola) as it may increase side effects such as nervousness and palpitations. · Notify your doctor immediately if you experience nausea, vomiting, irregular heartbeats, or seizures. · Do not smoke or stop smoking without consulting your doctor, as smoking affects how this medication works. · Keep a record of peak flow readings as directed by your healthcare provider. |
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