AMINOPHYLLINE IN SODIUM CHLORIDE 0.45% IN PLASTIC CONTAINER
Clinical safety rating
safeNo significant drug interactions Can cause hypernatremia and fluid overload.
Aminophylline is a complex of theophylline and ethylenediamine. Theophylline acts as a non-selective phosphodiesterase inhibitor, increasing intracellular cyclic AMP levels, leading to bronchodilation. It also blocks adenosine receptors, stimulates catecholamine release, and enhances diaphragmatic contractility. The ethylenediamine component increases solubility.
| Metabolism | Theophylline is metabolized primarily in the liver by cytochrome P450 isoenzymes, predominantly CYP1A2, with minor contributions from CYP2E1 and CYP3A4. Metabolism involves N-demethylation and oxidation. In neonates, metabolism is immature; in adults, ~90% is hepatically cleared. Ethylenediamine is minimally metabolized. |
| Excretion | Renal excretion of unchanged drug (about 10-20%) and metabolites (primarily 1,3-dimethyluric acid, 1-methyluric acid, 3-methylxanthine). Billary/fecal excretion is negligible. |
| Half-life | Terminal elimination half-life: 3-12 hours in adults (mean 5-6 hours); prolonged in hepatic impairment, heart failure, COPD, and neonates (up to 30 hours). Smoking reduces half-life by 30-50%. |
| Protein binding | Theophylline (active moiety): approximately 40% bound to plasma proteins, primarily albumin. Protein binding decreases in neonates, hepatic cirrhosis, and uremia. |
| Volume of Distribution | Apparent volume of distribution: approximately 0.4-0.6 L/kg (average 0.45 L/kg). Indicates distribution into total body water; slightly higher in neonates and premature infants. |
| Bioavailability | Oral: 96-100% for immediate-release tablets; 50-70% for some sustained-release formulations depending on formulation. Rectal: 70-80% (variable). IV: 100%. |
| Onset of Action | Intravenous: onset within 5-30 minutes; oral (immediate-release): 30-60 minutes; rectal: variable, 15-60 minutes. |
| Duration of Action | Duration of bronchodilation: 6-8 hours after IV or oral immediate-release; sustained-release formulations provide 8-12 hours. Clinical effect correlates with serum concentration (10-20 mcg/mL). |
| Molecular Weight | 420.43 |
Loading dose: 5-6 mg/kg IV over 20-30 minutes (if not on theophylline). Maintenance: 0.5-0.7 mg/kg/h IV continuous infusion.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR >30 mL/min. For GFR 10-30 mL/min: reduce maintenance dose by 50% and monitor serum theophylline levels. For GFR <10 mL/min: reduce maintenance dose by 50% and extend dosing interval or use with caution. |
| Liver impairment | Child-Pugh A: reduce dose by 50%. Child-Pugh B: reduce dose by 75%. Child-Pugh C: contraindicated or use with extreme caution, reduce dose by 80% and monitor levels. |
| Pediatric use | Loading dose: 1 mg/kg IV (if not on theophylline). Maintenance: Continuous infusion: age 6 months-1 year: 0.5 mg/kg/h; age 1-9 years: 0.8 mg/kg/h; age 9-12 years: 0.7 mg/kg/h; age 12-16 years: 0.6 mg/kg/h. Maximum daily dose: 24 mg/kg/day. |
| Geriatric use | Consider lower initial doses due to decreased clearance. Use ideal body weight. Start at lower maintenance infusion rate (e.g., 0.3 mg/kg/h) and titrate based on serum levels and clinical response. Monitor for toxicity. |
| 1st trimester | Use only if clearly needed; risk of fetal tachycardia and neonatal apnea with high doses. |
| 2nd trimester | Use only if clearly needed; monitor maternal levels to avoid toxicity. |
| 3rd trimester | Use with caution near term; may cause neonatal irritability, apnea, or hypoglycemia. |
Clinical note
No significant drug interactions Can cause hypernatremia and fluid overload.
| FDA category | Animal |
| Placental transfer | Aminophylline crosses the placenta; fetal serum levels approximate maternal levels. |
| Breastfeeding | Aminophylline is excreted into breast milk in low amounts (about 1% of maternal dose). Monitor infant for irritability, sleep disturbance, or feeding problems. Consider risk-benefit. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C. First trimester: Limited human data; animal studies show no teratogenicity but some developmental delays at high doses. Second and third trimesters: Use only if benefit outweighs risk; may cause fetal tachycardia or irritability due to adenosine receptor blockade. Avoid near term due to potential neonatal irritability. |
| Fetal Monitoring | Monitor maternal heart rate and respiratory status. Assess fetal heart rate and uterine activity if used for preterm labor or in third trimester. Monitor serum theophylline levels (target 10–20 mcg/mL) to avoid toxicity. |
| Fertility Effects | No known direct effects on human fertility. Animal studies at high doses have shown reversible impairment in spermatogenesis. No evidence of significant impact on female fertility. |
■ FDA Black Box Warning
None
| Common Effects | fluid replacement |
| Serious Effects |
Hypersensitivity to aminophylline or theophyllineActive peptic ulcer diseaseSeizure disorder (uncontrolled)
| Precautions | Narrow therapeutic index; serum theophylline levels must be monitored to avoid toxicity. Risk of seizures, cardiac arrhythmias, and death, especially at high serum concentrations. Caution in patients with hepatic impairment, congestive heart failure, cor pulmonale, fever, and in the elderly. Drug interactions with cimetidine, fluoroquinolones, macrolides, oral contraceptives, and other CYP1A2 inhibitors can increase toxicity. |
| Food/Dietary | Avoid large amounts of caffeine-containing foods and beverages (coffee, tea, cola, chocolate) as they can potentiate theophylline effects and increase risk of toxicity. A high-protein diet may increase theophylline clearance; maintain consistent dietary habits. |
| Clinical Pearls | Aminophylline is a bronchodilator used primarily for asthma and COPD exacerbations. Monitor serum theophylline levels closely due to narrow therapeutic index (10-20 mcg/mL). Administer IV infusion over 30 minutes to avoid hypotension. Caution in patients with cardiac arrhythmias, hyperthyroidism, or seizure disorders. Drug interactions include cimetidine, fluoroquinolones, and macrolides which increase theophylline levels. |
| Patient Advice | Take this medication exactly as prescribed; do not stop or change dose without consulting your doctor. · Avoid excessive caffeine intake (coffee, tea, chocolate, cola) as it may increase side effects like jitteriness and palpitations. · Report any symptoms of toxicity such as nausea, vomiting, insomnia, rapid heart rate, or seizures immediately. · Inform your healthcare provider of all other medications, especially antibiotics, heart medications, or seizure drugs. · Do not chew or crush the solution; it is for intravenous use only under medical supervision. |
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