AMINOPHYLLINE IN SODIUM CHLORIDE 0.45%
Clinical safety rating
safeNo significant drug interactions Can cause hypernatremia and fluid overload.
Aminophylline is a complex of theophylline and ethylenediamine, acting as a phosphodiesterase inhibitor, increasing intracellular cAMP levels; nonselective adenosine receptor antagonist; enhances cardiac inotropy, bronchodilation, and CNS stimulation.
| Metabolism | Hepatic via cytochrome P450 enzymes (CYP1A2, CYP3A4, CYP2E1); saturable kinetics; extensive first-pass metabolism. |
| Excretion | Renal excretion of unchanged theophylline (10-20%) and metabolites (80-90%). In neonates, renal excretion of unchanged drug is higher (up to 50%). Biliary/fecal excretion is negligible. |
| Half-life | Terminal elimination half-life is 6-12 hours in adults, 1-5 hours in children (due to faster clearance), 20-30 hours in premature neonates, and 10-15 hours in patients with hepatic cirrhosis or heart failure. Clinical context: dosing interval adjustment required based on half-life; prolonged half-life in hepatic impairment or cardiac decompensation increases risk of toxicity. |
| Protein binding | Approximately 40% bound to plasma proteins, mainly albumin. In neonates, preterm infants, and patients with hepatic cirrhosis, protein binding is reduced (free fraction increases). Binding is also saturable at high theophylline concentrations. |
| Volume of Distribution | Volume of distribution is approximately 0.45 L/kg (range 0.3-0.7 L/kg) in adults. In neonates, Vd is larger (~0.6-0.8 L/kg). Clinical meaning: Vd indicates extensive distribution into body water; loading doses are calculated using Vd (e.g., 1 mg/kg raises serum concentration by ~2 mcg/mL). |
| Bioavailability | Oral immediate-release: 100% (well absorbed). Rectal: 80-100% (absorption may be erratic). IV: 100%. No significant first-pass metabolism. |
| Onset of Action | Intravenous (IV): Onset within minutes, peak effect at 15-30 minutes. Oral immediate-release: 30-60 minutes. Oral sustained-release: 1-2 hours. Rectal: 30-60 minutes. |
| Duration of Action | IV: 6-8 hours (varies with dose and clearance). Oral immediate-release: 4-6 hours. Oral sustained-release: 8-12 hours. Clinical notes: Duration is prolonged in patients with reduced clearance; sustained-release formulations provide more consistent serum levels. |
| Molecular Weight | 420.39 |
Loading dose: 5-6 mg/kg IV over 20-30 minutes, then continuous infusion: 0.5-0.7 mg/kg/hour IV.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required for GFR >10 mL/min. For GFR <10 mL/min, reduce infusion rate by 50%. |
| Liver impairment | Child-Pugh Class A: reduce dose by 25%; Class B: reduce dose by 50%; Class C: reduce dose by 75%. |
| Pediatric use | Loading dose: 5-6 mg/kg IV over 20-30 minutes; continuous infusion: 0.5-0.7 mg/kg/hour (age-dependent, with lower doses for younger children). |
| Geriatric use | Elderly patients may have reduced clearance; consider starting at the lower end of dosing range (e.g., 0.3-0.5 mg/kg/hour) and titrate based on serum levels. |
| 1st trimester | Associated with risk of teratogenicity (oral clefts, cardiovascular malformations) in early pregnancy; use only if clearly needed. |
| 2nd trimester | May cause fetal tachycardia and jitteriness; avoid high doses. Use with caution. |
| 3rd trimester | Neonatal effects: jitteriness, tachycardia, vomiting, and apnea after birth. Avoid near term. |
Clinical note
No significant drug interactions Can cause hypernatremia and fluid overload.
| FDA category | Animal |
| Placental transfer | Crosses placenta readily; fetal serum levels approximate maternal levels. |
| Breastfeeding | Excreted into breast milk; may cause irritability and insomnia in infants. Use with caution and monitor infant. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data; no increased risk of major malformations observed in human studies. Second and third trimesters: Risk of fetal tachycardia and jitteriness with high maternal doses; may cause transient neonatal tachycardia with chronic use. No documented teratogenicity. |
| Fetal Monitoring | Monitor maternal serum theophylline levels (therapeutic range 5-15 mcg/mL), heart rate, respiratory rate, and signs of toxicity (tachycardia, nausea, seizures). Fetal monitoring: heart rate for tachycardia; assess for neonatal withdrawal or toxicity at birth. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment. Minimal impact expected. |
■ FDA Black Box Warning
Theophylline toxicity is dose-related and can be fatal; monitor serum theophylline levels closely; use with caution in patients with risk factors for reduced clearance (e.g., hepatic impairment, heart failure, elderly).
| Common Effects | fluid replacement |
| Serious Effects |
Hypersensitivity to aminophylline or theophyllineSeizure disorder (unless adequately controlled)Active peptic ulcer disease
| Precautions | Narrow therapeutic index; severe toxicity can occur at levels >20 mcg/mL, Seizures and arrhythmias may occur without preceding symptoms, Variable clearance due to drug interactions, disease states, age, and smoking, Use with caution in peptic ulcer disease, seizure disorders, hyperthyroidism, and cardiac disease |
| Food/Dietary | Avoid high-dose caffeine (coffee, tea, energy drinks, chocolate) as it may increase risk of side effects like nausea, anxiety, and tachycardia. Charcoal-broiled foods and a high-protein diet may increase theophylline clearance. Consistent dietary intake is recommended. |
| Clinical Pearls | Aminophylline is a bronchodilator that releases theophylline. Monitor serum theophylline levels (therapeutic range 5-15 mcg/mL). Avoid in patients with active peptic ulcer disease, seizure disorders, or hypersensitivity to xanthines. Caution in hepatic impairment, heart failure, and elderly due to reduced clearance. Drug interactions with cimetidine, ciprofloxacin, and macrolides increase theophylline levels. |
| Patient Advice | Do not exceed prescribed dose. Take exactly as directed. · Avoid caffeine-containing products (coffee, tea, cola, chocolate) as they may increase side effects. · Report symptoms of toxicity: nausea, vomiting, insomnia, rapid heart rate, palpitations, or seizures. · Do not crush or chew extended-release forms; take with food if gastric upset occurs. · Do not stop abruptly without consulting your healthcare provider. |
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