THEOPHYLLINE 0.2% AND DEXTROSE 5% IN PLASTIC CONTAINER
Clinical safety rating: safe
Many drugs can increase (eg ciprofloxacin) or decrease (eg phenytoin) levels due to CYP1A2 metabolism Has a narrow therapeutic index and can cause seizures and arrhythmias in overdose.
Theophylline is a methylxanthine that causes bronchodilation by inhibiting phosphodiesterase, leading to increased intracellular cAMP, and by antagonizing adenosine receptors. It also enhances mucociliary clearance and improves diaphragmatic contractility.
| Metabolism | Hepatic via cytochrome P450 1A2 (CYP1A2) and, to lesser extent, CYP2E1 and CYP3A4. Metabolic steps include N-demethylation and oxidation to 1,3-dimethyluric acid. |
| Excretion | Primarily hepatic metabolism (90%), with renal excretion of metabolites and unchanged drug (10-15% unchanged in adults, higher in neonates). Biliary/fecal elimination is negligible (<5%). |
| Half-life | Terminal half-life is 3-8 hours in adults (mean 5-6 hours), 1-5 hours in smokers, 20-30 hours in premature neonates, and 3-12 hours in children. Half-life is prolonged in hepatic cirrhosis, heart failure, and elderly patients. |
| Protein binding | Approximately 40-60% bound to albumin. Binding is reduced in neonates, patients with hepatic cirrhosis, or hypoalbuminemia. |
| Volume of Distribution | Vd approximately 0.45 L/kg (range 0.3-0.7 L/kg). Distributes into extracellular fluid; higher Vd in premature neonates (0.6-0.9 L/kg) and patients with obesity or ascites. |
| Bioavailability | Oral immediate-release: 96-100%. Oral sustained-release: 90-100%. Rectal: 75-100% (solution) or 60-80% (suppository). Intravenous: 100%. |
| Onset of Action | Intravenous: Onset within minutes (peak bronchodilation at 15-30 min). Oral immediate-release: Onset 30-60 min. Rectal: Onset variable (20-60 min). |
| Duration of Action | Intravenous: Duration 4-8 hours depending on infusion rate. Oral immediate-release: Duration 6-8 hours. Oral sustained-release: Duration 12-24 hours. Rectal: Duration 4-6 hours. |
Intravenous loading dose of 5-6 mg/kg ideal body weight over 20-30 minutes, then continuous infusion of 0.4-0.6 mg/kg/hour. For acute bronchospasm, 0.2% theophylline in 5% dextrose is used. Target serum concentration 10-20 mcg/mL.
| Dosage form | INJECTABLE |
| Renal impairment | No specific GFR-based dose adjustment required as theophylline clearance is minimally affected by renal function. However, monitor for accumulation of metabolites in severe renal impairment (GFR <10 mL/min). |
| Liver impairment | Child-Pugh Class A: Reduce dose by 25%. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Reduce dose by 75% or alternative therapy. Monitor serum levels. |
| Pediatric use | Intravenous loading dose: 5-6 mg/kg ideal body weight (if no recent theophylline). Maintenance infusion: Age 6 weeks-6 months: 0.5 mg/kg/hour; 6 months-1 year: 0.6-0.7 mg/kg/hour; 1-9 years: 0.8-1.0 mg/kg/hour; 9-12 years: 0.7-0.9 mg/kg/hour; 12-16 years: 0.5-0.7 mg/kg/hour. Target serum concentration 5-15 mcg/mL for children. |
| Geriatric use | Reduce maintenance dose by 25-50% due to decreased clearance. Start with 0.3 mg/kg/hour continuous infusion. Monitor serum levels closely (target 5-15 mcg/mL) and adjust based on clinical response and toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Many drugs can increase (eg ciprofloxacin) or decrease (eg phenytoin) levels due to CYP1A2 metabolism Has a narrow therapeutic index and can cause seizures and arrhythmias in overdose.
| FDA category | Animal |
| Breastfeeding | Theophylline is excreted into breast milk with milk-to-plasma ratio of approximately 0.6-0.7. Infant exposure is low (~1% maternal dose), but may cause irritability in sensitive infants. Use with caution and monitor infant for signs of toxicity. |
| Teratogenic Risk |
■ FDA Black Box Warning
None
| Common Effects | COPD |
| Serious Effects |
["Hypersensitivity to theophylline or any component of the formulation","Active untreated seizure disorder","Uncontrolled cardiac arrhythmias","Active peptic ulcer disease"]
| Precautions | ["Serious and life-threatening adverse reactions can occur including seizure and cardiac arrhythmias; monitor serum theophylline levels closely.","Use with caution in patients with peptic ulcer, seizure disorders, cardiac arrhythmias, hepatic impairment, or acute infection.","Theophylline clearance is significantly decreased in patients with heart failure, liver disease, and in smokers; dosage reduction required."] |
Loading safety data…
| Theophylline crosses the placenta. First trimester: No consistent evidence of major malformations, but association with preterm labor and low birth weight. Second and third trimesters: Risk of neonatal toxicity (jitteriness, tachycardia, vomiting) if maternal levels high. Avoid near term due to risk of neonatal apnea and irritability. |
| Fetal Monitoring | Monitor maternal serum theophylline levels (target 5-12 mcg/mL), heart rate, respiratory status, and signs of toxicity (nausea, tachycardia, arrhythmias). Fetal monitoring: heart rate and growth ultrasound. Neonatal monitoring for withdrawal or toxicity after delivery. |
| Fertility Effects | No known adverse effects on fertility in humans. Limited animal data show no significant reproductive impairment. |