THEOPHYLLINE 0.04% 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.
Inhibits phosphodiesterase, increasing intracellular cAMP; antagonizes adenosine receptors; stimulates catecholamine release; enhances respiratory muscle contractility.
| Metabolism | Hepatic via CYP1A2, CYP2E1, and CYP3A4; exhibits nonlinear pharmacokinetics at high doses. |
| Excretion | Renal: approximately 10% unchanged; hepatic metabolism (90%): primarily via CYP1A2, 1A2-mediated N-demethylation and 8-hydroxylation. Metabolites (3-methylxanthine, 1-methyluric acid, 1,3-dimethyluric acid) are excreted renally. Biliary/fecal excretion is negligible. |
| Half-life | Terminal elimination half-life: Adults (non-smokers) 7–9 hours; smokers (cigarette/marijuana) 4–5 hours; children (1–9 years) 3–5 hours; neonates 20–30 hours; elderly (>60 years) and patients with hepatic cirrhosis or heart failure may have half-life >24 hours. Half-life is dose-dependent due to saturable metabolism. |
| Protein binding | Approximately 40% bound to albumin in therapeutic concentrations (10–20 mcg/mL). Binding is saturable and decreases in hypoalbuminemia, uremia, and neonates (premature: ~20–30% bound). |
| Volume of Distribution | Vd: ~0.45 L/kg (range 0.3–0.7 L/kg). Clinical meaning: distributes into total body water; higher Vd in neonates and patients with obesity or liver disease; lower Vd in dehydration. |
| Bioavailability | Intravenous: 100%. Oral immediate-release: 96–100%. No first-pass metabolism. Bioavailability of oral liquids is nearly complete. |
| Onset of Action | Intravenous: onset of bronchodilation within 5–10 minutes after loading dose; peak effect at 15–30 minutes. |
| Duration of Action | Duration of bronchodilation: 6–8 hours after IV administration. Sustained-release oral formulations provide 8–12 hours; immediate-release oral: 4–6 hours. Clinical note: aminophylline (theophylline ethylenediamine) is the IV form; theophylline base is infused. |
IV infusion: Loading dose 5 mg/kg (if no prior theophylline) over 30 minutes, then continuous infusion at 0.4 mg/kg/h for adults (non-smoking, otherwise higher). Target serum concentration 10-20 mcg/mL.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment; theophylline is primarily hepatically metabolized. |
| Liver impairment | Child-Pugh Class A: reduce dose by 50%; Child-Pugh Class B: reduce dose by 50% and monitor levels; Child-Pugh Class C: contraindicated or use with extreme caution. |
| Pediatric use | IV infusion: Loading dose 5-6 mg/kg over 30 minutes, then continuous infusion: 1-9 years: 0.8 mg/kg/h; 9-12 years: 0.7 mg/kg/h; 12-16 years: 0.5 mg/kg/h. Adjust to serum levels. |
| Geriatric use | Reduce dose by 30-50% due to decreased clearance; start at 0.2 mg/kg/h continuous infusion after loading; monitor serum levels closely. |
| 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 a milk-to-plasma (M/P) ratio of approximately 0.6-0.7. Breastfed infants are exposed to about 1-10% of the maternal weight-adjusted dose. Infant serum levels are typically low, but irritability and jitteriness have been reported. USPHS recommends caution; monitor infant for signs of theophylline toxicity. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning for theophylline in this formulation.
| Common Effects | COPD |
| Serious Effects |
["Hypersensitivity to theophylline or any component","History of seizure disorder","Uncontrolled arrhythmias","Active peptic ulcer disease"]
| Precautions | ["Seizures","Cardiac arrhythmias","Hypotension","Hypokalemia","Hyperglycemia","Interaction with multiple drugs altering theophylline clearance"] |
Loading safety data…
| Theophylline crosses the placenta and has been associated with neonatal toxicity (irritability, tremors, tachycardia) at high maternal serum concentrations. First trimester: No clear evidence of major malformations, but limited data. Second/third trimesters: Risk of fetal tachycardia and neonatal withdrawal symptoms if maternal levels exceed therapeutic range. Chronic high doses may be associated with intrauterine growth restriction. |
| Fetal Monitoring | Maternal serum theophylline levels should be monitored to maintain therapeutic range (5-15 mcg/mL). Fetal heart rate monitoring and uterine activity assessment if used near term. Neonatal observation for signs of theophylline toxicity (tachycardia, irritability) after delivery. |
| Fertility Effects | No direct evidence of fertility impairment in humans. In animal studies, high doses caused testicular atrophy and altered spermatogenesis, but clinical significance is unknown. Limited data on effects on female fertility. |