THEOPHYLLINE 0.4% 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 xanthine derivative that inhibits phosphodiesterase, increasing intracellular cAMP, and antagonizes adenosine receptors. It causes bronchodilation, anti-inflammatory effects, and stimulates respiratory drive.
| Metabolism | Primarily hepatic via CYP1A2, with minor contributions from CYP2E1 and CYP3A4. First-pass metabolism occurs. Approximately 90% of a dose is metabolized, and 10% excreted unchanged in urine. Metabolites include 1,3-dimethyluric acid, 1-methyluric acid, and 3-methylxanthine. |
| Excretion | Renal excretion of unchanged drug (10%) and metabolites (90%); primarily hepatic metabolism with metabolites excreted in urine; <1% fecal. |
| Half-life | Terminal elimination half-life is 3-8 hours in healthy adults, prolonged in liver disease (up to 30 hours), heart failure, and COPD; shortens in smokers. |
| Protein binding | 40-60% bound to albumin. |
| Volume of Distribution | 0.3-0.7 L/kg; approximates total body water; increased in neonates and elderly. |
| Bioavailability | Oral: 96-100% (immediate-release); extended-release: 80-100% (formulation-dependent). |
| Onset of Action | IV infusion: immediate onset (within 1-2 minutes); oral immediate-release: 30-60 min; oral extended-release: 1-2 hours. |
| Duration of Action | IV: variable; oral immediate-release: 4-6 hours; oral extended-release: 8-24 hours depending on formulation; IV infusion provides continuous effect. |
Initial loading dose: 5-6 mg/kg IV over 20-30 min (if not on theophylline); maintenance: 0.4-0.6 mg/kg/hr IV continuous infusion.
| Dosage form | INJECTABLE |
| Renal impairment | GFR < 10 mL/min: reduce dose by 50% and monitor serum levels; GFR 10-50 mL/min: consider 50% of usual dose; no adjustment for GFR > 50 mL/min. |
| Liver impairment | Child-Pugh Class A: reduce dose by 50%; Class B: reduce dose by 75%; Class C: reduce dose by 80-90% or avoid use. |
| Pediatric use | Loading dose: 5-6 mg/kg IV; maintenance: infants <1yr: 0.2-0.5 mg/kg/hr; children 1-9yr: 0.8-1.0 mg/kg/hr; children 9-16yr: 0.5-0.7 mg/kg/hr. |
| Geriatric use | Elderly patients: use lower end of dosing range (e.g., 0.3-0.4 mg/kg/hr) due to decreased clearance; monitor serum theophylline 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; M/P ratio approximately 0.6-0.7. Infant exposure is about 10-20% of maternal weight-adjusted dose. Monitor infant for irritability, insomnia, and tachycardia. Benefits of breastfeeding generally outweigh low risk with maternal therapeutic levels. |
| Teratogenic Risk |
■ FDA Black Box Warning
None.
| Common Effects | COPD |
| Serious Effects |
Absolute: Hypersensitivity to theophylline or any component. Relative: Active peptic ulcer disease, uncontrolled seizure disorder, severe cardiac disease (e.g., acute tachyarrhythmias), severe hepatic impairment, and concomitant use of drugs that significantly interfere with theophylline metabolism (e.g., cimetidine, fluoroquinolones).
| Precautions | Theophylline has a narrow therapeutic index. Serious toxicity can occur at levels >20 mcg/mL. Use caution in patients with cardiac disease, hepatic impairment, peptic ulcer, hypothyroidism, and elderly. Monitor serum levels, especially when initiating or adjusting therapy. Avoid abrupt discontinuation. Risk of seizures in susceptible patients. |
Loading safety data…
| First trimester: No increased risk of major malformations based on limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: Risk of fetal tachycardia and jitteriness at high maternal serum levels; apnea, seizures, and death reported in neonates with toxic maternal levels. Avoid near term due to prolonged half-life in neonate. |
| Fetal Monitoring | Monitor maternal theophylline serum levels (target 5-15 mcg/mL), heart rate, and respiratory status. Fetal heart rate monitoring and ultrasound for growth restriction, especially in third trimester. Neonatal monitoring for apnea, tachycardia, and irritability postpartum. |
| Fertility Effects | No evidence of adverse effects on fertility in animal or human studies. Theophylline may improve ovarian function in women with asthma by reducing inflammation; no direct impairment of fertility reported. |