THEOPHYLLINE IN 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.
Nonselective phosphodiesterase (PDE) inhibitor; increases intracellular cAMP and cGMP, causing bronchodilation, anti-inflammatory effects, and central nervous system stimulation.
| Metabolism | Hepatic metabolism via CYP1A2, CYP2E1, and CYP3A4; saturable pharmacokinetics at therapeutic concentrations. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 10% of elimination; the remainder is hepatically metabolized, with metabolites (primarily 1,3-dimethyluric acid, 1-methyluric acid, and 3-methylxanthine) excreted renally. Biliary/fecal excretion is minimal. |
| Half-life | Terminal elimination half-life is 3-8 hours in healthy adults (mean ~6 h), prolonged in liver disease (up to 30 h), heart failure, COPD, and in neonates; smoking induces metabolism, reducing half-life to 4-5 h. |
| Protein binding | Approximately 40% bound to albumin; binding is reversible and non-saturable at therapeutic concentrations. |
| Volume of Distribution | Vd ~0.45 L/kg (range 0.3-0.7 L/kg); reflects distribution into total body water and some tissue binding, indicating extensive extravascular distribution. |
| Bioavailability | Intravenous administration yields 100% bioavailability; oral immediate-release formulations have ~96% bioavailability, but rectal and intramuscular routes are erratic and not recommended. |
| Onset of Action | Intravenous infusion: bronchodilation onset within 15-30 minutes. |
| Duration of Action | Duration of bronchodilation is 8-12 hours with sustained therapeutic levels; clinical effect wanes as drug levels fall below 5 mcg/mL. |
Loading dose: 5-6 mg/kg IV over 30 minutes (if not on theophylline). Maintenance: 0.4-0.6 mg/kg/hr IV continuous infusion; target serum concentration 5-15 mcg/mL.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment; however, monitor serum levels closely in patients with renal dysfunction due to decreased clearance. |
| Liver impairment | Child-Pugh Class A: reduce dose by 50%; Child-Pugh Class B: reduce dose by 60%; Child-Pugh Class C: reduce dose by 70% or avoid use; monitor serum levels. |
| Pediatric use | Loading: 5-6 mg/kg IV; maintenance: <1 year: 0.2-0.5 mg/kg/hr; 1-9 years: 0.5-0.8 mg/kg/hr; >9 years: 0.4-0.6 mg/kg/hr; target 5-15 mcg/mL. |
| Geriatric use | Reduce infusion rate by 20-30% from adult dose; monitor serum theophylline levels closely due to decreased clearance and increased sensitivity. |
| 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 0.7. Infant serum levels can reach therapeutic concentrations; irritability and insomnia have been reported in nursing infants. Use with caution; monitor infant for signs of toxicity. The American Academy of Pediatrics considers it compatible with breastfeeding. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning for theophylline.
| Common Effects | COPD |
| Serious Effects |
["Hypersensitivity to theophylline or any component.","Concomitant use with ephedrine or other sympathomimetics (except in carefully monitored patients).","Peptic ulcer disease, seizure disorders (relative)."]
| Precautions | ["Narrow therapeutic index; monitor serum theophylline concentrations.","Risk of seizures, cardiac arrhythmias, and death with toxicity.","Use caution in patients with cardiac disorders, severe hypertension, hyperthyroidism, seizure disorders, and liver disease.","Drug interactions: cimetidine, fluoroquinolones, macrolides, oral contraceptives, allopurinol, etc. can increase levels."] |
Loading safety data…
| First trimester: No established association with major malformations; however, maternal use may be associated with a slight increased risk of respiratory distress and apnea in neonates. Second and third trimesters: Theophylline crosses the placenta; maternal levels near toxic range may cause fetal tachycardia and irritability. Chronic high doses may lead to neonatal withdrawal symptoms. |
| Fetal Monitoring | Monitor maternal serum theophylline concentrations (target 5-15 mcg/mL), heart rate, and respiratory status. Fetal monitoring for tachycardia and non-stress tests if maternal levels are high. Assess neonatal for signs of toxicity or withdrawal after delivery. |
| Fertility Effects | No known adverse effects on fertility in humans. Theophylline may have mild effects on sperm motility in vitro at very high concentrations, but no clinical significance. |