THEOPHYLLINE 0.16% 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.
Nonselective phosphodiesterase inhibitor; increases intracellular cAMP levels, leading to bronchodilation, anti-inflammatory effects, and stimulation of respiratory drive.
| Metabolism | Primarily hepatic via cytochrome P450 isoenzymes CYP1A2 and CYP3A4; also metabolized by xanthine oxidase and N-acetyltransferase. |
| Excretion | Renal: ~50% unchanged in adults (higher in neonates); <15% as metabolites (1,3-dimethyluric acid, 1-methyluric acid, 3-methylxanthine). Biliary/fecal: minimal (<5%). |
| Half-life | Terminal half-life: ~7-9 hours in healthy adults (range 3-12 hours); prolonged in hepatic cirrhosis, heart failure, COPD, and neonates (up to 30 hours); shortened in smokers and children (1-5 hours). |
| Protein binding | ~40% bound, primarily to albumin. |
| Volume of Distribution | Vd: ~0.5 L/kg (range 0.3-0.7 L/kg). Distributes into total body water, with higher Vd in neonates and patients with hepatic disease. |
| Bioavailability | IV: 100%; oral immediate-release: 96-100%; oral sustained-release: ~80-100% (varies by formulation). |
| Onset of Action | IV: within minutes; oral immediate-release: 30-60 min; oral sustained-release: 1-2 hours. |
| Duration of Action | IV: 4-6 hours (dose-dependent); oral immediate-release: 6-8 hours; oral sustained-release: 8-12 hours (up to 24 hours for once-daily formulations). Continuous IV infusion provides steady-state. |
IV infusion: Loading dose 5 mg/kg (if no recent theophylline), then maintenance 0.4-0.6 mg/kg/h for adults, titrated to serum concentration 5-15 mcg/mL.
| Dosage form | INJECTABLE |
| Renal impairment | No routine dose adjustment for GFR >10 mL/min. For GFR <10 mL/min, reduce dose by 50% and monitor serum levels. |
| Liver impairment | Child-Pugh A: reduce dose by 50%; Child-Pugh B: reduce by 75%; Child-Pugh C: contraindicated or reduce by 90% with close monitoring. |
| Pediatric use | IV infusion: Loading dose 5 mg/kg (if no recent theophylline), then maintenance: 1-6 months: 0.5 mg/kg/h; 6-12 months: 0.6-0.9 mg/kg/h; 1-9 years: 0.8-1.0 mg/kg/h; 9-12 years: 0.7-0.9 mg/kg/h; 12-16 years: 0.5-0.7 mg/kg/h. Titrate to serum level 5-15 mcg/mL. |
| Geriatric use | Reduce maintenance infusion by 25-50% due to decreased clearance. Start at 0.2-0.3 mg/kg/h and titrate to serum concentration 5-10 mcg/mL. |
| 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. Milk-to-plasma ratio (M/P) is approximately 0.6-0.7. Infant dose via milk is about 1-10% of maternal weight-adjusted dose. Rare reports of infant irritability and insomnia. Monitoring of infant for signs of theophylline toxicity (e.g., irritability, jitteriness) is recommended. Benefit of breastfeeding likely outweighs minimal risk, but caution if maternal levels are high or infant is premature/neonatal. |
■ FDA Black Box Warning
No FDA black box warning exists for this formulation.
| Common Effects | COPD |
| Serious Effects |
Hypersensitivity to theophylline or any component of the formulation. Caution in patients with active peptic ulcer disease or seizure disorders (relative contraindication).
| Precautions | Severe toxicity at serum concentrations >20 mcg/mL; risk of seizures, cardiac arrhythmias, and death. Use with caution in patients with cardiac disease, hepatic impairment, seizure disorders, or hypothyroidism. Monitor serum theophylline levels regularly. |
Loading safety data…
| Teratogenic Risk | Theophylline crosses the placenta. First trimester: Limited data; no clear teratogenic signal, but high doses may be associated with a small increased risk of congenital malformations. Second and third trimesters: No known teratogenic risk; however, neonatal toxicity (e.g., irritability, tachycardia) may occur if maternal levels are supratherapeutic. Respiratory distress and apnea have been reported in neonates exposed near term. |
| Fetal Monitoring | Monitor maternal serum theophylline levels (therapeutic range 10-20 mcg/mL; lower end preferred in pregnancy). Assess for signs of toxicity (nausea, vomiting, palpitations, seizures). Fetal: Nonstress test or biophysical profile if indicated for maternal condition. Neonatal: Observe for symptoms of withdrawal or toxicity (tachycardia, irritability) after delivery. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies report no impairment of fertility at clinically relevant doses. |