THEOPHYLLINE 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 inhibits phosphodiesterase, increasing intracellular cAMP. It also antagonizes adenosine receptors, leading to bronchodilation, anti-inflammatory effects, and respiratory stimulation.
| Metabolism | Primarily hepatic via cytochrome P450 enzymes, CYP1A2 and CYP3A4; also CYP2E1. Metabolized to 3-methylxanthine, 1-methyluric acid, and 1,3-dimethyluric acid. |
| Excretion | Approximately 90% of theophylline is eliminated via hepatic metabolism. The major metabolites are 1,3-dimethyluric acid (40-60%), 1-methyluric acid (20-25%), and 3-methylxanthine (10-15%). About 10% is excreted unchanged in the urine. Renal clearance of the parent drug is negligible in adults but may be significant in neonates. Fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life is 7-9 hours in healthy adults. In children (1-9 years), half-life is shorter: 3-5 hours. In neonates and patients with hepatic cirrhosis, congestive heart failure, or COPD, half-life is prolonged: 10-30 hours. Cigarette smoking and chronic alcohol consumption induce metabolism, reducing half-life to 4-5 hours. |
| Protein binding | Protein binding is approximately 40% (range 35-50%) primarily to albumin. Binding is decreased in neonates, elderly, patients with hepatic cirrhosis, and uremia, leading to increased free fraction and potential toxicity. |
| Volume of Distribution | Volume of distribution is 0.45 L/kg (range 0.3-0.7 L/kg). This approximates total body water, indicating distribution into extracellular and intracellular fluids. Vd is increased in premature neonates, patients with chronic liver disease, and those with congestive heart failure. Pregnancy and obesity also increase Vd. |
| Bioavailability | Intravenous: 100%. Oral immediate-release: 100%. Sustained-release: 90-100% (varies by formulation). Rectal solution/enema: 75-100%. Rectal suppository: 60-80% (erratic absorption). Intramuscular: 75-85% but not recommended due to pain and unpredictable absorption. |
| Onset of Action | For intravenous infusion, onset of bronchodilation occurs within 5-10 minutes after loading dose. Peak effect is achieved at the end of the infusion. For oral immediate-release forms, onset is 30-45 minutes. Rectal administration via enema or suppository has onset of 30-60 minutes. Intramuscular injection is not recommended due to pain and erratic absorption. |
| Duration of Action | Duration is 6-8 hours following intravenous administration. With sustained-release oral formulations, duration is 8-12 hours for 12-hour formulations and up to 24 hours for 24-hour formulations. Theophylline's duration is influenced by serum concentration; therapeutic levels (10-20 mcg/mL) provide sustained bronchodilation. Toxicity may occur with prolonged elevated levels. |
Loading dose: 5 mg/kg IV (for patients not currently receiving theophylline). Maintenance dose: 0.4-0.6 mg/kg/hour IV continuous infusion. Target serum theophylline concentration 10-20 mcg/mL.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR >10 mL/min. For GFR <10 mL/min, reduce dose by 50% and monitor serum concentrations. |
| Liver impairment | Child-Pugh Class A: reduce dose by 50%. Child-Pugh Class B: reduce dose by 75%. Child-Pugh Class C: use alternative therapy or reduce dose by 80% with close monitoring. |
| Pediatric use | Loading dose: 5-6 mg/kg IV (if not on theophylline). Maintenance: 0.5-0.9 mg/kg/hour IV continuous infusion for children >1 year. For infants 6-52 weeks: dose (mg/kg/h) = (0.008 x age in weeks) + 0.21. Target concentration 10-20 mcg/mL. |
| Geriatric use | Reduce initial dose by 50% and titrate slowly. Maintenance infusion 0.2-0.4 mg/kg/hour. Monitor serum concentrations closely to avoid 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 an M/P ratio approximately 0.7. Infant serum levels may reach 10% of maternal levels. Risk of irritability and insomnia in nursing infants. Consider alternative agents or monitor infant for adverse effects. Avoid in preterm infants or those with compromised respiratory function. |
| Teratogenic Risk |
■ FDA Black Box Warning
Theophylline has a narrow therapeutic index. Serum concentrations should be monitored to avoid toxicity. Doses must be individualized based on serum levels.
| Common Effects | COPD |
| Serious Effects |
Hypersensitivity to theophylline or any component of the formulation; active seizure disorder (unless controlled with medication); acute porphyria.
| Precautions | Monitor serum theophylline concentrations due to narrow therapeutic range. Use caution in patients with cardiac disease, hepatic impairment, seizure disorders, or peptic ulcer disease. Drug interactions can significantly alter metabolism. |
Loading safety data…
| Theophylline crosses the placenta. First trimester: Limited data, but associated with transient neonatal tachycardia and irritability; no consistent evidence of major malformations. Second and third trimesters: Risk of neonatal apnea, tachycardia, hypoglycemia, and vomiting at birth; maternal toxicity (seizures, arrhythmias) can be fatal to fetus. Use only if clearly needed. |
| Fetal Monitoring | Monitor maternal serum theophylline levels (therapeutic range 5-15 mcg/mL for asthma), heart rate, rhythm, and signs of toxicity (nausea, vomiting, tachycardia, arrhythmias, seizures). Fetal assessment: nonstress test and biophysical profile if signs of fetal distress; neonatal monitoring for apnea, tachycardia, and hypoglycemia at delivery. |
| Fertility Effects | No specific data on human fertility impairment. Animal studies have not shown significant reproductive toxicity. Theophylline may theoretically affect uterine contractility, but no conclusive evidence on fertility. |