THEO-DUR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for THEO-DUR (THEO-DUR).
Inhibits phosphodiesterase, increasing cAMP levels; antagonizes adenosine receptors; enhances contractility of skeletal and cardiac muscle, and relaxes bronchial smooth muscle.
| Metabolism | Primarily hepatic via CYP1A2 and CYP3A4; also by N-acetylation and CYP2E1. |
| Excretion | Primarily hepatic metabolism by CYP1A2 and CYP3A4; renal excretion of unchanged drug accounts for approximately 10% in adults, up to 50% in neonates; biliary/fecal excretion negligible. |
| Half-life | Terminal elimination half-life: 3-9 hours in adults (smokers: 4-5 hours; nonsmokers: 6-9 hours); 20-30 hours in premature neonates; 1-5 hours in children. Prolonged in hepatic cirrhosis, heart failure, and with CYP1A2 inhibitors. |
| Protein binding | Approximately 40-60% bound primarily to albumin. Lower in neonates, cirrhotics, and uremic patients. |
| Volume of Distribution | Vd: 0.3-0.7 L/kg. Distributes into total body water; higher Vd in neonates (0.6-0.8 L/kg) and with acidosis. |
| Bioavailability | Oral: nearly 100% for immediate-release; extended-release formulations have 90-100% relative bioavailability compared to immediate-release. |
| Onset of Action | Oral (immediate-release): 15-30 minutes; Oral (extended-release): 1-2 hours. |
| Duration of Action | Immediate-release: 6 hours; Extended-release (THEO-DUR): 12-24 hours. Sustained bronchodilation for 12 hours with twice-daily dosing; therapeutic serum levels maintained. |
300-600 mg orally twice daily
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | GFR 10-50 mL/min: reduce dose by 25%; GFR <10 mL/min: reduce dose by 50% |
| Liver impairment | Child-Pugh A: reduce dose by 50%; Child-Pugh B or C: reduce dose by 75-80% |
| Pediatric use | Initial: 10-20 mg/kg/day orally divided q12h; titrate based on serum levels (therapeutic range 5-15 mcg/mL) |
| Geriatric use | Start at lowest effective dose; monitor serum levels; decrease dose by 25-50% due to reduced clearance |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for THEO-DUR (THEO-DUR).
| Breastfeeding | Theophylline is excreted into breast milk with an M/P ratio of approximately 0.7. Infant exposure via milk is about 1-10% of maternal weight-adjusted dose. May cause irritability or insomnia in neonates. Use with caution, and monitor infant for signs of theophylline toxicity. Breastfeeding is generally considered acceptable if maternal levels are within therapeutic range and infant is observed. |
| Teratogenic Risk | Theophylline (THEO-DUR) is not known to be a major human teratogen. First trimester: limited data show no consistent increase in major malformations; however, case reports suggest a possible association with cardiovascular defects and oral clefts, though risk is low. Second and third trimesters: chronic high doses may cause fetal tachycardia and irritability; no structural teratogenicity reported. Overall, FDA Pregnancy Category C; risk vs benefit must be considered. |
■ FDA Black Box Warning
No
| Serious Effects |
["Hypersensitivity to theophylline or any component of the formulation.","Concurrent use with ticlopidine or cimetidine (due to significant drug interactions)"]
| Precautions | ["Risk of serious or fatal cardiovascular adverse events, including seizures and arrhythmias, especially at high doses.","Use with caution in patients with peptic ulcer, seizure disorders, cardiac disease, or hepatic impairment.","Monitor serum theophylline levels to avoid toxicity.","May exacerbate GERD."] |
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| Fetal Monitoring | Monitor maternal serum theophylline trough levels (target 5-15 mcg/mL) every 1-2 weeks and after dose changes. Assess fetal heart rate and movements in third trimester; consider nonstress test if maternal dose is high. Monitor for maternal signs of toxicity (nausea, tachycardia, palpitations, seizures). In neonate, monitor for theophylline effects (tachycardia, jitteriness) if mother on high doses near delivery. |
| Fertility Effects | No conclusive evidence of adverse effects on fertility in humans. Animal studies have not shown impaired fertility. However, poorly controlled asthma may negatively impact fertility and pregnancy outcomes. |