THEO-DUR
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 180.16 |
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 | Studies in pregnant women have not demonstrated a risk to the fetus in the first trimester. However, theophylline crosses the placenta, and fetal serum concentrations approximate maternal levels. Use only if clearly needed. |
| 2nd trimester | No evidence of teratogenicity in second trimester. Maternal toxicity may occur at high doses, but therapeutic doses are generally considered safe. Monitor maternal serum levels to avoid toxicity. |
| 3rd trimester | Theophylline use in third trimester may cause transient neonatal tachycardia, jitteriness, and irritability. Neonatal withdrawal has been reported after chronic maternal use. Use cautiously and monitor neonate. |
Clinical note
Comprehensive clinical and safety monograph for THEO-DUR (THEO-DUR).
| Placental transfer | Theophylline readily crosses the placenta. Umbilical cord serum concentrations are similar to maternal serum concentrations (cord:maternal ratio approximately 0.9-1.0). Fetal metabolism is limited; elimination half-life in neonates is prolonged. |
| Breastfeeding | Theophylline is excreted into human milk in small quantities. Peak milk levels occur 1-2 hours after dose. In one study, mean milk:plasma ratio was 0.66. Adverse effects in nursing infants include irritability, insomnia, and feeding problems. Use with caution in breastfeeding women, especially with high maternal doses. Consider monitoring infant serum levels if signs of toxicity appear. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
No
| Serious Effects |
Hypersensitivity to theophylline or any component of the formulationHistory of seizure disorder (unless adequately controlled with anticonvulsants)Active peptic ulcer diseaseUncontrolled arrhythmiasSevere coronary artery diseaseHyperthyroidism (untreated or inadequately controlled) - relative contraindication; absolute if thyrotoxicosis
| 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. |
| Food/Dietary | Food does not significantly affect absorption of sustained-release formulations; however, high-fat meals may slow absorption. Avoid large amounts of caffeine-containing foods/beverages. Charcoal-broiled foods may increase metabolism. |
| Clinical Pearls | Theo-Dur (theophylline) has a narrow therapeutic index; target serum concentration is 5-15 mcg/mL. Levels >20 mcg/mL increase toxicity risk. Monitor levels, especially with hepatic impairment, heart failure, or drugs that alter CYP1A2 metabolism (e.g., cimetidine, fluoroquinolones). Avoid use in active seizure disorders unless controlled. Use with caution in peptic ulcer disease. |
| Patient Advice | Take exactly as prescribed; do not change dose or stop without consulting doctor. · Do not crush or chew sustained-release tablets; swallow whole. · Avoid excessive caffeine intake (coffee, tea, chocolate) as it may increase side effects. · Report symptoms of toxicity: nausea, vomiting, insomnia, palpitations, seizures. · Keep regular appointments for blood level monitoring. |
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