THEOPHYL-SR
Clinical safety rating
cautionComprehensive clinical and safety monograph for THEOPHYL-SR (THEOPHYL-SR).
Theophylline is a methylxanthine that inhibits phosphodiesterase, increasing cyclic AMP levels, and antagonizes adenosine receptors, leading to bronchodilation and anti-inflammatory effects.
| Metabolism | Hepatic via CYP1A2, CYP2E1, and CYP3A4; demethylation and oxidation to inactive metabolites (1-methyluric acid, 3-methylxanthine, 1,3-dimethyluric acid). |
| Excretion | Renal: ~10% unchanged; Hepatic metabolism (90%) via CYP1A2, 3A4; metabolites (caffeine, 3-methylxanthine) excreted renally. Total clearance predominantly hepatic. |
| Half-life | Adults: 8-10 hours (range 3-12); Neonates: 20-30 hours; Smokers: 4-5 hours; Cirrhosis: 30-40 hours. Dose adjustments needed based on half-life variations. |
| Protein binding | 40-60% primarily to albumin. |
| Volume of Distribution | 0.3-0.5 L/kg (1.0-1.5 L/kg in neonates). Reflects distribution into total body water; higher in dehydrated states. |
| Bioavailability | Oral immediate-release: 96-100%; Sustained-release: 90-100% (variable among formulations). |
| Onset of Action | Oral immediate-release: 30-60 min; Oral sustained-release (Theophyll-SR): 1-3 hours; IV: 5-15 min. |
| Duration of Action | Sustained-release: 12-24 hours depending on formulation; Immediate-release: 4-6 hours. Therapeutic effect correlates with serum concentration 10-20 mcg/mL. |
| Molecular Weight | 180.16 |
300 mg orally every 12 hours, with dosing titrated to achieve serum trough concentrations of 5-15 mcg/mL.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No specific GFR-based adjustment required, but serum concentrations should be monitored due to altered clearance. For GFR <10 mL/min, reduce dose by 50% and monitor levels. |
| 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 80% and monitor serum concentrations closely. |
| Pediatric use | Initial dose: 5 mg/kg/day orally in 2 divided doses, increasing by 2 mg/kg/day every 3 days to maximum 20 mg/kg/day, with monitoring of serum concentrations. |
| Geriatric use | Start at lower end of dosing range (e.g., 200 mg every 12 hours) and titrate slowly due to reduced hepatic clearance; monitor serum concentrations and adjust to therapeutic trough of 5-15 mcg/mL. |
| 1st trimester | Theophylline crosses the placenta. There are no adequate studies in pregnant women. First-trimester use has been associated with a small increased risk of congenital malformations, but data are conflicting. Use only if clearly needed. |
| 2nd trimester | Second-trimester use may require dose adjustments due to altered pharmacokinetics. Monitor serum levels and adjust dose to maintain therapeutic range. No known specific teratogenic risk beyond background. |
| 3rd trimester | Third-trimester use may lead to neonatal theophylline toxicity if maternal levels are high. Neonatal side effects include irritability, tachycardia, and vomiting. Use with caution; monitor maternal levels and consider neonatal monitoring after delivery. |
Clinical note
Comprehensive clinical and safety monograph for THEOPHYL-SR (THEOPHYL-SR).
| Placental transfer | Theophylline crosses the placenta readily, achieving fetal serum concentrations similar to maternal levels. Cord blood concentrations are approximately 50-100% of maternal levels. |
| Breastfeeding | Theophylline is excreted into breast milk in small amounts (approximately 1% of maternal dose). While generally considered compatible with breastfeeding, high maternal doses can cause irritability or insomnia in nursing infants. Monitor infant for signs of theophylline toxicity. The American Academy of Pediatrics classifies theophylline as 'Maternal medication usually compatible with breastfeeding'. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No increased risk of major malformations reported in humans; animal studies show fetal harm at high doses. Second trimester: Potential for maternal tachycardia and uterine relaxation, not teratogenic. Third trimester: Risk of neonatal apnea, bradycardia, and jitteriness at birth if maternal levels are supratherapeutic; no structural anomalies. |
| Fetal Monitoring | Monitor maternal serum theophylline levels (therapeutic range 5-15 mcg/mL, target 8-12 mcg/mL in pregnancy). Assess maternal heart rate and symptoms of toxicity (tachycardia, nausea, seizures). Fetal monitoring for tachycardia and growth restriction. Neonatal monitoring for withdrawal or toxicity (apnea, irritability) after delivery. |
| Fertility Effects | No known direct effect on fertility in humans; potential for reduced fertility at toxic doses in animal studies. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to theophylline or any component of the formulationPre-existing cardiac arrhythmias (e.g., tachyarrhythmias) unless pacemaker is in placeUntreated seizures
| Precautions | Use with caution in patients with cardiac disease (e.g., arrhythmias), seizure disorders, peptic ulcer disease, hepatic impairment, and in elderly patients. Monitor serum theophylline levels to avoid toxicity. |
| Food/Dietary | Avoid large amounts of caffeine-containing foods/beverages (coffee, tea, cola, chocolate) as they may increase adverse effects. Charcoal-broiled foods can increase clearance, potentially decreasing effectiveness. High-carbohydrate/low-protein diets may increase theophylline levels. St. John's wort may decrease theophylline levels. |
| Clinical Pearls | Theophylline has a narrow therapeutic index (10-20 mcg/mL). Monitor levels due to significant interindividual pharmacokinetic variability. Smoking induces metabolism; dose adjustments needed when starting/stopping smoking. Avoid in tachyarrhythmias, seizure disorders, or peptic ulcer disease. Cimetidine, ciprofloxacin, and erythromycin increase theophylline levels. Convert between immediate-release and sustained-release formulations cautiously. Use with caution in heart failure, liver disease, and elderly patients due to reduced clearance. |
| Patient Advice | Take exactly as prescribed; do not crush or chew sustained-release tablets. · Do not change brands or formulations without consulting your doctor. · Avoid large amounts of caffeine (coffee, tea, cola) as it may increase side effects. · Report symptoms of toxicity: persistent nausea/vomiting, insomnia, tremors, seizures, or rapid/irregular heartbeat. · If you smoke, inform your doctor, as dose adjustments may be needed. · Keep all appointments for blood level monitoring. · Do not stop abruptly; may cause rebound bronchospasm. |
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