THEOCLEAR L.A.-260
Clinical safety rating: caution
Comprehensive clinical and safety monograph for THEOCLEAR L.A.-260 (THEOCLEAR L.A.-260).
Theophylline causes bronchodilation by inhibiting phosphodiesterase, increasing cAMP levels, and antagonizing adenosine receptors.
| Metabolism | Hepatic via CYP1A2, CYP2E1, and CYP3A4; undergoes N-demethylation and oxidation. |
| Excretion | Renal elimination of unchanged drug (10%) and hepatic metabolism (90%). Metabolism is primarily via CYP1A2 and CYP3A4, with metabolites excreted in urine (about 80% of the dose) and feces (about 20%). |
| Half-life | Terminal elimination half-life is approximately 6-12 hours in adults (range 3-12 hours, prolonged in congestive heart failure, liver disease, and with certain drugs). In neonates, half-life is prolonged (24-36 hours). |
| Protein binding | Approximately 40% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution: 0.4-0.5 L/kg, indicating distribution into total body water. Higher Vd in neonates and patients with obesity. |
| Bioavailability | Oral bioavailability: 96% to 100% for immediate-release formulations; sustained-release formulations have similar bioavailability but with prolonged absorption. |
| Onset of Action | Oral administration: Onset of action occurs within 1-2 hours after ingestion of a sustained-release formulation. Peak effect correlates with peak serum concentration at 4-6 hours. |
| Duration of Action | Duration of action: 8-12 hours for sustained-release formulations. Clinical effects (bronchodilation) persist as long as serum levels remain within therapeutic range (5-15 mcg/mL). |
Theophylline (THEOCLEAR L.A.-260) 260 mg orally every 12 hours. Adjust dose based on serum theophylline concentrations to achieve 5-15 mcg/mL.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No specific GFR-based dose adjustment recommended; however, monitor serum levels closely in renal impairment (CrCl <30 mL/min) due to potential accumulation of metabolites. |
| Liver impairment | Avoid use in Child-Pugh class C; for Child-Pugh class A or B, reduce dose by 50% and monitor serum concentrations. |
| Pediatric use | Children 6 months-9 years: Starting dose 12-14 mg/kg/day orally divided every 4-6 hours (immediate-release) or every 12 hours (sustained-release). Children 9-16 years: 12-14 mg/kg/day (max 900 mg/day) divided every 6-8 hours (immediate-release) or every 12 hours (sustained-release). Adjust to serum level 5-15 mcg/mL. |
| Geriatric use | Elderly patients (≥60 years): Start at 300 mg/day orally (sustained-release) in divided doses every 12 hours; titrate slowly, monitor serum levels, as clearance is reduced. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for THEOCLEAR L.A.-260 (THEOCLEAR L.A.-260).
| Breastfeeding | Theophylline is excreted into breast milk (M/P ratio approximately 0.6-0.7). Mean milk concentration is about 60-70% of maternal plasma. Relative infant dose is ~10% of maternal weight-adjusted dose. May cause irritability or insomnia in nursing infants, especially at high maternal doses. Benefits likely outweigh risks for asthma therapy, but monitor infant for signs of theophylline toxicity. |
| Teratogenic Risk | Theophylline is not a major teratogen. First trimester: No increased risk of major malformations based on population data. Second and third trimesters: Use may be associated with transient neonatal toxemia (e.g., jitteriness, tachycardia, vomiting) if maternal levels are high near term. Risk of respiratory distress syndrome or neonatal apnea is theoretical only. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to theophylline or any component; active seizure disorder not controlled by therapy.
| Precautions | Monitor serum theophylline levels to avoid toxicity; use with caution in patients with cardiac disease, seizure disorders, hepatic impairment, or COPD exacerbation; may interact with multiple drugs altering clearance. |
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| Fetal Monitoring | Monitor maternal serum theophylline concentrations (target 5-15 mcg/mL), heart rate, CNS stimulation, and signs of toxicity (tachycardia, nausea, seizures). Fetal assessment includes fetal heart rate monitoring during third trimester. Neonatal monitoring for signs of theophylline withdrawal (e.g., bradycardia, apnea) if maternal use continued until delivery. |
| Fertility Effects | Theophylline is not known to affect human fertility adversely. Animal studies show no impairment of fertility. |