THEOCLEAR L.A.-260
Clinical safety rating
cautionComprehensive 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). |
| Molecular Weight | 180.16 |
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 | Theophylline crosses the placenta and may cause fetal tachycardia. Use only if clearly needed. No well-controlled studies in first trimester, but risk appears low at therapeutic doses. |
| 2nd trimester | Theophylline crosses the placenta. Use with caution; maintain maternal levels within therapeutic range to avoid fetal toxicity. |
| 3rd trimester | Theophylline can cause neonatal irritability, apnea, and withdrawal. Monitor infant for signs of toxicity. Use only if necessary and adjust dose near term. |
Clinical note
Comprehensive clinical and safety monograph for THEOCLEAR L.A.-260 (THEOCLEAR L.A.-260).
| Placental transfer | Theophylline readily crosses the placenta with fetal serum concentrations approximating maternal levels. Cord blood levels are typically 70-100% of maternal serum levels. |
| Breastfeeding | Theophylline is excreted into breast milk (about 10% of maternal serum concentration). Peak milk levels occur 1-3 hours after dose. In full-term infants, risk is low at maternal therapeutic doses, but observe for irritability or feeding problems. Avoid breastfeeding if maternal levels are supratherapeutic. Consider timing feeds before dose. |
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to theophylline or any componentActive seizure disorder (uncontrolled)Symptomatic cardiac arrhythmias (e.g., ventricular tachycardia)
| 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. |
| Food/Dietary | Avoid excessive intake of caffeine-containing foods and beverages (coffee, tea, cola, chocolate) as they may potentiate theophylline's CNS stimulant effects and toxicity. Concurrent ingestion of charcoal-broiled meats may increase theophylline clearance, potentially reducing efficacy. Grapefruit juice has been reported to increase theophylline levels; limit intake. A high-protein diet may increase clearance; maintain consistent dietary habits. |
| Clinical Pearls | Theo-24 (theophylline extended-release) has a narrow therapeutic index (5-15 mcg/mL). Monitor serum levels due to significant interindividual variability in clearance. Avoid in patients with active peptic ulcer disease or seizure disorders unless absolutely necessary. Cimetidine, ciprofloxacin, and macrolides increase levels; smoking and rifampin decrease levels. Use with caution in heart failure, hepatic impairment, and elderly due to reduced clearance. For acute exacerbations, consider short-acting beta-agonists first. |
| Patient Advice | Take exactly as prescribed, do not crush or chew extended-release tablets. · Avoid sudden discontinuation; may require tapering. · Report symptoms of toxicity: nausea, vomiting, insomnia, jitteriness, palpitations, or seizures. · Limit caffeine intake (coffee, tea, cola, chocolate) as it may increase side effects. · Discuss all medications with your doctor, especially antibiotics and heartburn drugs (cimetidine, ciprofloxacin). · Do not smoke; smoking increases metabolism and may require dose adjustments. · If you miss a dose, take it as soon as remembered unless close to next dose; do not double up. |
Loading safety data…