THEOLAIR-SR
Clinical safety rating
cautionComprehensive clinical and safety monograph for THEOLAIR-SR (THEOLAIR-SR).
Theophylline is a methylxanthine that relaxes bronchial smooth muscle by inhibiting phosphodiesterase, increasing cAMP, and antagonizing adenosine receptors.
| Metabolism | Primarily metabolized by hepatic CYP1A2, with minor contributions from CYP2E1 and CYP3A4. Extensive first-pass metabolism. Metabolites excreted renally. |
| Excretion | Renal (10% unchanged) and hepatic metabolism (90%). Metabolites excreted in urine. |
| Half-life | Adults: 8 hours (range 5-12). Children: 3.5 hours (range 1-8). Smokers: 4-5 hours. Congestive heart failure/hepatic cirrhosis: >24 hours. |
| Protein binding | 40% bound, primarily to albumin. |
| Volume of Distribution | 0.45 L/kg. Distributes into total body water; higher in premature infants and patients with cirrhosis. |
| Bioavailability | Oral (extended-release): 96-100%. |
| Onset of Action | Oral (extended-release): 1-2 hours. |
| Duration of Action | Oral (extended-release): 8-12 hours. |
| Molecular Weight | 180.16 |
Oral: 300-600 mg every 12 hours; sustained-release formulation; adjust based on serum theophylline concentrations (target 5-15 mcg/mL).
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No specific GFR-based dose adjustment required; use with caution in renal impairment due to altered clearance; monitor serum concentrations. |
| Liver impairment | Child-Pugh Class A: Reduce dose by 50%. Child-Pugh Class B: Reduce dose by 50% and monitor closely. Child-Pugh Class C: Consider alternative therapy; if used, reduce dose by 75% with frequent monitoring. |
| Pediatric use | Children >1 year: Initial 16 mg/kg/day or 400 mg/day (whichever is less) divided every 12 hours; maximum dose: 24 mg/kg/day (not to exceed 900 mg/day). Target serum concentration 5-15 mcg/mL. |
| Geriatric use | Over 60 years: Lower initial dose (e.g., 300 mg/day) due to decreased clearance; titrate slowly; monitor serum theophylline concentrations closely to avoid toxicity. |
| 1st trimester | Theophylline crosses the placenta; limited data suggest no major teratogenic risk, but use only if clearly needed due to potential adverse effects (e.g., fetal tachycardia). |
| 2nd trimester | Theophylline use may be associated with increased risk of preterm labor; monitor maternal serum levels and adjust dose to maintain therapeutic efficacy with lowest possible exposure. |
| 3rd trimester | Theophylline can cause neonatal irritability, jitteriness, and tachycardia; if used, monitor infant for signs of toxicity. Dose reduction may be needed near term. |
Clinical note
Comprehensive clinical and safety monograph for THEOLAIR-SR (THEOLAIR-SR).
| Placental transfer | Theophylline readily crosses the placenta, achieving cord blood levels similar to maternal serum concentrations. |
| Breastfeeding | Theophylline is excreted into breast milk in low concentrations (approximately 10% of maternal serum level). The American Academy of Pediatrics considers it compatible with breastfeeding, but monitor infant for irritability or poor feeding, especially in neonates or if maternal doses are high. |
| Lactation Rating | L3 (Limited data) |
| Teratogenic Risk | Theophylline crosses the placenta. First trimester: No clear evidence of major malformations in human studies, but animal studies show some risk at high doses (skeletal variations). Second trimester: No specific risks; use if benefit outweighs risk. Third trimester: Fetal tachycardia, jitteriness, and withdrawal symptoms (irritability, vomiting) in neonates due to transplacental accumulation. Avoid near term if possible. |
| Fetal Monitoring | Monitor maternal serum theophylline levels (target 5-15 mcg/mL during pregnancy due to altered pharmacokinetics); fetal heart rate monitoring (tachycardia); neonatal monitoring for signs of theophylline toxicity or withdrawal (tachycardia, jitteriness, feeding difficulty); consider Doppler studies if preeclampsia risk. Maternal signs: nausea, vomiting, palpitations, insomnia. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies at high doses showed no significant impact on reproductive parameters. |
■ FDA Black Box Warning
Theophylline has a narrow therapeutic index; serum levels must be monitored to avoid toxicity. Dose-related adverse effects include seizures and arrhythmias.
| Serious Effects |
Hypersensitivity to theophylline or any component of the formulationPorphyria (acute intermittent porphyria, variegate porphyria)
| Precautions | Risk of seizure and arrhythmia at toxic levels; monitor serum theophylline concentrations closely. Use with caution in patients with heart failure, hepatic impairment, chronic alcoholism, and viral infections. Interactions with drugs affecting CYP1A2 (e.g., ciprofloxacin, fluvoxamine, smoking cessation) require dose adjustment. |
| Food/Dietary | High-fat meals may increase absorption; avoid drastic dietary changes. Concurrent caffeine intake can increase theophylline effects and toxicity risk. Charcoal-broiled foods and a high-protein diet may decrease theophylline levels. Grapefruit juice may increase theophylline levels (moderate interaction). |
| Clinical Pearls | Theolair-SR is a sustained-release theophylline formulation. Monitor serum theophylline levels (therapeutic range 10-20 mcg/mL) to avoid toxicity, especially in patients with hepatic impairment or those on interacting drugs. Tachyphylaxis may occur with chronic use. Caution in patients with peptic ulcer, seizure disorders, or cardiac arrhythmias. Levels may be affected by smoking cessation, fever, or medications like cimetidine, fluoroquinolones, and macrolides. |
| Patient Advice | Take this medication exactly as prescribed; do not crush or chew the sustained-release tablets. · Avoid taking with large amounts of caffeine (coffee, tea, soda) as it may increase side effects. · Report symptoms of toxicity: nausea, vomiting, restlessness, insomnia, rapid heartbeat, or seizures. · Do not change brands or dosing schedule without consulting your provider. · Maintain consistent intake of food and avoid sudden changes in diet that may affect absorption. |
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