THEOLAIR-SR
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for THEOLAIR-SR (THEOLAIR-SR).
| Breastfeeding | Theophylline is excreted into breast milk. Milk/plasma ratio approximately 0.6-0.7. Infant exposure is about 1-10% of maternal weight-adjusted dose, leading to potentially therapeutic or toxic levels in infant serum. Possible effects include irritability, insomnia, and feeding intolerance. Use with caution; monitor infant for adverse effects. |
| 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. |
■ 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 formulation. Patients with pre-existing cardiac arrhythmias (e.g., atrial fibrillation, ventricular tachycardia) unless controlled. History of seizure disorder (use only if benefits outweigh risks).
| 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. |
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| 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. |