CHOLEDYL SA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CHOLEDYL SA (CHOLEDYL SA).
Choledyl SA (theophylline, sustained-release) is a methylxanthine that inhibits phosphodiesterase, increasing intracellular cAMP, and blocks adenosine receptors, leading to bronchodilation and anti-inflammatory effects.
| Metabolism | Primarily hepatic via CYP1A2, with minor contributions from CYP2E1 and CYP3A4; exhibits nonlinear pharmacokinetics at higher concentrations. |
| Excretion | Renal: 90% as unchanged drug and metabolites (theophylline metabolites including 1,3-dimethyluric acid, 3-methylxanthine, and 1-methyluric acid). Biliary/fecal: <10%. |
| Half-life | Terminal elimination half-life: 7-9 hours in healthy adults; prolonged in hepatic cirrhosis (up to 30 hours), heart failure, COPD, and in neonates; shortened in smokers and cystic fibrosis. |
| Protein binding | 55-60% bound, primarily to albumin. |
| Volume of Distribution | 0.45 L/kg (0.3-0.7 L/kg). Reflects distribution into total body water, with lower Vd in obese patients when adjusted for ideal body weight. |
| Bioavailability | Oral: 100% for choline theophyllinate (Choledyl) as it is completely absorbed; the sustained-action formulation (Choledyl SA) has equivalent bioavailability to immediate-release. |
| Onset of Action | Oral: Peak bronchodilation occurs 1-2 hours post-dose; clinical effect may begin within 30 minutes. |
| Duration of Action | Duration: 8-12 hours for sustained-action formulation (Choledyl SA). Clinical note: Requires monitoring of serum theophylline levels (target 10-20 mcg/mL) to maintain efficacy and avoid toxicity. |
400 mg orally every 12 hours (sustained-release); maximum 800 mg every 12 hours.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 50-80 mL/min: 50% of usual dose; GFR <50 mL/min: avoid use due to accumulation of choline and theophylline. |
| Liver impairment | Child-Pugh A: 50% of usual dose; Child-Pugh B: 25% of usual dose; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for use in children under 12 years due to lack of safety data. |
| Geriatric use | Initiate at 400 mg every 12 hours; titrate slowly with monitoring of serum theophylline levels due to reduced clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CHOLEDYL SA (CHOLEDYL SA).
| Breastfeeding | Theophylline is excreted into breast milk with M/P ratio approximately 0.6-0.7. Infant may receive 1-10% of maternal dose. Monitor infant for irritability, insomnia, and tachycardia. Use caution; benefit should outweigh risk. Alternative agents may be preferred. |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate studies in pregnant women. In animal studies, theophylline (active metabolite) caused fetal toxicity at high doses. First trimester: risk unknown; use only if benefit outweighs risk. Second/third trimester: possible fetal tachycardia and irritability; avoid near term due to potential neonatal apnea, jitteriness, and withdrawal symptoms. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to theophylline or any component of the formulation.","Acute myocardial infarction with bradycardia or tachyarrhythmias.","Active seizure disorder not controlled with anticonvulsant therapy."]
| Precautions | ["Theophylline has narrow therapeutic index; serum levels must be monitored to avoid toxicity (toxicity risk increases above 20 mcg/mL).","Concomitant use with other xanthines may potentiate toxicity.","Use with caution in patients with cardiovascular disease (e.g., arrhythmias), seizure disorders, hepatic impairment, or peptic ulcer disease.","Drug interactions: CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine) increase theophylline levels; CYP1A2 inducers (e.g., phenytoin, rifampin) decrease levels.","Risk of hypokalemia and hypophosphatemia with high doses or prolonged use."] |
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| Fetal Monitoring | Monitor maternal serum theophylline levels (target 5-15 mcg/mL), pulmonary function tests, and signs of toxicity (nausea, tachycardia, arrhythmias). Fetal monitoring: heart rate assessment for tachycardia; consider non-stress test if maternal levels high or signs of toxicity. Preterm infants: risk of apnea and bradycardia. |
| Fertility Effects | Limited data. Theophylline may affect uterine contractility; no direct evidence of impaired fertility in humans. Animal studies showed no significant reproductive toxicity at doses used clinically. |