CHOLEDYL
Clinical safety rating
cautionComprehensive clinical and safety monograph for CHOLEDYL (CHOLEDYL).
Choledyl is a salt of theophylline (1,3-dimethylxanthine) and choline. Theophylline acts as a bronchodilator by inhibiting phosphodiesterase (PDE) and antagonizing adenosine receptors, resulting in increased intracellular cAMP and smooth muscle relaxation. It also enhances respiratory drive and diaphragm contractility.
| Metabolism | Primarily metabolized by hepatic cytochrome P450 enzymes, mainly CYP1A2, with minor contributions from CYP2E1 and CYP3A4. |
| Excretion | Primarily renal excretion of theophylline metabolites (1,3-dimethyluric acid, 3-methylxanthine, 1-methyluric acid), with 10% unchanged drug; biliary/fecal < 5%. |
| Half-life | Terminal elimination half-life: 7-9 hours (non-smoking adults); 4-5 hours (smokers); 20-30 hours (premature neonates, hepatic cirrhosis, CHF); clinical context: dose adjustment required for smokers and hepatic impairment. |
| Protein binding | 40% bound, primarily to albumin. |
| Volume of Distribution | Vd: 0.5 L/kg (0.3-0.7 L/kg); clinical meaning: distributes into total body water, with higher volume in premature neonates. |
| Bioavailability | Oral immediate-release: 100%; oral sustained-release: 85-95%; rectal: 90-100% (variable). |
| Onset of Action | Oral immediate-release: 30-60 minutes; oral sustained-release: 1-2 hours; rectal solution: 15-30 minutes. |
| Duration of Action | Immediate-release: 4-6 hours; sustained-release: 8-12 hours; clinical notes: sustained-release preferred for steady bronchodilation. |
| Molecular Weight | 283.33 |
200-400 mg orally 4 times daily, not to exceed 2.4 g/day; or as sustained-release tablets: 400-600 mg twice daily.
| Dosage form | SOLUTION |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 50%; GFR <30 mL/min: administer 200 mg every 12-24 hours; consider monitoring serum theophylline levels. |
| Liver impairment | Child-Pugh A: reduce dose by 50%; Child-Pugh B: reduce dose by 75%; Child-Pugh C: contraindicated or reduce dose by 90% with close monitoring of serum levels. |
| Pediatric use | Not recommended for children under 6 years; for children 6-12 years: 10-12 mg/kg/day divided every 6-8 hours; for adolescents: same as adult dosing, adjusted based on serum levels. |
| Geriatric use | Start at 200 mg twice daily; adjust based on serum theophylline levels (target 5-15 mcg/mL); monitor for toxicity due to reduced clearance. |
| 1st trimester | No adequate studies in pregnant women. Use only if potential benefit justifies potential risk to fetus. Animal studies have not been reported. |
| 2nd trimester | No adequate studies in pregnant women. Use only if potential benefit justifies potential risk to fetus. |
| 3rd trimester | No adequate studies in pregnant women. Use only if potential benefit justifies potential risk to fetus. May cause neonatal withdrawal if used near term. |
Clinical note
Comprehensive clinical and safety monograph for CHOLEDYL (CHOLEDYL).
| Placental transfer | Theophylline, the active moiety, crosses the placenta freely. Umbilical cord serum concentrations approximate maternal serum levels. |
| Breastfeeding | Oxtriphylline (the choline salt of theophylline) is excreted into breast milk in small amounts. The concentration in milk is approximately two-thirds of maternal serum levels. Irritability and insomnia have been reported in nursing infants. Use with caution, monitor infant for signs of theophylline toxicity. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Choledyl (theophylline oxtriphylline) is a xanthine derivative. In pregnancy, theophylline crosses the placenta. First trimester: No consistent evidence of major malformations, but some studies suggest a small increased risk of congenital heart defects. Second and third trimesters: Fetal tachycardia, jitteriness, and hypoglycemia can occur with maternal high levels. Neonatal withdrawal and respiratory distress have been reported. |
| Fetal Monitoring | Monitor maternal serum theophylline levels (target 5-15 mcg/mL), heart rate, and signs of toxicity (tachycardia, nausea, insomnia). Fetal: Consider fetal heart rate monitoring if maternal levels are high or signs of toxicity. Neonatal: Monitor for tachycardia, jitteriness, and hypoglycemia after delivery if used near term. |
| Fertility Effects | No known significant effects on human fertility. Animal studies have not shown impairment of fertility. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to oxtriphylline or any component of the formulationHypersensitivity to xanthine derivatives (e.g., caffeine, theobromine)
| Precautions | Risk of toxicity due to narrow therapeutic index; serum levels should be monitored carefully., Use with caution in patients with peptic ulcer, cardiac arrhythmias, seizure disorders, or hyperthyroidism., May exacerbate gastroesophageal reflux disease., Concomitant use with other xanthine derivatives may increase toxicity. |
| Food/Dietary | High-fat meals may increase absorption; avoid charbroiled meats which decrease theophylline clearance. Consistent caffeine intake should be maintained to avoid fluctuations in drug levels. |
| Clinical Pearls | Choledyl (oxtriphylline) is a bronchodilator; monitor theophylline levels due to narrow therapeutic index. Avoid in patients with peptic ulcer or seizure disorders. Cautious use with hepatic impairment or heart failure. Dose adjustment needed with cimetidine, ciprofloxacin, or macrolides due to decreased clearance. |
| Patient Advice | Take with food if GI upset occurs. · Avoid excessive caffeine (coffee, tea, cola) as it may increase side effects. · Do not crush or chew sustained-release forms. · Seek medical attention for rapid heartbeat, seizures, or severe nausea. · Report signs of toxicity: persistent vomiting, confusion, or palpitations. |
Loading safety data…