OXTRIPHYLLINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OXTRIPHYLLINE (OXTRIPHYLLINE).
Xanthine derivative that inhibits phosphodiesterase, increasing intracellular cyclic AMP; also antagonizes adenosine receptors, leading to bronchodilation and stimulation of respiratory drive.
| Metabolism | Hepatic via CYP1A2 and CYP2E1; exhibits nonlinear pharmacokinetics at high doses. |
| Excretion | Renal: ~70-80% as unchanged drug and metabolites (including theophylline); biliary/fecal: minimal (<10%) |
| Half-life | Adults: 3-5 hours (non-smokers); smokers: 4-6 hours; children: 1-4 hours; neonates: 20-30 hours; congestive heart failure or hepatic cirrhosis: prolonged up to 10-20 hours. Note: Oxtriphylline is a choline salt of theophylline, and its half-life reflects theophylline kinetics. |
| Protein binding | Approximately 40-60% bound to plasma albumin; decreases in neonates and patients with hepatic disease |
| Volume of Distribution | 0.45-0.7 L/kg; approximates total body water; increased in premature infants (0.8-1.0 L/kg) and in cirrhosis |
| Bioavailability | Oral: 100%; rectal: >90% |
| Onset of Action | Oral: 15-30 minutes; peak effect: 1-2 hours after dose |
| Duration of Action | Oral immediate-release: 4-6 hours; extended-release: 8-12 hours; clinical effect duration corresponds to therapeutic serum theophylline levels (5-15 mcg/mL) |
200 mg orally every 6 hours, or 400 mg orally every 8-12 hours; maximum 600 mg per dose.
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | For GFR 30-50 mL/min: reduce dose by 50% and extend interval to every 8-12 hours. For GFR <30 mL/min: avoid use or reduce to 200 mg every 12 hours with close monitoring. |
| Liver impairment | Child-Pugh A: no adjustment needed. Child-Pugh B: reduce dose by 50% and monitor levels. Child-Pugh C: contraindicated or use with extreme caution, maximum 200 mg every 12 hours. |
| Pediatric use | For children >1 year: 5 mg/kg orally every 6 hours; maximum 200 mg per dose. For infants 6-12 months: 4 mg/kg every 8 hours. Not recommended for neonates. |
| Geriatric use | Initiate at 200 mg orally every 8-12 hours; titrate slowly, monitor for CNS excitation and arrhythmias. Use lower end of dosing range due to reduced clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OXTRIPHYLLINE (OXTRIPHYLLINE).
| Breastfeeding | Excreted into breast milk in small amounts. M/P ratio not determined. Use with caution; monitor infant for irritability, insomnia, and jitteriness. American Academy of Pediatrics considers compatible with breastfeeding, but preferable to use lowest effective dose. |
| Teratogenic Risk | Pregnancy Category C. No well-controlled studies in humans. Animal studies have shown adverse effects (fetal resorption, skeletal anomalies) at high doses. Risk cannot be ruled out; use only if clearly needed. First trimester: potential for teratogenicity based on animal data. Second/third trimesters: potential for respiratory alkalosis and electrolyte disturbances in fetus due to maternal alkalosis; avoid near term as may cause fetal tachycardia. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to oxitriphylline or any xanthine derivative","Acute myocardial infarction","Uncontrolled arrhythmias","Preexisting seizure disorder (relative)"]
| Precautions | ["Seizures: Risk increases with high serum levels (particularly >20 mcg/mL) and in patients with preexisting seizure disorders.","Cardiotoxicity: Includes ventricular arrhythmias and atrial fibrillation; risk increased with underlying cardiac disease or hypoxemia.","Gastrointestinal effects: Nausea, vomiting, and diarrhea are common; may indicate toxicity."] |
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| Fetal Monitoring | Monitor maternal serum theophylline levels (target 5-15 mcg/mL), heart rate, respiratory rate, and signs of toxicity (nausea, vomiting, tachycardia, arrhythmias). Fetal monitoring: heart rate assessment for tachycardia. Neonatal monitoring: observe for withdrawal symptoms (irritability, jitteriness) after birth. |
| Fertility Effects | Limited data. No known significant effect on human fertility. Animal studies show no impairment of fertility at therapeutic doses. |