OXTRIPHYLLINE
Clinical safety rating
cautionComprehensive 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) |
| Molecular Weight | 283.33 |
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 | Limited human data; avoid use in first trimester unless benefit outweighs risk. Animal studies show no teratogenicity, but fetal hypoxia possible from maternal tachycardia. |
| 2nd trimester | Use with caution; may cause fetal tachycardia and irritability. Monitor maternal levels and fetal heart rate. |
| 3rd trimester | Avoid near term; neonatal withdrawal (jitteriness, vomiting) reported. May inhibit uterine contractions, prolong labor. |
Clinical note
Comprehensive clinical and safety monograph for OXTRIPHYLLINE (OXTRIPHYLLINE).
| Placental transfer | Readily crosses placenta; cord blood concentrations approximate 0.5-1.0 times maternal levels. Higher transfer with maternal toxicity. |
| Breastfeeding | Excreted into breast milk in small amounts (approximately 1% of maternal dose). No adverse effects reported in infants; however, monitor for irritability or sleep disturbance. Use with caution, especially in preterm or compromised infants. |
| Lactation Rating | L2 (Probably Compatible) |
| 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. |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to oxtriphylline or any xanthine derivativeSeizure disorder (lowered seizure threshold)Active peptic ulcer diseaseSevere cardiac arrhythmias (e.g., uncontrolled atrial fibrillation)
| 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. |
| Food/Dietary | Avoid or limit high-caffeine foods and beverages (coffee, tea, chocolate, cola) as they may potentiate side effects. Also avoid chargrilled meats and cruciferous vegetables (e.g., broccoli, cabbage) as they may alter theophylline metabolism. |
| Clinical Pearls | Oxtriphylline is a bronchodilator (xanthine derivative) with similar efficacy to theophylline. Monitor serum theophylline levels (target 5-15 mcg/mL) due to narrow therapeutic index. Caution in hepatic impairment, heart failure, and elderly. Drug interactions include CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine) and inducers (e.g., carbamazepine, rifampin). Avoid rapid IV administration to prevent hypotension and arrhythmias. |
| Patient Advice | Take exactly as prescribed; do not crush or chew enteric-coated tablets. · Avoid excessive caffeine intake (coffee, tea, cola, chocolate) as it may increase side effects. · Report symptoms of toxicity: nausea, vomiting, insomnia, rapid heart rate, or seizures. · Do not stop abruptly; taper under medical supervision. · Keep a diary of peak flow readings if used for asthma. |
Loading safety data…