TRUPHYLLINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRUPHYLLINE (TRUPHYLLINE).
Truphylline is a xanthine derivative that inhibits phosphodiesterase (PDE) and blocks adenosine receptors, leading to bronchodilation, increased respiratory drive, and anti-inflammatory effects.
| Metabolism | Truphylline is metabolized primarily by the liver via cytochrome P450 enzymes, mainly CYP1A2, CYP2E1, and CYP3A4. Metabolism involves N-demethylation and oxidation. |
| Excretion | Renal excretion of unchanged drug (80-90%) and metabolites; biliary/fecal elimination <10%. |
| Half-life | Terminal half-life: adults 6-8 hours, children 3-5 hours, neonates 24+ hours. Prolonged in hepatic or cardiac impairment. |
| Protein binding | Primarily albumin: 40-60% bound; reduced in uremia, cirrhosis, or hypoalbuminemia. |
| Volume of Distribution | Approximately 0.5 L/kg (0.3-0.7 L/kg). Higher in neonates and patients with metabolic acidosis. Distributes into breast milk and crosses placenta. |
| Bioavailability | Oral: nearly 100% for immediate-release formulations; sustained-release formulations show variable absorption (80-100%). IV: 100%. |
| Onset of Action | Oral immediate-release: 30-45 minutes; IV: 5-10 minutes. |
| Duration of Action | Oral immediate-release: 4-6 hours; sustained-release: 12-24 hours. Monitor serum levels for toxicity. |
Aminophylline 5-6 mg/kg IV loading dose over 20-30 minutes, then 0.5-0.7 mg/kg/h continuous IV infusion; theophylline 300-600 mg PO daily divided q6-12h, titrated to serum theophylline level of 5-15 mcg/mL.
| Dosage form | SUPPOSITORY |
| Renal impairment | No specific GFR-based dose adjustment; theophylline elimination is not significantly altered in renal impairment. However, monitor serum levels due to possible accumulation in severe renal failure. |
| Liver impairment | Child-Pugh A: reduce dose by 50%; Child-Pugh B or C: reduce dose by 75% or use alternative therapy; monitor serum theophylline levels closely. |
| Pediatric use | IV (as aminophylline): loading dose 6 mg/kg, then continuous infusion: 1-9 years: 0.8 mg/kg/h; 9-12 years: 0.7 mg/kg/h; 12-16 years: 0.6 mg/kg/h. Oral theophylline: 5 mg/kg/day divided q6-12h, titrate to serum level 5-15 mcg/mL. |
| Geriatric use | Start at lowest effective dose; theophylline clearance is reduced; initial dose not to exceed 400 mg/day; monitor serum levels and avoid levels >15 mcg/mL due to increased toxicity risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRUPHYLLINE (TRUPHYLLINE).
| Breastfeeding | Excreted into breast milk; M/P ratio approximately 0.6. Infant serum levels may reach therapeutic concentrations; use with caution and monitor infant for irritability and poor feeding. |
| Teratogenic Risk | Insufficient human data; animal studies show no evidence of teratogenicity at clinically relevant doses. Avoid in first trimester unless benefit outweighs risk due to theoretical concerns with methylxanthines. |
| Fetal Monitoring |
■ FDA Black Box Warning
There is no specific FDA black box warning for truphylline.
| Serious Effects |
["Hypersensitivity to truphylline or other xanthines (e.g., theophylline, caffeine)","Acute myocardial infarction with bradycardia","Seizure disorder (relative contraindication unless controlled)","Peptic ulcer disease (may exacerbate)"]
| Precautions | ["Seizures: Can occur at therapeutic doses, especially in patients with preexisting seizure disorders.","Cardiovascular effects: May cause tachyarrhythmias, hypotension, and cardiac arrest.","Hepatic impairment: Requires dose reduction due to decreased clearance.","Drug interactions: Levels may be increased by CYP1A2 inhibitors (e.g., cimetidine, fluvoxamine) or decreased by inducers (e.g., phenytoin, rifampin).","Monitoring: Serum theophylline levels should be monitored to avoid toxicity.","Geriatric use: Increased risk of toxicity due to reduced clearance."] |
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| Monitor maternal theophylline serum concentrations (target 5-15 mcg/mL), heart rate, and respiratory status. Fetal monitoring for tachycardia and growth restriction if used long-term. |
| Fertility Effects | No direct evidence of impaired fertility. Theophylline may theoretically affect sperm motility at high concentrations; clinical significance unknown. |