T-PHYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for T-PHYL (T-PHYL).
T-PHYL is a theophylline derivative that inhibits phosphodiesterase, leading to increased intracellular cAMP levels, resulting in bronchodilation and anti-inflammatory effects. It also antagonizes adenosine receptors.
| Metabolism | Primarily hepatic via cytochrome P450 enzymes, including CYP1A2, CYP2E1, and CYP3A4; also undergoes N-demethylation and oxidation. |
| Excretion | Renal (10% unchanged), hepatic metabolism (90%) with metabolites excreted in urine |
| Half-life | 7-9 hours in adults; prolonged in hepatic cirrhosis (up to 30 hours), heart failure, or with CYP1A2 inhibitors |
| Protein binding | 40% bound, primarily to albumin |
| Volume of Distribution | 0.45-0.6 L/kg, approximating total body water; higher in neonates and patients with obesity |
| Bioavailability | Oral immediate-release: 96-100%; oral sustained-release: 80-90% |
| Onset of Action | Oral immediate-release: 30-60 min; IV: 5-10 min |
| Duration of Action | Oral immediate-release: 4-6 hours; oral sustained-release: 8-12 hours; IV: 6-8 hours; duration affected by formulation and patient factors |
400 mg orally every 6 hours, or 200 mg orally every 4 hours for sustained-release.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For GFR 10-50 mL/min: administer every 8-12 hours; for GFR <10 mL/min: administer every 12-24 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: reduce dose by 75%. |
| Pediatric use | Starting dose 5 mg/kg/day orally divided every 6 hours; titrate to maximum 10 mg/kg/day. |
| Geriatric use | Start at lowest effective dose (200 mg every 6 hours) and monitor for toxicity due to reduced clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for T-PHYL (T-PHYL).
| Breastfeeding | Excreted into breast milk in low amounts (M/P ratio ~0.3-0.5). Use with caution; monitor infant for irritability or poor feeding. |
| Teratogenic Risk | First trimester: Possible increase in congenital malformations (e.g., cardiovascular, neural tube defects) based on animal studies and limited human data. Second/third trimester: Risk of fetal tachycardia, irritability, and neonatal withdrawal with chronic use. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning is currently required for T-PHYL.
| Serious Effects |
Hypersensitivity to theophylline or any component of the formulation, concomitant use with ephedrine in children.
| Precautions | Narrow therapeutic index; monitor serum concentrations. Use with caution in patients with cardiac disorders, hepatic impairment, or peptic ulcer disease. Risk of seizures at high doses. Avoid abrupt discontinuation. |
Loading safety data…
| Maternal: Serum drug levels (therapeutic range 10-20 mcg/mL), heart rate, blood pressure, and signs of toxicity. Fetal: Heart rate monitoring, ultrasound for growth assessment if prolonged use. |
| Fertility Effects | No established effect on fertility in humans; animal studies show no impairment. |