T-PHYL
Clinical safety rating
cautionComprehensive 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 |
| Molecular Weight | 180.16 |
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 | Use only if clearly needed; no adequate studies in pregnant women. Risk cannot be ruled out. |
| 2nd trimester | Use caution; monitor maternal respiratory status and fetal heart rate. May cause maternal tachycardia. |
| 3rd trimester | Avoid near term; may inhibit uterine contractions and cause neonatal jitteriness, tachycardia, or hypoglycemia. |
Clinical note
Comprehensive clinical and safety monograph for T-PHYL (T-PHYL).
| Placental transfer | Readily crosses placenta; cord blood levels approximate maternal serum levels. |
| Breastfeeding | Excreted in breast milk in small amounts; monitor infant for signs of theophylline toxicity such as irritability or insomnia. Consider alternative agents in breastfeeding women, especially with high maternal doses. |
| Lactation Rating | L3 (Moderately Safe) |
| 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 | 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. |
■ FDA Black Box Warning
No FDA black box warning is currently required for T-PHYL.
| Serious Effects |
Hypersensitivity to theophylline or any componentPre-existing cardiac arrhythmias (e.g., tachycardia)Seizure disorders (unless adequately controlled)Active peptic ulcer disease
| 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. |
| Food/Dietary | High-protein foods reduce theophylline clearance; high-carbohydrate foods increase clearance. Avoid charcoal-broiled meats and caffeine-containing products (coffee, tea, cola) as they may increase toxicity. Consistency in diet is important to maintain stable serum levels. |
| Clinical Pearls | T-PHYL (theophylline) requires therapeutic drug monitoring to maintain serum concentrations between 5-15 mcg/mL; levels >20 mcg/mL increase toxicity risk. Cigarette smoking induces its metabolism, requiring dose adjustments. Use with caution in patients with CHF, hepatic impairment, or fever, as clearance decreases. Avoid concurrent use of ciprofloxacin, cimetidine, or macrolides which can elevate levels. |
| Patient Advice | Take exactly as prescribed; do not change dose without consulting your doctor. · Avoid smoking and alcohol; these can alter theophylline levels in your blood. · Report symptoms of toxicity such as nausea, vomiting, insomnia, tremors, or rapid heartbeat. · Do not take over-the-counter medications unless approved by your doctor. · Maintain consistent dietary habits; avoid high-protein or high-carbohydrate diets that affect clearance. |
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