THEOPHYL-225
Clinical safety rating: caution
Comprehensive clinical and safety monograph for THEOPHYL-225 (THEOPHYL-225).
Theophylline is a methylxanthine that inhibits phosphodiesterase, leading to increased intracellular cAMP levels, and antagonizes adenosine receptors (A1, A2). This results in bronchodilation, reduced airway inflammation, and enhanced diaphragmatic contractility.
| Metabolism | Primarily hepatic via CYP1A2 and to a lesser extent CYP2E1, CYP3A4; exhibits nonlinear pharmacokinetics at high concentrations. |
| Excretion | Renal: 10% unchanged; hepatic metabolism (CYP1A2, CYP3A4) accounts for ~90% of elimination, with metabolites (e.g., 3-methylxanthine, 1,3-dimethyluric acid) excreted renally. |
| Half-life | Terminal half-life: 3–12 hours (adults); shorter (1–5 hours) in children and smokers; prolonged in hepatic cirrhosis, heart failure, or elderly. Steady-state achieved in 1–2 days. |
| Protein binding | Approximately 40% bound to albumin (primarily); binding is concentration-independent. |
| Volume of Distribution | 0.3–0.7 L/kg; distributes freely into tissues and breast milk; Vd reflects moderate tissue penetration and rapid equilibration. |
| Bioavailability | Oral: 100% (complete absorption); bioavailability not significantly affected by food. Rectal: ~80% (variable due to absorption site). |
| Onset of Action | Oral: 30–60 minutes (immediate-release); 1–3 hours (extended-release). IV: 15–30 minutes. Rectal: 30–60 minutes. |
| Duration of Action | Immediate-release: 4–6 hours. Extended-release: 8–12 hours (or 12–24 hours for once-daily formulations). Duration correlates with half-life and formulation. |
225 mg orally every 6 hours; adjust based on serum theophylline levels to maintain therapeutic range 10-20 mcg/mL.
| Dosage form | ELIXIR |
| Renal impairment | No specific GFR-based adjustment required; monitor serum theophylline levels as renal impairment may affect clearance. |
| Liver impairment | Child-Pugh A: reduce dose by 50%; Child-Pugh B: reduce dose by 50-75%; Child-Pugh C: reduce dose by 75-90% or consider alternative. Frequent serum level monitoring is mandatory. |
| Pediatric use | Initial: 5 mg/kg orally every 6 hours; titrate based on serum levels. Usual maintenance: 10-20 mg/kg/day divided every 6 hours. Not recommended under 1 year without specialist advice. |
| Geriatric use | Start at lower dose (e.g., 112.5 mg every 6 hours) due to decreased clearance; titrate slowly with close serum level monitoring. Target lower end of therapeutic range (8-12 mcg/mL) if tolerated. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for THEOPHYL-225 (THEOPHYL-225).
| Breastfeeding | Theophylline is excreted into breast milk; M/P ratio approximately 0.7. Infant serum levels can reach therapeutic levels, especially with maternal doses >10 mg/kg/day. Use with caution; monitor infant for signs of irritability or insomnia. AAP considers compatible with breastfeeding but observe infant. |
| Teratogenic Risk | Theophylline crosses the placenta. First trimester: No clear association with major malformations in human studies, but limited data. Second/third trimester: Risk of fetal tachycardia, jitteriness, and irritability at high maternal serum levels (toxicity). May cause transient neonatal withdrawal symptoms (apnea, vomiting) if used near term. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Limited data available |
| Serious Effects |
["Hypersensitivity to theophylline or other xanthines (e.g., caffeine, theobromine)","Pre-existing cardiac arrhythmias, particularly tachyarrhythmias","Active seizure disorder","Severe hepatic impairment"]
| Precautions | ["Narrow therapeutic index; serum levels must be monitored (target 5-15 mcg/mL)","Risk of seizure and cardiac arrhythmias at toxic levels","Increased seizure risk in patients with preexisting seizure disorders","Use with caution in liver impairment, congestive heart failure, and elderly","May cause tachycardia, palpitations, and exacerbation of arrhythmias"] |
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| Fetal Monitoring | Monitor maternal serum theophylline levels (target 5-12 mcg/mL), heart rate, and signs of toxicity (nausea, palpitations, seizures). Fetal monitoring: assess heart rate for tachycardia, especially at higher maternal levels. Consider ultrasound for fetal growth if used long-term. |
| Fertility Effects | No significant adverse effects on fertility in human studies. Animal studies show no impairment at clinically relevant doses. |