SOMOPHYLLIN-DF
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SOMOPHYLLIN-DF (SOMOPHYLLIN-DF).
Theophylline relaxes bronchial smooth muscle by inhibiting phosphodiesterase, increasing intracellular cAMP, and blocking adenosine receptors.
| Metabolism | Primarily hepatic via CYP1A2, CYP2E1, and CYP3A4; first-pass metabolism; ~90% metabolized, <10% excreted unchanged. |
| Excretion | Renal excretion of unchanged drug: approximately 10%; hepatic metabolism accounts for >90% of elimination; metabolites are excreted renally. Less than 5% eliminated in feces. |
| Half-life | Terminal elimination half-life: 3–12 hours in healthy adults; prolonged in hepatic impairment (up to 30 hours), congestive heart failure, and in neonates; also prolonged in elderly and patients with fever or viral illness. Half-life is shorter in smokers (4–5 hours). |
| Protein binding | Approximately 40% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution: 0.45 L/kg; distributes freely into body water, with higher distribution in neonates and patients with liver disease. |
| Bioavailability | Oral immediate-release: 96–100%; oral extended-release (Somophyllin-DF): 80–100% relative to intravenous, with reduced absorption due to slower release. |
| Onset of Action | Intravenous: immediate; oral immediate-release: 30 minutes; oral extended-release (Somophyllin-DF): 1–2 hours. |
| Duration of Action | Intravenous: 4–6 hours; oral immediate-release: 4–6 hours; oral extended-release: 8–12 hours (Somophyllin-DF). Duration depends on serum concentration (therapeutic range: 5–15 mcg/mL). |
Oral: 300-600 mg every 12 hours; extended-release tablets. Titrate to serum theophylline concentration of 5-15 mcg/mL.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment. However, monitor serum levels in patients with renal failure receiving theophylline as metabolites may accumulate. |
| Liver impairment | Child-Pugh Class A: Reduce dose by 50%. Child-Pugh Class B: Reduce dose by 60-75%. Child-Pugh Class C: Reduce dose by 80-90%. Monitor serum levels closely. |
| Pediatric use | Oral: Initial 16 mg/kg/day or 400 mg/day (whichever is less) in divided doses every 12 hours; extended-release. Adjust based on serum levels. Maximum 20 mg/kg/day or 800 mg/day. |
| Geriatric use | Elderly patients: Start at lower end of dosing range, 300-400 mg/day in divided doses. Monitor serum levels frequently due to decreased clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SOMOPHYLLIN-DF (SOMOPHYLLIN-DF).
| Breastfeeding | Theophylline is excreted into breast milk with a milk-to-plasma ratio approximately 0.67. Infant serum levels can reach therapeutic or toxic concentrations, especially in preterm or neonatal infants. Caution advised; monitor infant for irritability or poor feeding. Use only if clearly needed. |
| Teratogenic Risk | Theophylline (SOMOPHYLLIN-DF) is not a major human teratogen. First trimester: Retrospective studies show no significant increase in congenital anomalies, but data are limited. Second/third trimester: Fetal tachycardia, irritability, and jitteriness can occur due to transplacental passage; risk of neonatal withdrawal if used near term. Avoid high doses near delivery. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to theophylline or xanthines, active peptic ulcer disease, uncontrolled seizure disorders.
| Precautions | Cardiovascular toxicity (arrhythmias), seizure risk, hypersensitivity reactions, interactions with fluoroquinolones and macrolides, smoking cessation reduces clearance, monitor serum theophylline levels. |
Loading safety data…
| Fetal Monitoring | Measure maternal serum theophylline concentrations regularly (target 5-15 mcg/mL). Monitor fetal heart rate and uterine activity. Assess maternal liver function, cardiac status, and signs of toxicity (nausea, vomiting, tachycardia, seizures). |
| Fertility Effects | No well-controlled studies. Theophylline may reduce uterine contractility, but effect on fertility is unknown. No evidence of impaired fertility in animal studies at clinically relevant doses. |