SOMOPHYLLIN-DF
Clinical safety rating
cautionComprehensive 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). |
| Molecular Weight | 180.16 |
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 | Avoid unless benefit outweighs risk. Animal studies show teratogenicity; limited human data. |
| 2nd trimester | Use with caution; monitor maternal serum levels and fetal growth. |
| 3rd trimester | Use with caution; may cause neonatal irritability, tachycardia, and poor feeding. |
Clinical note
Comprehensive clinical and safety monograph for SOMOPHYLLIN-DF (SOMOPHYLLIN-DF).
| Placental transfer | Theophylline readily crosses the placenta; fetal serum levels approximate maternal levels. |
| Breastfeeding | Theophylline is excreted into breast milk; infant serum levels can reach therapeutic range. Monitor infant for irritability, insomnia, and poor feeding. Consider benefit versus risk. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to theophylline or any componentHistory of seizure disorders (unless adequately controlled)Active peptic ulcer disease
| Precautions | Cardiovascular toxicity (arrhythmias), seizure risk, hypersensitivity reactions, interactions with fluoroquinolones and macrolides, smoking cessation reduces clearance, monitor serum theophylline levels. |
| Food/Dietary | Avoid excessive caffeine intake (coffee, tea, cola, chocolate, energy drinks) as it can increase stimulant effects and risk of toxicity. Charcoal-broiled foods may increase metabolism of theophylline, potentially reducing effectiveness. High-protein/low-carbohydrate diets may reduce clearance; high-carbohydrate/low-protein diets may increase clearance. Grapefruit juice does not significantly interact, but consistent intake pattern is advised. |
| Clinical Pearls | Verify controlled-release properties: do not crush or chew tablets. Monitor theophylline levels closely due to narrow therapeutic index (10-20 mcg/mL). Use with caution in patients with CHF, hepatic impairment, or febrile illness as clearance may decrease. Cigarette smoking increases clearance; adjust dose accordingly. Concurrent use with cimetidine, fluoroquinolones, or macrolides can significantly increase levels. |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. Swallow tablets whole—do not crush or chew. Avoid consuming large amounts of caffeine (coffee, tea, cola, chocolate) as it may increase side effects. Report symptoms of toxicity: persistent nausea, vomiting, insomnia, jitteriness, or rapid heart rate. Do not smoke or stop smoking without telling your doctor; smoking changes how this medicine works. Keep all appointments for blood tests to check drug levels. Store at room temperature, away from moisture and heat. |
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