SOMOPHYLLIN-T
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SOMOPHYLLIN-T (SOMOPHYLLIN-T).
Theophylline is a methylxanthine that inhibits phosphodiesterase, leading to increased intracellular cAMP levels, causing bronchodilation, and also acts as an adenosine receptor antagonist.
| Metabolism | Primarily hepatic via CYP1A2, CYP2E1, and CYP3A4; underwent N-demethylation and oxidation to active metabolites (caffeine and 3-methylxanthine). |
| Excretion | Approximately 90% is eliminated via hepatic metabolism (primarily via CYP1A2, CYP3A4), and about 10% is excreted unchanged in the urine. Renal clearance accounts for <10% of total clearance in adults. Biliary/fecal excretion is minimal (less than 5%). |
| Half-life | Terminal elimination half-life is approximately 8 hours in healthy adults (range 3-13 hours). In neonates, it is prolonged (20-30 h). In smokers, half-life is reduced to 4-5 h. In patients with hepatic cirrhosis or heart failure, half-life may exceed 24 hours. |
| Protein binding | Approximately 40% bound to plasma proteins, primarily albumin. Binding is saturable and decreases in uremia. |
| Volume of Distribution | Approximately 0.45 L/kg (range 0.3-0.7 L/kg). This reflects distribution throughout total body water with some tissue binding. |
| Bioavailability | Oral immediate-release: 96% (well absorbed). Oral sustained-release (SOMOPHYLLIN-T): approximately 90-100% relative to immediate-release. Intravenous: 100%. |
| Onset of Action | Oral immediate-release: 15-30 minutes. Oral sustained-release (SOMOPHYLLIN-T): 1-2 hours. Intravenous: within minutes. |
| Duration of Action | Oral immediate-release: 4-6 hours. Oral sustained-release (SOMOPHYLLIN-T): 8-12 hours (dose-dependent). Intravenous: variable; infusion maintains levels. Duration is prolonged in hepatic impairment or heart failure. |
Oral: 200-400 mg twice daily (12-hourly). Dose titration: start 200 mg twice daily, increase by 200 mg/day every 3 days as tolerated to achieve serum theophylline level 5-15 mcg/mL. Maximum: 800 mg/day or 400 mg twice daily.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required in renal impairment. Theophylline pharmacokinetics minimally affected by GFR; however, monitor for accumulation in severe impairment (CrCl <10 mL/min) due to altered clearance. |
| Liver impairment | Child-Pugh Class A: Reduce dose by 50% of normal dose. Child-Pugh Class B: Reduce dose by 70% of normal dose. Child-Pugh Class C: Reduce dose by 80% of normal dose; frequent monitoring of serum levels recommended. |
| Pediatric use | Oral: 6-12 years: 10-16 mg/kg/day (max 400 mg/day) divided every 12 hours. 12-16 years: 10-16 mg/kg/day (max 600 mg/day) divided every 12 hours. Initiate at lower end of dose range and titrate based on therapeutic drug monitoring. Target trough serum concentration: 5-15 mcg/mL. |
| Geriatric use | Elderly patients require cautious dosing: start at 200 mg once daily (or 100 mg twice daily) due to reduced clearance. Titrate slowly with frequent monitoring of serum levels. Target the lower end of therapeutic range (5-10 mcg/mL). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SOMOPHYLLIN-T (SOMOPHYLLIN-T).
| Breastfeeding | Theophylline is excreted into breast milk with an M/P ratio of 0.6-0.7. Infant serum levels are typically subtherapeutic, but irritability and insomnia have been reported. Benefits of breastfeeding likely outweigh risks at maternal therapeutic doses. |
| Teratogenic Risk | First trimester: Limited data; no increased risk of major congenital anomalies reported in human studies. Second and third trimesters: Use with caution due to potential fetal tachycardia and jitteriness. High doses may lead to neonatal withdrawal. Overall, theophylline is considered relatively low risk compared to other xanthines. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to theophylline or any component of the formulation.","History of seizure disorder (relative, based on risk-benefit).","Cardiac arrhythmias (relative)."]
| Precautions | ["Risk of serious adverse events including seizures, cardiac arrhythmias, and death, especially with serum levels >20 mcg/mL.","Cautious use in patients with peptic ulcer disease, hyperthyroidism, seizure disorders, and cardiac disease.","Geriatric patients and those with hepatic impairment require dose adjustments.","Drug interactions with fluoroquinolones, macrolides, cimetidine, and allopurinol may increase theophylline levels.","Smoking induces metabolism, requiring higher doses."] |
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| Fetal Monitoring | Maternal: Serum theophylline levels (target 5-15 mcg/mL), heart rate, signs of toxicity (nausea, insomnia, arrhythmias). Fetal: Heart rate monitoring for tachycardia; neonatal monitoring for jitteriness, feeding intolerance after delivery. |
| Fertility Effects | No definitive evidence of impaired fertility in males or females. Theophylline may improve respiratory function in subfertile women with asthma, potentially positively impacting fertility. |