SOMOPHYLLIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SOMOPHYLLIN (SOMOPHYLLIN).
Theophylline is a methylxanthine that relaxes bronchial smooth muscle by inhibiting phosphodiesterase, increasing cAMP levels, and antagonizing adenosine receptors. It also has anti-inflammatory and immunomodulatory effects.
| Metabolism | Primarily hepatic via cytochrome P450 enzymes, mainly CYP1A2, with minor contributions from CYP2E1 and CYP3A4. Metabolized to 3-methylxanthine, 1,3-dimethyluric acid, and 1-methyluric acid. |
| Excretion | Theophylline is primarily eliminated by hepatic metabolism (>90%), with only about 10-15% excreted unchanged in urine. Renal excretion of the parent drug is minor; however, metabolites are excreted renally. Biliary/fecal excretion accounts for less than 1%. |
| Half-life | The terminal elimination half-life of theophylline is approximately 8 hours in healthy non-smoking adults (range 3-12 hours). It is prolonged in patients with hepatic cirrhosis (up to 30 hours), heart failure (up to 30 hours), and in neonates (20-30 hours). Smoking (including marijuana) decreases half-life to 4-5 hours. Half-life is shorter in children (3-5 hours). Clinical context: Due to narrow therapeutic index, half-life variability necessitates therapeutic drug monitoring. |
| Protein binding | Theophylline is approximately 40% bound to plasma proteins, primarily albumin. Protein binding is decreased in neonates, patients with hepatic disease, and in the presence of unbound fatty acids. |
| Volume of Distribution | The apparent volume of distribution (Vd) of theophylline is approximately 0.45 L/kg (range 0.3-0.7 L/kg). This approximates total body water. Vd is increased in premature infants (0.6-0.8 L/kg) and patients with hepatic disease. Clinical meaning: Vd is used to calculate loading dose. |
| Bioavailability | Oral immediate-release: 96-100% (rapidly and completely absorbed). Oral sustained-release: 80-100% depending on formulation. Rectal enema: 80-100%. Rectal suppository: 70-90%. IV: 100%. |
| Onset of Action | Intravenous (IV) bolus: Onset of bronchodilation occurs within 5-15 minutes. IV infusion: steady state achieved in about 4 half-lives. Oral immediate-release: onset within 30-60 minutes. Oral sustained-release: onset delayed, typically 2-4 hours. Rectal (enema/suppository): onset within 30-60 minutes. |
| Duration of Action | IV bolus: Duration of bronchodilation is 4-6 hours. Oral immediate-release: 4-6 hours. Oral sustained-release: 8-12 hours for twice-daily formulations, up to 24 hours for once-daily formulations. Clinical note: sustained-release forms designed to maintain therapeutic concentrations with fewer side effects. |
Oral: 200–400 mg every 6 hours; IV: 6 mg/kg loading dose over 30 minutes, then 0.4–0.6 mg/kg/h continuous infusion.
| Dosage form | ENEMA |
| Renal impairment | No adjustment necessary in renal impairment as theophylline is primarily hepatically metabolized. However, in severe renal failure (CrCl <10 mL/min), consider reducing dose by 25%. |
| Liver impairment | Child-Pugh Class A: reduce dose by 25%; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: reduce dose by 75% or avoid use. |
| Pediatric use | Loading dose: 6 mg/kg IV; maintenance: <1 year: (0.2 x age in weeks) + 5 mg/kg/day divided q4-6h; 1-9 years: 20-24 mg/kg/day divided q4-6h; >9 years: 16 mg/kg/day divided q4-6h. |
| Geriatric use | Elderly patients >60 years: reduce maintenance dose by 25-50% due to decreased clearance; monitor serum levels closely; target 5-15 mg/L. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SOMOPHYLLIN (SOMOPHYLLIN).
| Breastfeeding | Excreted into breast milk with M/P ratio approximately 0.6-0.9. Infant serum levels may reach therapeutic range at maternal doses >10 mg/kg/day; monitor infant for irritability or insomnia. Generally considered compatible with breastfeeding but use lowest effective dose. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No well-controlled studies; potential risk of minor malformations based on animal data. Second and third trimesters: No evidence of major teratogenicity; risk of fetal tachycardia and irritability due to transplacental passage; avoid high doses near term. |
■ FDA Black Box Warning
None. However, close monitoring of serum theophylline levels is required due to narrow therapeutic index.
| Serious Effects |
Hypersensitivity to theophylline or any component; active seizure disorder; uncontrolled cardiac arrhythmias; peptic ulcer disease (relative).
| Precautions | Serum levels must be monitored to avoid toxicity (target 5-15 mcg/mL). Use with caution in patients with cardiac disease, seizure disorders, hepatic impairment, and elderly. Drug interactions (e.g., cimetidine, fluoroquinolones, macrolides) can increase levels. Smoking induces metabolism leading to decreased efficacy. |
Loading safety data…
| Fetal Monitoring | Maternal: Serum theophylline levels (target 5-15 mcg/mL), heart rate, respiratory status, signs of toxicity (nausea, tachycardia, arrhythmias). Fetal: Heart rate monitoring during labor; consider ultrasound for growth if high doses used. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility at therapeutic doses. |