SOMOPHYLLIN-CRT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SOMOPHYLLIN-CRT (SOMOPHYLLIN-CRT).
Theophylline acts as a bronchodilator via nonselective phosphodiesterase inhibition, increasing intracellular cAMP levels. It also antagonizes adenosine receptors and may have anti-inflammatory effects.
| Metabolism | Primarily hepatic via cytochrome P450 enzymes, mainly CYP1A2, with minor contributions from CYP2E1 and CYP3A4. Metabolism is saturable, leading to nonlinear pharmacokinetics. Less than 15% excreted unchanged in urine. |
| Excretion | Primarily hepatic metabolism (90%) via CYP1A2 and CYP3A4; renal excretion of unchanged drug accounts for ~10% in adults, with minor biliary/fecal elimination (<1%). |
| Half-life | Terminal elimination half-life: 8-10 hours in adults (non-smokers); prolonged to 12-16 hours in elderly or hepatic impairment; reduced to 4-6 hours in smokers (CYP1A2 induction). |
| Protein binding | ~40% bound to albumin (primarily); binding is concentration-independent. |
| Volume of Distribution | 0.4-0.6 L/kg (slightly higher in infants); approximates total body water; distributes widely into tissues including breast milk and CNS. |
| Bioavailability | Oral immediate-release: 80-100%; Oral sustained-release: 90-100% (with less fluctuation); Rectal: 75-90% (variable due to absorption). |
| Onset of Action | Oral: 30-60 minutes (peak concentration at 1-2 hours fasting); Rectal: 30-60 minutes (suppository); IV: immediate (peak at end of infusion). |
| Duration of Action | Oral sustained-release: 8-12 hours (12-24 hours for twice-daily dosing); IV: 6-8 hours for a single dose; clinical effect duration correlates with serum concentration >5 mcg/mL. |
Theophylline 400 mg orally once daily (24-hour extended-release). Titrate based on serum theophylline levels; target trough 5-15 mcg/mL.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No specific dose adjustment required for GFR >30 mL/min. For GFR 10-30 mL/min: reduce dose by 25% and monitor levels. For GFR <10 mL/min: reduce dose by 50% and monitor closely. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% and monitor levels. Child-Pugh Class C: reduce dose by 75% or consider alternative; monitor levels closely. |
| Pediatric use | Children >1 year: initial dose 10-16 mg/kg/day orally q12h (extended-release). Titrate to serum theophylline levels of 5-15 mcg/mL. Maximum 400 mg/day or 16 mg/kg/day, whichever is less. |
| Geriatric use | Elderly patients: start at lowest possible dose (e.g., 200-300 mg once daily) due to reduced clearance. Monitor serum theophylline levels closely; target lower end of therapeutic range (5-12 mcg/mL). Avoid use if possible due to increased risk of toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SOMOPHYLLIN-CRT (SOMOPHYLLIN-CRT).
| Breastfeeding | Theophylline is excreted into breast milk with an M/P ratio of approximately 0.67. Breastfeeding is generally considered compatible but may cause irritability or sleep disturbances in the infant. Monitor infant for signs of theophylline toxicity. Use lowest effective maternal dose. |
| Teratogenic Risk | Theophylline (active ingredient in SOMOPHYLLIN-CRT) is classified as FDA Pregnancy Category C. First trimester: Limited human data; animal studies show embryotoxicity at high doses but no major malformations. Second and third trimesters: No established teratogenicity; may cause neonatal toxicity (irritability, jitteriness, vomiting) if maternal levels are high near term. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
Theophylline has a narrow therapeutic index; toxicity can occur at doses only slightly above therapeutic levels. Serious and potentially fatal adverse events, including seizures and cardiac arrhythmias, can occur, especially in patients with preexisting conditions or those receiving concurrent medications that affect theophylline clearance.
| Serious Effects |
["Hypersensitivity to theophylline or any component of the formulation","Pre-existing seizure disorders (relative)","Active peptic ulcer disease (relative)","Uncontrolled cardiac arrhythmias (relative)"]
| Precautions | ["Monitor serum theophylline concentrations closely due to narrow therapeutic index (10-20 mcg/mL).","Use with caution in patients with cardiac disorders (e.g., arrhythmias), hepatic impairment, renal dysfunction, seizure disorders, and in elderly patients.","May exacerbate gastric ulcers and gastroesophageal reflux.","Drug interactions: CYP1A2 inhibitors (e.g., cimetidine, fluoroquinolones, macrolides) increase levels; CYP1A2 inducers (e.g., smoking, rifampin, phenytoin) decrease levels."] |
Loading safety data…
| Fetal Monitoring | Monitor maternal serum theophylline concentrations (target 5-15 mcg/mL), heart rate, and respiratory status. Fetal monitoring for heart rate changes (tachycardia) and growth. Assess for neonatal adverse effects if used near term. |
| Fertility Effects | No conclusive evidence of adverse effects on female or male fertility in humans. Animal studies show no significant reproductive toxicity at clinically relevant doses. |