SOMOPHYLLIN-CRT
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 180.16 |
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 | Limited human data; animal studies show risk. Use only if clearly needed due to limited alternatives for severe asthma. |
| 2nd trimester | No known teratogenic risk but monitor maternal theophylline levels; adjust dose to avoid toxicity. May cause fetal tachycardia. |
| 3rd trimester | Theophylline crosses placenta; neonatal withdrawal and irritability reported. Monitor neonate for caffeine-like effects. |
Clinical note
Comprehensive clinical and safety monograph for SOMOPHYLLIN-CRT (SOMOPHYLLIN-CRT).
| Placental transfer | Theophylline readily crosses the placenta; fetal cord blood levels approximate maternal serum levels. Placental transfer is well documented. |
| Breastfeeding | Theophylline is excreted into breast milk; infant serum levels may reach therapeutic levels. Monitor infant for irritability, insomnia, and feeding problems. Use with caution; consider alternative therapies if possible. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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 componentActive peptic ulcer diseaseUncontrolled seizure disorder
| 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. |
| Food/Dietary | Avoid charcoal-broiled foods as they may decrease theophylline levels. High-fat meals can alter absorption; take consistently with regard to meals. Caffeine-containing foods and beverages should be limited due to additive stimulation. |
| Clinical Pearls | SOMOPHYLLIN-CRT (theophylline) is a controlled-release formulation for chronic asthma/COPD. Monitor serum theophylline levels (target 5-15 mcg/mL). Avoid in active seizures. Use with caution in hepatic impairment, heart failure, and elderly. Cimetidine, fluoroquinolones, and macrolides increase levels; smoking and phenytoin decrease levels. |
| Patient Advice | Swallow tablets whole; do not crush or chew. · Take at the same time each day with a full glass of water. · Avoid excessive caffeine (coffee, tea, cola, chocolate) to prevent increased stimulation. · Report nausea, vomiting, insomnia, palpitations, or seizures immediately. · Do not change brand or formulation without consulting your doctor. · Store at room temperature, away from moisture. |
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