PHYLLOCONTIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PHYLLOCONTIN (PHYLLOCONTIN).
Sustained-release theophylline; nonselective phosphodiesterase (PDE) inhibitor, adenosine receptor antagonist, and histone deacetylase activator. Bronchodilation via relaxation of bronchial smooth muscle; also reduces airway hyperresponsiveness and inflammation.
| Metabolism | Primarily hepatic via CYP1A2, with minor contributions from CYP2E1 and CYP3A4. Metabolites: 1,3-dimethyluric acid, 3-methylxanthine, and 1-methyluric acid. |
| Excretion | Renal: approximately 10% unchanged; hepatic metabolism accounts for ~90% of clearance; metabolites eliminated renally. |
| Half-life | Terminal elimination half-life: 3-8 hours in non-smoking adults; reduced to 1.5-5 hours in smokers; prolonged to 10-30 hours in heart failure or hepatic cirrhosis. |
| Protein binding | Approximately 40-60% bound, primarily to albumin. |
| Volume of Distribution | 0.45 L/kg (range 0.3-0.7 L/kg), approximating total body water; increased in neonates and cirrhosis. |
| Bioavailability | Oral immediate-release: 96-100%; sustained-release: 90-100%; rectal: approximately 80-90%. |
| Onset of Action | Oral immediate-release: 1-2 hours; intravenous: within 5-15 minutes; rectal: 1-3 hours. |
| Duration of Action | Immediate-release: 4-6 hours; sustained-release: 8-12 hours; intravenous: 6-12 hours depending on infusion rate. |
| Action Class | Theophylline & its derivatives |
For chronic obstructive pulmonary disease and asthma: initial dose 225 mg orally twice daily; may increase to 450 mg twice daily. Based on theophylline, target serum concentration 5-15 mcg/mL.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR < 30 mL/min: reduce dose by 50% and monitor serum levels; avoid use if possible due to accumulation risk. |
| Liver impairment | Child-Pugh Class A: reduce dose by 50%; Child-Pugh Class B: reduce dose by 75%; Child-Pugh Class C: contraindicated. Monitor serum levels closely. |
| Pediatric use | Weight-based dosing (theophylline): 10-16 mg/kg/day orally divided every 6-12 hours; individualize based on serum levels (target 5-10 mcg/mL). Use immediate-release formulations; sustained-release not recommended. |
| Geriatric use | Lower initial doses (e.g., 112.5 mg twice daily) due to decreased clearance; monitor serum levels and adjust to target 5-10 mcg/mL. Avoid in elderly with cardiac arrhythmias or seizures. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PHYLLOCONTIN (PHYLLOCONTIN).
| Breastfeeding | Lactation summary: Theophylline is excreted into breast milk with an M/P ratio of approximately 0.7. Infant serum levels can reach 1-10% of maternal levels. Monitor infant for irritability, insomnia, and feeding difficulties. Generally considered compatible with breastfeeding if maternal levels are therapeutic; avoid high doses. |
| Teratogenic Risk | Teratogenic risk profile: Theophylline (active ingredient in Phyllocontin) is Pregnancy Category C. First trimester: Limited data suggest no major teratogenic risk, but animal studies show potential fetal toxicity at high doses. Second and third trimesters: Theophylline crosses the placenta; fetal serum levels approximate maternal levels. Adverse effects include fetal tachycardia, jitteriness, and neonatal respiratory distress. Risk of neonatal apnea and withdrawal symptoms at delivery. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to theophylline; pre-existing cardiac arrhythmias (unless appropriate monitoring); active peptic ulcer disease.
| Precautions | Narrow therapeutic index; monitor serum theophylline levels. Risk of toxicity (seizures, arrhythmias) at high doses. Caution in patients with peptic ulcer, seizure disorders, cardiac disease, hepatic impairment, or in elderly. Drug interactions (CYP1A2 inducers/inhibitors). |
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| Fetal Monitoring | Maternal-fetal monitoring: Monitor maternal serum theophylline levels (therapeutic range 5-15 mcg/mL), pulmonary function, and signs of toxicity (nausea, tachycardia, arrhythmias, seizures). Fetal monitoring includes heart rate assessment for tachycardia and growth ultrasounds. Neonatal monitoring for withdrawal symptoms postpartum. |
| Fertility Effects | Fertility effects: No known direct effects on human fertility. Animal studies show no significant impact on mating or fertility indices at clinically relevant doses. |