PHYLLOCONTIN
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 246.26 |
| 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 | Avoid due to potential teratogenicity; use only if benefit outweighs risk. |
| 2nd trimester | Use with caution; monitor fetal growth and amniotic fluid. |
| 3rd trimester | May cause neonatal hypoglycemia, tachycardia, and jitteriness; use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for PHYLLOCONTIN (PHYLLOCONTIN).
| Placental transfer | Crosses placenta readily; fetal serum levels approximate maternal levels. |
| Breastfeeding | Excreted into breast milk in small amounts; monitor infant for signs of caffeine-like stimulation (irritability, poor sleep). |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to theophyllineAcute myocardial infarctionHyperthyroidismSeizure disorders
| 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). |
| Food/Dietary | Avoid high-protein or charcoal-broiled foods, as they can decrease theophylline levels. Caffeine-containing foods and beverages (e.g., coffee, tea, cola, chocolate) may increase theophylline levels and toxicity risk. Consistent dietary habits are important to maintain stable serum levels. |
| Clinical Pearls | PHYLLOCONTIN (sustained-release theophylline) is a bronchodilator with a narrow therapeutic index (5-15 mcg/mL). Monitor trough levels before dose escalation. Cigarette smoking, phenytoin, and rifampin induce metabolism, requiring dose increases. Conversely, cimetidine, ciprofloxacin, and fluvoxamine inhibit metabolism, necessitating dose reductions. Use with caution in hepatic impairment, heart failure, and elderly patients due to reduced clearance. |
| Patient Advice | Take this medication exactly as prescribed, usually every 12 hours, with or without food. · Do not crush or chew the extended-release tablets; swallow them whole. · Avoid smoking and avoid changing your smoking habits while on this medication, as it affects the drug level. · Limit or avoid caffeine-containing products (coffee, tea, cola, chocolate) as they may increase side effects. · Report symptoms of toxicity such as nausea, vomiting, insomnia, jitteriness, or rapid heartbeat to your healthcare provider immediately. · Do not change your dose or stop taking this medication without consulting your doctor. |
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