DURAPHYL
Clinical safety rating
cautionComprehensive clinical and safety monograph for DURAPHYL (DURAPHYL).
Bronchodilator via beta-2 adrenergic receptor agonism; increases cAMP, relaxes bronchial smooth muscle.
| Metabolism | Primarily hepatic via CYP450 (CYP2D6, CYP3A4) and catechol-O-methyltransferase (COMT). |
| Excretion | Primarily hepatic metabolism (CYP1A2, CYP3A4) with renal excretion of metabolites. Less than 10% excreted unchanged in urine; approximately 70% recovered in urine as metabolites, 30% in feces. |
| Half-life | Terminal elimination half-life is 7–9 hours in adults with normal hepatic function; prolonged to 20–30 hours in hepatic cirrhosis or heart failure. In neonates, half-life may exceed 30 hours due to immature CYP450 enzymes. |
| Protein binding | Approximately 40% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.45–0.50 L/kg, approximating total body water. Higher Vd (0.6–0.7 L/kg) in premature neonates and patients with hepatic cirrhosis due to reduced protein binding. |
| Bioavailability | Oral immediate-release: 96–100%; oral extended-release: 90–100%; rectal: 80–90%; intramuscular: 100% (but not recommended due to erratic absorption). |
| Onset of Action | Intravenous: immediate (within minutes). Oral: 30–60 minutes (immediate-release); 2–4 hours (extended-release). Inhalation: 5–15 minutes. |
| Duration of Action | Immediate-release oral: 4–6 hours. Extended-release oral: 8–12 hours (therapeutic serum levels 10–20 mcg/mL). Intravenous infusion: sustained for duration of infusion. Duration is dose-dependent and influenced by hepatic clearance. |
| Molecular Weight | 292.38 |
5 mg orally twice daily, increased to 10 mg twice daily after one week if tolerated; maximum dose 20 mg twice daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR ≥30 mL/min: no adjustment. GFR 15–29 mL/min: reduce dose by 50% and administer once daily. GFR <15 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% and administer once daily. Child-Pugh Class C: contraindicated. |
| Pediatric use | Children ≥12 years: initiate at 2.5 mg orally twice daily, increase to 5 mg twice daily after one week; maximum 10 mg twice daily. Children 6–11 years: 1.25 mg orally twice daily, increase to 2.5 mg twice daily after one week; maximum 5 mg twice daily. Children <6 years: not established. |
| Geriatric use | Initiate at 2.5 mg orally twice daily, increase to 5 mg twice daily after one week; maximum 10 mg twice daily. Monitor renal function and adjust per renal dosing. |
| 1st trimester | Avoid; animal studies show teratogenicity; no adequate human studies. |
| 2nd trimester | Avoid; risk of fetal tachycardia and hypoglycemia. |
| 3rd trimester | Avoid; may cause fetal tachycardia, hypoglycemia, and premature labor due to beta-adrenergic effects. |
Clinical note
Comprehensive clinical and safety monograph for DURAPHYL (DURAPHYL).
| Placental transfer | Crosses placenta; fetal blood levels similar to maternal. |
| Breastfeeding | Excreted in breast milk; potential for cardiac stimulation in infant. Use caution, only if clearly needed. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | DURAPHYL (theophylline) is not associated with major congenital malformations in humans; however, third-trimester use may cause transient neonatal tachycardia, irritability, and jitteriness due to transplacental passage. Limited data suggest no increased risk of first-trimester major defects after therapeutic doses, but high doses near term may lead to caffeine-like withdrawal in neonates. |
| Fetal Monitoring | Monitor maternal serum theophylline concentrations (target 5–15 mcg/mL) due to decreased clearance in late pregnancy. Fetal heart rate monitoring may be considered for signs of tachycardia. Neonatal monitoring for transient tachypnea, irritability, or jitteriness for 48 hours post-delivery. |
| Fertility Effects | Theophylline has no known adverse effects on fertility in humans based on available data; no studies indicate impairment of spermatogenesis or ovarian function at therapeutic doses. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to terbutaline or any componentTachyarrhythmiasHypertrophic obstructive cardiomyopathySevere hypertensionPulmonary hypertension
| Precautions | Paradoxical bronchospasm, Cardiovascular effects (tachycardia, arrhythmia, hypertension), Hypokalemia, Hyperglycemia, Immediate hypersensitivity reactions |
| Food/Dietary | Avoid high-fat meals which may slow absorption. Avoid charcoal-broiled foods which can decrease effectiveness. Limit caffeine intake. Grapefruit juice may increase absorption; avoid excessive consumption. |
| Clinical Pearls | Duraphyl (theophylline) has a narrow therapeutic index; monitor serum levels to maintain 10-20 mcg/mL. Avoid in patients with seizure disorders unless adequately controlled. Cimetidine, ciprofloxacin, and macrolides increase levels; rifampin and phenytoin decrease levels. Use with caution in hepatic impairment and congestive heart failure. |
| Patient Advice | Take exactly as prescribed; do not change dose without consulting your doctor. · Avoid caffeine (coffee, tea, cola, chocolate) as it may increase side effects like nausea, jitteriness, and insomnia. · Report symptoms of toxicity: persistent nausea, vomiting, rapid heartbeat, seizures, or insomnia. · Do not stop suddenly; tapering may be needed to prevent worsening of breathing problems. · Inform your doctor if you start or stop smoking, as smoking affects theophylline levels. · Keep a regular schedule; take at the same times each day with a full glass of water. |
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