DURAPHYL
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DURAPHYL (DURAPHYL).
| Breastfeeding | Theophylline is excreted into breast milk with an estimated M/P ratio of 0.6–0.7. Infant serum levels may reach 10–50% of maternal therapeutic concentrations. Irritability and sleep disturbance have been reported in breastfed infants. Benefit-risk assessment indicates cautious use; consider monitoring infant for signs of theophylline toxicity. |
| 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. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Hypersensitivity to active ingredient or excipients","Cardiac arrhythmias (especially tachyarrhythmias)"]
| Precautions | ["Paradoxical bronchospasm","Cardiovascular effects (tachycardia, arrhythmia, hypertension)","Hypokalemia","Hyperglycemia","Immediate hypersensitivity reactions"] |
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| 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. |