DILOR-400
Clinical safety rating
cautionComprehensive clinical and safety monograph for DILOR-400 (DILOR-400).
Phosphodiesterase inhibitor; inhibits PDE4 and PDE5, leading to increased intracellular cAMP and cGMP, resulting in bronchodilation and vasodilation.
| Metabolism | Hepatic metabolism via CYP1A2, CYP3A4, and CYP2E1; undergoes N-demethylation and oxidation to inactive metabolites. |
| Excretion | Renal (70% unchanged), hepatic metabolism (30%) |
| Half-life | 3.1 hours (terminal elimination half-life; may increase in hepatic impairment or congestive heart failure) |
| Protein binding | 40% bound, primarily to albumin |
| Volume of Distribution | 0.5 L/kg (approximates total body water; indicates distribution into extracellular fluid) |
| Bioavailability | Oral: 95-100% (well absorbed from gastrointestinal tract) |
| Onset of Action | Oral: 15-30 minutes; Intravenous: less than 5 minutes |
| Duration of Action | Oral: 6-8 hours; Intravenous: 4-6 hours (duration may be prolonged with sustained-release formulations) |
| Molecular Weight | 254.24 |
400 mg orally every 6 to 8 hours; maximum daily dose 2400 mg.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: 400 mg every 8-12 hours; GFR <10 mL/min: 400 mg every 12-24 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: 400 mg every 8-12 hours; Child-Pugh Class C: 400 mg every 12-24 hours. |
| Pediatric use | 6 months to 2 years: 8-12 mg/kg/day divided every 6 hours; 2-12 years: 12-16 mg/kg/day divided every 6 hours; maximum 600 mg/day. |
| Geriatric use | Start at lower end of dosing range (400 mg every 8 hours) and titrate based on renal function and tolerability. |
| 1st trimester | No human data; animal studies show no teratogenic effects at therapeutic doses. Use only if potential benefit justifies risk. |
| 2nd trimester | No known fetal harm reported; limited human data. Caution advised. |
| 3rd trimester | May inhibit uterine contractions near term; avoid use during labor. No known adverse fetal effects. |
Clinical note
Comprehensive clinical and safety monograph for DILOR-400 (DILOR-400).
| Placental transfer | Crosses placenta; maternal serum levels correlate with cord blood levels. Limited data suggest minimal accumulation in fetus. |
| Breastfeeding | Dyphylline is excreted into breast milk in small amounts. Infant plasma levels are likely low, but irritability and insomnia have been reported. Use with caution, monitoring infant for signs of xanthine toxicity. |
| Lactation Rating | L3 (Limited data; potential adverse effects) |
| Teratogenic Risk | Teratogenic potential: Pregnancy Category C. First trimester: Limited human data, animal studies show fetal toxicity at high doses. Second and third trimesters: Potential for transient neonatal hypoglycemia, tachycardia, and irritability due to maternal xanthine exposure. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal serum theophylline levels (if applicable, as diphylline is a theophylline derivative) to avoid toxicity. Assess fetal heart rate and growth if used chronically. Monitor neonatal for signs of xanthine toxicity (tachycardia, irritability) after delivery. |
| Fertility Effects | Limited data. No specific studies on fertility impact. In animal studies, no adverse effects on reproductive function at therapeutic doses. Potential for hormonal imbalance with high doses, but clinical significance unknown. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to dyphylline or any xanthine derivativePeptic ulcer disease (active)Seizure disorders (unless adequately controlled with anticonvulsants)
| Precautions | Cardiovascular: May cause hypotension, tachycardia, or arrhythmias; use with caution in patients with cardiovascular disease., CNS: May cause insomnia, anxiety, or seizures; adjust dose in elderly or with hepatic impairment., Renal: Excreted largely unchanged; caution in renal impairment., Drug interactions: Increased toxicity with cimetidine, ciprofloxacin, and others that inhibit CYP1A2. |
| Food/Dietary | Avoid high-caffeine foods (coffee, tea, cola, chocolate) as they increase risk of side effects. Charcoal-broiled foods may decrease drug absorption. High-fat meals may delay absorption; take on an empty stomach for consistent effect. |
| Clinical Pearls | DILOR-400 (diprophylline) is a xanthine bronchodilator with similar efficacy to theophylline but with reduced central nervous system stimulation. Monitor serum levels for therapeutic range (10-20 mcg/mL). Caution in patients with peptic ulcer disease, hyperthyroidism, or seizure disorders. Adjust dose in hepatic impairment and elderly. Avoid concurrent use with other xanthines. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · Do not crush or chew extended-release tablets. · Report nausea, vomiting, palpitations, or seizures immediately. · Avoid caffeine-containing foods and beverages. · Do not smoke or stop smoking without consulting doctor as dose may need adjustment. · Keep a regular dosing schedule; do not double up missed doses. |
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