DILOR-400
Clinical safety rating: caution
Comprehensive 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) |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DILOR-400 (DILOR-400).
| Breastfeeding | Diphylline (active ingredient) is excreted into breast milk. M/P ratio not established. Potential for irritability and sleep disturbance in infants. Caution advised; consider alternative therapies. |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to dyphylline or any xanthine derivative.","Acute myocardial infarction.","Hypotension.","Uncontrolled arrhythmias."]
| 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."] |
Loading safety data…
| 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. |