DILATRATE-SR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DILATRATE-SR (DILATRATE-SR).
DILATRATE-SR (isosorbide dinitrate) is a vasodilator that relaxes vascular smooth muscle via the release of nitric oxide (NO), which activates guanylate cyclase, increasing cGMP levels. This leads to venous and arterial dilation, reducing preload and afterload.
| Metabolism | Hepatic metabolism via glutathione reductase to mononitrates and further to inactive metabolites; CYP450 enzymes not significantly involved. |
| Excretion | Renal excretion of inactive metabolites accounts for approximately 60-80% of clearance, with biliary/fecal elimination contributing 20-40%. |
| Half-life | Terminal half-life is 4-6 hours, but clinical effect lasts 8-12 hours due to sustained-release formulation. |
| Protein binding | Isosorbide dinitrate is approximately 28% bound to albumin. |
| Volume of Distribution | Vd is 2-4 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral SR: 20-30% due to extensive first-pass metabolism; sublingual: 40-60%; intravenous: 100%. |
| Onset of Action | Oral (SR): 20-45 minutes; sublingual: 1-3 minutes; intravenous: immediate. |
| Duration of Action | SR formulation: 8-12 hours; sublingual: 30-60 minutes; intravenous: 3-5 minutes after infusion stops. |
40 mg orally twice daily, 6–8 hours apart, as sustained-release formulation. Maximum dose: 160 mg twice daily.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No specific guidelines; use caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation of active metabolite. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use or use with extreme caution. |
| Pediatric use | Safety and efficacy not established; no approved pediatric dosing. |
| Geriatric use | Initiate at lowest effective dose (e.g., 20 mg twice daily); titrate slowly due to increased sensitivity and higher fall risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DILATRATE-SR (DILATRATE-SR).
| Breastfeeding | Excreted into breast milk; M/P ratio unknown. Use with caution; monitor infant for hypotension and methemoglobinemia. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: limited human data, animal studies show fetal harm. Second/third trimesters: may cause fetal bradycardia, hypoxia due to maternal hypotension; avoid use near term due to risk of uterine relaxation and postpartum hemorrhage. |
| Fetal Monitoring |
■ FDA Black Box Warning
Do not use DILATRATE-SR with phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) or riociguat, as this can cause severe hypotension.
| Serious Effects |
Hypersensitivity to nitrates, concurrent use with PDE5 inhibitors or riociguat, severe anemia, closed-angle glaucoma (relative), cardiogenic shock, and acute myocardial infarction with low filling pressures.
| Precautions | May cause severe hypotension, especially in volume-depleted patients; tolerance may develop with prolonged use; avoid abrupt discontinuation to prevent rebound angina; use with caution in patients with hypertrophic cardiomyopathy, aortic stenosis, or increased intracranial pressure. |
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| Monitor maternal blood pressure, heart rate, and fetal heart rate. Assess for signs of maternal hypotension, fetal distress, and uterine activity. |
| Fertility Effects | No established adverse effects on fertility; limited data available. |