NITRO-DUR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NITRO-DUR (NITRO-DUR).
Nitroglycerin is a prodrug that is converted to nitric oxide (NO) in vascular smooth muscle, activating guanylyl cyclase, increasing cGMP, leading to vasodilation primarily in veins and arteries.
| Metabolism | Metabolized by glutathione S-transferases (GSTs) in the liver and erythrocytes, producing glycerol dinitrate and nitrite ions. |
| Excretion | Primarily renal (>80% as inactive metabolites; <1% unchanged nitroglycerin). Minor biliary/fecal elimination. |
| Half-life | 2–3 minutes (nitroglycerin); prolonged to ~30 minutes for active metabolites. Clinical context: Requires frequent dosing or continuous administration for sustained effect. |
| Protein binding | ~60% (mainly to albumin). |
| Volume of Distribution | ~3 L/kg (extensive tissue distribution). |
| Bioavailability | Transdermal: ~70% (relative to IV). Oral: <10% (extensive first-pass metabolism). |
| Onset of Action | Transdermal: 30–60 minutes (plasma levels); 60–120 minutes for hemodynamic effects. |
| Duration of Action | Transdermal: 8–12 hours (therapeutic effect); tolerance develops with continuous use; requires 10–12 hour nitrate-free interval. |
Transdermal: Initial 0.2-0.4 mg/h applied once daily, titrate to 0.4-0.8 mg/h; maximum 0.8 mg/h. Remove for 10-12 hours daily to prevent tolerance.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | No dose adjustment needed for any degree of renal impairment. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Use with caution, consider dose reduction by 25-50% due to reduced metabolism. Child-Pugh Class C: Avoid use or use minimal effective dose (e.g., 0.2 mg/h) with close monitoring. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no standard dosing guidelines. |
| Geriatric use | Start at low end of dosing range (0.2 mg/h), titrate slowly, monitor for hypotension and dizziness. Increased sensitivity due to age-related vascular changes; may require extended nitrate-free interval (e.g., 12-14 hours). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NITRO-DUR (NITRO-DUR).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Use with caution, monitor infant for hypotension or methemoglobinemia; consider pump and discard if high doses used. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Animal studies show fetal harm, but no adequate human studies; potential risk cannot be ruled out. Second and third trimesters: Possible fetal bradycardia, hypotension, and reduced placental perfusion; avoid near term due to risk of maternal hypotension and fetal distress. |
| Fetal Monitoring |
■ FDA Black Box Warning
Do not use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) due to risk of severe hypotension.
| Serious Effects |
Concomitant use with PDE-5 inhibitors; severe anemia; increased intracranial pressure; hypersensitivity to nitroglycerin; acute circulatory failure; constrictive pericarditis; pericardial tamponade.
| Precautions | Hypotension, especially in hypovolemic patients; tolerance with chronic use; paradoxical bradycardia and increased angina; exacerbate hypertrophic cardiomyopathy; avoid abrupt discontinuation. |
Loading safety data…
| Monitor maternal blood pressure and heart rate; fetal heart rate monitoring during prolonged use; assess uterine tone and contractions; watch for signs of methemoglobinemia. |
| Fertility Effects | No adequate studies; animal data suggest no significant impairment of fertility at clinically relevant doses. |