TRANSDERM-NITRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRANSDERM-NITRO (TRANSDERM-NITRO).
Nitroglycerin is converted to nitric oxide (NO), which activates guanylate cyclase, increasing cGMP in vascular smooth muscle, leading to vasodilation.
| Metabolism | Extensively metabolized in the liver by glutathione reductase and via denitration. Metabolites include dinitrates and mononitrates. |
| Excretion | Renal (primarily) and biliary; ~60-80% of the dose is excreted renally as metabolites, with <1% unchanged. Fecal excretion accounts for ~10-20%. |
| Half-life | Terminal elimination half-life is approximately 1-4 minutes after IV administration due to rapid metabolism. After transdermal application, the apparent half-life is 3-4 hours due to continued absorption from the skin depot, resulting in a prolonged clinical effect. |
| Protein binding | Approximately 60% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 3 L/kg; large volume of distribution indicates extensive tissue binding and distribution to peripheral compartments. |
| Bioavailability | Transdermal: approximately 80-90% of the dose is absorbed systemically across the skin, though first-pass metabolism is avoided, resulting in high bioavailability relative to oral (oral bioavailability is <20% due to extensive hepatic first-pass metabolism). |
| Onset of Action | Transdermal: 30-60 minutes to reach therapeutic effect (e.g., angina prophylaxis). |
| Duration of Action | Transdermal: 8-12 hours after patch removal due to skin reservoir; steady-state maintained with continuous wear. Effects persist for 30-60 minutes after removal. |
Initial dose 0.2-0.4 mg/hour transdermally once daily. Titrate to 0.4-0.8 mg/hour. Maximum 0.8 mg/hour.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, reduce dose by 50%. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: avoid use. |
| Pediatric use | Not recommended for pediatric use due to lack of safety and efficacy data. |
| Geriatric use | Initiate at low end of dosing range (0.2 mg/hour). Titrate cautiously due to increased sensitivity and risk of hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRANSDERM-NITRO (TRANSDERM-NITRO).
| Breastfeeding | Excreted in breast milk; M/P ratio unknown. Use with caution, monitor infant for hypotension and methemoglobinemia. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Limited human data; animal studies show fetal toxicity at high doses. Second and third trimesters: Risk of fetal bradycardia, hypoxia, and reduced uteroplacental blood flow; may cause preterm labor if used near term. |
| Fetal Monitoring |
■ FDA Black Box Warning
Not recommended for use in patients with elevated intracranial pressure (e.g., head trauma, cerebral hemorrhage) or severe anemia.
| Serious Effects |
["Concomitant use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil)","Severe anemia","Increased intracranial pressure","Hypersensitivity to nitroglycerin or components","Circulatory failure and shock","Constrictive pericarditis, pericardial tamponade, restrictive cardiomyopathy"]
| Precautions | ["Hypotension, especially when used with phosphodiesterase-5 inhibitors (e.g., sildenafil)","Tolerance may develop with continuous use","Abrupt discontinuation may precipitate angina","Use caution in patients with hypovolemia, hypotension, or acute myocardial infarction with low filling pressures","May cause methemoglobinemia, especially with high doses"] |
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| Maternal: Heart rate, blood pressure, signs of hypotension. Fetal: Heart rate monitoring for bradycardia; consider uterine activity monitoring if tocolytic use. |
| Fertility Effects | No known adverse effects on fertility in humans; animal studies have not shown impairment. |