NITROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NITROL (NITROL).
NITROL (nitroglycerin) is a vasodilator that relaxes vascular smooth muscle via the release of nitric oxide (NO), which activates guanylate cyclase and increases cyclic guanosine monophosphate (cGMP) levels, leading to vasodilation.
| Metabolism | Primarily metabolized by nitrate reductase in the liver; also undergoes denitration by glutathione-dependent organic nitrate reductase and by hemoglobin in red blood cells. |
| Excretion | Renal: minimal, <1% unchanged; extensive metabolism by liver, metabolites excreted renally. Biliary/fecal: negligible. |
| Half-life | 1-4 minutes for nitroglycerin; clinical effect disappears within 30-60 minutes due to rapid metabolism and redistribution. |
| Protein binding | Approximately 60% bound to albumin. |
| Volume of Distribution | 3.3 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Sublingual: ~40-60% (first-pass metabolism); Oral: <10% due to high first-pass; Transdermal: ~20-30% with continuous delivery; Intravenous: 100%. |
| Onset of Action | Sublingual tablet: 1-3 minutes; Transdermal: 30-60 minutes; Intravenous: immediate; Topical ointment: 15-30 minutes. |
| Duration of Action | Sublingual: 30-60 minutes; Transdermal: 8-12 hours with patch removal, tolerance develops rapidly; Intravenous: duration dependent on infusion rate; Topical: 3-4 hours. |
| Action Class | Alkaloids-cytotoxic agents |
| Brand Substitutes | Netalem 2mg Injection |
Sublingual: 0.3-0.6 mg every 5 minutes as needed for angina, up to 3 doses in 15 minutes. Translingual spray: 1-2 sprays (0.4 mg/spray) under tongue every 5 minutes as needed, max 3 doses in 15 minutes. Transdermal: 0.2-0.8 mg/hour patch applied daily for 12-14 hours. Intravenous: Initial 5 mcg/min, titrate by 5 mcg/min every 3-5 minutes until response, usual range 10-200 mcg/min.
| Dosage form | INJECTABLE |
| Renal impairment | No specific adjustment for GFR; monitor for hypotension and methemoglobinemia in severe impairment. Use with caution in dialysis patients. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50% and titrate carefully. Child-Pugh C: Avoid use or use with extreme caution, consider alternative therapy. |
| Pediatric use | Sublingual/translingual: 5 mcg/kg/dose every 5-10 minutes as needed for acute angina, max 4 doses. IV: Start 0.25-0.5 mcg/kg/min, titrate by 0.5-1 mcg/kg/min, max 5 mcg/kg/min. Not recommended for neonates due to risk of methemoglobinemia. |
| Geriatric use | Start at low end of adult dose (sublingual 0.3 mg, transdermal 0.2 mg/hr, IV 5 mcg/min). Titrate slowly due to increased sensitivity and risk of hypotension. Monitor for orthostatic hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NITROL (NITROL).
| Breastfeeding | Not known if nitroglycerin is excreted in human milk. M/P ratio not available. Because of potential for serious adverse reactions in nursing infants, discontinue nursing or discontinue drug, taking into account importance of drug to mother. Use with caution if breastfeeding; avoid high doses or continuous exposure. |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate studies in pregnant women. In animal studies, nitroglycerin has been shown to be embryotoxic in rats and rabbits at doses 20 times the human dose. Use in first trimester only if clearly needed. During second and third trimesters, may be used for management of preterm labor or pregnancy-induced hypertension, but monitor for maternal hypotension and fetal bradycardia. |
■ FDA Black Box Warning
Contraindicated in patients with erectile dysfunction who are using phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil) due to risk of severe hypotension.
| Serious Effects |
Hypersensitivity to nitroglycerin or any component; severe anemia; increased intracranial pressure (e.g., head trauma, cerebral hemorrhage); concurrent use with PDE-5 inhibitors; right ventricular infarction; constrictive pericarditis; cardiac tamponade.
| Precautions | Risk of severe hypotension and syncope, especially in volume-depleted patients or those with low systolic blood pressure; tolerance and cross-tolerance with other nitrates may develop; abrupt cessation may precipitate angina; caution in patients with hypertrophic obstructive cardiomyopathy. |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate; fetal heart rate monitoring during infusion in pregnancy. Assess for signs of hypotension, headache, and reflex tachycardia. In obstetrics, monitor uterine contractions and fetal heart rate pattern continuously. For intravenous use, monitor ECG and invasive blood pressure in acute settings. |
| Fertility Effects | No data on effect of nitroglycerin on human fertility. Animal studies have not shown impaired fertility at therapeutic doses. Potential transient effects due to vasodilation and hormonal changes not established. |