NITROGLYCERIN
Clinical safety rating
cautionComprehensive clinical and safety monograph for NITROGLYCERIN (NITROGLYCERIN).
Nitroglycerin is a vasodilator that is converted to nitric oxide (NO) in vascular smooth muscle cells. NO activates guanylyl cyclase, increasing cGMP levels, leading to dephosphorylation of myosin light chains and vasodilation. Predominantly dilates venous capacitance vessels, reducing preload; also dilates coronary arteries at higher doses.
| Metabolism | Metabolized primarily by hepatic glutathione-organic nitrate reductase and cytochrome P450 enzymes (CYP3A4) to inorganic nitrite and denitrated metabolites; also undergoes extrahepatic metabolism in erythrocytes and vascular tissue. |
| Excretion | Metabolized extensively by hepatic glutathione-organic nitrate reductase and other non-specific esterases; renal excretion of metabolites accounts for approximately 50%, with fecal elimination of about 20-30%. Less than 1% of unchanged drug is excreted renally. |
| Half-life | Terminal half-life: 1–4 minutes for the parent compound; clinical effects dissipate within the same time frame, correlating with rapid metabolism. |
| Protein binding | Approximately 60% bound to albumin. |
| Volume of Distribution | Approximately 3.3 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Sublingual: 40–60% due to first-pass metabolism; buccal: 40–60%; transdermal: 10–20% (limited by skin permeability). |
| Onset of Action | Sublingual tablet: 1–3 minutes; IV infusion: immediate (1–2 minutes); transdermal patch: 30–60 minutes; buccal spray: 1–2 minutes. |
| Duration of Action | Sublingual: 30–60 minutes (relief of acute angina); IV: 3–5 minutes post-infusion; transdermal patch: up to 12–14 hours (with nitrate-free interval to avoid tolerance); buccal spray: 30–60 minutes. |
| Molecular Weight | 227.09 |
Sublingual: 0.3-0.6 mg every 5 minutes up to 3 doses for angina; Transdermal: 0.2-0.8 mg/hour patch applied daily for 12-14 hours; Intravenous: 5-200 mcg/min continuous infusion for acute coronary syndromes or heart failure; Topical 2% ointment: 15-30 mg (0.5-1 inch) every 6-8 hours.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment, including end-stage renal disease. |
| Liver impairment | Child-Pugh Class A: No adjustment; Child-Pugh Class B: Consider 25% dose reduction; Child-Pugh Class C: Avoid use or use with extreme caution, consider 50% dose reduction. |
| Pediatric use | Safety and efficacy not established; limited data: IV infusion 0.25-1 mcg/kg/min titrated to effect; sublingual 5-10 mcg/kg per dose (max 0.6 mg) every 5-10 minutes as needed for angina. |
| Geriatric use | Start at lowest dose; sublingual 0.3 mg, transdermal 0.2 mg/hour; increased sensitivity to hypotension and syncope; monitor for orthostatic hypotension; may require reduced dosing frequency. |
| 1st trimester | Contraindicated in first trimester due to risk of fetal bradycardia and hypotension. Use only if benefit outweighs risk. |
| 2nd trimester | Use with caution; may cause fetal heart rate changes and hypotension. Consider alternative agents. |
| 3rd trimester | Use with caution near term; may cause maternal hypotension and reduce uterine blood flow. Avoid during labor for acute tocolysis. |
Clinical note
Comprehensive clinical and safety monograph for NITROGLYCERIN (NITROGLYCERIN).
| Placental transfer | NITROGLYCERIN crosses the placenta. Studies show detectable levels in fetal circulation. Degree of transfer is significant, with fetal serum concentrations approximately 10-15% of maternal levels. |
| Breastfeeding | NITROGLYCERIN is excreted into breast milk in small amounts. No adverse effects reported in infants. However, due to its vasodilatory effects, caution is advised, especially in preterm or low-birth-weight infants. |
| Lactation Rating | L3: Moderately Safe |
| Teratogenic Risk | Insufficient human data; animal studies do not indicate teratogenicity. Avoid in first trimester unless clearly needed. No known increased risk of major malformations. Use caution in third trimester due to potential maternal hypotension reducing uteroplacental perfusion. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and symptoms of hypotension. Fetal heart rate monitoring during intravenous infusion. |
| Fertility Effects | No known adverse effects on fertility in humans. |
■ FDA Black Box Warning
Do not use nitroglycerin with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) as this can cause severe hypotension. Concomitant use with soluble guanylyl cyclase stimulators (e.g., riociguat) is contraindicated.
| Serious Effects |
Severe anemiaIncreased intracranial pressure (e.g., head trauma, cerebral hemorrhage)Closed-angle glaucomaHypersensitivity to nitratesUse of phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil) within 24-48 hoursRight ventricular infarction with cardiogenic shockHypertrophic obstructive cardiomyopathyConstrictive pericarditis
| Precautions | Hypotension, Tachycardia, Paradoxical bradycardia, Increased intracranial pressure (use with caution in cerebral hemorrhage or head trauma), Hypertrophic cardiomyopathy (may exacerbate outflow obstruction), Tolerance with prolonged use (intermittent dosing with nitrate-free interval recommended), Abrupt withdrawal may precipitate angina |
| Food/Dietary | Avoid alcohol consumption while taking nitroglycerin due to risk of severe hypotension and syncope. No other significant food interactions. |
| Clinical Pearls | Use with caution in patients with hypertrophic obstructive cardiomyopathy due to risk of syncope. Nitroglycerin is contraindicated with phosphodiesterase-5 inhibitors (e.g., sildenafil) due to severe hypotension. Sublingual tablets should be taken at first sign of angina; if pain persists after 5 minutes, call 911. Tolerance develops with continuous exposure, so use nitrate-free intervals (10-12 hours daily) for transdermal patches. Administer intravenous nitroglycerin with non-PVC tubing to avoid drug absorption. Monitor for hypotension, reflex tachycardia, and headache. Do not use in patients with severe anemia, increased intracranial pressure, or right ventricular infarction. |
| Patient Advice | Take sublingual nitroglycerin at the first sign of chest pain; sit down before taking to prevent dizziness. · Place the tablet under the tongue or in the buccal pouch and allow it to dissolve completely; do not swallow. · If pain is not relieved within 5 minutes, call 911 immediately; you may take a second tablet while waiting. · Do not take this medication if you have taken erectile dysfunction drugs (e.g., sildenafil, tadalafil) within the last 24-48 hours. · Store sublingual tablets in the original glass bottle with the cap tightly closed to protect from light and moisture; do not transfer to another container. · Expect a headache or flushing after taking; these usually diminish with continued use. · If using a transdermal patch, apply to a hairless area of skin and rotate sites daily; remove at bedtime to prevent tolerance. · Avoid alcohol while taking this medication as it can increase the risk of hypotension. · Seek emergency help if you experience severe dizziness, fainting, or difficulty breathing. |
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