NITROGLYCERIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NITROGLYCERIN (NITROGLYCERIN).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for NITROGLYCERIN (NITROGLYCERIN).

Breastfeeding	Excreted into breast milk in very low amounts; M/P ratio not established. Considered compatible with breastfeeding; monitor infant for hypotension.
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

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to nitroglycerin or any component","Concomitant use with phosphodiesterase-5 inhibitors (within 24 hours for sildenafil, vardenafil; 48 hours for tadalafil)","Concomitant use with soluble guanylyl cyclase stimulators (riociguat)","Severe anemia","Increased intracranial pressure (e.g., head trauma, cerebral hemorrhage)","Constrictive pericarditis","Pericardial tamponade","Restrictive cardiomyopathy","Acute myocardial infarction with low left ventricular filling pressure","Circulatory failure (shock)"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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NITROGLYCERIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NITROGLYCERIN (NITROGLYCERIN).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for NITROGLYCERIN (NITROGLYCERIN).

Breastfeeding	Excreted into breast milk in very low amounts; M/P ratio not established. Considered compatible with breastfeeding; monitor infant for hypotension.
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