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Nitroglycerin (glyceryl trinitrate): Drug information

Nitroglycerin (glyceryl trinitrate): Drug information
(For additional information see "Nitroglycerin (glyceryl trinitrate): Patient drug information" and see "Nitroglycerin (glyceryl trinitrate): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • GoNitro;
  • Minitran [DSC];
  • Nitro-Bid;
  • Nitro-Dur;
  • Nitro-Time;
  • Nitrolingual;
  • NitroMist [DSC];
  • Nitrostat;
  • Rectiv
Brand Names: Canada
  • APO-Nitroglycerin [DSC];
  • Minitran [DSC];
  • MYLAN-Nitro;
  • Nitro-Dur;
  • Nitroject;
  • Nitrolingual;
  • RHO-Nitro;
  • Transderm-Nitro [DSC];
  • Trinipatch 0.2;
  • Trinipatch 0.4;
  • Trinipatch 0.6
Pharmacologic Category
  • Antianginal Agent;
  • Antidote, Extravasation;
  • Vasodilator
Dosing: Adult

Note: Safety: If a patient who has taken a phosphodiesterase-5 inhibitor for erectile dysfunction develops chest pain, delay nitrate therapy for ≥12 hours after taking avanafil, ≥24 hours after taking sildenafil or vardenafil, and ≥48 hours after taking tadalafil (Ref).

Acute decompensated heart failure

Acute decompensated heart failure (adjunctive agent):

Note: May consider in patients with volume overload in the absence of symptomatic hypotension to help relieve congestion and dyspnea as an adjunct to IV diuretics (Ref).

Continuous infusion: IV: Initial: 5 to 10 mcg/minute; titrate as needed based on response and tolerability in increments of 5 to 10 mcg/minute every 3 to 5 minutes up to 200 mcg/minute. Lower doses produce venous dilation; however, arterial vasodilation may occur at high doses. Tachyphylaxis develops within 24 to 48 hours of continuous administration; transition to long-term oral heart failure therapies as soon as possible for ongoing hemodynamic control (Ref).

Anal fissure

Anal fissure (alternative agent):

Note: Administer topically as a local vasodilator in conjunction with supportive measures. A 0.2% ointment is not commercially available and must be prepared by a licensed compounding facility (Ref).

Peri-anal 0.2% or 0.4% ointment: After cleansing, apply around fissure(s) twice daily as directed for 4 weeks; if symptoms persist, continue treatment for another 4 weeks for a total duration of 8 weeks (Ref).

Angina pectoris

Angina pectoris:

Note: Recommended for acute angina. For prevention of recurrent angina, may use in combination with other anti-anginal therapy (eg, a beta-blocker) (Ref).

Acute angina:

Note: If pain is not relieved or worsens 3 to 5 minutes after 1 sublingual or translingual dose, seek immediate emergency medical attention (eg, call 911) (Ref).

Sublingual powder (0.4 mg/packet): Initial: 1 or 2 packets at onset; repeat every 5 minutes if angina persists; may administer up to 3 packets in a 15-minute period (Ref).

Sublingual tablet: Initial: 0.3 or 0.4 mg at onset; repeat every 5 minutes if angina persists; may administer up to 3 tablets in a 15-minute period (Ref). For patients with refractory angina in the emergency department, up to 0.6 mg as a single dose may be considered (Ref).

Translingual 0.4 mg/spray: Initial: 1 or 2 sprays at onset; repeat every 5 minutes if angina persists; may administer up to 3 sprays in a 15-minute period (Ref).

Continuous IV infusion:

Note: Consider IV therapy if angina is not relieved with other dosage forms. Avoid in patients with hypotension (eg, systolic BP <90 mm Hg or >30 mm Hg below baseline), marked bradycardia (eg, <50 beats per minute) or tachycardia (eg, >100 beats per minute), and/or suspected right ventricular infarction (Ref).

Initial: 5 to 10 mcg/minute with continuous cardiac monitoring; titrate as needed to relieve angina symptoms in increments of 5 mcg/minute every 5 to 10 minutes up to 20 mcg/minute; if angina persists at a dose of 20 mcg/minute, may increase by 10 to 20 mcg/minute every 3 to 5 minutes to a maximum dose of 400 mcg/minute (Ref). Tachyphylaxis develops within 24 to 48 hours of continuous nitrate administration.

Prevention of angina (adjunctive therapy):

Sublingual powder (0.4 mg/packet): Initial: 1 packet 5 to 10 minutes prior to activities that may provoke angina.

Sublingual tablet: Initial: 0.3 or 0.4 mg 5 to 10 minutes prior to activities that may provoke angina.

Translingual 0.4 mg/spray: Initial: 1 or 2 sprays 5 to 10 minutes prior to activities that may provoke angina.

Topical 2% ointment: Initial: Apply ½ inch upon rising and apply another ½ inch 6 hours later; if necessary, the dose may be doubled to 1 inch and subsequently doubled again to 2 inches if response is inadequate. Recommended maximum frequency of administration is 2 doses/day. Include a nitrate-free interval of ~10 to 12 hours each day to minimize the risk of tolerance.

Topical patch, transdermal: Initial: 0.2 to 0.4 mg/hour; increase dose as needed based on response and tolerability to a maximum of 0.8 mg/hour. Use a patch-on period of 12 to 14 hours/day and patch-off period (nitrate-free interval) of 10 to 12 hours/day to minimize the risk of tolerance.

ER capsule, oral: Initial: 2.5 to 6.5 mg 3 to 4 times daily; increase dose as needed based on response and tolerability to 26 mg 4 times daily. Include a nitrate-free interval of ~10 to 12 hours each day to minimize the risk of tolerance.

Extravasation management, sympathomimetic vasopressors

Extravasation management, sympathomimetic vasopressors (alternative agent) (off-label use):

Note: Nitroglycerin is an alternative if phentolamine is not available (Ref).

Topical 2% ointment: Apply a 1-inch strip to site of ischemia; may repeat every 8 hours if needed (Ref).

Hypertension, perioperative

Hypertension, perioperative (alternative agent):

Note: For patients with chronic hypertension prior to surgery, restart oral therapies as soon as appropriate once hemodynamically stable. Address underlying causes (eg, pain, agitation, withdrawal, hypervolemia) prior to initiating antihypertensive therapy. Generally used for patients with hypervolemia who are not responsive to IV diuretic therapy, particularly if there is known or suspected ischemic heart disease or heart failure (Ref).

Continuous IV infusion: Initial: 5 to 10 mcg/minute; increase based on BP response and tolerability in increments of 5 mcg/minute every 3 to 5 minutes up to 20 mcg/minute; if no response at a dose of 20 mcg/minute, may increase by 10 to 20 mcg/minute every 3 to 5 minutes to a maximum dose of 200 mcg/minute. Lower doses primarily produce venous dilation; however, arterial vasodilation may occur at high doses (Ref). Tachyphylaxis develops within 24 to 48 hours of continuous nitrate administration; if vasodilator requirements continue longer than 24 to 48 hours, transition to an alternative IV or oral vasodilator.

Hypertensive emergency

Hypertensive emergency (alternative agent) (off-label use):

Note: Limitations of use include variable efficacy compared to other agents (eg, inconsistent and transient BP response), possible reflex tachycardia, and possible reduced cardiac output. May be used as adjunctive therapy for patients with acute coronary syndrome or acute pulmonary edema. In general, goal of therapy is to reduce mean arterial pressure by ~10% to 20% over the first hour, then by an additional 5% to 15% over the next 23 hours (Ref).

Continuous IV infusion: Initial: 5 mcg/minute; increase based on BP response and tolerability in increments of 5 mcg/minute every 3 to 5 minutes up to 20 mcg/minute; if no response at a dose of 20 mcg/minute, may increase by 10 to 20 mcg/minute every 3 to 5 minutes to a maximum dose of 200 mcg/minute. Lower doses produce venous dilation; however, arterial vasodilation may occur at high doses (Ref). Tachyphylaxis develops within 24 to 48 hours of continuous nitrate administration; if vasodilator requirements continue longer than 24 to 48 hours, transition to an alternative IV or oral vasodilator.

Uterine relaxation

Uterine relaxation (off-label use):

Note: May be used for obstetric emergencies (eg, uterine inversion, difficult fetal extraction due to uterine contraction, internal podalic version of a second twin) or to facilitate extraction of a trapped placenta, external cephalic version, or replacement of deeply prolapsed fetal membranes before placement of a cerclage (Ref). Dosing provided is an example and may vary based on indication.

IV: 50 mcg once; may repeat at 1-minute intervals as needed to sufficiently relax the uterus; maximum total dose: 250 mcg (Ref). If urgent uterine relaxation is required (eg, for fetal extraction), may use initial bolus of 100 to 200 mcg (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (<1% excreted in the urine) (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (large Vd): No supplemental dose or dosage adjustment necessary (Ref).

Peritoneal dialysis: Unlikely to be dialyzed (large Vd): No dosage adjustment necessary (Ref).

CRRT: No dosage adjustment necessary (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Pediatric

(For additional information see "Nitroglycerin (glyceryl trinitrate): Pediatric drug information")

Heart failure; cardiogenic shock

Heart failure; cardiogenic shock: Limited data available: Note: Continuous IV infusion dosing units vary by age (mcg/kg/minute or mcg/minute); extra precautions should be taken. In adults, tolerance to the hemodynamic and antianginal effects can develop within 24 hours of continuous use; nitrate-free interval (10 to 12 hours/day) is recommended to avoid tolerance development; gradually decrease dose in patients receiving nitroglycerin for prolonged periods to avoid withdrawal reaction (Ref).

Infants and Children: Continuous IV infusion: Initial: 0.25 to 0.5 mcg/kg/minute; titrate by 1 mcg/kg/minute every 15 to 20 minutes as needed; faster titration may be necessary in some patients; in adults, titration every 3 to 5 minutes has been suggested. Usual dose range: 1 to 5 mcg/kg/minute; usual maximum dose: 10 mcg/kg/minute (Ref); doses up to 20 mcg/kg/minute may be used (Ref).

Adolescents: Continuous IV infusion: Initial: 5 to 10 mcg/minute; titrate to a maximum dose of 200 mcg/minute. Note: In adults, doses are titrated every 3 to 5 minutes as needed (Ref).

Extravasation, treatment

Extravasation (sympathomimetic vasopressors), treatment (alternative to phentolamine): Very limited data available; dosing based on experience in neonatal patients; optimal dosing has not been established:

Infants, Children, and Adolescents: Topical: 2% ointment: 4 mm/kg applied as a thin ribbon to the affected areas; after 8 hours if no improvement, the dose may be repeated at the affected site (Ref). The maximum reported dose is application of a 1-inch strip to the affected site in a neonate (Ref); however, this is greater than the usual initial adult dose (1/2 inch) for angina; hypotension may occur; carefully monitor blood pressure (Ref). Note: Minimal data available from clinical trials/case reports; however, use has been described in reviews of extravasation treatment (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Aerosol Solution, Translingual:

NitroMist: 400 mcg/spray (4.1 g [DSC], 8.5 g [DSC]) [contains menthol]

Capsule Extended Release, Oral:

Nitro-Time: 2.5 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10)]

Nitro-Time: 6.5 mg [contains fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]

Nitro-Time: 9 mg [contains fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]

Generic: 2.5 mg [DSC], 6.5 mg [DSC], 9 mg [DSC]

Ointment, Rectal:

Rectiv: 0.4% (30 g) [contains propylene glycol]

Ointment, Transdermal:

Nitro-Bid: 2% (1 g, 30 g, 60 g)

Packet, Sublingual:

GoNitro: 400 mcg (1 ea, 36 ea [DSC])

Patch 24 Hour, Transdermal:

Minitran: 0.1 mg/hr (30 ea [DSC]); 0.2 mg/hr (30 ea [DSC]); 0.4 mg/hr (30 ea [DSC]); 0.6 mg/hr (30 ea [DSC])

Nitro-Dur: 0.1 mg/hr (1 ea, 30 ea, 100 ea); 0.2 mg/hr (1 ea, 30 ea); 0.3 mg/hr (1 ea, 30 ea, 100 ea); 0.4 mg/hr (1 ea, 30 ea); 0.6 mg/hr (1 ea, 30 ea); 0.8 mg/hr (1 ea, 30 ea, 100 ea)

Generic: 0.1 mg/hr (1 ea, 30 ea); 0.2 mg/hr (1 ea, 30 ea); 0.4 mg/hr (1 ea, 30 ea); 0.6 mg/hr (1 ea, 30 ea, 4350 ea [DSC])

Solution, Intravenous:

Generic: 25 mg (250 mL); 50 mg (250 mL); 100 mg (250 mL); 5 mg/mL (10 mL)

Solution, Translingual:

Nitrolingual: 0.4 mg/spray (4.9 g, 12 g) [contains alcohol, usp]

Generic: 0.4 mg/spray (4.9 g, 12 g)

Tablet Sublingual, Sublingual:

Nitrostat: 0.3 mg, 0.4 mg, 0.6 mg

Generic: 0.3 mg, 0.4 mg, 0.6 mg

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Patch 24 Hour, Transdermal:

Minitran: 0.2 mg/hr ([DSC]); 0.4 mg/hr ([DSC]); 0.6 mg/hr ([DSC])

Nitro-Dur: 0.2 mg/hr (30 ea); 0.4 mg/hr (30 ea); 0.6 mg/hr (30 ea); 0.8 mg/hr (30 ea)

Transderm-Nitro: 0.2 mg/hr ([DSC]); 0.4 mg/hr ([DSC]); 0.6 mg/hr ([DSC])

Trinipatch 0.2: 0.2 mg/hr (30 ea, 100 ea)

Trinipatch 0.4: 0.4 mg/hr (30 ea, 100 ea)

Trinipatch 0.6: 0.6 mg/hr (30 ea, 100 ea)

Generic: 0.2 mg/hr (30 ea); 0.4 mg/hr (30 ea); 0.6 mg/hr (30 ea); 0.8 mg/hr (30 ea)

Solution, Intravenous:

Nitroject: 5 mg/mL (10 mL)

Generic: 50 mg (250 mL); 5 mg/mL (10 mL); 400-5 MCG/ML-% (250 mL)

Solution, Translingual:

Nitrolingual: 0.4 mg/spray (4.9 g, 14.49 g) [contains alcohol, usp]

RHO-Nitro: 0.4 mg/spray (1 ea) [contains alcohol, usp]

Generic: 0.4 mg/spray (1 ea)

Administration: Adult

IV: Prepare in glass bottles, EXCEL or PAB containers. Adsorption occurs to soft plastic (eg, PVC); use administration sets intended for nitroglycerin. Avoid in-line IV filters that adsorb nitroglycerin. Administer via infusion pump.

Intra-anal ointment: Using a finger covering (eg, plastic wrap, surgical glove, finger cot), place finger beside 1 inch measuring guide on the box and squeeze ointment the length of the measuring line directly onto covered finger. Insert ointment into the anal canal using the covered finger up to first finger joint (do not insert further than the first finger joint) and apply ointment around the side of the anal canal. If intra-anal application is too painful, may apply the ointment to the outside of the anus. Wash hands following application.

ER capsule: Swallow whole. Do not chew, break, or crush. Administer with a full glass of water.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Topical ointment and transdermal formulations are available. If safety and efficacy of nitroglycerin can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, selection of ointment, transdermal, or alternative therapy should be considered in high-risk patients.

Sublingual powder: Empty the contents of packet under the tongue, close mouth, and breathe normally. Allow powder to dissolve without swallowing. Do not rinse or spit for 5 minutes after dosing.

Sublingual tablet: Do not chew, crush, or swallow sublingual tablet. Place under tongue and allow to dissolve. Alternately, may be placed in the buccal pouch. May take small sip of water prior to placing tablet under the tongue to aid dissolution.

Topical ointment: Wash hands prior to and after use. Application site should be clean, dry, and hair free. Apply to chest or back with the applicator or dose-measuring paper. Spread in a thin layer over a 2.25 x 3.5 inch area. Do not rub into skin. Tape applicator into place.

Extravasation management, sympathomimetic vasopressors (alternative agent) (off-label use): Stop vesicant infusion immediately and disconnect IV line (leave needle/cannula in place); gently aspirate extravasated solution from the IV line (do NOT flush the line); remove needle/cannula; elevate extremity. Apply nitroglycerin ointment as a thin ribbon to site of ischemia (Ref). May also apply dry warm compresses (Ref).

Topical patch, transdermal: Application site should be clean, dry, and hair free. Remove patch after 12 to 14 hours. Rotate patch sites. Dispose of any used of unused patches by folding adhesive ends together, replace in pouch or sealed container and discard properly in trash, away from children and pets.

Translingual spray: Do not shake container. Prior to initial use, the pump must be primed by spraying 5 times (Nitrolingual) or 10 times (Nitromist) into the air. Priming sprays should be directed away from patient and others. Release spray onto or under tongue. Close mouth immediately after administration; do not inhale spray. Do not expectorate or rinse the mouth for 5 to 10 minutes following administration. Content of the container should be checked periodically; when the container is held upright, the end of the pump should be covered by the fluid in the bottle or the remaining sprays will not deliver the intended dose. If pump is unused for 6 weeks, a single priming spray (Nitrolingual) or 2 priming sprays (Nitromist) should be completed. If pump is unused for 3 months, re-prime with up to 5 sprays (Nitrolingual).

Administration: Pediatric

Parenteral: Continuous IV infusion: Vials (concentrated solution): Not for direct injection; must be diluted prior to administration; premixed solution in glass containers (100 mcg/mL, 200 mcg/mL, 400 mcg/mL) is available. Administer via infusion pump. Adsorption to soft plastic (eg, PVC) occurs; special administration sets intended for nitroglycerin (nonpolyvinyl chloride) must be used; some inline IV filters also adsorb nitroglycerin; use of these filters should be avoided.

Topical ointment: Wash hands prior to and after use. Application site should be clean, dry, and hair free. Do not rub into skin.

Extravasation (sympathomimetic vasopressors), treatment: Stop vesicant infusion immediately and disconnect IV line (leave needle/cannula in place); gently aspirate extravasated solution from the IV line (do NOT flush the line); remove needle/cannula; elevate extremity. Apply nitroglycerin ointment as a thin ribbon to site of ischemia (Ref). May also apply dry warm compresses (Ref).

Usual Infusion Concentrations: Adult

Note: Premixed solutions available

IV infusion: 50 mg in 250 mL (concentration: 200 mcg/mL) or 100 mg in 250 mL (concentration: 400 mcg/mL) of D5W

Usual Infusion Concentrations: Pediatric

Note: Premixed solutions available.

IV infusion: 100 mcg/mL, 200 mcg/mL, or 400 mcg/mL.

Use: Labeled Indications

Oral administration: Treatment or prevention of angina pectoris.

IV administration: Treatment of angina pectoris; acute decompensated heart failure; perioperative hypertension; induction of intraoperative hypotension.

Intra-anal administration (Rectiv ointment): Treatment of moderate to severe pain associated with chronic anal fissure.

Use: Off-Label: Adult

Extravasation management, sympathomimetic vasopressors; Hypertensive emergency; Uterine relaxation

Medication Safety Issues
Sound-alike/look-alike issues:

Nitroglycerin may be confused with nitrofurantoin, nitroprusside

Nitro-Bid may be confused with Macrobid

Nitroderm may be confused with NicoDerm

Nitrol may be confused with Nizoral

Nitrostat may be confused with Nilstat, nystatin

Other safety concerns:

Transdermal patch may contain conducting metal (eg, aluminum); remove patch prior to MRI.

International issues:

Nitrocor [Italy, Russia, and Venezuela] may be confused with Natrecor brand name for nesiritide [US, Canada, and multiple international markets]; Nutracort brand name for hydrocortisone in the [US and multiple international markets]; Nitro-Dur [US, Canada, and multiple international markets]

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Nervous system: Headache (patch, ointment: 50% to 64%; sublingual powder, lingual spray: >2%)

1% to 10%:

Cardiovascular: Hypotension (≤4%), peripheral edema (lingual spray: ≤2%), syncope (≤4%)

Gastrointestinal: Abdominal pain (lingual spray: ≤2%)

Nervous system: Dizziness (>2% to 6%), paresthesia (>2%)

Neuromuscular & skeletal: Asthenia (all sublingual forms: ≤2%)

Respiratory: Dyspnea (≤2%), pharyngitis (lingual spray: ≤2%), rhinitis (lingual spray: ≤2%)

Frequency not defined:

Cardiovascular: Flushing, orthostatic hypotension

Dermatologic: Diaphoresis

<1%, postmarketing, and/or case reports: Application site irritation (patch), circulatory shock, contact dermatitis (ointment, patch), drowsiness, exfoliative dermatitis, fixed drug eruption (ointment, patch), hypersensitivity reaction, hypoxemia (transient), lactic acidosis (Smith 2019), methemoglobinemia, nausea, nonimmune anaphylaxis, pallor, palpitations, rebound hypertension, restlessness, skin rash, tachycardia, vertigo, vomiting

Contraindications

Hypersensitivity to nitroglycerin, other nitrates or nitrites, or any component of the formulation (includes adhesives for transdermal product); concurrent use with phosphodiesterase-5 (PDE-5) inhibitors (avanafil, sildenafil, tadalafil, or vardenafil); concurrent use with soluble guanylate cyclase (sGC) stimulators (eg, riociguat); acute circulatory failure or shock; early myocardial infarction (sublingual tablet only; see Note below); increased intracranial pressure; severe anemia.

Additional contraindications for IV product: Constrictive pericarditis; increased intracranial pressure; pericardial tamponade; restrictive cardiomyopathy.

Canadian labeling: Additional contraindications for translingual product (not in manufacturer's US labeling): Closed angle glaucoma; heart failure (aortic or mitral stenosis, constrictive pericarditis, or hypertrophic cardiomyopathy with left ventricular outflow tract obstruction).

Canadian labeling: Additional contraindications for transdermal patch (not in manufacturer's US labeling): orthostatic hypotension; myocardial insufficiency due to obstruction (eg, presence of aortic or mitral stenosis or of constrictive pericarditis); increased intraocular pressure.

Note : According to the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines of the management of ST-elevation myocardial infarction (STEMI) and the ACC/AHA guidelines for the management of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS), avoid nitrates in the following conditions: Hypotension (SBP <90 mm Hg or >30 mm Hg below baseline), marked bradycardia or tachycardia, and right ventricular infarction (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]). Sublingual nitroglycerin may be used as initial treatment of ongoing chest pain in patients who may have STEMI or NSTE-ACS (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]).

Warnings/Precautions

Concerns related to adverse effects:

• Headache: Dose-related headaches may occur, especially during initial dosing.

• Hypotension/bradycardia: Severe hypotension and shock may occur (even with small doses); paradoxical bradycardia and increased angina pectoris may accompany hypotension. Orthostatic hypotension may also occur; ethanol may accentuate this. Use with caution in volume depletion, preexisting hypotension, constrictive pericarditis, aortic or mitral stenosis, and extreme caution with inferior wall myocardial infarction (MI) and suspected right ventricular involvement. According to the American College of Cardiology Foundation/American Heart Association, avoid use in patients with severe hypotension (SBP <90 mm Hg or >30 mm Hg below baseline), marked bradycardia or tachycardia, and right ventricular MI (ACCF/AHA [O'Gara 2013]).

• Increased intracranial pressure: Nitroglycerin may precipitate or aggravate increased intracranial pressure and subsequently may worsen clinical outcomes in patients with neurologic injury (eg, intracranial hemorrhage, traumatic brain injury) (Rangel-Castilla 2008). Use is contraindicated in patients with increased intracranial pressure.

Disease-related concerns:

• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Avoid use in patients with hypertrophic cardiomyopathy with left ventricular outflow tract obstruction; nitrates may reduce preload, exacerbating obstruction and cause hypotension or syncope and/or worsening of heart failure (HF) (AHA/ACC [Ommen 2020]).

Dosage form specific issues:

• Intra-anal ointment: Use caution when treating rectal anal fissures with nitroglycerin in patients with suspected or known significant cardiovascular disorders (eg, cardiomyopathies, HF, acute MI); intra-anal nitroglycerin administration may decrease systolic BP and decrease arterial vascular resistance.

• Long-acting agents: Avoid use of long-acting agents in acute MI or acute HF; cannot easily reverse effects if adverse events develop.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

• Transdermal patches: May contain conducting metal (eg, aluminum); remove patch prior to MRI.

Other warnings/precautions:

• Tolerance: May occur; cross tolerance to other nitro compounds have been reported. Appropriate dosing is needed to minimize tolerance development.

Warnings: Additional Pediatric Considerations

Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults, including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alteplase: Nitroglycerin may decrease the serum concentration of Alteplase. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Anticholinergic Agents: May decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Apomorphine: Nitroglycerin may enhance the hypotensive effect of Apomorphine. Management: Patients taking apomorphine should lie down before and after taking sublingual nitroglycerin. Monitor blood pressure for hypotension and orthostatic hypotension when these agents are combined. Risk D: Consider therapy modification

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Dapoxetine: May enhance the orthostatic hypotensive effect of Vasodilators (Organic Nitrates). Risk C: Monitor therapy

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): May diminish the vasodilatory effect of Nitroglycerin. Nitroglycerin may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Management: Avoid the use of ergot derivatives in patients receiving nitroglycerin for angina (or in any angina patient) if possible. If combined, monitor for decreased effects of nitroglycerin and increased adverse effects of the ergot derivative (eg, ergotism). Risk D: Consider therapy modification

Heparin: Nitroglycerin may diminish the anticoagulant effect of Heparin. Nitroglycerin may decrease the serum concentration of Heparin. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Vasodilators (Organic Nitrates). Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk X: Avoid combination

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Rilmenidine: Vasodilators (Organic Nitrates) may enhance the hypotensive effect of Rilmenidine. Risk C: Monitor therapy

Riociguat: Vasodilators (Organic Nitrates) may enhance the hypotensive effect of Riociguat. Risk X: Avoid combination

Rosiglitazone: Vasodilators (Organic Nitrates) may enhance the adverse/toxic effect of Rosiglitazone. Specifically, a greater risk of ischemia and other adverse effects has been associated with this combination in some pooled analyses. Risk C: Monitor therapy

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy

Pregnancy Considerations

Nitroglycerin crosses the placenta (David 2000).

Following a single maternal IV bolus dose of nitroglycerin at the time of incision prior to cesarean delivery, concentrations in the umbilical cord at birth were significantly lower than the maternal plasma (~1 minute after dosing); a wide variation in maternal plasma concentrations was observed (David 2000). Following application of a transdermal patch 0.4 mg/hour to pregnant women 20 to 36 weeks gestation, concentrations of nitroglycerin were low but detectable in the fetal serum ~1 to 4 hours after the patch was applied (fetal/maternal ratio: 0.23) (Bustard 2003).

IV nitroglycerin is recommended for use in pregnant females with preeclampsia when severe hypertension is associated with pulmonary edema (ESC [Regitz-Zagrosek 2018]). Based on its ability to produce smooth muscle relaxation, nitroglycerin may be used in obstetrical procedures when immediate relaxation of the uterus is needed, such as: uterine inversion following delivery (ACOG 183 2017), uterine relaxation during removal of retained placental tissue (ASA 2016), and management of breech delivery (Caponas 2001; Cluver 2015). Additional data may be necessary to further define the role of nitroglycerin for preterm labor (ACOG 171 2016; Duckitt 2014).

Breastfeeding Considerations

It is not known if nitroglycerin is present in breast milk.

Information related to the use of nitroglycerin and breastfeeding is limited (Böttiger 2010; O’Sullivan 2011). Adverse events were not noted in breastfeeding infants of mothers using topical nitroglycerin for anal fissures (Taylor 2008). Use of nitroglycerin ointment has been noted in a case report for the treatment of Raynaud phenomenon of the nipple. Breastfeeding was discontinued prior to therapy. Signs and symptoms resolved within a few weeks (O’Sullivan 2011). According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Blood pressure, heart rate; consult individual institutional policies and procedures

Mechanism of Action

Nitroglycerin forms free radical nitric oxide. In smooth muscle, nitric oxide activates guanylate cyclase which increases guanosine 3’5’ monophosphate (cGMP) leading to dephosphorylation of myosin light chains and smooth muscle relaxation. Produces a vasodilator effect on the peripheral veins and arteries with more prominent effects on the veins. Primarily reduces cardiac oxygen demand by decreasing preload (left ventricular end-diastolic pressure); may modestly reduce afterload; dilates coronary arteries and improves collateral flow to ischemic regions. For use in rectal fissures, intra-anal administration results in decreased sphincter tone and intra-anal pressure.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Sublingual tablet: 1 to 3 minutes; Translingual spray: Similar to sublingual tablet; Extended release: ~60 minutes; Topical: 15 to 30 minutes; Transdermal: ~30 minutes; IV: Immediate

Peak effect: Sublingual powder: 7 minutes; Sublingual tablet: 5 minutes; Translingual spray: 4 to 15 minutes; Extended release: 2.5 to 4 hours; Topical: ~60 minutes; Transdermal: 120 minutes; IV: Immediate

Duration: Sublingual tablet: At least 25 minutes; Translingual spray: Similar to sublingual tablet; Extended release: 4 to 8 hours (Gibbons 2003); Topical: 7 hours; Transdermal: 10 to 12 hours; IV: 3 to 5 minutes

Distribution: Vd: ~3 L/kg

Protein binding: 60%

Metabolism: Extensive first-pass effect; metabolized hepatically to glycerol di- and mononitrate metabolites via liver reductase enzyme; subsequent metabolism to glycerol and organic nitrate; nonhepatic metabolism via red blood cells and vascular walls also occurs

Half-life elimination: ~1 to 4 minutes

Excretion: Urine (as inactive metabolites)

Pricing: US

Capsule, controlled release (Nitro-Time Oral)

2.5 mg (per each): $0.87

6.5 mg (per each): $1.00

9 mg (per each): $1.03

Ointment (Nitro-Bid Transdermal)

2% (per gram): $1.42

Ointment (Rectiv Rectal)

0.4% (per gram): $25.63

Pack (GoNitro Sublingual)

400 mcg (per each): $8.17

Patch, 24-hour (Nitro-Dur Transdermal)

0.1 mg/hour (per each): $28.12

0.2 mg/hour (per each): $30.25

0.3 mg/hour (per each): $63.59

0.4 mg/hour (per each): $33.91

0.6 mg/hour (per each): $36.78

0.8 mg/hour (per each): $68.96

Patch, 24-hour (Nitroglycerin Transdermal)

0.1 mg/hour (per each): $1.86 - $2.56

0.2 mg/hour (per each): $1.90 - $2.60

0.4 mg/hour (per each): $2.17 - $2.91

0.6 mg/hour (per each): $2.40 - $3.15

Solution (Nitroglycerin in D5W Intravenous)

100 mcg/mL 5% (per mL): $0.10

200 mcg/mL 5% (per mL): $0.11

Solution (Nitroglycerin Intravenous)

5 mg/mL (per mL): $1.71

Solution (Nitroglycerin Translingual)

0.4 mg/spray (per gram): $45.81

Solution (Nitrolingual Translingual)

0.4 mg/spray (per gram): $67.37

Sublingual (Nitroglycerin Sublingual)

0.3 mg (per each): $0.47

0.4 mg (per each): $1.02 - $1.03

0.6 mg (per each): $0.47

Sublingual (Nitrostat Sublingual)

0.3 mg (per each): $0.85

0.4 mg (per each): $1.85

0.6 mg (per each): $0.85

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Angiderm Patch (KR);
  • Anginine (AU);
  • Angised (HR, KW, SG);
  • Cardiocare (EG);
  • Cardiplast (ES);
  • Cardispray (AE);
  • Cardnit (PK);
  • Deponit (BE, CN, DE, HU, LU, MY, PE, PH);
  • Deponit NT (IL);
  • Dermatrans (ES);
  • Diafusor (LU);
  • Domitral (VN);
  • Enetege (UY);
  • Epinitril (FR);
  • Glytrin (IE, TR);
  • Glytrin Spray (NZ, SG);
  • Herzer (JP);
  • Lycinate (AU);
  • Millisrol (JP);
  • Minitran (AU, BE, CR, DO, GR, GT, HN, LU, MT, PA, SV, UY);
  • Myonit Insta (MY);
  • Myovin (IN);
  • Natispray (LU);
  • Nifutoin (TW);
  • Niglinar (PE);
  • Nit-Ret (CZ);
  • Nitracor (PL);
  • Nitradisc (LU, MX, PT);
  • Nitradisc TTS (GR);
  • Nitral (ID);
  • Nitriderm TTS (FR);
  • Nitril (LK);
  • Nitro (FI, HU);
  • Nitro Mack (LU);
  • Nitro Mack Retard (AE, AT, CY, CZ, GR, IQ, IR, JO, KW, LY, OM, QA, SA, SY, YE);
  • Nitro Pohl (HU);
  • Nitro-Dur (AE, AU, BB, CH, ES, HU, IT, NO, PL, PT, QA, SA);
  • Nitro-Dur 10 (IL);
  • Nitro-Mack (PL);
  • Nitro-Pflaster (DE);
  • Nitro-Pflaster-ratiopharm (LU);
  • Nitrobaat (BE, NL);
  • Nitrocard (PL);
  • Nitrocerin (GR);
  • Nitrocine (CN, EE, ID, IE);
  • Nitrocine 5 (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE);
  • Nitrocontin (BF, BJ, CI, ET, GH, GM, GN, IN, KE, LK, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TW, TZ, UG, ZA, ZM, ZW);
  • Nitrocontin Continus (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE);
  • Nitrocor (IT);
  • Nitroderm (VE);
  • Nitroderm TTS (AE, AR, AT, BE, BF, BJ, BM, BR, BS, BZ, CH, CI, CL, CY, DE, EC, EG, ES, ET, GH, GM, GN, GY, HR, HU, IN, IQ, IR, IT, JM, JO, KE, KW, LR, LU, LY, MA, ML, MR, MT, MU, MW, NE, NG, NZ, OM, PL, PT, QA, RO, SA, SC, SD, SL, SN, SR, SY, TH, TN, TT, TW, TZ, UG, YE, ZA, ZM, ZW);
  • Nitroderm TTS Ext (CZ);
  • Nitroderm TTS-5 (NI);
  • Nitrodisc (BM, BS, BZ, GY, JM, MY, SR, TT);
  • Nitrodom (AR);
  • Nitrodyl (GR, LU);
  • Nitrodyl TTS (GR);
  • Nitrogesic (UY);
  • Nitroglycerinum (PL);
  • Nitroglycerinum prolongatum (PL);
  • Nitroject (LB);
  • Nitrol (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE);
  • Nitrolingual (AE, AT, BE, CH, DE, DK, EG, GB, GR, HK, HU, IE, KR, LT, LU, MT, NL, PH, PT, SE, SI, TW);
  • Nitrolingual Pumpspray (AU);
  • Nitrolingual Spray (KR, NZ, PH);
  • Nitromack Retard (PY);
  • Nitromax (UA);
  • Nitromex (NO, SE);
  • Nitromint (HU, PL, RO, SK, TH, UA);
  • Nitromint Aerosol (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW);
  • Nitromint Retard (AE, BM, BS, BZ, CY, GY, IQ, IR, JM, JO, KW, LY, OM, SA, SR, SY, TT, YE);
  • Nitronal (FR, RO);
  • Nitronal Aqueous (PH);
  • Nitronal Spray (FR);
  • Nitrong (BE, LU, MT, TR);
  • Nitrong Retard (AT, GR);
  • Nitroplast (ES);
  • Nitroplus (LK);
  • Nitrosol Spray (MY);
  • Nitrostat (TW);
  • Nitrovas (BD);
  • Nitrozell Retard (AT, NL);
  • NTG (ID);
  • Nysconitrine (LU);
  • Nyserin (PH);
  • Perlinganit (BG, HU, KR, LU, PL);
  • Ratiopharm (DE);
  • Rectogesic (AU, BE, CH, CZ, DE, DK, FI, FR, GB, IE, IT, NL, NO, NZ, PT, SE, SG, SK, TR);
  • Rectogesic Ointment (KR);
  • Sustac (AE, BM, BS, BZ, CY, GY, HR, HU, IQ, IR, JM, JO, KW, LY, OM, SA, SR, SY, TT, YE);
  • Sustonit (PL);
  • Transiderm Nitro (AU, FI, IE, NL, NO, SE);
  • Tridil (BR);
  • Trimonit (PL);
  • Trinipatch (BE, LU);
  • Venitrin (IT);
  • Willlong (LU);
  • Yumenin (TW)


For country code abbreviations (show table)
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  48. Minitran (nitroglycerin) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; December 2014.
  49. Nitro-Bid (nitroglycerin) [prescribing information]. Melville, NY: Savage Pharmaceuticals; September 2011
  50. Nitro-Dur (nitroglycerin) [prescribing information]. Orlando, FL: Ingenus Pharmaceuticals LLC; September 2017.
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