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Nitroglycerin

Medically reviewed by Drugs.com. Last updated on Oct 2, 2020.

Pronunciation

(nye troe GLI ser in)

Index Terms

  • Glyceryl Trinitrate
  • GTN
  • Nitroglycerol
  • NTG
  • TNG
  • Tridil

Dosage Forms

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, 8.5 g) [contains menthol]

Generic: 400 mcg/spray (4.1 g [DSC], 8.5 g [DSC])

Capsule Extended Release, Oral:

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

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

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

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)

Patch 24 Hour, Transdermal:

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

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

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

Solution, Intravenous:

Generic: 25 mg (250 mL); 50 mg (250 mL, 500 mL [DSC]); 100 mg (250 mL); 200 mg (500 mL [DSC]); 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

Brand Names: U.S.

  • GoNitro
  • Minitran
  • Nitro-Bid
  • Nitro-Dur
  • Nitro-Time
  • Nitrolingual
  • NitroMist
  • Nitrostat
  • Rectiv

Pharmacologic Category

  • Antianginal Agent
  • Antidote, Extravasation
  • Vasodilator

Pharmacology

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.

Distribution

Vd: ~3 L/kg

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

Excretion

Urine (as inactive metabolites)

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 of Action

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

Half-Life Elimination

~1 to 4 minutes

Protein Binding

60%

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.

Off Label Uses

Extravasation management, sympathomimetic vasopressors

Clinical experience suggests utility of topical nitroglycerin in the management of sympathomimetic vasopressor extravasations [Hurst 2004], [Reynolds 2014].

Hypertensive emergency

Based on the American College of Cardiology/American Heart Association guideline for the prevention, detection, evaluation, and management of high blood pressure in adults, nitroglycerin is an option for hypertensive emergency, especially if there is concomitant acute coronary syndrome or pulmonary edema [ACC/AHA [Whelton 2018]].

Uterine relaxation

Based on its ability to relax smooth muscle, nitroglycerin has been used in observational studies and case reports to induce uterine relaxation in obstetrical procedures such as removal of a retained placenta or when uterine inversion occurs following childbirth [Altabef 1992], [Axemo 1998], [Bayhi 1992], [Chedraui 2003], [Dayan 1996], [Dufour 1997], [Lowenwirt 1997].

Based on the American College of Obstetricians and Gynecologists guidelines for the treatment of postpartum hemorrhage, nitroglycerin is an option when uterine relaxation is needed in the management of uterine inversion [ACOG 183 2017]. Based on the American Society of Anesthesiologists practice guidelines for obstetric anesthesia, nitroglycerin may be used as an alternative agent for uterine relaxation during removal of retained placental tissue [ASA 2016].

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 obstructive cardiomyopathy).

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]).

Dosing: Adult

Note: Safety: Contraindicated in patients taking a phosphodiesterase 5 (PDE5) inhibitor for any indication or a soluble guanylate cyclase inhibitor (eg, riociguat) due to potentially severe hypotension. In general, if a patient who has taken a PDE5 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 (Khera 2020; Stendra [avanafil] prescribing information). Consult drug interactions database for more information. In addition, avoid or use with caution in patients likely to develop hypotension or in whom hypotension could result in serious decompensation, including those with hypertrophic cardiomyopathy, severe aortic stenosis, or right ventricular infarction.

Acute decompensated heart failure (adjunctive therapy):

Note: Consider in patients with volume overload and without symptomatic hypotension to help relieve dyspnea when response to IV diuretics is not adequate (ACCF/AHA [Yancy 2013]).

Continuous IV infusion: 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 a maximum of 200 mcg/minute. Lower doses produce venous dilation; however, arterial vasodilation may occur at high doses (Colucci 2020; Coons 2011; Mebazaa 2016). Tachyphylaxis develops within 24 to 48 hours of continuous administration. Hemodynamic control after this initial period can be maintained by transitioning to long-term oral therapy for heart failure (Colucci 2020).

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 (Bleday 2020).

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 (Bacher 1997; Bleday 2020; Kennedy 1999; Lund 1997; Zuberi 2000).

Angina:

Note: Recommended for acute angina. For prevention of recurrent angina, may use in combination with other anti-anginal therapy (eg, a beta-blocker) (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]).

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) (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]).

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 (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]).

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 (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]). For patients with refractory angina in the emergency department, up to 0.6 mg as a single dose may be considered (Reeder 2020).

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 (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]).

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 (ACCF/AHA [O'Gara 2013]; Reeder 2020).

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 (ACCF/AHA [O'Gara 2013]; Reeder 2020; manufacturer's labeling). 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. Alternatively, some experts recommend applying patch 30 to 45 minutes prior to activities that may provoke angina and removing patch after activity is complete (Chaudhary 2020).

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 (alternative agent) (off-label use):

Note: Nitroglycerin is an alternative if phentolamine is not available (Reynolds 2014).

Topical 2% ointment: Apply a 1-inch strip to site of ischemia; may repeat every 8 hours if needed (Reynolds 2014).

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 (Broussard 2020; London 2020).

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 (Broussard 2020; London 2020; manufacturer's labeling). 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 (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 ~10% to 20% over the first hour, then 5% to 15% further over the next 23 hours, unless there is a compelling indication (eg, acute aortic dissection, severe preeclampsia, eclampsia) for more rapid BP and heart rate control (ACC/AHA [Whelton 2018]; Elliot 2020a; Marik 2011).

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 (ACC/AHA [Whelton 2018]; Elliot 2020b; Marik 2011). 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 (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 (Hofmeyr 2020; Macones 2020; Weeks 2020). 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 (Altabef 1992; Bayhi 1992; Chedraui 2003; Dayan 1996; Hofmeyr 2020; Macones 2020; Weeks 2020). If urgent uterine relaxation is required (eg, for fetal extraction), may use initial bolus of 100 to 200 mcg (Axemo 1998).

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Nitronal IV solution has been discontinued in the US for more than 1 year.

Note: Continuous IV infusion dosing units vary by age (mcg/kg/minute or mcg/minute); extra precautions should be taken. Tolerance to the hemodynamic and antianginal effects can develop within 24 to 48 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.

Heart failure; cardiogenic shock: Limited data available:

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 adolescents, 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 (AHA [Chameides 2011]; Artman 1987; Ilbawi 1985; Park 2014); doses up to 20 mcg/kg/minute may be used (Friedman 1985)

Adolescents: Continuous IV infusion: Initial: 5 to 10 mcg/minute; titrate every 3 to 5 minutes as needed to maximum rate of 200 mcg/minute (AHA [Chameides 2011]; Park 2014)

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 (Wong 1992). The maximum reported dose is application of a 1-inch strip to the affected site in a neonate (Denkler 1989); however, this is greater than the usual initial adult dose (1/2 inch) for angina; hypotension may occur; carefully monitor blood pressure (Reynolds 2014). Note: Minimal data available from clinical trials/case reports; however, use has been described in reviews of extravasation treatment (Reynolds 2014; Treadwell 2012).

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

Reconstitution

Vials: Dilute in D5W or NS; maximum concentration not to exceed 400 mcg/mL; prepare in glass bottles, EXCEL, or PAB containers (adsorption occurs to soft plastic (eg, PVC). Also available in premixed glass containers.

Administration

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 (Reynolds 2014; Wong 1992). May also apply dry warm compresses (Hurst 2004; Reynolds 2014).

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).

Storage

ER capsules: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

IV:

Premixed (glass container): Store at 25°C (77°F); brief exposure up to 40°C (104°F) does not adversely affect the product. Protect from light until time of use. Avoid excessive heat; protect from freezing.

Vial: Store intact vial at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light until time of use. Nitroglycerin diluted in D5W or NS in glass containers is physically and chemically stable for 48 hours at room temperature and for 7 days under refrigeration. In D5W or NS in EXCEL/PAB containers, it is physically and chemically stable for 24 hours at room temperature.

Rectal ointment: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Keep the tube tightly closed. Use within 8 weeks of first opening.

Sublingual powder: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 5°C to 40°C (41°F to 104°F).

Sublingual tablets: Store at 20°C to 25°C (68°F to 77°F) in original glass container.

Transdermal ointment: Store at 20°C to 25°C (68°F to 77°F). Close tightly immediately after use.

Transdermal patch: Store at 15°C to 30°C (59°F to 86°F).

Translingual spray: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not forcefully open or burn container after use. Do not spray toward flames.

Drug Interactions

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

Alfuzosin: May enhance the hypotensive effect of Nitroglycerin. Monitor therapy

Alteplase: Nitroglycerin may decrease the serum concentration of Alteplase. 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. Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

Ergot Derivatives: May diminish the vasodilatory effect of Nitroglycerin. This is of particular concern in patients being treated for angina. Nitroglycerin may increase the serum concentration of Ergot Derivatives. Avoid combination

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

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

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

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

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

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

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

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

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

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

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

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. 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. Consider therapy modification

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

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

Phosphodiesterase 5 Inhibitors: May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). 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. Monitor therapy

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

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

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

Riociguat: Vasodilators (Organic Nitrates) may enhance the hypotensive effect of Riociguat. 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. 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. Monitor therapy

Test Interactions

IV formulation: Due to propylene glycol content, triglyceride assays dependent on glycerol oxidase may be falsely elevated.

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

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: Avoid use in patients with hypertrophic cardiomyopathy with outflow tract obstruction; nitrates may reduce preload, exacerbating obstruction and cause hypotension or syncope and/or worsening of heart failure (HF) (ACCF/AHA [Gersh 2011]).

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.

Monitoring Parameters

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

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).

Patient Education

What is this drug used for?

Rectal:

• It is used to treat anal pain.

Injection:

• It is used to treat high blood pressure.

• It is used to treat heart failure (weak heart).

• It is used to treat chest pain or pressure.

All other products:

• It is used to treat chest pain or pressure.

• It is used to prevent chest pain or pressure.

All products:

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Burning or tingling of mouth

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe dizziness

• Passing out

• Persistent headache

• Fast heartbeat

• Slow heartbeat

• Flushing

• Blurred vision

• Dry mouth

• Sweating a lot

• Pale skin

• Severe nausea

• Severe vomiting

• Abnormal heartbeat

• Agitation

• Severe loss of strength and energy

• Chest pain

• Severe skin irritation

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions